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        <copyright>Newgen KnowledgeWorks</copyright>
        <item>
            <title><![CDATA[Towards enhancing coral heat tolerance: a “microbiome transplantation” treatment using inoculations of homogenized coral tissues]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1766073748958-b0073163-786b-4a61-bfab-69ec0fde7796/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-021-01053-6</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">Microbiome manipulation could enhance heat tolerance and help corals survive the pressures of ocean warming. We conducted coral microbiome transplantation (CMT) experiments using the reef-building corals, <i>Pocillopora</i> and <i>Porites</i>, and investigated whether this technique can benefit coral heat resistance while modifying the bacterial microbiome. Initially, heat-tolerant donors were identified in the wild. We then used fresh homogenates made from coral donor tissues to inoculate conspecific, heat-susceptible recipients and documented their bleaching responses and microbiomes by 16S rRNA gene metabarcoding.</p></div><div class="section" id="N65552"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">Recipients of both coral species bleached at lower rates compared to the control group when exposed to short-term heat stress (34 °C). One hundred twelve (<i>Pocillopora</i> sp.) and sixteen (<i>Porites</i> sp.) donor-specific bacterial species were identified in the microbiomes of recipients indicating transmission of bacteria. The amplicon sequence variants of the majority of these transmitted bacteria belonged to known, putatively symbiotic bacterial taxa of corals and were linked to the observed beneficial effect on the coral stress response. Microbiome dynamics in our experiments support the notion that microbiome community evenness and dominance of one or few bacterial species, rather than host-species identity, were drivers for microbiome stability in a holobiont context.</p></div><div class="section" id="N65564"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">Our results suggest that coral recipients likely favor the uptake of putative bacterial symbionts, recommending to include these taxonomic groups in future coral probiotics screening efforts. Our study suggests a scenario where these donor-specific bacterial symbionts might have been more efficient in supporting the recipients to resist heat stress compared to the native symbionts present in the control group. These findings urgently call for further experimental investigation of the mechanisms of action underlying the beneficial effect of CMT and for field-based long-term studies testing the persistence of the effect.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1766073748958-b0073163-786b-4a61-bfab-69ec0fde7796/assets/40168_2021_1053_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65579"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65582">The online version contains supplementary material available at 10.1186/s40168-021-01053-6.</p></div>]]></description>
            <pubDate><![CDATA[2021-05-06T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Androgen-induced gut dysbiosis disrupts glucolipid metabolism and endocrinal functions in polycystic ovary syndrome]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1766073578334-4ee2e02b-4b81-4e83-8b1e-9de4e2f74f55/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-021-01046-5</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">The characteristics of polycystic ovary syndrome (PCOS), a common reproductive endocrinal disorder, are high incidence, complicated aetiology and poor therapeutic effects. PCOS patients frequently exhibit gut dysbiosis; however, its roles in the regulation of metabolic and endocrinal balances in PCOS pathophysiology are not clear.</p></div><div class="section" id="N65546"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">In this study, gut dysbiosis was reproduced in dehydroepiandrosterone (DHEA)-induced PCOS-like rats. An antibiotic cocktail was used to eliminate gut microbiota during DHEA treatment; however, depletion of the gut microbiota did not prevent the occurrence of PCOS phenotypes in DHEA-treated rats. DHEA-shaped gut microbiota transplanted to pseudo germ-free recipients trigged disturbances in hepatic glucolipid metabolism and reproductive hormone imbalance. The clinical features of PCOS may be correlated with the relative abundance of gut microbes and the levels of faecal metabolites in faecal microbiota transplantation (FMT) recipient rats.</p></div><div class="section" id="N65552"><h3 class="BHead" id="nov000-3">Conclusion</h3><p class="para" id="Par3">These findings indicate that androgen-induced gut microbiota dysbiosis may aggravate metabolic and endocrinal malfunction in PCOS.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1766073578334-4ee2e02b-4b81-4e83-8b1e-9de4e2f74f55/assets/40168_2021_1046_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65567"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65570">The online version contains supplementary material available at 10.1186/s40168-021-01046-5.</p></div>]]></description>
            <pubDate><![CDATA[2021-05-06T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Iron status influences non-alcoholic fatty liver disease in obesity through the gut microbiome]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1766073508680-32798080-353a-4c7f-ac3f-d801af25daf9/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-021-01052-7</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">The gut microbiome and iron status are known to play a role in the pathophysiology of non-alcoholic fatty liver disease (NAFLD), although their complex interaction remains unclear.</p></div><div class="section" id="N65546"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">Here, we applied an integrative systems medicine approach (faecal metagenomics, plasma and urine metabolomics, hepatic transcriptomics) in 2 well-characterised human cohorts of subjects with obesity (discovery <i>n</i> = 49 and validation <i>n</i> = 628) and an independent cohort formed by both individuals with and without obesity (<i>n</i> = 130), combined with in vitro and animal models. Serum ferritin levels, as a markers of liver iron stores, were positively associated with liver fat accumulation in parallel with lower gut microbial gene richness, composition and functionality. Specifically, ferritin had strong negative associations with the <i>Pasteurellaceae</i>, <i>Leuconostocaceae</i> and <i>Micrococcaea</i> families. It also had consistent negative associations with several <i>Veillonella</i>, <i>Bifidobacterium</i> and <i>Lactobacillus</i> species, but positive associations with <i>Bacteroides</i> and <i>Prevotella</i> spp. Notably, the ferritin-associated bacterial families had a strong correlation with iron-related liver genes. In addition, several bacterial functions related to iron metabolism (transport, chelation, heme and siderophore biosynthesis) and NAFLD (fatty acid and glutathione biosynthesis) were also associated with the host serum ferritin levels. This iron-related microbiome signature was linked to a transcriptomic and metabolomic signature associated to the degree of liver fat accumulation through hepatic glucose metabolism. In particular, we found a consistent association among serum ferritin, <i>Pasteurellaceae</i> and <i>Micrococcacea</i> families, bacterial functions involved in histidine transport, the host circulating histidine levels and the liver expression of <i>GYS2</i> and <i>SEC24B.</i> Serum ferritin was also related to bacterial glycine transporters, the host glycine serum levels and the liver expression of glycine transporters. The transcriptomic findings were replicated in human primary hepatocytes, where iron supplementation also led to triglycerides accumulation and induced the expression of lipid and iron metabolism genes in synergy with palmitic acid. We further explored the direct impact of the microbiome on iron metabolism and liver fact accumulation through transplantation of faecal microbiota into recipient’s mice. In line with the results in humans, transplantation from ‘high ferritin donors’ resulted in alterations in several genes related to iron metabolism and fatty acid accumulation in recipient’s mice.</p></div><div class="section" id="N65597"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">Altogether, a significant interplay among the gut microbiome, iron status and liver fat accumulation is revealed, with potential significance for target therapies.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1766073508680-32798080-353a-4c7f-ac3f-d801af25daf9/assets/40168_2021_1052_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65612"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65615">The online version contains supplementary material available at 10.1186/s40168-021-01052-7.</p></div>]]></description>
            <pubDate><![CDATA[2021-05-07T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Diet, obesity, and the gut microbiome as determinants modulating metabolic outcomes in a non-human primate model]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1766072434316-77e541cc-2824-4d7b-88e1-9057c3fb11e9/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-021-01069-y</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Abstract</h3></div><div class="section" id="N65543"><h3 class="BHead" id="nov000-2">Background</h3><p class="para" id="Par1">The objective of this study was to increase understanding of the complex interactions between diet, obesity, and the gut microbiome of adult female non-human primates (NHPs). Subjects consumed either a Western (<i>n</i>=15) or Mediterranean (<i>n</i>=14) diet designed to represent human dietary patterns for 31 months. Body composition was determined using CT, fecal samples were collected, and shotgun metagenomic sequencing was performed. Gut microbiome results were grouped by diet and adiposity.</p></div><div class="section" id="N65555"><h3 class="BHead" id="nov000-3">Results</h3><p class="para" id="Par2">Diet was the main contributor to gut microbiome bacterial diversity. Adiposity within each diet was associated with subtle shifts in the proportional abundance of several taxa. Mediterranean diet-fed NHPs with lower body fat had a greater proportion of <i>Lactobacillus animalis</i> than their higher body fat counterparts. Higher body fat Western diet-fed NHPs had more <i>Ruminococcus champaneliensis</i> and less <i>Bacteroides uniformis</i> than their low body fat counterparts. Western diet-fed NHPs had significantly higher levels of <i>Prevotella copri</i> than Mediterranean diet NHPs. Western diet-fed subjects were stratified by <i>P. copri</i> abundance (<i>P. copri</i><sup>HIGH</sup> versus <i>P. copri</i><sup>LOW</sup>), which was not associated with adiposity. Overall, Western diet-fed animals in the <i>P. copri</i><sup>HIGH</sup> group showed greater proportional abundance of <i>B. ovatus</i>, <i>B. faecis</i>, <i>P. stercorea</i>, <i>P. brevis</i>, and <i>Faecalibacterium prausnitzii</i> than those in the Western <i>P. copri</i><sup>LOW</sup> group. Western diet <i>P. copri</i><sup>LOW</sup> subjects had a greater proportion of <i>Eubacterium siraeum</i>. <i>E. siraeum</i> negatively correlated with <i>P. copri</i> proportional abundance regardless of dietary consumption. In the Western diet group, Shannon diversity was significantly higher in <i>P. copri</i><sup>LOW</sup> when compared to <i>P. copri</i><sup>HIGH</sup> subjects. Furthermore, gut <i>E. siraeum</i> abundance positively correlated with HDL plasma cholesterol indicating that those in the <i>P. copri</i><sup>LOW</sup> population may represent a more metabolically healthy population. Untargeted metabolomics on urine and plasma from Western diet-fed <i>P. copri</i><sup>HIGH</sup> and <i>P. copri</i><sup>LOW</sup> subjects suggest early kidney dysfunction in Western diet-fed <i>P. copri</i><sup>HIGH</sup> subjects.</p></div><div class="section" id="N65658"><h3 class="BHead" id="nov000-4">Conclusions</h3><p class="para" id="Par3">In summary, the data indicate diet to be the major influencer of gut bacterial diversity. However, diet and adiposity must be considered together when analyzing changes in abundance of specific bacterial taxa. Interestingly, <i>P. copri</i> appears to mediate metabolic dysfunction in Western diet-fed NHPs.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1766072434316-77e541cc-2824-4d7b-88e1-9057c3fb11e9/assets/40168_2021_1069_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65677"><h3 class="BHead" id="nov000-5">Supplementary Information</h3><p class="para" id="N65680">The online version contains supplementary material available at 10.1186/s40168-021-01069-y.</p></div>]]></description>
            <pubDate><![CDATA[2021-05-05T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Assessing Child Abuse Hotline Inquiries in the Wake of COVID-19]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1766071475036-ea0e77ad-a9da-4be6-b9ff-a81d511109f5/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1001/jamapediatrics.2021.0525</link>
            <description><![CDATA[<p class="para" id="N65540">This cross-sectional study assesses inquiries to a child distress hotline during the COVID-19 pandemic compared with inquiries during the same period the previous year.</p>]]></description>
            <pubDate><![CDATA[2021-05-03T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Whole lung tissue is the preferred sampling method for amplicon-based characterization of murine lung microbiota]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1766070166829-9145d1ea-4af1-4bc8-8477-8a4514357eec/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-021-01055-4</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">Low-biomass microbiome studies (such as those of the lungs, placenta, and skin) are vulnerable to contamination and sequencing stochasticity, which obscure legitimate microbial signal. While human lung microbiome studies have rigorously identified sampling strategies that reliably capture microbial signal from these low-biomass microbial communities, the optimal sampling strategy for characterizing murine lung microbiota has not been empirically determined. Performing accurate, reliable characterization of murine lung microbiota and distinguishing true microbial signal from noise in these samples will be critical for further mechanistic microbiome studies in mice.</p></div><div class="section" id="N65546"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">Using an analytic approach grounded in microbial ecology, we compared bacterial DNA from the lungs of healthy adult mice collected via two common sampling approaches: homogenized whole lung tissue and bronchoalveolar lavage (BAL) fluid. We quantified bacterial DNA using droplet digital PCR, characterized bacterial communities using 16S rRNA gene sequencing, and systematically assessed the quantity and identity of bacterial DNA in both specimen types. We compared bacteria detected in lung specimens to each other and to potential source communities: negative (background) control specimens and paired oral samples. By all measures, whole lung tissue in mice contained greater bacterial signal and less evidence of contamination than did BAL fluid. Relative to BAL fluid, whole lung tissue exhibited a greater quantity of bacterial DNA, distinct community composition, decreased sample-to-sample variation, and greater biological plausibility when compared to potential source communities. In contrast, bacteria detected in BAL fluid were minimally different from those of procedural, reagent, and sequencing controls.</p></div><div class="section" id="N65552"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">An ecology-based analytical approach discriminates signal from noise in this low-biomass microbiome study and identifies whole lung tissue as the preferred specimen type for murine lung microbiome studies. Sequencing, analysis, and reporting of potential source communities, including negative control specimens and contiguous biological sites, are crucial for biological interpretation of low-biomass microbiome studies, independent of specimen type.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1766070166829-9145d1ea-4af1-4bc8-8477-8a4514357eec/assets/40168_2021_1055_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65567"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65570">The online version contains supplementary material available at 10.1186/s40168-021-01055-4.</p></div>]]></description>
            <pubDate><![CDATA[2021-05-05T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Association of Oral Corticosteroid Bursts With Severe Adverse Events in Children]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1766067648841-dadafe42-96ee-4442-83f0-e8b728a39db7/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1001/jamapediatrics.2021.0433</link>
            <description><![CDATA[<div class="section" id="ab-poi210016-1"><h3 class="BHead" id="nov000-1">Question</h3><p class="para" id="N65546">Are there potential harms associated with oral corticosteroid bursts (defined as the use of oral corticosteroids for 14 or fewer days) in children?</p></div><div class="section" id="ab-poi210016-2"><h3 class="BHead" id="nov000-2">Findings</h3><p class="para" id="N65552">In this nationwide population-based study of 1 064 587 children who received a single corticosteroid burst, a burst was associated with 1.4- to 2.2-fold increased risk of gastrointestinal bleeding, sepsis, and pneumonia within the first month after corticosteroid initiation.</p></div><div class="section" id="ab-poi210016-3"><h3 class="BHead" id="nov000-3">Meaning</h3><p class="para" id="N65558">This study suggests that clinicians should be aware of potentially severe adverse events associated with corticosteroid bursts in children.</p></div><div class="section" id="ab-poi210016-4"><h3 class="BHead" id="nov000-1">Importance</h3><p class="para" id="N65543">The adverse effects from the long-term use of oral corticosteroids are known, but, to our knowledge, few studies have reported the risk of corticosteroid bursts, particularly among children.</p></div><div class="section" id="ab-poi210016-5"><h3 class="BHead" id="nov000-2">Objective</h3><p class="para" id="N65549">To quantify the associations of corticosteroid bursts with severe adverse events, including gastrointestinal (GI) bleeding, sepsis, pneumonia, and glaucoma, in children.</p></div><div class="section" id="ab-poi210016-6"><h3 class="BHead" id="nov000-3">Design, Setting, and Participants</h3><p class="para" id="N65555">This study used data derived from the National Health Insurance Research Database in Taiwan from January 1, 2013, to December 31, 2017, on children younger than 18 years of age and used a self-controlled case series design. Data were analyzed from January 1 to July 30, 2020.</p></div><div class="section" id="ab-poi210016-7"><h3 class="BHead" id="nov000-4">Exposure</h3><p class="para" id="N65561">Oral corticosteroid bursts (defined as oral corticosteroid use for ≤14 days).</p></div><div class="section" id="ab-poi210016-8"><h3 class="BHead" id="nov000-5">Main Outcomes and Measures</h3><p class="para" id="N65567">Incidence rates were calculated of 4 severe adverse events (GI bleeding, sepsis, pneumonia, and glaucoma) in children who did or did not receive corticosteroid bursts. Conditional fixed-effect Poisson regression was used to estimate incidence rate ratios (IRRs) of severe adverse events within 5 to 30 days and 31 to 90 days after initiation of corticosteroid bursts.</p></div><div class="section" id="ab-poi210016-9"><h3 class="BHead" id="nov000-6">Results</h3><p class="para" id="N65573">Among 4 542 623 children, 23% (1 064 587; 544 268 boys [51.1%]; mean [SD] age, 9.7 [5.8] years) were prescribed a single corticosteroid burst. The most common indications were acute respiratory tract infections and allergic diseases. The incidence rate differences per 1000 person-years between children administered a single corticosteroid burst and those not prescribed corticosteroids were 0.60 (95% CI, 0.55-0.64) for GI bleeding, 0.03 (95% CI, 0.02-0.05) for sepsis, 9.35 (95% CI, 9.19-9.51) for pneumonia, and 0.01 (95% CI, 0.01-0.03) for glaucoma. The IRRs within 5 to 30 days after initiating corticosteroid bursts were 1.41 (95% CI, 1.27-1.57) for GI bleeding, 2.02 (95% CI, 1.55-2.64) for sepsis, 2.19 (95% CI, 2.13-2.25) for pneumonia, and 0.98 (95% CI, 0.85-1.13) for glaucoma; the IRRs within the subsequent 31 to 90 days were 1.10 (95% CI, 1.02-1.19) for GI bleeding, 1.08 (95% CI, 0.88-1.32) for sepsis, 1.09 (95% CI, 1.07-1.11) for pneumonia, and 0.95 (95% CI, 0.85-1.06) for glaucoma.</p></div><div class="section" id="ab-poi210016-10"><h3 class="BHead" id="nov000-7">Conclusions and Relevance</h3><p class="para" id="N65579">This study suggests that corticosteroid bursts, which are commonly prescribed for children with respiratory and allergic conditions, are associated with a 1.4- to 2.2-fold increased risk of GI bleeding, sepsis, and pneumonia within the first month after initiation of corticosteroid therapy that is attenuated during the subsequent 31 to 90 days.</p></div><p class="para" id="N65540">This study examines the associations of corticosteroid bursts with severe adverse events, including gastrointestinal bleeding, sepsis, pneumonia, and glaucoma, in children.</p>]]></description>
            <pubDate><![CDATA[2021-04-19T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Association of Oral Corticosteroid Bursts With Severe Adverse Events in Children]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1766067648841-dadafe42-96ee-4442-83f0-e8b728a39db7/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1001/jamapediatrics.2021.0433</link>
            <description><![CDATA[<div class="section" id="ab-poi210016-1"><h3 class="BHead" id="nov000-1">Question</h3><p class="para" id="N65546">Are there potential harms associated with oral corticosteroid bursts (defined as the use of oral corticosteroids for 14 or fewer days) in children?</p></div><div class="section" id="ab-poi210016-2"><h3 class="BHead" id="nov000-2">Findings</h3><p class="para" id="N65552">In this nationwide population-based study of 1 064 587 children who received a single corticosteroid burst, a burst was associated with 1.4- to 2.2-fold increased risk of gastrointestinal bleeding, sepsis, and pneumonia within the first month after corticosteroid initiation.</p></div><div class="section" id="ab-poi210016-3"><h3 class="BHead" id="nov000-3">Meaning</h3><p class="para" id="N65558">This study suggests that clinicians should be aware of potentially severe adverse events associated with corticosteroid bursts in children.</p></div><div class="section" id="ab-poi210016-4"><h3 class="BHead" id="nov000-1">Importance</h3><p class="para" id="N65543">The adverse effects from the long-term use of oral corticosteroids are known, but, to our knowledge, few studies have reported the risk of corticosteroid bursts, particularly among children.</p></div><div class="section" id="ab-poi210016-5"><h3 class="BHead" id="nov000-2">Objective</h3><p class="para" id="N65549">To quantify the associations of corticosteroid bursts with severe adverse events, including gastrointestinal (GI) bleeding, sepsis, pneumonia, and glaucoma, in children.</p></div><div class="section" id="ab-poi210016-6"><h3 class="BHead" id="nov000-3">Design, Setting, and Participants</h3><p class="para" id="N65555">This study used data derived from the National Health Insurance Research Database in Taiwan from January 1, 2013, to December 31, 2017, on children younger than 18 years of age and used a self-controlled case series design. Data were analyzed from January 1 to July 30, 2020.</p></div><div class="section" id="ab-poi210016-7"><h3 class="BHead" id="nov000-4">Exposure</h3><p class="para" id="N65561">Oral corticosteroid bursts (defined as oral corticosteroid use for ≤14 days).</p></div><div class="section" id="ab-poi210016-8"><h3 class="BHead" id="nov000-5">Main Outcomes and Measures</h3><p class="para" id="N65567">Incidence rates were calculated of 4 severe adverse events (GI bleeding, sepsis, pneumonia, and glaucoma) in children who did or did not receive corticosteroid bursts. Conditional fixed-effect Poisson regression was used to estimate incidence rate ratios (IRRs) of severe adverse events within 5 to 30 days and 31 to 90 days after initiation of corticosteroid bursts.</p></div><div class="section" id="ab-poi210016-9"><h3 class="BHead" id="nov000-6">Results</h3><p class="para" id="N65573">Among 4 542 623 children, 23% (1 064 587; 544 268 boys [51.1%]; mean [SD] age, 9.7 [5.8] years) were prescribed a single corticosteroid burst. The most common indications were acute respiratory tract infections and allergic diseases. The incidence rate differences per 1000 person-years between children administered a single corticosteroid burst and those not prescribed corticosteroids were 0.60 (95% CI, 0.55-0.64) for GI bleeding, 0.03 (95% CI, 0.02-0.05) for sepsis, 9.35 (95% CI, 9.19-9.51) for pneumonia, and 0.01 (95% CI, 0.01-0.03) for glaucoma. The IRRs within 5 to 30 days after initiating corticosteroid bursts were 1.41 (95% CI, 1.27-1.57) for GI bleeding, 2.02 (95% CI, 1.55-2.64) for sepsis, 2.19 (95% CI, 2.13-2.25) for pneumonia, and 0.98 (95% CI, 0.85-1.13) for glaucoma; the IRRs within the subsequent 31 to 90 days were 1.10 (95% CI, 1.02-1.19) for GI bleeding, 1.08 (95% CI, 0.88-1.32) for sepsis, 1.09 (95% CI, 1.07-1.11) for pneumonia, and 0.95 (95% CI, 0.85-1.06) for glaucoma.</p></div><div class="section" id="ab-poi210016-10"><h3 class="BHead" id="nov000-7">Conclusions and Relevance</h3><p class="para" id="N65579">This study suggests that corticosteroid bursts, which are commonly prescribed for children with respiratory and allergic conditions, are associated with a 1.4- to 2.2-fold increased risk of GI bleeding, sepsis, and pneumonia within the first month after initiation of corticosteroid therapy that is attenuated during the subsequent 31 to 90 days.</p></div><p class="para" id="N65540">This study examines the associations of corticosteroid bursts with severe adverse events, including gastrointestinal bleeding, sepsis, pneumonia, and glaucoma, in children.</p>]]></description>
            <pubDate><![CDATA[2021-04-19T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Maternal and Neonatal Morbidity and Mortality Among Pregnant Women With and Without COVID-19 Infection]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1766066817988-c04c3341-b7cf-4ecf-bb3b-4bdd50c8e34d/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1001/jamapediatrics.2021.1050</link>
            <description><![CDATA[<p class="para" id="N65540">This cohort study assesses the association between COVID-19 and maternal and neonatal outcomes in pregnant women with COVID-19 diagnosis compared with concomitantly enrolled pregnant women without COVID-19 diagnosis.</p><div class="section" id="ab-poi210025-1"><h3 class="BHead" id="nov000-1">Question</h3><p class="para" id="N65546">To what extent does COVID-19 in pregnancy alter the risks of adverse maternal and neonatal outcomes compared with pregnant individuals without COVID-19?</p></div><div class="section" id="ab-poi210025-2"><h3 class="BHead" id="nov000-2">Findings</h3><p class="para" id="N65552">In this multinational cohort study of 2130 pregnant women in 18 countries, women with COVID-19 diagnosis were at increased risk of a composite maternal morbidity and mortality index. Newborns of women with COVID-19 diagnosis had significantly higher severe neonatal morbidity index and severe perinatal morbidity and mortality index compared with newborns of women without COVID-19 diagnosis.</p></div><div class="section" id="ab-poi210025-3"><h3 class="BHead" id="nov000-3">Meaning</h3><p class="para" id="N65558">This study indicates a consistent association between pregnant individuals with COVID-19 diagnosis and higher rates of adverse outcomes, including maternal mortality, preeclampsia, and preterm birth compared with pregnant individuals without COVID-19 diagnosis.</p></div><div class="section" id="ab-poi210025-4"><h3 class="BHead" id="nov000-1">Importance</h3><p class="para" id="N65543">Detailed information about the association of COVID-19 with outcomes in pregnant individuals compared with not-infected pregnant individuals is much needed.</p></div><div class="section" id="ab-poi210025-5"><h3 class="BHead" id="nov000-2">Objective</h3><p class="para" id="N65549">To evaluate the risks associated with COVID-19 in pregnancy on maternal and neonatal outcomes compared with not-infected, concomitant pregnant individuals.</p></div><div class="section" id="ab-poi210025-6"><h3 class="BHead" id="nov000-3">Design, Setting, and Participants</h3><p class="para" id="N65555">In this cohort study that took place from March to October 2020, involving 43 institutions in 18 countries, 2 unmatched, consecutive, not-infected women were concomitantly enrolled immediately after each infected woman was identified, at any stage of pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed up until hospital discharge.</p></div><div class="section" id="ab-poi210025-7"><h3 class="BHead" id="nov000-4">Exposures</h3><p class="para" id="N65561">COVID-19 in pregnancy determined by laboratory confirmation of COVID-19 and/or radiological pulmonary findings or 2 or more predefined COVID-19 symptoms.</p></div><div class="section" id="ab-poi210025-8"><h3 class="BHead" id="nov000-5">Main Outcomes and Measures</h3><p class="para" id="N65567">The primary outcome measures were indices of (maternal and severe neonatal/perinatal) morbidity and mortality; the individual components of these indices were secondary outcomes. Models for these outcomes were adjusted for country, month entering study, maternal age, and history of morbidity.</p></div><div class="section" id="ab-poi210025-9"><h3 class="BHead" id="nov000-6">Results</h3><p class="para" id="N65573">A total of 706 pregnant women with COVID-19 diagnosis and 1424 pregnant women without COVID-19 diagnosis were enrolled, all with broadly similar demographic characteristics (mean [SD] age, 30.2 [6.1] years). Overweight early in pregnancy occurred in 323 women (48.6%) with COVID-19 diagnosis and 554 women (40.2%) without. Women with COVID-19 diagnosis were at higher risk for preeclampsia/eclampsia (relative risk [RR], 1.76; 95% CI, 1.27-2.43), severe infections (RR, 3.38; 95% CI, 1.63-7.01), intensive care unit admission (RR, 5.04; 95% CI, 3.13-8.10), maternal mortality (RR, 22.3; 95% CI, 2.88-172), preterm birth (RR, 1.59; 95% CI, 1.30-1.94), medically indicated preterm birth (RR, 1.97; 95% CI, 1.56-2.51), severe neonatal morbidity index (RR, 2.66; 95% CI, 1.69-4.18), and severe perinatal morbidity and mortality index (RR, 2.14; 95% CI, 1.66-2.75). Fever and shortness of breath for any duration was associated with increased risk of severe maternal complications (RR, 2.56; 95% CI, 1.92-3.40) and neonatal complications (RR, 4.97; 95% CI, 2.11-11.69). Asymptomatic women with COVID-19 diagnosis remained at higher risk only for maternal morbidity (RR, 1.24; 95% CI, 1.00-1.54) and preeclampsia (RR, 1.63; 95% CI, 1.01-2.63). Among women who tested positive (98.1% by real-time polymerase chain reaction), 54 (13%) of their neonates tested positive. Cesarean delivery (RR, 2.15; 95% CI, 1.18-3.91) but not breastfeeding (RR, 1.10; 95% CI, 0.66-1.85) was associated with increased risk for neonatal test positivity.</p></div><div class="section" id="ab-poi210025-10"><h3 class="BHead" id="nov000-7">Conclusions and Relevance</h3><p class="para" id="N65579">In this multinational cohort study, COVID-19 in pregnancy was associated with consistent and substantial increases in severe maternal morbidity and mortality and neonatal complications when pregnant women with and without COVID-19 diagnosis were compared. The findings should alert pregnant individuals and clinicians to implement strictly all the recommended COVID-19 preventive measures.</p></div>]]></description>
            <pubDate><![CDATA[2021-04-22T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Maternal and Neonatal Morbidity and Mortality Among Pregnant Women With and Without COVID-19 Infection]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1766066817988-c04c3341-b7cf-4ecf-bb3b-4bdd50c8e34d/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1001/jamapediatrics.2021.1050</link>
            <description><![CDATA[<p class="para" id="N65540">This cohort study assesses the association between COVID-19 and maternal and neonatal outcomes in pregnant women with COVID-19 diagnosis compared with concomitantly enrolled pregnant women without COVID-19 diagnosis.</p><div class="section" id="ab-poi210025-1"><h3 class="BHead" id="nov000-1">Question</h3><p class="para" id="N65546">To what extent does COVID-19 in pregnancy alter the risks of adverse maternal and neonatal outcomes compared with pregnant individuals without COVID-19?</p></div><div class="section" id="ab-poi210025-2"><h3 class="BHead" id="nov000-2">Findings</h3><p class="para" id="N65552">In this multinational cohort study of 2130 pregnant women in 18 countries, women with COVID-19 diagnosis were at increased risk of a composite maternal morbidity and mortality index. Newborns of women with COVID-19 diagnosis had significantly higher severe neonatal morbidity index and severe perinatal morbidity and mortality index compared with newborns of women without COVID-19 diagnosis.</p></div><div class="section" id="ab-poi210025-3"><h3 class="BHead" id="nov000-3">Meaning</h3><p class="para" id="N65558">This study indicates a consistent association between pregnant individuals with COVID-19 diagnosis and higher rates of adverse outcomes, including maternal mortality, preeclampsia, and preterm birth compared with pregnant individuals without COVID-19 diagnosis.</p></div><div class="section" id="ab-poi210025-4"><h3 class="BHead" id="nov000-1">Importance</h3><p class="para" id="N65543">Detailed information about the association of COVID-19 with outcomes in pregnant individuals compared with not-infected pregnant individuals is much needed.</p></div><div class="section" id="ab-poi210025-5"><h3 class="BHead" id="nov000-2">Objective</h3><p class="para" id="N65549">To evaluate the risks associated with COVID-19 in pregnancy on maternal and neonatal outcomes compared with not-infected, concomitant pregnant individuals.</p></div><div class="section" id="ab-poi210025-6"><h3 class="BHead" id="nov000-3">Design, Setting, and Participants</h3><p class="para" id="N65555">In this cohort study that took place from March to October 2020, involving 43 institutions in 18 countries, 2 unmatched, consecutive, not-infected women were concomitantly enrolled immediately after each infected woman was identified, at any stage of pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed up until hospital discharge.</p></div><div class="section" id="ab-poi210025-7"><h3 class="BHead" id="nov000-4">Exposures</h3><p class="para" id="N65561">COVID-19 in pregnancy determined by laboratory confirmation of COVID-19 and/or radiological pulmonary findings or 2 or more predefined COVID-19 symptoms.</p></div><div class="section" id="ab-poi210025-8"><h3 class="BHead" id="nov000-5">Main Outcomes and Measures</h3><p class="para" id="N65567">The primary outcome measures were indices of (maternal and severe neonatal/perinatal) morbidity and mortality; the individual components of these indices were secondary outcomes. Models for these outcomes were adjusted for country, month entering study, maternal age, and history of morbidity.</p></div><div class="section" id="ab-poi210025-9"><h3 class="BHead" id="nov000-6">Results</h3><p class="para" id="N65573">A total of 706 pregnant women with COVID-19 diagnosis and 1424 pregnant women without COVID-19 diagnosis were enrolled, all with broadly similar demographic characteristics (mean [SD] age, 30.2 [6.1] years). Overweight early in pregnancy occurred in 323 women (48.6%) with COVID-19 diagnosis and 554 women (40.2%) without. Women with COVID-19 diagnosis were at higher risk for preeclampsia/eclampsia (relative risk [RR], 1.76; 95% CI, 1.27-2.43), severe infections (RR, 3.38; 95% CI, 1.63-7.01), intensive care unit admission (RR, 5.04; 95% CI, 3.13-8.10), maternal mortality (RR, 22.3; 95% CI, 2.88-172), preterm birth (RR, 1.59; 95% CI, 1.30-1.94), medically indicated preterm birth (RR, 1.97; 95% CI, 1.56-2.51), severe neonatal morbidity index (RR, 2.66; 95% CI, 1.69-4.18), and severe perinatal morbidity and mortality index (RR, 2.14; 95% CI, 1.66-2.75). Fever and shortness of breath for any duration was associated with increased risk of severe maternal complications (RR, 2.56; 95% CI, 1.92-3.40) and neonatal complications (RR, 4.97; 95% CI, 2.11-11.69). Asymptomatic women with COVID-19 diagnosis remained at higher risk only for maternal morbidity (RR, 1.24; 95% CI, 1.00-1.54) and preeclampsia (RR, 1.63; 95% CI, 1.01-2.63). Among women who tested positive (98.1% by real-time polymerase chain reaction), 54 (13%) of their neonates tested positive. Cesarean delivery (RR, 2.15; 95% CI, 1.18-3.91) but not breastfeeding (RR, 1.10; 95% CI, 0.66-1.85) was associated with increased risk for neonatal test positivity.</p></div><div class="section" id="ab-poi210025-10"><h3 class="BHead" id="nov000-7">Conclusions and Relevance</h3><p class="para" id="N65579">In this multinational cohort study, COVID-19 in pregnancy was associated with consistent and substantial increases in severe maternal morbidity and mortality and neonatal complications when pregnant women with and without COVID-19 diagnosis were compared. The findings should alert pregnant individuals and clinicians to implement strictly all the recommended COVID-19 preventive measures.</p></div>]]></description>
            <pubDate><![CDATA[2021-04-22T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Synergistic action of the gut microbiota in environmental RNA interference in a leaf beetle]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1766065431606-c14ffa49-0740-4c8c-af8d-708e614db28d/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-021-01066-1</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">RNA interference (RNAi) has emerged as an efficient tool to control insect pests. When insects ingest double-stranded RNAs (dsRNAs) targeted against essential genes, strong gene silencing and mortality can be induced. To exert their function, dsRNA molecules must pass through the insect’s gut and enter epithelial cells and/or the hemolymph. Gut bacteria are known to play multifarious roles in food digestion and nutrition, and confer protection against pathogens and parasites. Whether there is a cross talk between gut bacteria and ingested dsRNAs and whether the microbiome affects RNAi efficiency are unknown.</p></div><div class="section" id="N65546"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">Here, using a leaf beetle gut microbiota system, we investigated whether gut bacteria interact with dsRNA molecules and how the gut microbiota affects RNAi responses in insects. We first showed that the leaf beetle <i>Plagiodera versicolora</i> (Coleoptera) is highly susceptible to RNAi. We then demonstrated that ingestion of dsRNAs by non-axenic <i>P. versicolora</i> larvae results in (i) significantly accelerated mortality compared with axenic larvae, and (ii) overgrowth and dysbiosis of the gut microbiota. The latter may be caused by bacterial utilization of dsRNA degradation products. Furthermore, we found that <i>Pseudomonas putida</i>, a gut bacterium of <i>P. versicolora</i>, acts as major accelerator of the death of <i>P. versicolora</i> larvae by transitioning from commensal to pathogenic lifestyle.</p></div><div class="section" id="N65567"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">The present study illuminates the complex interplay between lethal dsRNA, the insect host, and its gut microbiota. The ingestion of dsRNA by the leaf beetle caused a dysbiosis of gut bacterial community, and the dsRNA degradation products by host insect preferentially promoted the growth of an entomopathogenic bacterium, which accelerated dsRNA lethality to the insect. Our findings reveal a synergistic role of the gut microbiota in dsRNA-induced mortality of pest insects, and provide new insights in the mechanisms of RNAi-based pest control.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1766065431606-c14ffa49-0740-4c8c-af8d-708e614db28d/assets/40168_2021_1066_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65583"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65586">The online version contains supplementary material available at 10.1186/s40168-021-01066-1.</p></div>]]></description>
            <pubDate><![CDATA[2021-05-04T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Protist diversity and community complexity in the rhizosphere of switchgrass are dynamic as plants develop]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1766047301246-747d9b6f-2d3b-419a-8346-d9e99886161c/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-021-01042-9</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">Despite their widespread distribution and ecological importance, protists remain one of the least understood components of the soil and rhizosphere microbiome. Knowledge of the roles that protists play in stimulating organic matter decomposition and shaping microbiome dynamics continues to grow, but there remains a need to understand the extent to which biological and environmental factors mediate protist community assembly and dynamics. We hypothesize that protists communities are filtered by the influence of plants on their rhizosphere biological and physicochemical environment, resulting in patterns of protist diversity and composition that mirror previously observed diversity and successional dynamics in rhizosphere bacterial communities.</p></div><div class="section" id="N65546"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">We analyzed protist communities associated with the rhizosphere and bulk soil of switchgrass (SG) plants (<i>Panicum virgatum</i>) at different phenological stages, grown in two marginal soils as part of a large-scale field experiment. Our results reveal that the diversity of protists is lower in rhizosphere than bulk soils, and that temporal variations depend on soil properties but are less pronounced in rhizosphere soil. Patterns of significantly prevalent protists groups in the rhizosphere suggest that most protists play varied ecological roles across plant growth stages and that some plant pathogenic protists and protists with omnivorous diets reoccur over time in the rhizosphere. We found that protist co-occurrence network dynamics are more complex in the rhizosphere compared to bulk soil. A phylogenetic bin-based null model analysis showed that protists’ community assembly in our study sites is mainly controlled by homogenous selection and dispersal limitation, with stronger selection in rhizosphere than bulk soil as SG grew and senesced.</p></div><div class="section" id="N65555"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">We demonstrate that environmental filtering is a dominant determinant of overall protist community properties and that at the rhizosphere level, plant control on the physical and biological environment is a critical driver of protist community composition and dynamics. Since protists are key contributors to plant nutrient availability and bacterial community composition and abundance, mapping and understanding their patterns in rhizosphere soil is foundational to understanding the ecology of the root-microbe-soil system.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1766047301246-747d9b6f-2d3b-419a-8346-d9e99886161c/assets/40168_2021_1042_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65570"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65573">The online version contains supplementary material available at 10.1186/s40168-021-01042-9.</p></div>]]></description>
            <pubDate><![CDATA[2021-04-28T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Effectiveness of Targeted Interventions on Treatment of Infants With Bronchiolitis]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1766041832330-4dfa1aab-0e01-4ab2-bef3-939635cc3e2b/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1001/jamapediatrics.2021.0295</link>
            <description><![CDATA[<div class="section" id="ab-poi210010-1"><h3 class="BHead" id="nov000-1">Question</h3><p class="para" id="N65546">Can the evidence-based treatment of infants with bronchiolitis be improved by using targeted interventions to deimplement low-value care?</p></div><div class="section" id="ab-poi210010-2"><h3 class="BHead" id="nov000-2">Findings</h3><p class="para" id="N65552">In this international cluster randomized clinical trial of 26 hospitals and 3727 infants, an absolute risk difference favoring intervention hospitals was seen in compliance with 5 evidence-based recommendations in the treatment of infants with bronchiolitis.</p></div><div class="section" id="ab-poi210010-3"><h3 class="BHead" id="nov000-3">Meaning</h3><p class="para" id="N65558">Use of targeted interventions improved the treatment of infants with bronchiolitis by deimplementing the use of ineffective and potentially harmful therapies and management; these results are important for bronchiolitis management, deimplementation science, and future interventions in acute care pediatrics.</p></div><p class="para" id="N65541">This cluster randomized clinical trial uses data from 26 hospitals to investigate whether evidence-based treatment of infants with bronchiolitis can be improved by using targeted interventions to deimplement low-value care.</p><div class="section" id="ab-poi210010-4"><h3 class="BHead" id="nov000-1">Importance</h3><p class="para" id="N65543">In developed countries, bronchiolitis is the most common reason for infants to be admitted to the hospital, and all international bronchiolitis guidelines recommend supportive care; however, significant variation in practice continues with infants receiving non–evidence-based therapies. Deimplementation research aims to reduce the use of low-value care, and advancing science in this area is critical to delivering evidence-based care.</p></div><div class="section" id="ab-poi210010-5"><h3 class="BHead" id="nov000-2">Objective</h3><p class="para" id="N65549">To determine the effectiveness of targeted interventions vs passive dissemination of an evidence-based bronchiolitis guideline in improving treatment of infants with bronchiolitis.</p></div><div class="section" id="ab-poi210010-6"><h3 class="BHead" id="nov000-3">Design, Setting, and Participants</h3><p class="para" id="N65555">This international, multicenter cluster randomized clinical trial included 26 hospitals (clusters) in Australia and New Zealand providing tertiary or secondary pediatric care (13 randomized to intervention, 13 to control) during the 2017 bronchiolitis season. Data were collected on 8003 infants for the 3 bronchiolitis seasons (2014-2016) before the implementation period and 3727 infants for the implementation period (2017 bronchiolitis season, May 1-November 30). Data were analyzed from November 16, 2018, to December 9, 2020.</p></div><div class="section" id="ab-poi210010-7"><h3 class="BHead" id="nov000-4">Interventions</h3><p class="para" id="N65561">Interventions were developed using theories of behavior change to target key factors that influence bronchiolitis management. These interventions included site-based clinical leads, stakeholder meetings, a train-the-trainer workshop, targeted educational delivery, other educational and promotional materials, and audit and feedback.</p></div><div class="section" id="ab-poi210010-8"><h3 class="BHead" id="nov000-5">Main Outcomes and Measures</h3><p class="para" id="N65567">The primary outcome was compliance during the first 24 hours of care with no use of chest radiography, albuterol, glucocorticoids, antibiotics, and epinephrine, measured retrospectively from medical records of randomly selected infants with bronchiolitis who presented to the hospital. There were no patient-level exclusions.</p></div><div class="section" id="ab-poi210010-9"><h3 class="BHead" id="nov000-6">Results</h3><p class="para" id="N65573">A total of 26 hospitals were randomized without dropouts. Analysis was by intention to treat. Baseline data collected on 8003 infants for 3 bronchiolitis seasons (2014-2016) before the implementation period were similar between intervention and control hospitals. Implementation period data were collected on 3727 infants, including 2328 boys (62%) and 1399 girls (38%), with a mean (SD) age of 6.0 (3.2) months. A total of 459 (12%) were Māori (New Zealand), and 295 (8%) were Aboriginal/Torres Strait Islander (Australia). Compliance with recommendations was 85.1% (95% CI, 82.6%-89.7%) in intervention hospitals vs 73.0% (95% CI, 65.3%-78.8%) in control hospitals (adjusted risk difference, 14.1%; 95% CI, 6.5%-21.7%; <i>P</i> &lt; .001).</p></div><div class="section" id="ab-poi210010-10"><h3 class="BHead" id="nov000-7">Conclusions and Relevance</h3><p class="para" id="N65582">Targeted interventions led to improved treatment of infants with bronchiolitis. This study has important implications for bronchiolitis management and the development of effective interventions to deimplement low-value care.</p></div><div class="section" id="ab-poi210010-11"><h3 class="BHead" id="nov000-8">Trial Registration</h3><p class="para" id="N65588">Australian and New Zealand Clinical Trials Registry: ACTRN12616001567415.</p></div>]]></description>
            <pubDate><![CDATA[2021-04-12T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Effectiveness of Targeted Interventions on Treatment of Infants With Bronchiolitis]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1766041832330-4dfa1aab-0e01-4ab2-bef3-939635cc3e2b/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1001/jamapediatrics.2021.0295</link>
            <description><![CDATA[<div class="section" id="ab-poi210010-1"><h3 class="BHead" id="nov000-1">Question</h3><p class="para" id="N65546">Can the evidence-based treatment of infants with bronchiolitis be improved by using targeted interventions to deimplement low-value care?</p></div><div class="section" id="ab-poi210010-2"><h3 class="BHead" id="nov000-2">Findings</h3><p class="para" id="N65552">In this international cluster randomized clinical trial of 26 hospitals and 3727 infants, an absolute risk difference favoring intervention hospitals was seen in compliance with 5 evidence-based recommendations in the treatment of infants with bronchiolitis.</p></div><div class="section" id="ab-poi210010-3"><h3 class="BHead" id="nov000-3">Meaning</h3><p class="para" id="N65558">Use of targeted interventions improved the treatment of infants with bronchiolitis by deimplementing the use of ineffective and potentially harmful therapies and management; these results are important for bronchiolitis management, deimplementation science, and future interventions in acute care pediatrics.</p></div><p class="para" id="N65541">This cluster randomized clinical trial uses data from 26 hospitals to investigate whether evidence-based treatment of infants with bronchiolitis can be improved by using targeted interventions to deimplement low-value care.</p><div class="section" id="ab-poi210010-4"><h3 class="BHead" id="nov000-1">Importance</h3><p class="para" id="N65543">In developed countries, bronchiolitis is the most common reason for infants to be admitted to the hospital, and all international bronchiolitis guidelines recommend supportive care; however, significant variation in practice continues with infants receiving non–evidence-based therapies. Deimplementation research aims to reduce the use of low-value care, and advancing science in this area is critical to delivering evidence-based care.</p></div><div class="section" id="ab-poi210010-5"><h3 class="BHead" id="nov000-2">Objective</h3><p class="para" id="N65549">To determine the effectiveness of targeted interventions vs passive dissemination of an evidence-based bronchiolitis guideline in improving treatment of infants with bronchiolitis.</p></div><div class="section" id="ab-poi210010-6"><h3 class="BHead" id="nov000-3">Design, Setting, and Participants</h3><p class="para" id="N65555">This international, multicenter cluster randomized clinical trial included 26 hospitals (clusters) in Australia and New Zealand providing tertiary or secondary pediatric care (13 randomized to intervention, 13 to control) during the 2017 bronchiolitis season. Data were collected on 8003 infants for the 3 bronchiolitis seasons (2014-2016) before the implementation period and 3727 infants for the implementation period (2017 bronchiolitis season, May 1-November 30). Data were analyzed from November 16, 2018, to December 9, 2020.</p></div><div class="section" id="ab-poi210010-7"><h3 class="BHead" id="nov000-4">Interventions</h3><p class="para" id="N65561">Interventions were developed using theories of behavior change to target key factors that influence bronchiolitis management. These interventions included site-based clinical leads, stakeholder meetings, a train-the-trainer workshop, targeted educational delivery, other educational and promotional materials, and audit and feedback.</p></div><div class="section" id="ab-poi210010-8"><h3 class="BHead" id="nov000-5">Main Outcomes and Measures</h3><p class="para" id="N65567">The primary outcome was compliance during the first 24 hours of care with no use of chest radiography, albuterol, glucocorticoids, antibiotics, and epinephrine, measured retrospectively from medical records of randomly selected infants with bronchiolitis who presented to the hospital. There were no patient-level exclusions.</p></div><div class="section" id="ab-poi210010-9"><h3 class="BHead" id="nov000-6">Results</h3><p class="para" id="N65573">A total of 26 hospitals were randomized without dropouts. Analysis was by intention to treat. Baseline data collected on 8003 infants for 3 bronchiolitis seasons (2014-2016) before the implementation period were similar between intervention and control hospitals. Implementation period data were collected on 3727 infants, including 2328 boys (62%) and 1399 girls (38%), with a mean (SD) age of 6.0 (3.2) months. A total of 459 (12%) were Māori (New Zealand), and 295 (8%) were Aboriginal/Torres Strait Islander (Australia). Compliance with recommendations was 85.1% (95% CI, 82.6%-89.7%) in intervention hospitals vs 73.0% (95% CI, 65.3%-78.8%) in control hospitals (adjusted risk difference, 14.1%; 95% CI, 6.5%-21.7%; <i>P</i> &lt; .001).</p></div><div class="section" id="ab-poi210010-10"><h3 class="BHead" id="nov000-7">Conclusions and Relevance</h3><p class="para" id="N65582">Targeted interventions led to improved treatment of infants with bronchiolitis. This study has important implications for bronchiolitis management and the development of effective interventions to deimplement low-value care.</p></div><div class="section" id="ab-poi210010-11"><h3 class="BHead" id="nov000-8">Trial Registration</h3><p class="para" id="N65588">Australian and New Zealand Clinical Trials Registry: ACTRN12616001567415.</p></div>]]></description>
            <pubDate><![CDATA[2021-04-12T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[An atlas of the tissue and blood metagenome in cancer reveals novel links between bacteria, viruses and cancer]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1766038229400-d5d0e489-1072-4fa9-8a12-b261e15a9964/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-021-01039-4</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">Host tissue infections by bacteria and viruses can cause cancer. Known viral carcinogenic mechanisms are disruption of the host genome via genomic integration and expression of oncogenic viral proteins. An important bacterial carcinogenic mechanism is chronic inflammation. Massively parallel sequencing now routinely generates datasets large enough to contain detectable traces of bacterial and viral nucleic acids of taxa that colonize the examined tissue or are integrated into the host genome. However, this hidden resource has not been comprehensively studied in large patient cohorts.</p></div><div class="section" id="N65546"><h3 class="BHead" id="nov000-2">Methods</h3><p class="para" id="Par2">In the present study, 3025 whole genome sequencing datasets and, where available, corresponding RNA-seq datasets are leveraged to gain insight into novel links between viruses, bacteria, and cancer. Datasets were obtained from multiple International Cancer Genome Consortium studies, with additional controls added from the 1000 genome project. A customized pipeline based on KRAKEN was developed and validated to identify bacterial and viral sequences in the datasets. Raw results were stringently filtered to reduce false positives and remove likely contaminants.</p></div><div class="section" id="N65552"><h3 class="BHead" id="nov000-3">Results</h3><p class="para" id="Par3">The resulting map confirms known links and expands current knowledge by identifying novel associations. Moreover, the detection of certain bacteria or viruses is associated with profound differences in patient and tumor phenotypes, such as patient age, tumor stage, survival, and somatic mutations in cancer genes or gene expression profiles.</p></div><div class="section" id="N65558"><h3 class="BHead" id="nov000-4">Conclusions</h3><p class="para" id="Par4">Overall, these results provide a detailed, unprecedented map of links between viruses, bacteria, and cancer that can serve as a reference for future studies and further experimental validation.</p><p class="para" id="Par5">
<div class="imageVideo"><img src="/dataresources/secured/content-1766038229400-d5d0e489-1072-4fa9-8a12-b261e15a9964/assets/40168_2021_1039_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65573"><h3 class="BHead" id="nov000-5">Supplementary Information</h3><p class="para" id="N65576">The online version contains supplementary material available at 10.1186/s40168-021-01039-4.</p></div>]]></description>
            <pubDate><![CDATA[2021-04-22T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[The pregnane X receptor drives sexually dimorphic hepatic changes in lipid and xenobiotic metabolism in response to gut microbiota in mice]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1766037454944-0896a420-cd02-4462-bf1a-55b2869ad3a9/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-021-01050-9</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">The gut microbiota–intestine–liver relationship is emerging as an important factor in multiple hepatic pathologies, but the hepatic sensors and effectors of microbial signals are not well defined.</p></div><div class="section" id="N65546"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">By comparing publicly available liver transcriptomics data from conventional vs. germ-free mice, we identified pregnane X receptor (PXR, NR1I2) transcriptional activity as strongly affected by the absence of gut microbes. Microbiota depletion using antibiotics in <i>Pxr</i><sup><i>+/+</i></sup>
<i>vs Pxr</i><sup><i>-/-</i></sup> C57BL/6J littermate mice followed by hepatic transcriptomics revealed that most microbiota-sensitive genes were PXR-dependent in the liver in males, but not in females. Pathway enrichment analysis suggested that microbiota–PXR interaction controlled fatty acid and xenobiotic metabolism. We confirmed that antibiotic treatment reduced liver triglyceride content and hampered xenobiotic metabolism in the liver from <i>Pxr</i><sup>+/+</sup> but not <i>Pxr</i><sup>-/-</sup> male mice.</p></div><div class="section" id="N65574"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">These findings identify PXR as a hepatic effector of microbiota-derived signals that regulate the host’s sexually dimorphic lipid and xenobiotic metabolisms in the liver. Thus, our results reveal a potential new mechanism for unexpected drug–drug or food–drug interactions.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1766037454944-0896a420-cd02-4462-bf1a-55b2869ad3a9/assets/40168_2021_1050_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65589"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65592">The online version contains supplementary material available at 10.1186/s40168-021-01050-9.</p></div>]]></description>
            <pubDate><![CDATA[2021-04-20T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Association of Race/Ethnicity and Social Disadvantage With Autism Prevalence in 7 Million School Children in England]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1766028589257-e3bc609c-c460-4089-b429-3a84535af93f/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1001/jamapediatrics.2021.0054</link>
            <description><![CDATA[<div class="section" id="ab-poi210003-1"><h3 class="BHead" id="nov000-1">Question</h3><p class="para" id="N65546">What is the prevalence of autism spectrum disorder (ASD) in the total English state school population, and what are the social determinants associated with ASD status?</p></div><div class="section" id="ab-poi210003-2"><h3 class="BHead" id="nov000-2">Findings</h3><p class="para" id="N65552">In this ASD prevalence cohort study of 7 047 238 pupils, national English prevalence was 1.76%, with marked differences according to racial/ethnic group. The highest prevalence was found in Black pupils (2.11%) and the lowest in Roma/Irish Travelers (0.85%), with important variability across geographic areas.</p></div><div class="section" id="ab-poi210003-3"><h3 class="BHead" id="nov000-3">Meaning</h3><p class="para" id="N65558">These results show differences in ASD prevalence estimates across racial/ethnic minority groups in England, which could be attributable to diagnostic biases, possible differences in detection and referral, or differential phenotypic prevalence for racial/ethnic minority groups.</p></div><p class="para" id="N65540">This national cohort study evaluates whether socioeconomic disadvantage is associated with autism spectrum disorder prevalence and the likelihood of accessing autism services in racial/ethnic minority groups and disadvantaged groups among school pupils in England.</p><div class="section" id="ab-poi210003-4"><h3 class="BHead" id="nov000-1">Importance</h3><p class="para" id="N65543">The global prevalence of autism spectrum disorder (ASD) has been reported to be between 1% and 2% of the population, with little research in Black, Asian, and other racial/ethnic minority groups. Accurate estimates of ASD prevalence are vital to planning diagnostic, educational, health, and social care services and may detect possible access barriers to diagnostic pathways and services and inequalities based on social determinants of health.</p></div><div class="section" id="ab-poi210003-5"><h3 class="BHead" id="nov000-2">Objective</h3><p class="para" id="N65549">To evaluate whether socioeconomic disadvantage is associated with ASD prevalence and the likelihood of accessing ASD services in racial/ethnic minority and disadvantaged groups in England.</p></div><div class="section" id="ab-poi210003-6"><h3 class="BHead" id="nov000-3">Design, Setting, and Participants</h3><p class="para" id="N65555">This case-control prevalence cohort study used the Spring School Census 2017 from the Pupil Level Annual Schools Census of the National Pupil Database, which is a total population sample that includes all English children, adolescents, and young adults aged 2 to 21 years in state-funded education. Data were collected on January 17, 2017, and analyzed from August 2, 2018, to January 28, 2020.</p></div><div class="section" id="ab-poi210003-7"><h3 class="BHead" id="nov000-4">Exposures</h3><p class="para" id="N65561">Age and sex were treated as a priori confounders while assessing correlates of ASD status according to (1) race/ethnicity, (2) social disadvantage, (3) first language spoken, (4) Education, Health and Care Plan or ASD Special Educational Needs and Disability support status, and (5) mediation analysis to assess how social disadvantage and language might affect ASD status.</p></div><div class="section" id="ab-poi210003-8"><h3 class="BHead" id="nov000-5">Main Outcomes and Measures</h3><p class="para" id="N65567">Sex- and age-standardized ASD prevalence by race/ethnicity and 326 English local authority districts in pupils aged 5 to 19 years.</p></div><div class="section" id="ab-poi210003-9"><h3 class="BHead" id="nov000-6">Results</h3><p class="para" id="N65573">The final population sample consisted of 7 047 238 pupils (50.99% male; mean [SD] age, 10.18 [3.47] years) and included 119 821 pupils with ASD, of whom 21 660 also had learning difficulties (18.08%). The standardized prevalence of ASD was 1.76% (95% CI, 1.75%-1.77%), with male pupils showing a prevalence of 2.81% (95% CI, 2.79%-2.83%) and female pupils a prevalence of 0.65% (95% CI, 0.64%-0.66%), for a male-to-female ratio (MFR) of 4.32:1. Standardized prevalence was highest in Black pupils (2.11% [95% CI, 2.06%-2.16%]; MFR, 4.68:1) and lowest in Roma/Irish Travelers (0.85% [95% CI, 0.67%-1.03%]; MFR, 2.84:1). Pupils with ASD were more likely to face social disadvantage (adjusted prevalence ratio, 1.61; 95% CI, 1.59-1.63) and to speak English as an additional language (adjusted prevalence ratio, 0.64; 95% CI, 0.63-0.65). The effect of race/ethnicity on ASD status was mediated mostly through social disadvantage, with Black pupils having the largest effect (standardized mediation coefficient, 0.018; <i>P</i> &lt; .001) and 12.41% of indirect effects through this way.</p></div><div class="section" id="ab-poi210003-10"><h3 class="BHead" id="nov000-7">Conclusions and Relevance</h3><p class="para" id="N65582">These findings suggest that significant differences in ASD prevalence exist across racial/ethnic groups and geographic areas and local authority districts, indicating possible differential phenotypic prevalence or differences in detection or referral for racial/ethnic minority groups.</p></div>]]></description>
            <pubDate><![CDATA[2021-03-29T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Association of Race/Ethnicity and Social Disadvantage With Autism Prevalence in 7 Million School Children in England]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1766028589257-e3bc609c-c460-4089-b429-3a84535af93f/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1001/jamapediatrics.2021.0054</link>
            <description><![CDATA[<div class="section" id="ab-poi210003-1"><h3 class="BHead" id="nov000-1">Question</h3><p class="para" id="N65546">What is the prevalence of autism spectrum disorder (ASD) in the total English state school population, and what are the social determinants associated with ASD status?</p></div><div class="section" id="ab-poi210003-2"><h3 class="BHead" id="nov000-2">Findings</h3><p class="para" id="N65552">In this ASD prevalence cohort study of 7 047 238 pupils, national English prevalence was 1.76%, with marked differences according to racial/ethnic group. The highest prevalence was found in Black pupils (2.11%) and the lowest in Roma/Irish Travelers (0.85%), with important variability across geographic areas.</p></div><div class="section" id="ab-poi210003-3"><h3 class="BHead" id="nov000-3">Meaning</h3><p class="para" id="N65558">These results show differences in ASD prevalence estimates across racial/ethnic minority groups in England, which could be attributable to diagnostic biases, possible differences in detection and referral, or differential phenotypic prevalence for racial/ethnic minority groups.</p></div><p class="para" id="N65540">This national cohort study evaluates whether socioeconomic disadvantage is associated with autism spectrum disorder prevalence and the likelihood of accessing autism services in racial/ethnic minority groups and disadvantaged groups among school pupils in England.</p><div class="section" id="ab-poi210003-4"><h3 class="BHead" id="nov000-1">Importance</h3><p class="para" id="N65543">The global prevalence of autism spectrum disorder (ASD) has been reported to be between 1% and 2% of the population, with little research in Black, Asian, and other racial/ethnic minority groups. Accurate estimates of ASD prevalence are vital to planning diagnostic, educational, health, and social care services and may detect possible access barriers to diagnostic pathways and services and inequalities based on social determinants of health.</p></div><div class="section" id="ab-poi210003-5"><h3 class="BHead" id="nov000-2">Objective</h3><p class="para" id="N65549">To evaluate whether socioeconomic disadvantage is associated with ASD prevalence and the likelihood of accessing ASD services in racial/ethnic minority and disadvantaged groups in England.</p></div><div class="section" id="ab-poi210003-6"><h3 class="BHead" id="nov000-3">Design, Setting, and Participants</h3><p class="para" id="N65555">This case-control prevalence cohort study used the Spring School Census 2017 from the Pupil Level Annual Schools Census of the National Pupil Database, which is a total population sample that includes all English children, adolescents, and young adults aged 2 to 21 years in state-funded education. Data were collected on January 17, 2017, and analyzed from August 2, 2018, to January 28, 2020.</p></div><div class="section" id="ab-poi210003-7"><h3 class="BHead" id="nov000-4">Exposures</h3><p class="para" id="N65561">Age and sex were treated as a priori confounders while assessing correlates of ASD status according to (1) race/ethnicity, (2) social disadvantage, (3) first language spoken, (4) Education, Health and Care Plan or ASD Special Educational Needs and Disability support status, and (5) mediation analysis to assess how social disadvantage and language might affect ASD status.</p></div><div class="section" id="ab-poi210003-8"><h3 class="BHead" id="nov000-5">Main Outcomes and Measures</h3><p class="para" id="N65567">Sex- and age-standardized ASD prevalence by race/ethnicity and 326 English local authority districts in pupils aged 5 to 19 years.</p></div><div class="section" id="ab-poi210003-9"><h3 class="BHead" id="nov000-6">Results</h3><p class="para" id="N65573">The final population sample consisted of 7 047 238 pupils (50.99% male; mean [SD] age, 10.18 [3.47] years) and included 119 821 pupils with ASD, of whom 21 660 also had learning difficulties (18.08%). The standardized prevalence of ASD was 1.76% (95% CI, 1.75%-1.77%), with male pupils showing a prevalence of 2.81% (95% CI, 2.79%-2.83%) and female pupils a prevalence of 0.65% (95% CI, 0.64%-0.66%), for a male-to-female ratio (MFR) of 4.32:1. Standardized prevalence was highest in Black pupils (2.11% [95% CI, 2.06%-2.16%]; MFR, 4.68:1) and lowest in Roma/Irish Travelers (0.85% [95% CI, 0.67%-1.03%]; MFR, 2.84:1). Pupils with ASD were more likely to face social disadvantage (adjusted prevalence ratio, 1.61; 95% CI, 1.59-1.63) and to speak English as an additional language (adjusted prevalence ratio, 0.64; 95% CI, 0.63-0.65). The effect of race/ethnicity on ASD status was mediated mostly through social disadvantage, with Black pupils having the largest effect (standardized mediation coefficient, 0.018; <i>P</i> &lt; .001) and 12.41% of indirect effects through this way.</p></div><div class="section" id="ab-poi210003-10"><h3 class="BHead" id="nov000-7">Conclusions and Relevance</h3><p class="para" id="N65582">These findings suggest that significant differences in ASD prevalence exist across racial/ethnic groups and geographic areas and local authority districts, indicating possible differential phenotypic prevalence or differences in detection or referral for racial/ethnic minority groups.</p></div>]]></description>
            <pubDate><![CDATA[2021-03-29T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Modified PCR protocol to increase sensitivity for determination of bacterial community composition]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1766021292898-4e86715b-1d45-4e11-8d7d-2d186b9c7ada/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-020-00958-y</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">The objective of this project was to increase the sensitivity of sequence-based bacterial community determination without impacting community composition or interfering with cluster formation during sequencing. Two PCR protocols (standard and modified) were examined in airway samples where we observed a large range in bacterial load (3.1–6.2 log<sub>10</sub> 16S rRNA gene copies/reaction). Tracheal aspirate (TA) samples (<i>n</i> = 99) were collected from sixteen children requiring mechanical ventilation at a single center. DNA was extracted, and total bacterial load (TBL) was assessed using qPCR. Amplification of 16S rRNA was attempted with both protocols in all samples.</p></div><div class="section" id="N65552"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">PCR product was observed using both protocols in 52 samples and in 24 additional samples only with the modified protocol. TBL, diversity metrics, and prominent taxa were compared for samples in three groups based on success of the two protocols (successful with both, success with modified only, unsuccessful for both). TBL differed significantly across the three groups (<i>p</i>&lt;0.001). Specifically, the modified protocol allowed amplification from samples with intermediate TBL. Shannon diversity was similar between the two protocols, and Morisita-Horn beta diversity index showed high agreement between the two protocols within samples (median value 0.9997, range 0.9947 to 1). We show that both protocols identify similar communities, and the technical variability of both protocols was very low. The use of limited PCR cycles was a key feature to limit impact of background by exclusion of 24% of samples with no evidence of bacterial DNA present in the sample.</p></div><div class="section" id="N65561"><h3 class="BHead" id="nov000-3">Conclusion</h3><p class="para" id="Par3">The modified amplification protocol represents a viable approach that increased sensitivity of bacterial community analysis, which is important for study of the human airway microbiome where bacterial load is highly variable.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1766021292898-4e86715b-1d45-4e11-8d7d-2d186b9c7ada/assets/40168_2020_958_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65577"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65580">The online version contains supplementary material available at 10.1186/s40168-020-00958-y.</p></div>]]></description>
            <pubDate><![CDATA[2021-04-13T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Microbial community characterization of shrimp survivors to AHPND challenge test treated with an effective shrimp probiotic (<i>Vibrio diabolicus</i>)]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1766021015794-b731a51c-f6dc-4727-b611-e4caa6f7962d/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-021-01043-8</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">Acute hepatopancreatic necrosis disease (AHPND) is an important shrimp bacterial disease caused by some <i>Vibrio</i> species. The severity of the impact of this disease on aquaculture worldwide has made it necessary to develop alternatives to prophylactic antibiotics use, such as the application of probiotics. To assess the potential to use probiotics in order to limit the detrimental effects of AHNPD, we evaluated the effect of the ILI strain, a <i>Vibrio</i> sp. bacterium and efficient shrimp probiotic, using metabarcoding (<i>16S rRNA</i> gene) on the gastrointestinal microbiota of shrimp after being challenged with AHPND-causing <i>V</i>. <i>parahaemolyticus</i>.</p></div><div class="section" id="N65561"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">We showed how the gastrointestinal microbiome of shrimp varied between healthy and infected organisms. Nevertheless, a challenge of working with AHPND-causing <i>Vibrio</i> pathogens and <i>Vibrio</i>-related bacteria as probiotics is the potential risk of the probiotic strain becoming pathogenic. Consequently, we evaluated whether ILI strain can acquire the plasmid pV-AHPND via horizontal transfer and further cause the disease in shrimp. Conjugation assays were performed resulting in a high frequency (70%) of colonies harboring the pv-AHPND. However, no shrimp mortality was observed when transconjugant colonies of the ILI strain were used in a challenge test using healthy shrimp. We sequenced the genome of the ILI strain and performed comparative genomics analyses using AHPND and non-AHPND <i>Vibrio</i> isolates. Using available phylogenetic and phylogenomics analyses, we reclassified the ILI strain as <i>Vibrio diabolicus</i>. In summary, this work represents an effort to study the role that probiotics play in the normal gastrointestinal shrimp microbiome and in AHPND-infected shrimp, showing that the ILI probiotic was able to control pathogenic bacterial populations in the host's gastrointestinal tract and stimulate the shrimp’s survival. The identification of probiotic bacterial species that are effective in the host’s colonization is important to promote animal health and prevent disease.</p></div><div class="section" id="N65579"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">This study describes probiotic bacteria capable of controlling pathogenic populations of bacteria in the shrimp gastrointestinal tract. Our work provides new insights into the complex dynamics between shrimp and the changes in the microbiota. It also addresses the practical application of probiotics to solve problems with pathogens that cause high mortality-rate in shrimp farming around the world.</p><p class="para" id="Par360">
<div class="imageVideo"><img src="/dataresources/secured/content-1766021015794-b731a51c-f6dc-4727-b611-e4caa6f7962d/assets/40168_2021_1043_MOESM6_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65594"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65597">The online version contains supplementary material available at 10.1186/s40168-021-01043-8.</p></div>]]></description>
            <pubDate><![CDATA[2021-04-12T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Isolation and characterisation of ΦcrAss002, a crAss-like phage from the human gut that infects <i>Bacteroides xylanisolvens</i>]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1766020916180-828421f1-e68a-41a0-b39b-b89892a86f43/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-021-01036-7</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">The gut phageome comprises a complex phage community of thousands of individual strains, with a few highly abundant bacteriophages. CrAss-like phages, which infect bacteria of the order Bacteroidales, are the most abundant bacteriophage family in the human gut and make an important contribution to an individual’s core virome. Based on metagenomic data, crAss-like phages form a family, with four sub-families and ten candidate genera. To date, only three representatives isolated in pure culture have been reported: ΦcrAss001 and two closely related phages DAC15 and DAC17; all are members of the less abundant candidate genus VI. The persistence at high levels of both crAss-like phage and their Bacteroidales hosts in the human gut has not been explained mechanistically, and this phage-host relationship can only be properly studied with isolated phage-host pairs from as many genera as possible.</p></div><div class="section" id="N65546"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">Faeces from a healthy donor with high levels of crAss-like phage was used to initiate a faecal fermentation in a chemostat, with selected antibiotics chosen to inhibit rapidly growing bacteria and selectively enrich for Gram-negative Bacteroidales. This had the objective of promoting the simultaneous expansion of crAss-like phages on their native hosts. The levels of seven different crAss-like phages expanded during the fermentation, indicating that their hosts were also present in the fermenter. The enriched supernatant was then tested against individual Bacteroidales strains isolated from the same faecal sample. This resulted in the isolation of a previously uncharacterised crAss-like phage of candidate genus IV of the proposed Alphacrassvirinae sub-family, ΦcrAss002, that infects the gut commensal <i>Bacteroides xylanisolvens</i>. ΦcrAss002 does not form plaques or spots on lawns of sensitive cells, nor does it lyse liquid cultures, even at high titres. In keeping with the co-abundance of phage and host in the human gut, ΦcrAss002 and <i>Bacteroides xylanisolvens</i> can also co-exist at high levels when co-cultured in laboratory media.</p></div><div class="section" id="N65558"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">We report the isolation and characterisation of ΦcrAss002, the first representative of the proposed Alphacrassvirinae sub-family of crAss-like phages. ΦcrAss002 cannot form plaques or spots on bacterial lawns but can co-exist with its host, <i>Bacteroides xylanisolvens</i>, at very high levels in liquid culture without impacting on bacterial numbers.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1766020916180-828421f1-e68a-41a0-b39b-b89892a86f43/assets/40168_2021_1036_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65577"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65580">The online version contains supplementary material available at 10.1186/s40168-021-01036-7.</p></div>]]></description>
            <pubDate><![CDATA[2021-04-12T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Niche partitioning in the <i>Rimicaris exoculata</i> holobiont: the case of the first symbiotic <i>Zetaproteobacteria</i>]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1766020862282-0b050a42-84c1-4c79-8af2-33d882ebfee5/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-021-01045-6</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">Free-living and symbiotic chemosynthetic microbial communities support primary production and higher trophic levels in deep-sea hydrothermal vents. The shrimp <i>Rimicaris exoculata</i>, which dominates animal communities along the Mid-Atlantic Ridge, houses a complex bacterial community in its enlarged cephalothorax. The dominant bacteria present are from the taxonomic groups <i>Campylobacteria</i>, <i>Desulfobulbia</i> (formerly <i>Deltaproteobacteria</i>), <i>Alphaproteobacteria</i>, <i>Gammaproteobacteria</i>, and some recently discovered iron oxyhydroxide-coated <i>Zetaproteobacteria</i>. This epibiotic consortium uses iron, sulfide, methane, and hydrogen as energy sources. Here, we generated shotgun metagenomes from <i>Rimicaris exoculata</i> cephalothoracic epibiotic communities to reconstruct and investigate symbiotic genomes. We collected specimens from three geochemically contrasted vent fields, TAG, Rainbow, and Snake Pit, to unravel the specificity, variability, and adaptation of <i>Rimicaris</i>–microbe associations.</p></div><div class="section" id="N65573"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">Our data enabled us to reconstruct 49 metagenome-assembled genomes (MAGs) from the TAG and Rainbow vent fields, including 16 with more than 90% completion and less than 5% contamination based on single copy core genes. These MAGs belonged to the dominant <i>Campylobacteria</i>, <i>Desulfobulbia</i>, <i>Thiotrichaceae</i>, and some novel candidate phyla radiation (CPR) lineages. In addition, most importantly, two MAGs in our collection were affiliated to <i>Zetaproteobacteria</i> and had no close relatives (average nucleotide identity ANI &lt; 77% with the closest relative <i>Ghiorsea bivora</i> isolated from TAG, and 88% with each other), suggesting potential novel species. Genes for Calvin-Benson Bassham (CBB) carbon fixation, iron, and sulfur oxidation, as well as nitrate reduction, occurred in both MAGs. However, genes for hydrogen oxidation and multicopper oxidases occurred in one MAG only, suggesting shared and specific potential functions for these two novel <i>Zetaproteobacteria</i> symbiotic lineages. Overall, we observed highly similar symbionts co-existing in a single shrimp at both the basaltic TAG and ultramafic Rainbow vent sites. Nevertheless, further examination of the seeming functional redundancy among these epibionts revealed important differences.</p></div><div class="section" id="N65597"><h3 class="BHead" id="nov000-3">Conclusion</h3><p class="para" id="Par3">These data highlight microniche partitioning in the <i>Rimicaris</i> holobiont and support recent studies showing that functional diversity enables multiple symbiont strains to coexist in animals colonizing hydrothermal vents.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1766020862282-0b050a42-84c1-4c79-8af2-33d882ebfee5/assets/40168_2021_1045_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65616"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65619">The online version contains supplementary material available at 10.1186/s40168-021-01045-6.</p></div>]]></description>
            <pubDate><![CDATA[2021-04-12T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Temporal landscape of human gut RNA and DNA virome in SARS-CoV-2 infection and severity]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1766011582128-706682d5-bfde-43f5-9fae-e9bac4685b22/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-021-01008-x</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">Coronavirus disease 2019 (COVID-19) caused by the enveloped RNA virus SARS-CoV-2 primarily affects the respiratory and gastrointestinal tracts. SARS-CoV-2 was isolated from fecal samples, and active viral replication was reported in human intestinal cells. The human gut also harbors an enormous amount of resident viruses (collectively known as the virome) that play a role in regulating host immunity and disease pathophysiology. Understanding gut virome perturbation that underlies SARS-CoV-2 infection and severity is an unmet need.</p></div><div class="section" id="N65546"><h3 class="BHead" id="nov000-2">Methods</h3><p class="para" id="Par2">We enrolled 98 COVID-19 patients with varying disease severity (3 asymptomatic, 53 mild, 34 moderate, 5 severe, 3 critical) and 78 non-COVID-19 controls matched for gender and co-morbidities. All subjects had fecal specimens sampled at inclusion. Blood specimens were collected for COVID-19 patients at admission to test for inflammatory markers and white cell counts. Among COVID-19 cases, 37 (38%) patients had serial fecal samples collected 2 to 3 times per week from time of hospitalization until after discharge. Using shotgun metagenomics sequencing, we sequenced and profiled the fecal RNA and DNA virome. We investigated alterations and longitudinal dynamics of the gut virome in association with disease severity and blood parameters.</p></div><div class="section" id="N65552"><h3 class="BHead" id="nov000-3">Results</h3><p class="para" id="Par3">Patients with COVID-19 showed underrepresentation of Pepper mild mottle virus (RNA virus) and multiple bacteriophage lineages (DNA viruses) and enrichment of environment-derived eukaryotic DNA viruses in fecal samples, compared to non-COVID-19 subjects. Such gut virome alterations persisted up to 30 days after disease resolution. Fecal virome in SARS-CoV-2 infection harbored more stress-, inflammation-, and virulence-associated gene encoding capacities including those pertaining to bacteriophage integration, DNA repair, and metabolism and virulence associated with their bacterial host. Baseline fecal abundance of 10 virus species (1 RNA virus, pepper chlorotic spot virus, and 9 DNA virus species) inversely correlated with disease COVID-19 severity. These viruses inversely correlated with blood levels of pro-inflammatory proteins, white cells, and neutrophils. Among the 10 COVID-19 severity-associated DNA virus species, 4 showed inverse correlation with age; 5 showed persistent lower abundance both during disease course and after disease resolution relative to non-COVID-19 subjects.</p></div><div class="section" id="N65558"><h3 class="BHead" id="nov000-4">Conclusions</h3><p class="para" id="Par4">Both enteric RNA and DNA virome in COVID-19 patients were different from non-COVID-19 subjects, which persisted after disease resolution of COVID-19. Gut virome may calibrate host immunity and regulate severity to SARS-CoV-2 infection. Our observation that gut viruses inversely correlated with both severity of COVID-19 and host age may partly explain that older subjects are prone to severe and worse COVID-19 outcomes. Altogether, our data highlight the importance of human gut virome in severity and potentially therapeutics of COVID-19.</p><p class="para" id="Par5">
<div class="imageVideo"><img src="/dataresources/secured/content-1766011582128-706682d5-bfde-43f5-9fae-e9bac4685b22/assets/40168_2021_1008_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65574"><h3 class="BHead" id="nov000-5">Supplementary Information</h3><p class="para" id="N65577">The online version contains supplementary material available at 10.1186/s40168-021-01008-x.</p></div>]]></description>
            <pubDate><![CDATA[2021-04-14T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[When your host shuts down: larval diapause impacts host-microbiome interactions in <i>Nasonia vitripennis</i>]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1766004128737-5fc9d4cc-9b10-4848-acd1-590ec0023c31/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-021-01037-6</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">The life cycles of many insect species include an obligatory or facultative diapause stage with arrested development and low metabolic activity as an overwintering strategy. Diapause is characterised by profound physiological changes in endocrine activity, cell proliferation and nutrient metabolism. However, little is known regarding host-microbiome interactions during diapause, despite the importance of bacterial symbionts for host nutrition and development. In this work, we investigated (i) the role of the microbiome for host nutrient allocation during diapause and (ii) the impact of larval diapause on microbiome dynamics in the parasitoid wasp <i>Nasonia vitripennis</i>, a model organism for host-microbiome interactions.</p></div><div class="section" id="N65549"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">Our results demonstrate that the microbiome is essential for host nutrient allocation during diapause in <i>N. vitripennis</i>, as axenic diapausing larvae had consistently lower glucose and glycerol levels than conventional diapausing larvae, especially when exposed to cold temperature. In turn, microbiome composition was altered in diapausing larvae, potentially due to changes in the surrounding temperature, host nutrient levels and a downregulation of host immune genes. Importantly, prolonged larval diapause had a transstadial effect on the adult microbiome, with unknown consequences for host fitness. Notably, the most dominant microbiome member, <i>Providencia</i> sp., was drastically reduced in adults after more than 4 months of larval diapause, while potential bacterial pathogens increased in abundance.</p></div><div class="section" id="N65561"><h3 class="BHead" id="nov000-3">Conclusion</h3><p class="para" id="Par3">This work investigates host-microbiome interactions during a crucial developmental stage, which challenges both the insect host and its microbial associates. The impact of diapause on the microbiome is likely due to several factors, including altered host regulatory mechanisms and changes in the host environment.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1766004128737-5fc9d4cc-9b10-4848-acd1-590ec0023c31/assets/40168_2021_1037_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65577"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65580">The online version contains supplementary material available at 10.1186/s40168-021-01037-6.</p></div>]]></description>
            <pubDate><![CDATA[2021-04-09T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Rhizosphere community selection reveals bacteria associated with reduced root disease]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1766003887811-b9d42c71-732f-4f82-9b5c-eb4a88e1fc92/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-020-00997-5</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">Microbes benefit plants by increasing nutrient availability, producing plant growth hormones, and protecting against pathogens. However, it is largely unknown how plants change root microbial communities.</p></div><div class="section" id="N65546"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">In this study, we used a multi-cycle selection system and infection by the soilborne fungal pathogen <i>Rhizoctonia solani</i> AG8 (hereafter AG8) to examine how plants impact the rhizosphere bacterial community and recruit beneficial microorganisms to suppress soilborne fungal pathogens and promote plant growth. Successive plantings dramatically enhanced disease suppression on susceptible wheat cultivars to AG8 in the greenhouse. Accordingly, analysis of the rhizosphere soil microbial community using deep sequencing of 16S rRNA genes revealed distinct bacterial community profiles assembled over successive wheat plantings. Moreover, the cluster of bacterial communities formed from the AG8-infected rhizosphere was distinct from those without AG8 infection. Interestingly, the bacterial communities from the rhizosphere with the lowest wheat root disease gradually separated from those with the worst wheat root disease over planting cycles. Successive monocultures and application of AG8 increased the abundance of some bacterial genera which have potential antagonistic activities, such as <i>Chitinophaga</i>, <i>Pseudomonas</i>, <i>Chryseobacterium</i>, and <i>Flavobacterium</i>, and a group of plant growth-promoting (PGP) and nitrogen-fixing microbes, including <i>Pedobacter</i>, <i>Variovorax</i>, and <i>Rhizobium</i>. Furthermore, 47 bacteria isolates belong to 35 species were isolated. Among them, eleven and five exhibited antagonistic activities to AG8 and <i>Rhizoctonia oryzae in vitro</i>, respectively. Notably, <i>Janthinobacterium</i> displayed broad antagonism against the soilborne pathogens <i>Pythium ultimum</i>, AG8, and <i>R. oryzae in vitro</i>, and disease suppressive activity to AG8 in soil.</p></div><div class="section" id="N65588"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">Our results demonstrated that successive wheat plantings and pathogen infection can shape the rhizosphere microbial communities and specifically accumulate a group of beneficial microbes. Our findings suggest that soil community selection may offer the potential for addressing agronomic concerns associated with plant diseases and crop productivity.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1766003887811-b9d42c71-732f-4f82-9b5c-eb4a88e1fc92/assets/40168_2020_997_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65603"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65606">The online version contains supplementary material available at 10.1186/s40168-020-00997-5.</p></div>]]></description>
            <pubDate><![CDATA[2021-04-09T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Association of Eviction With Adverse Birth Outcomes Among Women in Georgia, 2000 to 2016]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1766000271397-da07109e-71a4-4b34-8aba-ed97b58904ae/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1001/jamapediatrics.2020.6550</link>
            <description><![CDATA[<div class="section" id="ab-poi200102-1"><h3 class="BHead" id="nov000-1">Question</h3><p class="para" id="N65546">Is eviction during pregnancy associated with adverse birth outcomes, an important determinant of health across the life course?</p></div><div class="section" id="ab-poi200102-2"><h3 class="BHead" id="nov000-2">Findings</h3><p class="para" id="N65552">In this case-control study of 88 862 births in Georgia, eviction during pregnancy, particularly during the second and third trimester, was associated with reductions in infants’ weight and gestational age at birth compared with maternal eviction at any other time.</p></div><div class="section" id="ab-poi200102-3"><h3 class="BHead" id="nov000-3">Meaning</h3><p class="para" id="N65558">These findings suggest that housing, social, and medical assistance to pregnant women at risk for eviction might improve birth outcomes and health across the life course.</p></div><p class="para" id="N65540">This case-control study assesses the association of eviction during pregnancy with birth outcomes among women in Georgia.</p><div class="section" id="ab-poi200102-4"><h3 class="BHead" id="nov000-1">Importance</h3><p class="para" id="N65543">More than 2 million families face eviction annually, a number likely to increase due to the coronavirus disease 2019 pandemic. The association of eviction with newborns’ health remains to be examined.</p></div><div class="section" id="ab-poi200102-5"><h3 class="BHead" id="nov000-2">Objective</h3><p class="para" id="N65549">To determine the association of eviction actions during pregnancy with birth outcomes.</p></div><div class="section" id="ab-poi200102-6"><h3 class="BHead" id="nov000-3">Design</h3><p class="para" id="N65555">This case-control study compared birth outcomes of infants whose mothers were evicted during gestation with those whose mothers were evicted at other times. Participants included infants born to mothers who were evicted in Georgia from January 1, 2000, to December 31, 2016. Data were analyzed from March 1 to October 4, 2020.</p></div><div class="section" id="ab-poi200102-7"><h3 class="BHead" id="nov000-4">Exposures</h3><p class="para" id="N65561">Eviction actions occurring during gestation.</p></div><div class="section" id="ab-poi200102-8"><h3 class="BHead" id="nov000-5">Main Outcomes and Measures</h3><p class="para" id="N65567">Five metrics of neonatal health included birth weight (in grams), gestational age (in weeks), and dichotomized outcomes for low birth weight (LBW) (&lt;2500 g), prematurity (gestational age &lt;37.0 weeks), and infant death.</p></div><div class="section" id="ab-poi200102-9"><h3 class="BHead" id="nov000-6">Results</h3><p class="para" id="N65573">A total of 88 862 births to 45 122 mothers (mean [SD] age, 26.26 [5.76] years) who experienced 99 517 evictions were identified during the study period, including 10 135 births to women who had an eviction action during pregnancy and 78 727 births to mothers who had experienced an eviction action when not pregnant. Compared with mothers who experienced eviction actions at other times, eviction during pregnancy was associated with lower infant birth weight (difference, −26.88 [95% CI, −39.53 to 14.24] g) and gestational age (difference, −0.09 [95% CI, −0.16 to −0.03] weeks), increased rates of LBW (0.88 [95% CI, 0.23-1.54] percentage points) and prematurity (1.14 [95% CI, 0.21-2.06] percentage points), and a nonsignificant increase in mortality (1.85 [95% CI, −0.19 to 3.89] per 1000 births). The association of eviction with birth weight was strongest in the second and third trimesters of pregnancy, with birth weight reductions of 34.74 (95% CI, −57.51 to −11.97) and 35.80 (95% CI, −52.91 to −18.69) g, respectively.</p></div><div class="section" id="ab-poi200102-10"><h3 class="BHead" id="nov000-7">Conclusions and Relevance</h3><p class="para" id="N65579">These findings suggest that eviction actions during pregnancy are associated with adverse birth outcomes, which have been shown to have lifelong and multigenerational consequences. Ensuring housing, social, and medical assistance to pregnant women at risk for eviction may improve infant health.</p></div>]]></description>
            <pubDate><![CDATA[2021-03-01T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Association of Eviction With Adverse Birth Outcomes Among Women in Georgia, 2000 to 2016]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1766000271397-da07109e-71a4-4b34-8aba-ed97b58904ae/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1001/jamapediatrics.2020.6550</link>
            <description><![CDATA[<div class="section" id="ab-poi200102-1"><h3 class="BHead" id="nov000-1">Question</h3><p class="para" id="N65546">Is eviction during pregnancy associated with adverse birth outcomes, an important determinant of health across the life course?</p></div><div class="section" id="ab-poi200102-2"><h3 class="BHead" id="nov000-2">Findings</h3><p class="para" id="N65552">In this case-control study of 88 862 births in Georgia, eviction during pregnancy, particularly during the second and third trimester, was associated with reductions in infants’ weight and gestational age at birth compared with maternal eviction at any other time.</p></div><div class="section" id="ab-poi200102-3"><h3 class="BHead" id="nov000-3">Meaning</h3><p class="para" id="N65558">These findings suggest that housing, social, and medical assistance to pregnant women at risk for eviction might improve birth outcomes and health across the life course.</p></div><p class="para" id="N65540">This case-control study assesses the association of eviction during pregnancy with birth outcomes among women in Georgia.</p><div class="section" id="ab-poi200102-4"><h3 class="BHead" id="nov000-1">Importance</h3><p class="para" id="N65543">More than 2 million families face eviction annually, a number likely to increase due to the coronavirus disease 2019 pandemic. The association of eviction with newborns’ health remains to be examined.</p></div><div class="section" id="ab-poi200102-5"><h3 class="BHead" id="nov000-2">Objective</h3><p class="para" id="N65549">To determine the association of eviction actions during pregnancy with birth outcomes.</p></div><div class="section" id="ab-poi200102-6"><h3 class="BHead" id="nov000-3">Design</h3><p class="para" id="N65555">This case-control study compared birth outcomes of infants whose mothers were evicted during gestation with those whose mothers were evicted at other times. Participants included infants born to mothers who were evicted in Georgia from January 1, 2000, to December 31, 2016. Data were analyzed from March 1 to October 4, 2020.</p></div><div class="section" id="ab-poi200102-7"><h3 class="BHead" id="nov000-4">Exposures</h3><p class="para" id="N65561">Eviction actions occurring during gestation.</p></div><div class="section" id="ab-poi200102-8"><h3 class="BHead" id="nov000-5">Main Outcomes and Measures</h3><p class="para" id="N65567">Five metrics of neonatal health included birth weight (in grams), gestational age (in weeks), and dichotomized outcomes for low birth weight (LBW) (&lt;2500 g), prematurity (gestational age &lt;37.0 weeks), and infant death.</p></div><div class="section" id="ab-poi200102-9"><h3 class="BHead" id="nov000-6">Results</h3><p class="para" id="N65573">A total of 88 862 births to 45 122 mothers (mean [SD] age, 26.26 [5.76] years) who experienced 99 517 evictions were identified during the study period, including 10 135 births to women who had an eviction action during pregnancy and 78 727 births to mothers who had experienced an eviction action when not pregnant. Compared with mothers who experienced eviction actions at other times, eviction during pregnancy was associated with lower infant birth weight (difference, −26.88 [95% CI, −39.53 to 14.24] g) and gestational age (difference, −0.09 [95% CI, −0.16 to −0.03] weeks), increased rates of LBW (0.88 [95% CI, 0.23-1.54] percentage points) and prematurity (1.14 [95% CI, 0.21-2.06] percentage points), and a nonsignificant increase in mortality (1.85 [95% CI, −0.19 to 3.89] per 1000 births). The association of eviction with birth weight was strongest in the second and third trimesters of pregnancy, with birth weight reductions of 34.74 (95% CI, −57.51 to −11.97) and 35.80 (95% CI, −52.91 to −18.69) g, respectively.</p></div><div class="section" id="ab-poi200102-10"><h3 class="BHead" id="nov000-7">Conclusions and Relevance</h3><p class="para" id="N65579">These findings suggest that eviction actions during pregnancy are associated with adverse birth outcomes, which have been shown to have lifelong and multigenerational consequences. Ensuring housing, social, and medical assistance to pregnant women at risk for eviction may improve infant health.</p></div>]]></description>
            <pubDate><![CDATA[2021-03-01T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Association Between Preterm-Birth Phenotypes and Differential Morbidity, Growth, and Neurodevelopment at Age 2 Years]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765999642159-aec2ebd1-e9d1-4c4e-bdf2-252490e8e3db/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1001/jamapediatrics.2020.6087</link>
            <description><![CDATA[<div class="section" id="ab-poi200098-1"><h3 class="BHead" id="nov000-1">Question</h3><p class="para" id="N65546">Are specific phenotypes in preterm newborns associated with clinical, growth, and neurodevelopmental differences at age 2 years compared with term newborns?</p></div><div class="section" id="ab-poi200098-2"><h3 class="BHead" id="nov000-2">Findings</h3><p class="para" id="N65552">In this cohort study of 6529 preterm and term newborns who were followed up from birth to age 2 years, 8 preterm-birth phenotypes were identified: no main maternal, fetal, or placental condition detected (35%); infections (21%); preeclampsia (12%); fetal distress (10%); intrauterine growth restriction (8%); severe maternal disease (6%); bleeding (5%); and congenital anomaly (4%). Each phenotype was associated with substantial differences in neonatal morbidity and infant outcomes.</p></div><div class="section" id="ab-poi200098-3"><h3 class="BHead" id="nov000-3">Meaning</h3><p class="para" id="N65558">The study’s findings support the use of phenotypic classification for preterm births.</p></div><div class="section" id="ab-poi200098-4"><h3 class="BHead" id="nov000-1">Importance</h3><p class="para" id="N65543">The etiologic complexities of preterm birth remain inadequately understood, which may impede the development of better preventative and treatment measures.</p></div><div class="section" id="ab-poi200098-5"><h3 class="BHead" id="nov000-2">Objective</h3><p class="para" id="N65549">To examine the association between specific preterm-birth phenotypes and clinical, growth, and neurodevelopmental differences among preterm newborns compared with term newborns up to age 2 years.</p></div><div class="section" id="ab-poi200098-6"><h3 class="BHead" id="nov000-3">Design, Setting, and Participants</h3><p class="para" id="N65555">The INTERBIO-21st study included a cohort of preterm and term newborn singletons enrolled between March 2012 and June 2018 from maternity hospitals in 6 countries worldwide who were followed up from birth to age 2 years. All pregnancies were dated by ultrasonography. Data were analyzed from November 2019 to October 2020.</p></div><div class="section" id="ab-poi200098-7"><h3 class="BHead" id="nov000-4">Exposures/Interventions</h3><p class="para" id="N65561">Preterm-birth phenotypes.</p></div><div class="section" id="ab-poi200098-8"><h3 class="BHead" id="nov000-5">Main Outcomes and Measures</h3><p class="para" id="N65567">Infant size, health, nutrition, and World Health Organization motor development milestones assessed at ages 1 and 2 years; neurodevelopment evaluated at age 2 years using the INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA) tool.</p></div><div class="section" id="ab-poi200098-9"><h3 class="BHead" id="nov000-6">Results</h3><p class="para" id="N65573">A total of 6529 infants (3312 boys [50.7%]) were included in the analysis. Of those, 1381 were preterm births (mean [SD] gestational age at birth, 34.4 [0.1] weeks; 5148 were term births (mean [SD] gestational age at birth, 39.4 [0] weeks). Among 1381 preterm newborns, 8 phenotypes were identified: no main maternal, fetal, or placental condition detected (485 infants [35.1%]); infections (289 infants [20.9%]); preeclampsia (162 infants [11.7%]); fetal distress (131 infants [9.5%]); intrauterine growth restriction (110 infants [8.0%]); severe maternal disease (85 infants [6.2%]); bleeding (71 infants [5.1%]); and congenital anomaly (48 infants [3.5%]). For all phenotypes, a previous preterm birth was a risk factor for recurrence. Each phenotype displayed differences in neonatal morbidity and infant outcomes. For example, infants with the no main condition detected phenotype had low neonatal morbidity but increased morbidity and hospitalization incidence at age 1 year (odds ratio [OR], 2.2; 95% CI, 1.8-2.7). Compared with term newborns, the highest risk of scoring lower than the 10th centile of INTER-NDA normative values was observed in the fine motor development domain among newborns with the fetal distress (OR, 10.6; 95% CI, 5.1-22.2) phenotype.</p></div><div class="section" id="ab-poi200098-10"><h3 class="BHead" id="nov000-7">Conclusions and Relevance</h3><p class="para" id="N65579">Results of this study suggest that phenotypic classification may provide a better understanding of the etiologic factors and mechanisms associated with preterm birth than continuing to consider it an exclusively time-based entity.</p></div><p class="para" id="N65540">This cohort study, part of the INTERBIO-21st Newborn Study, an extension of the INTERGROWTH-21st Project, examines the association between preterm-birth phenotypes and clinical, growth, and neurodevelopmental differences among preterm newborns compared with term newborns up to age 2 years.</p>]]></description>
            <pubDate><![CDATA[2021-03-01T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Association Between Preterm-Birth Phenotypes and Differential Morbidity, Growth, and Neurodevelopment at Age 2 Years]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765999642159-aec2ebd1-e9d1-4c4e-bdf2-252490e8e3db/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1001/jamapediatrics.2020.6087</link>
            <description><![CDATA[<div class="section" id="ab-poi200098-1"><h3 class="BHead" id="nov000-1">Question</h3><p class="para" id="N65546">Are specific phenotypes in preterm newborns associated with clinical, growth, and neurodevelopmental differences at age 2 years compared with term newborns?</p></div><div class="section" id="ab-poi200098-2"><h3 class="BHead" id="nov000-2">Findings</h3><p class="para" id="N65552">In this cohort study of 6529 preterm and term newborns who were followed up from birth to age 2 years, 8 preterm-birth phenotypes were identified: no main maternal, fetal, or placental condition detected (35%); infections (21%); preeclampsia (12%); fetal distress (10%); intrauterine growth restriction (8%); severe maternal disease (6%); bleeding (5%); and congenital anomaly (4%). Each phenotype was associated with substantial differences in neonatal morbidity and infant outcomes.</p></div><div class="section" id="ab-poi200098-3"><h3 class="BHead" id="nov000-3">Meaning</h3><p class="para" id="N65558">The study’s findings support the use of phenotypic classification for preterm births.</p></div><div class="section" id="ab-poi200098-4"><h3 class="BHead" id="nov000-1">Importance</h3><p class="para" id="N65543">The etiologic complexities of preterm birth remain inadequately understood, which may impede the development of better preventative and treatment measures.</p></div><div class="section" id="ab-poi200098-5"><h3 class="BHead" id="nov000-2">Objective</h3><p class="para" id="N65549">To examine the association between specific preterm-birth phenotypes and clinical, growth, and neurodevelopmental differences among preterm newborns compared with term newborns up to age 2 years.</p></div><div class="section" id="ab-poi200098-6"><h3 class="BHead" id="nov000-3">Design, Setting, and Participants</h3><p class="para" id="N65555">The INTERBIO-21st study included a cohort of preterm and term newborn singletons enrolled between March 2012 and June 2018 from maternity hospitals in 6 countries worldwide who were followed up from birth to age 2 years. All pregnancies were dated by ultrasonography. Data were analyzed from November 2019 to October 2020.</p></div><div class="section" id="ab-poi200098-7"><h3 class="BHead" id="nov000-4">Exposures/Interventions</h3><p class="para" id="N65561">Preterm-birth phenotypes.</p></div><div class="section" id="ab-poi200098-8"><h3 class="BHead" id="nov000-5">Main Outcomes and Measures</h3><p class="para" id="N65567">Infant size, health, nutrition, and World Health Organization motor development milestones assessed at ages 1 and 2 years; neurodevelopment evaluated at age 2 years using the INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA) tool.</p></div><div class="section" id="ab-poi200098-9"><h3 class="BHead" id="nov000-6">Results</h3><p class="para" id="N65573">A total of 6529 infants (3312 boys [50.7%]) were included in the analysis. Of those, 1381 were preterm births (mean [SD] gestational age at birth, 34.4 [0.1] weeks; 5148 were term births (mean [SD] gestational age at birth, 39.4 [0] weeks). Among 1381 preterm newborns, 8 phenotypes were identified: no main maternal, fetal, or placental condition detected (485 infants [35.1%]); infections (289 infants [20.9%]); preeclampsia (162 infants [11.7%]); fetal distress (131 infants [9.5%]); intrauterine growth restriction (110 infants [8.0%]); severe maternal disease (85 infants [6.2%]); bleeding (71 infants [5.1%]); and congenital anomaly (48 infants [3.5%]). For all phenotypes, a previous preterm birth was a risk factor for recurrence. Each phenotype displayed differences in neonatal morbidity and infant outcomes. For example, infants with the no main condition detected phenotype had low neonatal morbidity but increased morbidity and hospitalization incidence at age 1 year (odds ratio [OR], 2.2; 95% CI, 1.8-2.7). Compared with term newborns, the highest risk of scoring lower than the 10th centile of INTER-NDA normative values was observed in the fine motor development domain among newborns with the fetal distress (OR, 10.6; 95% CI, 5.1-22.2) phenotype.</p></div><div class="section" id="ab-poi200098-10"><h3 class="BHead" id="nov000-7">Conclusions and Relevance</h3><p class="para" id="N65579">Results of this study suggest that phenotypic classification may provide a better understanding of the etiologic factors and mechanisms associated with preterm birth than continuing to consider it an exclusively time-based entity.</p></div><p class="para" id="N65540">This cohort study, part of the INTERBIO-21st Newborn Study, an extension of the INTERGROWTH-21st Project, examines the association between preterm-birth phenotypes and clinical, growth, and neurodevelopmental differences among preterm newborns compared with term newborns up to age 2 years.</p>]]></description>
            <pubDate><![CDATA[2021-03-01T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[A Comprehensive, Multisystemic Early Childhood Program and Obesity at Age 37 Years]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765999125709-7ffe384d-59a1-426f-bb0d-9e1129b4531e/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1001/jamapediatrics.2020.6721</link>
            <description><![CDATA[<p class="para" id="N65540">This cohort study analyzes reductions in obesity rates at age 37 years among individuals who participated in a multisystemic Child-Parent Center preschool program.</p>]]></description>
            <pubDate><![CDATA[2021-03-22T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Association Between Hypertensive Disorders of Pregnancy and Neurodevelopmental Outcomes Among Offspring]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765996270402-d12d7cda-c6e3-4deb-9f0d-a9892e2ef665/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1001/jamapediatrics.2020.6856</link>
            <description><![CDATA[<div class="section" id="ab-poi200106-1"><h3 class="BHead" id="nov000-1">Question</h3><p class="para" id="N65546">Are hypertensive disorders of pregnancy (HDP) associated with poorer neurodevelopmental outcomes in offspring independently of shared familial confounding factors?</p></div><div class="section" id="ab-poi200106-2"><h3 class="BHead" id="nov000-2">Findings</h3><p class="para" id="N65552">In this cohort study, offspring of HDP-complicated pregnancies had a somewhat higher incidence of autism spectrum disorders (ASDs), attention-deficit/hyperactivity disorder (ADHD), and intellectual disability (ID) and slightly lower overall cognitive performance. Analyses comparing siblings had less statistical power and indicated associations of a similar magnitude with ASDs and possibly ADHD only.</p></div><div class="section" id="ab-poi200106-3"><h3 class="BHead" id="nov000-3">Meaning</h3><p class="para" id="N65558">This study suggests that HDP are associated with modestly increased risks of ASDs and possibly ADHD in offspring, whereas associations with ID and cognitive performance are likely the result of confounding by shared familial characteristics.</p></div><div class="section" id="ab-poi200106-4"><h3 class="BHead" id="nov000-1">Importance</h3><p class="para" id="N65543">Hypertensive disorders of pregnancy (HDP) have been associated with poorer neurodevelopmental outcomes in offspring, but the role of familial confounding in these associations is unclear.</p></div><div class="section" id="ab-poi200106-5"><h3 class="BHead" id="nov000-2">Objective</h3><p class="para" id="N65549">To investigate associations of maternal HDP with risks in offspring of autism spectrum disorders (ASDs), attention-deficit/hyperactivity disorder (ADHD), and intellectual disability (ID), as well as variation in overall cognitive performance in offspring.</p></div><div class="section" id="ab-poi200106-6"><h3 class="BHead" id="nov000-3">Design, Setting, and Participants</h3><p class="para" id="N65555">This Swedish register-based study used data from a birth cohort divided into 1 085 024 individuals born between 1987 and 1996 and followed up until December 31, 2014, and 285 901 men born between 1982 and 1992 who attended assessments for military conscription, including a cognitive function test. Statistical analysis was performed from April 1, 2019, to June 1, 2020.</p></div><div class="section" id="ab-poi200106-7"><h3 class="BHead" id="nov000-4">Exposures</h3><p class="para" id="N65561">Diagnoses of HDP, which were provided by the Medical Birth Register.</p></div><div class="section" id="ab-poi200106-8"><h3 class="BHead" id="nov000-5">Main Outcomes and Measures</h3><p class="para" id="N65567">Diagnoses of ASDs, ADHD, and ID were extracted from the National Patient Register. Cognitive function was assessed using written tests and summarized as a single 9-point score. Whole-cohort and within-sibship analyses were performed; the latter accounted for unmeasured familial confounding factors shared by siblings.</p></div><div class="section" id="ab-poi200106-9"><h3 class="BHead" id="nov000-6">Results</h3><p class="para" id="N65573">The study included 1 085 024 individuals (556 912 male participants [51.3%]) born between 1987 and 1996 and 285 901 men born between 1982 and 1992 who attended assessments for military conscription. The prevalence of maternal HDP was 4.0% in the 1987-1996 birth cohort (n = 42 980) and 5.1% in the military conscription cohort (n = 14 515). A total of 15 858 participants received a diagnosis of ASD, 36 852 received a diagnosis of ADHD, and 8454 received a diagnosis of ID. The mean (SD) cognitive score among the men in the conscription cohort was 5.1 (1.9). In whole-cohort analyses with multivariable adjustment, HDP were associated with offspring ASDs (hazard ratio [HR], 1.22; 95% CI, 1.13-1.31), ADHD (HR, 1.10; 95% CI, 1.05-1.16), and ID (HR, 1.39; 95% CI, 1.27-1.53). Analyses comparing siblings discordant for HDP were less statistically powered but indicated estimates of similar magnitude for ASDs (HR, 1.19; 95% CI, 1.00-1.42) and possibly ADHD (HR, 1.09; 95% CI, 0.95-1.24), but not for ID (HR, 1.04; 95% CI, 0.83-1.29). Hypertensive disorders of pregnancy were associated with somewhat lower cognitive scores in whole-cohort analysis (mean difference comparing offspring exposed with those unexposed, −0.10; 95% CI, −0.13 to −0.07), but in within-sibship analysis, the association was null (mean difference, 0.00; 95% CI, −0.09 to 0.08).</p></div><div class="section" id="ab-poi200106-10"><h3 class="BHead" id="nov000-7">Conclusions and Relevance</h3><p class="para" id="N65579">The study results suggest that HDP are associated with small increased risks of ASDs and possibly ADHD in offspring, whereas associations with ID and cognitive performance are likely confounded by shared familial (environmental or genetic) factors.</p></div><p class="para" id="N65540">This cohort study investigates associations of maternal hypertensive disorders of pregnancy with risks in offspring of autism spectrum disorders, attention-deficit/hyperactivity disorder, and intellectual disability, as well as variation in overall cognitive performance in offspring.</p>]]></description>
            <pubDate><![CDATA[2021-03-22T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Association Between Hypertensive Disorders of Pregnancy and Neurodevelopmental Outcomes Among Offspring]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765996270402-d12d7cda-c6e3-4deb-9f0d-a9892e2ef665/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1001/jamapediatrics.2020.6856</link>
            <description><![CDATA[<div class="section" id="ab-poi200106-1"><h3 class="BHead" id="nov000-1">Question</h3><p class="para" id="N65546">Are hypertensive disorders of pregnancy (HDP) associated with poorer neurodevelopmental outcomes in offspring independently of shared familial confounding factors?</p></div><div class="section" id="ab-poi200106-2"><h3 class="BHead" id="nov000-2">Findings</h3><p class="para" id="N65552">In this cohort study, offspring of HDP-complicated pregnancies had a somewhat higher incidence of autism spectrum disorders (ASDs), attention-deficit/hyperactivity disorder (ADHD), and intellectual disability (ID) and slightly lower overall cognitive performance. Analyses comparing siblings had less statistical power and indicated associations of a similar magnitude with ASDs and possibly ADHD only.</p></div><div class="section" id="ab-poi200106-3"><h3 class="BHead" id="nov000-3">Meaning</h3><p class="para" id="N65558">This study suggests that HDP are associated with modestly increased risks of ASDs and possibly ADHD in offspring, whereas associations with ID and cognitive performance are likely the result of confounding by shared familial characteristics.</p></div><div class="section" id="ab-poi200106-4"><h3 class="BHead" id="nov000-1">Importance</h3><p class="para" id="N65543">Hypertensive disorders of pregnancy (HDP) have been associated with poorer neurodevelopmental outcomes in offspring, but the role of familial confounding in these associations is unclear.</p></div><div class="section" id="ab-poi200106-5"><h3 class="BHead" id="nov000-2">Objective</h3><p class="para" id="N65549">To investigate associations of maternal HDP with risks in offspring of autism spectrum disorders (ASDs), attention-deficit/hyperactivity disorder (ADHD), and intellectual disability (ID), as well as variation in overall cognitive performance in offspring.</p></div><div class="section" id="ab-poi200106-6"><h3 class="BHead" id="nov000-3">Design, Setting, and Participants</h3><p class="para" id="N65555">This Swedish register-based study used data from a birth cohort divided into 1 085 024 individuals born between 1987 and 1996 and followed up until December 31, 2014, and 285 901 men born between 1982 and 1992 who attended assessments for military conscription, including a cognitive function test. Statistical analysis was performed from April 1, 2019, to June 1, 2020.</p></div><div class="section" id="ab-poi200106-7"><h3 class="BHead" id="nov000-4">Exposures</h3><p class="para" id="N65561">Diagnoses of HDP, which were provided by the Medical Birth Register.</p></div><div class="section" id="ab-poi200106-8"><h3 class="BHead" id="nov000-5">Main Outcomes and Measures</h3><p class="para" id="N65567">Diagnoses of ASDs, ADHD, and ID were extracted from the National Patient Register. Cognitive function was assessed using written tests and summarized as a single 9-point score. Whole-cohort and within-sibship analyses were performed; the latter accounted for unmeasured familial confounding factors shared by siblings.</p></div><div class="section" id="ab-poi200106-9"><h3 class="BHead" id="nov000-6">Results</h3><p class="para" id="N65573">The study included 1 085 024 individuals (556 912 male participants [51.3%]) born between 1987 and 1996 and 285 901 men born between 1982 and 1992 who attended assessments for military conscription. The prevalence of maternal HDP was 4.0% in the 1987-1996 birth cohort (n = 42 980) and 5.1% in the military conscription cohort (n = 14 515). A total of 15 858 participants received a diagnosis of ASD, 36 852 received a diagnosis of ADHD, and 8454 received a diagnosis of ID. The mean (SD) cognitive score among the men in the conscription cohort was 5.1 (1.9). In whole-cohort analyses with multivariable adjustment, HDP were associated with offspring ASDs (hazard ratio [HR], 1.22; 95% CI, 1.13-1.31), ADHD (HR, 1.10; 95% CI, 1.05-1.16), and ID (HR, 1.39; 95% CI, 1.27-1.53). Analyses comparing siblings discordant for HDP were less statistically powered but indicated estimates of similar magnitude for ASDs (HR, 1.19; 95% CI, 1.00-1.42) and possibly ADHD (HR, 1.09; 95% CI, 0.95-1.24), but not for ID (HR, 1.04; 95% CI, 0.83-1.29). Hypertensive disorders of pregnancy were associated with somewhat lower cognitive scores in whole-cohort analysis (mean difference comparing offspring exposed with those unexposed, −0.10; 95% CI, −0.13 to −0.07), but in within-sibship analysis, the association was null (mean difference, 0.00; 95% CI, −0.09 to 0.08).</p></div><div class="section" id="ab-poi200106-10"><h3 class="BHead" id="nov000-7">Conclusions and Relevance</h3><p class="para" id="N65579">The study results suggest that HDP are associated with small increased risks of ASDs and possibly ADHD in offspring, whereas associations with ID and cognitive performance are likely confounded by shared familial (environmental or genetic) factors.</p></div><p class="para" id="N65540">This cohort study investigates associations of maternal hypertensive disorders of pregnancy with risks in offspring of autism spectrum disorders, attention-deficit/hyperactivity disorder, and intellectual disability, as well as variation in overall cognitive performance in offspring.</p>]]></description>
            <pubDate><![CDATA[2021-03-22T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Effect of fecal microbiota transplantation on neurological restoration in a spinal cord injury mouse model: involvement of brain-gut axis]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765977821839-031357da-3efb-487d-84ab-4bbe67361585/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-021-01007-y</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">Spinal cord injury (SCI) patients display disruption of gut microbiome, and gut dysbiosis exacerbate neurological impairment in SCI models. Cumulative data support an important role of gut microbiome in SCI. Here, we investigated the hypothesis that fecal microbiota transplantation (FMT) from healthy uninjured mice into SCI mice may exert a neuroprotective effect.</p></div><div class="section" id="N65546"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">FMT facilitated functional recovery, promoted neuronal axonal regeneration, improved animal weight gain and metabolic profiling, and enhanced intestinal barrier integrity and GI motility in SCI mice. High-throughput sequencing revealed that levels of phylum <i>Firmicutes</i>, family <i>Christensenellaceae</i>, and genus <i>Butyricimonas</i> were reduced in fecal samples of SCI mice, and FMT remarkably reshaped gut microbiome. Also, FMT-treated SCI mice showed increased amount of fecal short-chain fatty acids (SCFAs), which correlated with alteration of intestinal permeability and locomotor recovery. Furthermore, FMT downregulated IL-1β/NF-κB signaling in spinal cord and NF-κB signaling in gut following SCI.</p></div><div class="section" id="N65561"><h3 class="BHead" id="nov000-3">Conclusion</h3><p class="para" id="Par3">Our study demonstrates that reprogramming of gut microbiota by FMT improves locomotor and GI functions in SCI mice, possibly through the anti-inflammatory functions of SCFAs.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1765977821839-031357da-3efb-487d-84ab-4bbe67361585/assets/40168_2021_1007_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65576"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65579">The online version contains supplementary material available at 10.1186/s40168-021-01007-y.</p></div>]]></description>
            <pubDate><![CDATA[2021-03-07T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Dicer-like proteins influence Arabidopsis root microbiota independent of RNA-directed DNA methylation]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765933749164-971237fc-b7fc-4154-b4e0-905cb60b7473/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-020-00966-y</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">Plants are naturally associated with root microbiota, which are microbial communities influential to host fitness. Thus, it is important to understand how plants control root microbiota. Epigenetic factors regulate the readouts of genetic information and consequently many essential biological processes. However, it has been elusive whether RNA-directed DNA methylation (RdDM) affects root microbiota assembly.</p></div><div class="section" id="N65546"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">By applying 16S rRNA gene sequencing, we investigated root microbiota of Arabidopsis mutants defective in the canonical RdDM pathway, including <i>dcl234</i> that harbors triple mutation in the Dicer-like proteins DCL3, DCL2, and DCL4, which produce small RNAs for RdDM. Alpha diversity analysis showed reductions in microbe richness from the soil to roots, reflecting the selectivity of plants on root-associated bacteria. The <i>dcl234</i> triple mutation significantly decreases the levels of <i>Aeromonadaceae</i> and <i>Pseudomonadaceae</i>, while it increases the abundance of many other bacteria families in the root microbiota. However, mutants of the other examined key players in the canonical RdDM pathway showed similar microbiota as Col-0, indicating that the DCL proteins affect root microbiota in an RdDM-independent manner. Subsequently gene analysis by shotgun sequencing of root microbiome indicated a selective pressure on microbial resistance to plant defense in the <i>dcl234</i> mutant. Consistent with the altered plant-microbe interactions, <i>dcl234</i> displayed altered characters, including the mRNA and sRNA transcriptomes that jointly highlighted altered cell wall organization and up-regulated defense, the decreased cellulose and callose deposition in root xylem, and the restructured profile of root exudates that supported the alterations in gene expression and cell wall modifications.</p></div><div class="section" id="N65570"><h3 class="BHead" id="nov000-3">Conclusion</h3><p class="para" id="Par3">Our findings demonstrate an important role of the DCL proteins in influencing root microbiota through integrated regulation of plant defense, cell wall compositions, and root exudates. Our results also demonstrate that the canonical RdDM is dispensable for Arabidopsis root microbiota. These findings not only establish a connection between root microbiota and plant epigenetic factors but also highlight the complexity of plant regulation of root microbiota.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1765933749164-971237fc-b7fc-4154-b4e0-905cb60b7473/assets/40168_2020_966_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65586"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65589">The online version contains supplementary material available at 10.1186/s40168-020-00966-y.</p></div>]]></description>
            <pubDate><![CDATA[2021-02-26T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Discovery of novel community-relevant small proteins in a simplified human intestinal microbiome]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765925254052-633b89a2-d3eb-4077-b10f-a3b7bff2d86f/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-020-00981-z</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">The intestinal microbiota plays a crucial role in protecting the host from pathogenic microbes, modulating immunity and regulating metabolic processes. We studied the simplified human intestinal microbiota (SIHUMIx) consisting of eight bacterial species with a particular focus on the discovery of novel small proteins with less than 100 amino acids (= sProteins), some of which may contribute to shape the simplified human intestinal microbiota. Although sProteins carry out a wide range of important functions, they are still often missed in genome annotations, and little is known about their structure and function in individual microbes and especially in microbial communities.</p></div><div class="section" id="N65546"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">We created a multi-species integrated proteogenomics search database (iPtgxDB) to enable a comprehensive identification of novel sProteins. Six of the eight SIHUMIx species, for which no complete genomes were available, were sequenced and de novo assembled. Several proteomics approaches including two earlier optimized sProtein enrichment strategies were applied to specifically increase the chances for novel sProtein discovery. The search of tandem mass spectrometry (MS/MS) data against the multi-species iPtgxDB enabled the identification of 31 novel sProteins, of which the expression of 30 was supported by metatranscriptomics data. Using synthetic peptides, we were able to validate the expression of 25 novel sProteins. The comparison of sProtein expression in each single strain versus a multi-species community cultivation showed that six of these sProteins were only identified in the SIHUMIx community indicating a potentially important role of sProteins in the organization of microbial communities. Two of these novel sProteins have a potential antimicrobial function. Metabolic modelling revealed that a third sProtein is located in a genomic region encoding several enzymes relevant for the community metabolism within SIHUMIx.</p></div><div class="section" id="N65552"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">We outline an integrated experimental and bioinformatics workflow for the discovery of novel sProteins in a simplified intestinal model system that can be generically applied to other microbial communities. The further analysis of novel sProteins uniquely expressed in the SIHUMIx multi-species community is expected to enable new insights into the role of sProteins on the functionality of bacterial communities such as those of the human intestinal tract.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1765925254052-633b89a2-d3eb-4077-b10f-a3b7bff2d86f/assets/40168_2020_981_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65567"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65570">The online version contains supplementary material available at 10.1186/s40168-020-00981-z.</p></div>]]></description>
            <pubDate><![CDATA[2021-02-23T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[The bacterial communities of Alaskan mosses and their contributions to N<sub>2</sub>-fixation]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765924024257-5d67d16f-ad47-4f50-b9e9-84fcf42d8341/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-021-01001-4</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">Mosses in high-latitude ecosystems harbor diverse bacterial taxa, including N<sub>2</sub>-fixers which are key contributors to nitrogen dynamics in these systems. Yet the relative importance of moss host species, and environmental factors, in structuring these microbial communities and their N<sub>2</sub>-fixing potential remains unclear. We studied 26 boreal and tundra moss species across 24 sites in Alaska, USA, from 61 to 69° N. We used cultivation-independent approaches to characterize the variation in moss-associated bacterial communities as a function of host species identity and site characteristics. We also measured N<sub>2</sub>-fixation rates via <sup>15</sup>N<sub>2</sub> isotopic enrichment and identified potential N<sub>2</sub>-fixing bacteria using available literature and genomic information.</p></div><div class="section" id="N65564"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">Host species identity and host evolutionary history were both highly predictive of moss microbiome composition, highlighting strong phylogenetic coherence in these microbial communities. Although less important, light availability and temperature also influenced composition of the moss microbiome. Finally, we identified putative N<sub>2</sub>-fixing bacteria specific to some moss hosts, including potential N<sub>2</sub>-fixing bacteria outside well-studied cyanobacterial clades.</p></div><div class="section" id="N65576"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">The strong effect of host identity on moss-associated bacterial communities demonstrates mosses’ utility for understanding plant-microbe interactions in non-leguminous systems. Our work also highlights the likely importance of novel bacterial taxa to N<sub>2</sub>-fixation in high-latitude ecosystems.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1765924024257-5d67d16f-ad47-4f50-b9e9-84fcf42d8341/assets/40168_2021_1001_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65594"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65597">The online version contains supplementary material available at 10.1186/s40168-021-01001-4.</p></div>]]></description>
            <pubDate><![CDATA[2021-02-23T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Acquisition of oral microbiota is driven by environment, not host genetics]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765922506969-b8987300-a38c-44f3-b853-8526fc0b1997/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-020-00986-8</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">The oral microbiota is acquired very early, but the factors shaping its acquisition are not well understood. Previous studies comparing monozygotic (MZ) and dizygotic (DZ) twins have suggested that host genetics plays a role. However, all twins share an equal portion of their parent’s genome, so this model is not informative for studying parent-to-child transmission. We used a novel study design that allowed us to directly examine the genetics of transmission by comparing the oral microbiota of biological versus adoptive mother-child dyads.</p></div><div class="section" id="N65546"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">No difference was observed in how closely oral bacterial community profiles matched for adoptive versus biological mother-child pairs, indicating little if any effect of host genetics on the fidelity of transmission. Both adopted and biologic children more closely resembled their own mother as compared to unrelated women, supporting the role of contact and environment. Mother-child strain similarity increased with the age of the child, ruling out early effects of host genetic influence that are lost over time. No effect on the fidelity of mother-child strain sharing from vaginal birth or breast feeding was seen. Analysis of extended families showed that fathers and mothers were equally similar to their children, and that cohabitating couples showed even greater strain similarity than mother-child pairs. These findings support the role of contact and shared environment, and age, but not genetics, as determinants of microbial transmission, and were consistent at both species and strain level resolutions, and across multiple oral habitats. In addition, analysis of individual species all showed similar results.</p></div><div class="section" id="N65552"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">The host is clearly active in shaping the composition of the oral microbiome, since only a few of the many bacterial species in the larger environment are capable of colonizing the human oral cavity. Our findings suggest that these host mechanisms are universally shared among humans, since no effect of genetic relatedness on fidelity of microbial transmission could be detected. Instead our findings point towards contact and shared environment being the driving factors of microbial transmission, with a unique combination of these factors ultimately shaping the highly personalized human oral microbiome.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1765922506969-b8987300-a38c-44f3-b853-8526fc0b1997/assets/40168_2020_986_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65567"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65570">The online version contains supplementary material available at 10.1186/s40168-020-00986-8.</p></div>]]></description>
            <pubDate><![CDATA[2021-02-23T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Characterization of the human skin resistome and identification of two microbiota cutotypes]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765900279524-95061ea1-89a2-40a6-97b5-9e716f5b137f/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-020-00995-7</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">The human skin microbiota is considered to be essential for skin homeostasis and barrier function. Comprehensive analyses of its function would substantially benefit from a catalog of reference genes derived from metagenomic sequencing. The existing catalog for the human skin microbiome is based on samples from limited individuals from a single cohort on reference genomes, which limits the coverage of global skin microbiome diversity.</p></div><div class="section" id="N65546"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">In the present study, we have used shotgun metagenomics to newly sequence 822 skin samples from Han Chinese, which were subsequently combined with 538 previously sequenced North American samples to construct an integrated Human Skin Microbial Gene Catalog (iHSMGC). The iHSMGC comprised 10,930,638 genes with the detection of 4,879,024 new genes. Characterization of the human skin resistome based on iHSMGC confirmed that skin commensals, such as <i>Staphylococcus spp</i>, are an important reservoir of antibiotic resistance genes (ARGs). Further analyses of skin microbial ARGs detected microbe-specific and skin site-specific ARG signatures. Of note, the abundance of ARGs was significantly higher in Chinese than Americans, while multidrug-resistant bacteria (“superbugs”) existed on the skin of both Americans and Chinese. A detailed analysis of microbial signatures identified <i>Moraxella osloensis</i> as a species specific for Chinese skin. Importantly, <i>Moraxella osloensis</i> proved to be a signature species for one of two robust patterns of microbial networks present on Chinese skin, with <i>Cutibacterium acnes</i> indicating the second one. Each of such “cutotypes” was associated with distinct patterns of data-driven marker genes, functional modules, and host skin properties. The two cutotypes markedly differed in functional modules related to their metabolic characteristics, indicating that host-dependent trophic chains might underlie their development.</p></div><div class="section" id="N65564"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">The development of the iHSMGC will facilitate further studies on the human skin microbiome. In the present study, it was used to further characterize the human skin resistome. It also allowed to discover the existence of two cutotypes on the human skin. The latter finding will contribute to a better understanding of the interpersonal complexity of the skin microbiome.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1765900279524-95061ea1-89a2-40a6-97b5-9e716f5b137f/assets/40168_2020_995_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65580"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65583">The online version contains supplementary material available at 10.1186/s40168-020-00995-7.</p></div>]]></description>
            <pubDate><![CDATA[2021-02-17T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Mechanistic strategies of microbial communities regulating lignocellulose deconstruction in a UK salt marsh]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765900115332-7adbe77c-4752-4b8b-af58-b4ede0a923a8/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-020-00964-0</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">Salt marshes are major natural repositories of sequestered organic carbon with high burial rates of organic matter, produced by highly productive native flora. Accumulated carbon predominantly exists as lignocellulose which is metabolised by communities of functionally diverse microbes. However, the organisms that orchestrate this process and the enzymatic mechanisms employed that regulate the accumulation, composition and permanence of this carbon stock are not yet known. We applied meta-exo-proteome proteomics and 16S rRNA gene profiling to study lignocellulose decomposition in situ within the surface level sediments of a natural established UK salt marsh.</p></div><div class="section" id="N65546"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">Our studies revealed a community dominated by <i>Gammaproteobacteria</i>, <i>Bacteroidetes</i> and <i>Deltaproteobacteria</i> that drive lignocellulose degradation in the salt marsh. We identify 42 families of lignocellulolytic bacteria of which the most active secretors of carbohydrate-active enzymes were observed to be <i>Prolixibacteracea</i>, <i>Flavobacteriaceae</i>, <i>Cellvibrionaceae</i>, <i>Saccharospirillaceae</i>, <i>Alteromonadaceae</i>, <i>Vibrionaceae</i> and <i>Cytophagaceae</i>. These families secreted lignocellulose-active glycoside hydrolase (GH) family enzymes GH3, GH5, GH6, GH9, GH10, GH11, GH13 and GH43 that were associated with degrading <i>Spartina</i> biomass. While fungi were present, we did not detect a lignocellulolytic contribution from fungi which are major contributors to terrestrial lignocellulose deconstruction. Oxidative enzymes such as laccases, peroxidases and lytic polysaccharide monooxygenases that are important for lignocellulose degradation in the terrestrial environment were present but not abundant, while a notable abundance of putative esterases (such as carbohydrate esterase family 1) associated with decoupling lignin from polysaccharides in lignocellulose was observed.</p></div><div class="section" id="N65585"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">Here, we identify a diverse cohort of previously undefined bacteria that drive lignocellulose degradation in the surface sediments of the salt marsh environment and describe the enzymatic mechanisms they employ to facilitate this process. Our results increase the understanding of the microbial and molecular mechanisms that underpin carbon sequestration from lignocellulose within salt marsh surface sediments in situ and provide insights into the potential enzymatic mechanisms regulating the enrichment of polyphenolics in salt marsh sediments.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1765900115332-7adbe77c-4752-4b8b-af58-b4ede0a923a8/assets/40168_2020_964_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65600"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65603">The online version contains supplementary material available at 10.1186/s40168-020-00964-0.</p></div>]]></description>
            <pubDate><![CDATA[2021-02-17T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Modulating gut microbiota in a mouse model of Graves’ orbitopathy and its impact on induced disease]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765900073957-8b8dc378-537e-4ea0-a944-73e33eadf07d/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-020-00952-4</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">Graves’ disease (GD) is an autoimmune condition in which autoantibodies to the thyrotropin receptor (TSHR) cause hyperthyroidism. About 50% of GD patients also have Graves’ orbitopathy (GO), an intractable disease in which expansion of the orbital contents causes diplopia, proptosis and even blindness. Murine models of GD/GO, developed in different centres, demonstrated significant variation in gut microbiota composition which correlated with TSHR-induced disease heterogeneity. To investigate whether correlation indicates causation, we modified the gut microbiota to determine whether it has a role in thyroid autoimmunity. Female BALB/c mice were treated with either vancomycin, probiotic bacteria, human fecal material transfer (hFMT) from patients with severe GO or ddH2O from birth to immunization with TSHR-A subunit or beta-galactosidase (βgal; age ~ 6 weeks). Incidence and severity of GD (TSHR autoantibodies, thyroid histology, thyroxine level) and GO (orbital fat and muscle histology), lymphocyte phenotype, cytokine profile and gut microbiota were analysed at sacrifice (~ 22 weeks).</p></div><div class="section" id="N65546"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">In ddH2O-TSHR mice, 84% had pathological autoantibodies, 67% elevated thyroxine, 77% hyperplastic thyroids and 70% orbital pathology. <i>Firmicutes</i> were increased, and <i>Bacteroidetes</i> reduced relative to ddH2O-βgal; CCL5 was increased. The random forest algorithm at the genus level predicted vancomycin treatment with 100% accuracy but 74% and 70% for hFMT and probiotic, respectively. Vancomycin significantly reduced gut microbiota richness and diversity compared with all other groups; the incidence and severity of both GD and GO also decreased; reduced orbital pathology correlated positively with <i>Akkermansia</i> spp. whilst IL-4 levels increased. Mice receiving hFMT initially inherited their GO donors’ microbiota, and the severity of induced GD increased, as did the orbital brown adipose tissue volume in TSHR mice. Furthermore, genus <i>Bacteroides</i>, which is reduced in GD patients, was significantly increased by vancomycin but reduced in hFMT-treated mice. Probiotic treatment significantly increased CD25<sup>+</sup> Treg cells in orbital draining lymph nodes but exacerbated induced autoimmune hyperthyroidism and GO.</p></div><div class="section" id="N65567"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">These results strongly support a role for the gut microbiota in TSHR-induced disease. Whilst changes to the gut microbiota have a profound effect on quantifiable GD endocrine and immune factors, the impact on GO cellular changes is more nuanced. The findings have translational potential for novel, improved treatments.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1765900073957-8b8dc378-537e-4ea0-a944-73e33eadf07d/assets/40168_2020_952_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65582"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65585">The online version contains supplementary material available at 10.1186/s40168-020-00952-4.</p></div>]]></description>
            <pubDate><![CDATA[2021-02-16T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Genomic evidence for sulfur intermediates as new biogeochemical hubs in a model aquatic microbial ecosystem]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765899740392-37fa5668-f746-4ada-bc77-ca3c1d4a3160/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-021-00999-x</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">The sulfur cycle encompasses a series of complex aerobic and anaerobic transformations of S-containing molecules and plays a fundamental role in cellular and ecosystem-level processes, influencing biological carbon transfers and other biogeochemical cycles. Despite their importance, the microbial communities and metabolic pathways involved in these transformations remain poorly understood, especially for inorganic sulfur compounds of intermediate oxidation states (thiosulfate, tetrathionate, sulfite, polysulfides). Isolated and highly stratified, the extreme geochemical and environmental features of meromictic ice-capped Lake A, in the Canadian High Arctic, provided an ideal model ecosystem to resolve the distribution and metabolism of aquatic sulfur cycling microorganisms along redox and salinity gradients.</p></div><div class="section" id="N65546"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">Applying complementary molecular approaches, we identified sharply contrasting microbial communities and metabolic potentials among the markedly distinct water layers of Lake A, with similarities to diverse fresh, brackish and saline water microbiomes. Sulfur cycling genes were abundant at all depths and covaried with bacterial abundance. Genes for oxidative processes occurred in samples from the oxic freshwater layers, reductive reactions in the anoxic and sulfidic bottom waters and genes for both transformations at the chemocline. Up to 154 different genomic bins with potential for sulfur transformation were recovered, revealing a panoply of taxonomically diverse microorganisms with complex metabolic pathways for biogeochemical sulfur reactions. Genes for the utilization of sulfur cycle intermediates were widespread throughout the water column, co-occurring with sulfate reduction or sulfide oxidation pathways. The genomic bin composition suggested that in addition to chemical oxidation, these intermediate sulfur compounds were likely produced by the predominant sulfur chemo- and photo-oxidisers at the chemocline and by diverse microbial degraders of organic sulfur molecules.</p></div><div class="section" id="N65552"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">The Lake A microbial ecosystem provided an ideal opportunity to identify new features of the biogeochemical sulfur cycle. Our detailed metagenomic analyses across the broad physico-chemical gradients of this permanently stratified lake extend the known diversity of microorganisms involved in sulfur transformations over a wide range of environmental conditions. The results indicate that sulfur cycle intermediates and organic sulfur molecules are major sources of electron donors and acceptors for aquatic and sedimentary microbial communities in association with the classical sulfur cycle.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1765899740392-37fa5668-f746-4ada-bc77-ca3c1d4a3160/assets/40168_2021_999_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65568"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65571">The online version contains supplementary material available at 10.1186/s40168-021-00999-x.</p></div>]]></description>
            <pubDate><![CDATA[2021-02-16T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Taxonomic and functional analyses of intact microbial communities thriving in extreme, astrobiology-relevant, anoxic sites]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765899228661-4f218305-fb2b-4ccc-b19a-715cc5f09a98/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-020-00989-5</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">Extreme terrestrial, analogue environments are widely used models to study the limits of life and to infer habitability of extraterrestrial settings. In contrast to Earth’s ecosystems, potential extraterrestrial biotopes are usually characterized by a lack of oxygen.</p></div><div class="section" id="N65546"><h3 class="BHead" id="nov000-2">Methods</h3><p class="para" id="Par2">In the MASE project (Mars Analogues for Space Exploration), we selected representative anoxic analogue environments (permafrost, salt-mine, acidic lake and river, sulfur springs) for the comprehensive analysis of their microbial communities. We assessed the microbiome profile of intact cells by propidium monoazide-based amplicon and shotgun metagenome sequencing, supplemented with an extensive cultivation effort.</p></div><div class="section" id="N65552"><h3 class="BHead" id="nov000-3">Results</h3><p class="para" id="Par3">The information retrieved from microbiome analyses on the intact microbial community thriving in the MASE sites, together with the isolation of 31 model microorganisms and successful binning of 15 high-quality genomes allowed us to observe principle pathways, which pinpoint specific microbial functions in the MASE sites compared to moderate environments. The microorganisms were characterized by an impressive machinery to withstand physical and chemical pressures. All levels of our analyses revealed the strong and omnipresent dependency of the microbial communities on complex organic matter. Moreover, we identified an extremotolerant cosmopolitan group of 34 poly-extremophiles thriving in all sites.</p></div><div class="section" id="N65558"><h3 class="BHead" id="nov000-4">Conclusions</h3><p class="para" id="Par4">Our results reveal the presence of a core microbiome and microbial taxonomic similarities between saline and acidic anoxic environments. Our work further emphasizes the importance of the environmental, terrestrial parameters for the functionality of a microbial community, but also reveals a high proportion of living microorganisms in extreme environments with a high adaptation potential within habitability borders.</p><p class="para" id="Par5">
<div class="imageVideo"><img src="/dataresources/secured/content-1765899228661-4f218305-fb2b-4ccc-b19a-715cc5f09a98/assets/40168_2020_989_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65574"><h3 class="BHead" id="nov000-5">Supplementary Information</h3><p class="para" id="N65577">The online version contains supplementary material available at 10.1186/s40168-020-00989-5.</p></div>]]></description>
            <pubDate><![CDATA[2021-02-18T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[A gene co-association network regulating gut microbial communities in a Duroc pig population]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765899019772-efcddc9c-42bc-405c-8629-105dc1a66ce4/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-020-00994-8</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">Analyses of gut microbiome composition in livestock species have shown its potential to contribute to the regulation of complex phenotypes. However, little is known about the host genetic control over the gut microbial communities. In pigs, previous studies are based on classical “single-gene-single-trait” approaches and have evaluated the role of host genome controlling gut prokaryote and eukaryote communities separately.</p></div><div class="section" id="N65546"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">In order to determine the ability of the host genome to control the diversity and composition of microbial communities in healthy pigs, we undertook genome-wide association studies (GWAS) for 39 microbial phenotypes that included 2 diversity indexes, and the relative abundance of 31 bacterial and six commensal protist genera in 390 pigs genotyped for 70 K SNPs. The GWAS results were processed through a 3-step analytical pipeline comprised of (1) association weight matrix; (2) regulatory impact factor; and (3) partial correlation and information theory. The inferred gene regulatory network comprised 3561 genes (within a 5 kb distance from a relevant SNP–<i>P</i> &lt; 0.05) and 738,913 connections (SNP-to-SNP co-associations). Our findings highlight the complexity and polygenic nature of the pig gut microbial ecosystem. Prominent within the network were 5 regulators, <i>PRDM15</i>, <i>STAT1</i>, <i>ssc-mir-371</i>, <i>SOX9</i> and <i>RUNX2</i> which gathered 942, 607, 588, 284 and 273 connections, respectively. <i>PRDM15</i> modulates the transcription of upstream regulators of WNT and MAPK-ERK signaling to safeguard naive pluripotency and regulates the production of Th1- and Th2-type immune response. The signal transducer <i>STAT1</i> has long been associated with immune processes and was recently identified as a potential regulator of vaccine response to porcine reproductive and respiratory syndrome. The list of regulators was enriched for immune-related pathways, and the list of predicted targets includes candidate genes previously reported as associated with microbiota profile in pigs, mice and human, such as <i>SLIT3</i>, <i>SLC39A8</i>, <i>NOS1</i>, <i>IL1R2</i>, <i>DAB1</i>, <i>TOX3</i>, <i>SPP1</i>, <i>THSD7B</i>, <i>ELF2</i>, <i>PIANP</i>, <i>A2ML1</i>, and <i>IFNAR1</i>. Moreover, we show the existence of host-genetic variants jointly associated with the relative abundance of butyrate producer bacteria and host performance.</p></div><div class="section" id="N65612"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">Taken together, our results identified regulators, candidate genes, and mechanisms linked with microbiome modulation by the host. They further highlight the value of the proposed analytical pipeline to exploit pleiotropy and the crosstalk between bacteria and protists as significant contributors to host-microbiome interactions and identify genetic markers and candidate genes that can be incorporated in breeding program to improve host-performance and microbial traits.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1765899019772-efcddc9c-42bc-405c-8629-105dc1a66ce4/assets/40168_2020_994_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65628"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65631">The online version contains supplementary material available at 10.1186/s40168-020-00994-8.</p></div>]]></description>
            <pubDate><![CDATA[2021-02-21T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Functional metagenomics reveals differential chitin degradation and utilization features across free-living and host-associated marine microbiomes]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765863792625-a80ebd90-89aa-4f87-9f40-c273020b5a96/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-020-00970-2</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">Chitin ranks as the most abundant polysaccharide in the oceans yet knowledge of shifts in structure and diversity of chitin-degrading communities across marine niches is scarce. Here, we integrate cultivation-dependent and -independent approaches to shed light on the chitin processing potential within the microbiomes of marine sponges, octocorals, sediments, and seawater.</p></div><div class="section" id="N65546"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">We found that cultivatable host-associated bacteria in the genera <i>Aquimarina</i>, <i>Enterovibrio</i>, <i>Microbulbifer</i>, <i>Pseudoalteromonas</i>, <i>Shewanella</i>, and <i>Vibrio</i> were able to degrade colloidal chitin in vitro. Congruent with enzymatic activity bioassays, genome-wide inspection of cultivated symbionts revealed that <i>Vibrio</i> and <i>Aquimarina</i> species, particularly, possess several endo- and exo-chitinase-encoding genes underlying their ability to cleave the large chitin polymer into oligomers and dimers. Conversely, <i>Alphaproteobacteria</i> species were found to specialize in the utilization of the chitin monomer N-acetylglucosamine more often. Phylogenetic assessments uncovered a high degree of within-genome diversification of multiple, full-length endo-chitinase genes for <i>Aquimarina</i> and <i>Vibrio</i> strains, suggestive of a versatile chitin catabolism aptitude. We then analyzed the abundance distributions of chitin metabolism-related genes across 30 Illumina-sequenced microbial metagenomes and found that the endosymbiotic consortium of <i>Spongia officinalis</i> is enriched in polysaccharide deacetylases, suggesting the ability of the marine sponge microbiome to convert chitin into its deacetylated—and biotechnologically versatile—form chitosan. Instead, the abundance of endo-chitinase and chitin-binding protein-encoding genes in healthy octocorals leveled up with those from the surrounding environment but was found to be depleted in necrotic octocoral tissue. Using cultivation-independent, taxonomic assignments of endo-chitinase encoding genes, we unveiled previously unsuspected richness and divergent structures of chitinolytic communities across host-associated and free-living biotopes, revealing putative roles for uncultivated <i>Gammaproteobacteria</i> and <i>Chloroflexi</i> symbionts in chitin processing within sessile marine invertebrates.</p></div><div class="section" id="N65594"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">Our findings suggest that differential chitin degradation pathways, utilization, and turnover dictate the processing of chitin across marine micro-niches and support the hypothesis that inter-species cross-feeding could facilitate the co-existence of chitin utilizers within marine invertebrate microbiomes. We further identified chitin metabolism functions which may serve as indicators of microbiome integrity/dysbiosis in corals and reveal putative novel chitinolytic enzymes in the genus <i>Aquimarina</i> that may find applications in the blue biotechnology sector.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1765863792625-a80ebd90-89aa-4f87-9f40-c273020b5a96/assets/40168_2020_970_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65613"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65616">The online version contains supplementary material available at 10.1186/s40168-020-00970-2.</p></div>]]></description>
            <pubDate><![CDATA[2021-02-14T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Subcellular view of host–microbiome nutrient exchange in sponges: insights into the ecological success of an early metazoan–microbe symbiosis]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765863584860-4ecef71e-e9a0-42a2-80fb-43578bdedb4c/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-020-00984-w</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">Sponges are increasingly recognised as key ecosystem engineers in many aquatic habitats. They play an important role in nutrient cycling due to their unrivalled capacity for processing both dissolved and particulate organic matter (DOM and POM) and the exceptional metabolic repertoire of their diverse and abundant microbial communities. Functional studies determining the role of host and microbiome in organic nutrient uptake and exchange, however, are limited. Therefore, we coupled pulse-chase isotopic tracer techniques with nanoscale secondary ion mass spectrometry (NanoSIMS) to visualise the uptake and translocation of <sup>13</sup>C- and <sup>15</sup>N-labelled dissolved and particulate organic food at subcellular level in the high microbial abundance sponge <i>Plakortis angulospiculatus</i> and the low microbial abundance sponge <i>Halisarca caerulea.</i></p></div><div class="section" id="N65557"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">The two sponge species showed significant enrichment of DOM- and POM-derived <sup>13</sup>C and <sup>15</sup>N into their tissue over time. Microbial symbionts were actively involved in the assimilation of DOM, but host filtering cells (choanocytes) appeared to be the primary site of DOM and POM uptake in both sponge species overall, via pinocytosis and phagocytosis, respectively. Translocation of carbon and nitrogen from choanocytes to microbial symbionts occurred over time, irrespective of microbial abundance, reflecting recycling of host waste products by the microbiome.</p></div><div class="section" id="N65569"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">Here, we provide empirical evidence indicating that the prokaryotic communities of a high and a low microbial abundance sponge obtain nutritional benefits from their host-associated lifestyle. The metabolic interaction between the highly efficient filter-feeding host and its microbial symbionts likely provides a competitive advantage to the sponge holobiont in the oligotrophic environments in which they thrive, by retaining and recycling limiting nutrients. Sponges present a unique model to link nutritional symbiotic interactions to holobiont function, and, via cascading effects, ecosystem functioning, in one of the earliest metazoan–microbe symbioses.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1765863584860-4ecef71e-e9a0-42a2-80fb-43578bdedb4c/assets/40168_2020_984_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65584"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65587">The online version contains supplementary material available at 10.1186/s40168-020-00984-w.</p></div>]]></description>
            <pubDate><![CDATA[2021-02-14T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Prevalence of SARS-CoV-2 Infection in Children and Their Parents in Southwest Germany]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765852495412-1b4c2aa2-1b44-4079-bade-e60553616ff4/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1001/jamapediatrics.2021.0001</link>
            <description><![CDATA[<div class="section" id="ab-poi210001-1"><h3 class="BHead" id="nov000-1">Question</h3><p class="para" id="N65546">What is the rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and the seroprevalence of SARS-CoV-2 antibodies in children aged 1 to 10 years and a corresponding parent in a population-based sample in southwest Germany?</p></div><div class="section" id="ab-poi210001-2"><h3 class="BHead" id="nov000-2">Findings</h3><p class="para" id="N65552">This large-scale, multicenter, cross-sectional investigation of 4964 participants accurately determined anti–SARS-CoV-2 seropositivity by combining the results of enzyme-linked immunosorbent assay and immunofluorescence tests. The estimated SARS-CoV-2 seroprevalence was low in parents (1.8%) and 3-fold lower in children (0.6%).</p></div><div class="section" id="ab-poi210001-3"><h3 class="BHead" id="nov000-3">Meaning</h3><p class="para" id="N65558">The low seroprevalence of SARS-CoV-2 antibodies in young children in this study may indicate that they do not play a key role in SARS-CoV-2 spreading during the current pandemic.</p></div><p class="para" id="N65540">This cross-sectional investigation conducted in southwest Germany describes the rate of severe acute respiratory syndrome coronavirus 2 infections and the seroprevalence of antibodies in children aged 1 to 10 years, compared with a parent of each child, in a population-based sample.</p><div class="section" id="ab-poi210001-4"><h3 class="BHead" id="nov000-1">Importance</h3><p class="para" id="N65543">School and daycare closures were enforced as measures to confine the novel coronavirus disease 2019 (COVID-19) pandemic, based on the assumption that young children may play a key role in severe acute respiratory coronavirus 2 (SARS-CoV-2) spread. Given the grave consequences of contact restrictions for children, a better understanding of their contribution to the COVID-19 pandemic is of great importance.</p></div><div class="section" id="ab-poi210001-5"><h3 class="BHead" id="nov000-2">Objective</h3><p class="para" id="N65549">To describe the rate of SARS-CoV-2 infections and the seroprevalence of SARS-CoV-2 antibodies in children aged 1 to 10 years, compared with a corresponding parent of each child, in a population-based sample.</p></div><div class="section" id="ab-poi210001-6"><h3 class="BHead" id="nov000-3">Design, Setting, and Participants</h3><p class="para" id="N65555">This large-scale, multicenter, cross-sectional investigation (the COVID-19 BaWü study) enrolled children aged 1 to 10 years and a corresponding parent between April 22 and May 15, 2020, in southwest Germany.</p></div><div class="section" id="ab-poi210001-7"><h3 class="BHead" id="nov000-4">Exposures</h3><p class="para" id="N65561">Potential exposure to SARS-CoV-2.</p></div><div class="section" id="ab-poi210001-8"><h3 class="BHead" id="nov000-5">Main Outcomes and Measures</h3><p class="para" id="N65567">The main outcomes were infection and seroprevalence of SARS-CoV-2. Participants were tested for SARS-CoV-2 RNA from nasopharyngeal swabs by reverse transcription–polymerase chain reaction and SARS-CoV-2 specific IgG antibodies in serum by enzyme-linked immunosorbent assays and immunofluorescence tests. Discordant results were clarified by electrochemiluminescence immunoassays, a second enzyme-linked immunosorbent assay, or an in-house Luminex-based assay.</p></div><div class="section" id="ab-poi210001-9"><h3 class="BHead" id="nov000-6">Results</h3><p class="para" id="N65573">This study included 4964 participants: 2482 children (median age, 6 [range, 1-10] years; 1265 boys [51.0%]) and 2482 parents (median age, 40 [range, 23-66] years; 615 men [24.8%]). Two participants (0.04%) tested positive for SARS-CoV-2 RNA. The estimated SARS-CoV-2 seroprevalence was low in parents (1.8% [95% CI, 1.2–2.4%]) and 3-fold lower in children (0.6% [95% CI, 0.3-1.0%]). Among 56 families with at least 1 child or parent with seropositivity, the combination of a parent with seropositivity and a corresponding child with seronegativity was 4.3 (95% CI, 1.19-15.52) times higher than the combination of a parent who was seronegative and a corresponding child with seropositivity. We observed virus-neutralizing activity for 66 of 70 IgG-positive serum samples (94.3%).</p></div><div class="section" id="ab-poi210001-10"><h3 class="BHead" id="nov000-7">Conclusions and Relevance</h3><p class="para" id="N65579">In this cross-sectional study, the spread of SARS-CoV-2 infection during a period of lockdown in southwest Germany was particularly low in children aged 1 to 10 years. Accordingly, it is unlikely that children have boosted the pandemic. This SARS-CoV-2 prevalence study, which appears to be the largest focusing on children, is instructive for how ad hoc mass testing provides the basis for rational political decision-making in a pandemic.</p></div>]]></description>
            <pubDate><![CDATA[2021-01-22T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Prevalence of SARS-CoV-2 Infection in Children and Their Parents in Southwest Germany]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765852495412-1b4c2aa2-1b44-4079-bade-e60553616ff4/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1001/jamapediatrics.2021.0001</link>
            <description><![CDATA[<div class="section" id="ab-poi210001-1"><h3 class="BHead" id="nov000-1">Question</h3><p class="para" id="N65546">What is the rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and the seroprevalence of SARS-CoV-2 antibodies in children aged 1 to 10 years and a corresponding parent in a population-based sample in southwest Germany?</p></div><div class="section" id="ab-poi210001-2"><h3 class="BHead" id="nov000-2">Findings</h3><p class="para" id="N65552">This large-scale, multicenter, cross-sectional investigation of 4964 participants accurately determined anti–SARS-CoV-2 seropositivity by combining the results of enzyme-linked immunosorbent assay and immunofluorescence tests. The estimated SARS-CoV-2 seroprevalence was low in parents (1.8%) and 3-fold lower in children (0.6%).</p></div><div class="section" id="ab-poi210001-3"><h3 class="BHead" id="nov000-3">Meaning</h3><p class="para" id="N65558">The low seroprevalence of SARS-CoV-2 antibodies in young children in this study may indicate that they do not play a key role in SARS-CoV-2 spreading during the current pandemic.</p></div><p class="para" id="N65540">This cross-sectional investigation conducted in southwest Germany describes the rate of severe acute respiratory syndrome coronavirus 2 infections and the seroprevalence of antibodies in children aged 1 to 10 years, compared with a parent of each child, in a population-based sample.</p><div class="section" id="ab-poi210001-4"><h3 class="BHead" id="nov000-1">Importance</h3><p class="para" id="N65543">School and daycare closures were enforced as measures to confine the novel coronavirus disease 2019 (COVID-19) pandemic, based on the assumption that young children may play a key role in severe acute respiratory coronavirus 2 (SARS-CoV-2) spread. Given the grave consequences of contact restrictions for children, a better understanding of their contribution to the COVID-19 pandemic is of great importance.</p></div><div class="section" id="ab-poi210001-5"><h3 class="BHead" id="nov000-2">Objective</h3><p class="para" id="N65549">To describe the rate of SARS-CoV-2 infections and the seroprevalence of SARS-CoV-2 antibodies in children aged 1 to 10 years, compared with a corresponding parent of each child, in a population-based sample.</p></div><div class="section" id="ab-poi210001-6"><h3 class="BHead" id="nov000-3">Design, Setting, and Participants</h3><p class="para" id="N65555">This large-scale, multicenter, cross-sectional investigation (the COVID-19 BaWü study) enrolled children aged 1 to 10 years and a corresponding parent between April 22 and May 15, 2020, in southwest Germany.</p></div><div class="section" id="ab-poi210001-7"><h3 class="BHead" id="nov000-4">Exposures</h3><p class="para" id="N65561">Potential exposure to SARS-CoV-2.</p></div><div class="section" id="ab-poi210001-8"><h3 class="BHead" id="nov000-5">Main Outcomes and Measures</h3><p class="para" id="N65567">The main outcomes were infection and seroprevalence of SARS-CoV-2. Participants were tested for SARS-CoV-2 RNA from nasopharyngeal swabs by reverse transcription–polymerase chain reaction and SARS-CoV-2 specific IgG antibodies in serum by enzyme-linked immunosorbent assays and immunofluorescence tests. Discordant results were clarified by electrochemiluminescence immunoassays, a second enzyme-linked immunosorbent assay, or an in-house Luminex-based assay.</p></div><div class="section" id="ab-poi210001-9"><h3 class="BHead" id="nov000-6">Results</h3><p class="para" id="N65573">This study included 4964 participants: 2482 children (median age, 6 [range, 1-10] years; 1265 boys [51.0%]) and 2482 parents (median age, 40 [range, 23-66] years; 615 men [24.8%]). Two participants (0.04%) tested positive for SARS-CoV-2 RNA. The estimated SARS-CoV-2 seroprevalence was low in parents (1.8% [95% CI, 1.2–2.4%]) and 3-fold lower in children (0.6% [95% CI, 0.3-1.0%]). Among 56 families with at least 1 child or parent with seropositivity, the combination of a parent with seropositivity and a corresponding child with seronegativity was 4.3 (95% CI, 1.19-15.52) times higher than the combination of a parent who was seronegative and a corresponding child with seropositivity. We observed virus-neutralizing activity for 66 of 70 IgG-positive serum samples (94.3%).</p></div><div class="section" id="ab-poi210001-10"><h3 class="BHead" id="nov000-7">Conclusions and Relevance</h3><p class="para" id="N65579">In this cross-sectional study, the spread of SARS-CoV-2 infection during a period of lockdown in southwest Germany was particularly low in children aged 1 to 10 years. Accordingly, it is unlikely that children have boosted the pandemic. This SARS-CoV-2 prevalence study, which appears to be the largest focusing on children, is instructive for how ad hoc mass testing provides the basis for rational political decision-making in a pandemic.</p></div>]]></description>
            <pubDate><![CDATA[2021-01-22T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Population vs Individual Prediction of Poor Health From Results of Adverse Childhood Experiences Screening]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765851828096-1f1e6466-5119-475f-9e40-285a9d0f4809/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1001/jamapediatrics.2020.5602</link>
            <description><![CDATA[<div class="section" id="ab-poi200089-1"><h3 class="BHead" id="nov000-1">Question</h3><p class="para" id="N65546">Can screening for adverse childhood experiences (ACEs) accurately predict individual risk for later health problems?</p></div><div class="section" id="ab-poi200089-2"><h3 class="BHead" id="nov000-2">Findings</h3><p class="para" id="N65552">In 2 population-based birth cohorts (with a total of 2927 individuals) growing up 20 years and 20 000 km apart, ACE scores were associated with mean group differences in health problems independent of other information available to clinicians. However, ACE scores had low accuracy in predicting health problems at the individual level.</p></div><div class="section" id="ab-poi200089-3"><h3 class="BHead" id="nov000-3">Meaning</h3><p class="para" id="N65558">ACE scores can forecast mean group differences in later health problems; however, ACE scores have poor accuracy in identifying individuals at high risk for future health problems.</p></div><div class="section" id="ab-poi200089-4"><h3 class="BHead" id="nov000-1">Importance</h3><p class="para" id="N65543">Adverse childhood experiences (ACEs) are well-established risk factors for health problems in a population. However, it is not known whether screening for ACEs can accurately identify individuals who develop later health problems.</p></div><div class="section" id="ab-poi200089-5"><h3 class="BHead" id="nov000-2">Objective</h3><p class="para" id="N65549">To test the predictive accuracy of ACE screening for later health problems.</p></div><div class="section" id="ab-poi200089-6"><h3 class="BHead" id="nov000-3">Design, Setting, and Participants</h3><p class="para" id="N65555">This study comprised 2 birth cohorts: the Environmental Risk (E-Risk) Longitudinal Twin Study observed 2232 participants born during the period from 1994 to 1995 until they were aged 18 years (2012-2014); the Dunedin Multidisciplinary Health and Development Study observed 1037 participants born during the period from 1972 to 1973 until they were aged 45 years (2017-2019). Statistical analysis was performed from May 28, 2018, to July 29, 2020.</p></div><div class="section" id="ab-poi200089-7"><h3 class="BHead" id="nov000-4">Exposures</h3><p class="para" id="N65561">ACEs were measured prospectively in childhood through repeated interviews and observations in both cohorts. ACEs were also measured retrospectively in the Dunedin cohort through interviews at 38 years.</p></div><div class="section" id="ab-poi200089-8"><h3 class="BHead" id="nov000-5">Main Outcomes and Measures</h3><p class="para" id="N65567">Health outcomes were assessed at 18 years in E-Risk and at 45 years in the Dunedin cohort. Mental health problems were assessed through clinical interviews using the Diagnostic Interview Schedule. Physical health problems were assessed through interviews, anthropometric measurements, and blood collection.</p></div><div class="section" id="ab-poi200089-9"><h3 class="BHead" id="nov000-6">Results</h3><p class="para" id="N65573">Of 2232 E-Risk participants, 2009 (1051 girls [52%]) were included in the analysis. Of 1037 Dunedin cohort participants, 918 (460 boys [50%]) were included in the analysis. In E-Risk, children with higher ACE scores had greater risk of later health problems (any mental health problem: relative risk, 1.14 [95% CI, 1.10-1.18] per each additional ACE; any physical health problem: relative risk, 1.09 [95% CI, 1.07-1.12] per each additional ACE). ACE scores were associated with health problems independent of other information typically available to clinicians (ie, sex, socioeconomic disadvantage, and history of health problems). However, ACE scores had poor accuracy in predicting an individual’s risk of later health problems (any mental health problem: area under the receiver operating characteristic curve, 0.58 [95% CI, 0.56-0.61]; any physical health problem: area under the receiver operating characteristic curve, 0.60 [95% CI, 0.58-0.63]; chance prediction: area under the receiver operating characteristic curve, 0.50). Findings were consistent in the Dunedin cohort using both prospective and retrospective ACE measures.</p></div><div class="section" id="ab-poi200089-10"><h3 class="BHead" id="nov000-7">Conclusions and Relevance</h3><p class="para" id="N65579">This study suggests that, although ACE scores can forecast mean group differences in health, they have poor accuracy in predicting an individual’s risk of later health problems. Therefore, targeting interventions based on ACE screening is likely to be ineffective in preventing poor health outcomes.</p></div><p class="para" id="N65540">This cohort study uses data from 2 birth cohorts to test the predictive accuracy of adverse childhood experience screening for later health problems.</p>]]></description>
            <pubDate><![CDATA[2021-01-25T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Population vs Individual Prediction of Poor Health From Results of Adverse Childhood Experiences Screening]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765851828096-1f1e6466-5119-475f-9e40-285a9d0f4809/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1001/jamapediatrics.2020.5602</link>
            <description><![CDATA[<div class="section" id="ab-poi200089-1"><h3 class="BHead" id="nov000-1">Question</h3><p class="para" id="N65546">Can screening for adverse childhood experiences (ACEs) accurately predict individual risk for later health problems?</p></div><div class="section" id="ab-poi200089-2"><h3 class="BHead" id="nov000-2">Findings</h3><p class="para" id="N65552">In 2 population-based birth cohorts (with a total of 2927 individuals) growing up 20 years and 20 000 km apart, ACE scores were associated with mean group differences in health problems independent of other information available to clinicians. However, ACE scores had low accuracy in predicting health problems at the individual level.</p></div><div class="section" id="ab-poi200089-3"><h3 class="BHead" id="nov000-3">Meaning</h3><p class="para" id="N65558">ACE scores can forecast mean group differences in later health problems; however, ACE scores have poor accuracy in identifying individuals at high risk for future health problems.</p></div><div class="section" id="ab-poi200089-4"><h3 class="BHead" id="nov000-1">Importance</h3><p class="para" id="N65543">Adverse childhood experiences (ACEs) are well-established risk factors for health problems in a population. However, it is not known whether screening for ACEs can accurately identify individuals who develop later health problems.</p></div><div class="section" id="ab-poi200089-5"><h3 class="BHead" id="nov000-2">Objective</h3><p class="para" id="N65549">To test the predictive accuracy of ACE screening for later health problems.</p></div><div class="section" id="ab-poi200089-6"><h3 class="BHead" id="nov000-3">Design, Setting, and Participants</h3><p class="para" id="N65555">This study comprised 2 birth cohorts: the Environmental Risk (E-Risk) Longitudinal Twin Study observed 2232 participants born during the period from 1994 to 1995 until they were aged 18 years (2012-2014); the Dunedin Multidisciplinary Health and Development Study observed 1037 participants born during the period from 1972 to 1973 until they were aged 45 years (2017-2019). Statistical analysis was performed from May 28, 2018, to July 29, 2020.</p></div><div class="section" id="ab-poi200089-7"><h3 class="BHead" id="nov000-4">Exposures</h3><p class="para" id="N65561">ACEs were measured prospectively in childhood through repeated interviews and observations in both cohorts. ACEs were also measured retrospectively in the Dunedin cohort through interviews at 38 years.</p></div><div class="section" id="ab-poi200089-8"><h3 class="BHead" id="nov000-5">Main Outcomes and Measures</h3><p class="para" id="N65567">Health outcomes were assessed at 18 years in E-Risk and at 45 years in the Dunedin cohort. Mental health problems were assessed through clinical interviews using the Diagnostic Interview Schedule. Physical health problems were assessed through interviews, anthropometric measurements, and blood collection.</p></div><div class="section" id="ab-poi200089-9"><h3 class="BHead" id="nov000-6">Results</h3><p class="para" id="N65573">Of 2232 E-Risk participants, 2009 (1051 girls [52%]) were included in the analysis. Of 1037 Dunedin cohort participants, 918 (460 boys [50%]) were included in the analysis. In E-Risk, children with higher ACE scores had greater risk of later health problems (any mental health problem: relative risk, 1.14 [95% CI, 1.10-1.18] per each additional ACE; any physical health problem: relative risk, 1.09 [95% CI, 1.07-1.12] per each additional ACE). ACE scores were associated with health problems independent of other information typically available to clinicians (ie, sex, socioeconomic disadvantage, and history of health problems). However, ACE scores had poor accuracy in predicting an individual’s risk of later health problems (any mental health problem: area under the receiver operating characteristic curve, 0.58 [95% CI, 0.56-0.61]; any physical health problem: area under the receiver operating characteristic curve, 0.60 [95% CI, 0.58-0.63]; chance prediction: area under the receiver operating characteristic curve, 0.50). Findings were consistent in the Dunedin cohort using both prospective and retrospective ACE measures.</p></div><div class="section" id="ab-poi200089-10"><h3 class="BHead" id="nov000-7">Conclusions and Relevance</h3><p class="para" id="N65579">This study suggests that, although ACE scores can forecast mean group differences in health, they have poor accuracy in predicting an individual’s risk of later health problems. Therefore, targeting interventions based on ACE screening is likely to be ineffective in preventing poor health outcomes.</p></div><p class="para" id="N65540">This cohort study uses data from 2 birth cohorts to test the predictive accuracy of adverse childhood experience screening for later health problems.</p>]]></description>
            <pubDate><![CDATA[2021-01-25T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Toothbrush microbiomes feature a meeting ground for human oral and environmental microbiota]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765850724479-39c67869-031c-4997-8328-4f5c802dccd5/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-020-00983-x</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">While indoor microbiomes impact our health and well-being, much remains unknown about taxonomic and functional transitions that occur in human-derived microbial communities once they are transferred away from human hosts. Toothbrushes are a model to investigate the potential response of oral-derived microbiota to conditions of the built environment. Here, we characterize metagenomes of toothbrushes from 34 subjects to define the toothbrush microbiome and resistome and possible influential factors.</p></div><div class="section" id="N65546"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">Toothbrush microbiomes often comprised a dominant subset of human oral taxa and less abundant or site-specific environmental strains. Although toothbrushes contained lower taxonomic diversity than oral-associated counterparts (determined by comparison with the <i>Human Microbiome Project</i>), they had relatively broader antimicrobial resistance gene (ARG) profiles. Toothbrush resistomes were enriched with a variety of ARGs, notably those conferring multidrug efflux and putative resistance to triclosan, which were primarily attributable to versatile environmental taxa. Toothbrush microbial communities and resistomes correlated with a variety of factors linked to personal health, dental hygiene, and bathroom features.</p></div><div class="section" id="N65555"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">Selective pressures in the built environment may shape the dynamic mixture of human (primarily oral-associated) and environmental microbiota that encounter each other on toothbrushes. Harboring a microbial diversity and resistome distinct from human-associated counterparts suggests toothbrushes could potentially serve as a reservoir that may enable the transfer of ARGs.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1765850724479-39c67869-031c-4997-8328-4f5c802dccd5/assets/40168_2020_983_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65570"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65573">The online version contains supplementary material available at 10.1186/s40168-020-00983-x.</p></div>]]></description>
            <pubDate><![CDATA[2021-01-31T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Sensitivity of Dried Blood Spot Testing for Detection of Congenital Cytomegalovirus Infection]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765840920261-5dbc68b5-0038-4aa6-aa8e-3f89fc6e237c/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1001/jamapediatrics.2020.5441</link>
            <description><![CDATA[<p class="para" id="N65540">This cohort study assesses the sensitivity of dried blood spots polymerase chain reaction for newborn screening for congenital cytomegalovirus infection using saliva as the reference standard for screening, followed by collection of a urine sample for confirmation of congenital infection</p><div class="section" id="ab-poi200086-1"><h3 class="BHead" id="nov000-1">Question</h3><p class="para" id="N65546">What is the sensitivity of polymerase chain reaction testing for congenital cytomegalovirus deployed on dried blood spots obtained for universal newborn screening using current best methods?</p></div><div class="section" id="ab-poi200086-2"><h3 class="BHead" id="nov000-2">Findings</h3><p class="para" id="N65552">This cohort study of 12 554 newborns screened in a multisite study in Minnesota included 56 (4.5 per 1000) with confirmed congenital cytomegalovirus infection. The sensitivity of dried blood spots polymerase chain reaction testing was 85.7% with results of 2 laboratory results combined, which is substantially higher than reported in past studies.</p></div><div class="section" id="ab-poi200086-3"><h3 class="BHead" id="nov000-3">Meaning</h3><p class="para" id="N65558">The relatively high sensitivity of dried blood spots in the interim analysis of this study suggests their potential usefulness for universal cytomegalovirus screening as DNA extraction and polymerase chain reaction methodologies continue to improve.</p></div><div class="section" id="ab-poi200086-4"><h3 class="BHead" id="nov000-1">Importance</h3><p class="para" id="N65543">The sensitivity of dried blood spots (DBS) to identify newborns with congenital cytomegalovirus (cCMV) infection has not been evaluated in screening studies using the current, higher-sensitivity methods for DBS processing.</p></div><div class="section" id="ab-poi200086-5"><h3 class="BHead" id="nov000-2">Objective</h3><p class="para" id="N65549">To assess the sensitivity of DBS polymerase chain reaction (PCR) for newborn screening for cCMV infection using saliva as the reference standard for screening, followed by collection of a urine sample for confirmation of congenital infection.</p></div><div class="section" id="ab-poi200086-6"><h3 class="BHead" id="nov000-3">Design, Setting, and Participants</h3><p class="para" id="N65555">This population-based cohort study took place at 5 newborn nurseries and 3 neonatal intensive care units in the Minneapolis/Saint Paul area in Minnesota from April 2016 to June 2019. Newborns enrolled with parental consent were screened for cCMV using DBS obtained for routine newborn screening and saliva collected 1 to 2 days after birth. Dried blood spots were tested for CMV DNA by PCR at both the University of Minnesota (UMN) and the US Centers for Disease Control and Prevention (CDC). Saliva swabs were tested by CMV DNA PCR at the UMN laboratory only. Newborns who screened positive by saliva or DBS had a diagnostic urine sample obtained by primary care professionals, tested by PCR within 3 weeks of birth. Analysis began July 2019.</p></div><div class="section" id="ab-poi200086-7"><h3 class="BHead" id="nov000-4">Exposures</h3><p class="para" id="N65561">Detection of CMV from a saliva swab using a PCR assay.</p></div><div class="section" id="ab-poi200086-8"><h3 class="BHead" id="nov000-5">Main Outcomes and Measures</h3><p class="para" id="N65567">Number of children with urine-confirmed cCMV and the proportion of them who were CMV positive through DBS screening.</p></div><div class="section" id="ab-poi200086-9"><h3 class="BHead" id="nov000-6">Results</h3><p class="para" id="N65573">Of 12 554 individuals enrolled through June 2019 (of 25 000 projected enrollment), 56 newborns were confirmed to have cCMV (4.5 per 1000 [95% CI, 3.3-5.7]). Combined DBS results from either UMN or CDC had a sensitivity of 85.7% (48 of 56; 95% CI, 74.3%-92.6%), specificity of 100.0% (95% CI, 100.0%-100.0%), positive predictive value (PPV) of 98.0% (95% CI, 89.3%-99.6%), and negative predictive value (NPV) of 99.9% (95% CI, 99.9%-100.0%). Dried blood spot results from UMN had a sensitivity of 73.2% (95% CI, 60.4%-83.0%), specificity of 100.0% (100.0%-100.0%), PPV of 100.0% (95% CI, 91.4%-100.0%), and NPV of 99.9% (95% CI, 99.8%-99.9%). Dried blood spot results from CDC had a sensitivity of 76.8% (95% CI, 64.2%-85.9%), specificity of 100.0% (95% CI, 100.0%-100.0%), PPV of 97.7% (95% CI, 88.2%-99.6%), and NPV of 99.9% (95% CI, 99.8%-99.9%). Saliva swab results had a sensitivity of 92.9% (52 of 56; 95% CI, 83.0%-97.2%), specificity of 99.9% (95% CI, 99.9%-100.0%), PPV of 86.7% (95% CI, 75.8%-93.1%), and NPV of 100.0% (95% CI, 99.9%-100.0%).</p></div><div class="section" id="ab-poi200086-10"><h3 class="BHead" id="nov000-7">Conclusions and Relevance</h3><p class="para" id="N65579">This study demonstrates relatively high analytical sensitivity for DBS compared with previous studies that performed population-based screening. As more sensitive DNA extraction and PCR methods continue to emerge, DBS-based testing should remain under investigation as a potential low-cost, high-throughput option for cCMV screening.</p></div>]]></description>
            <pubDate><![CDATA[2021-02-01T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Sensitivity of Dried Blood Spot Testing for Detection of Congenital Cytomegalovirus Infection]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765840920261-5dbc68b5-0038-4aa6-aa8e-3f89fc6e237c/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1001/jamapediatrics.2020.5441</link>
            <description><![CDATA[<p class="para" id="N65540">This cohort study assesses the sensitivity of dried blood spots polymerase chain reaction for newborn screening for congenital cytomegalovirus infection using saliva as the reference standard for screening, followed by collection of a urine sample for confirmation of congenital infection</p><div class="section" id="ab-poi200086-1"><h3 class="BHead" id="nov000-1">Question</h3><p class="para" id="N65546">What is the sensitivity of polymerase chain reaction testing for congenital cytomegalovirus deployed on dried blood spots obtained for universal newborn screening using current best methods?</p></div><div class="section" id="ab-poi200086-2"><h3 class="BHead" id="nov000-2">Findings</h3><p class="para" id="N65552">This cohort study of 12 554 newborns screened in a multisite study in Minnesota included 56 (4.5 per 1000) with confirmed congenital cytomegalovirus infection. The sensitivity of dried blood spots polymerase chain reaction testing was 85.7% with results of 2 laboratory results combined, which is substantially higher than reported in past studies.</p></div><div class="section" id="ab-poi200086-3"><h3 class="BHead" id="nov000-3">Meaning</h3><p class="para" id="N65558">The relatively high sensitivity of dried blood spots in the interim analysis of this study suggests their potential usefulness for universal cytomegalovirus screening as DNA extraction and polymerase chain reaction methodologies continue to improve.</p></div><div class="section" id="ab-poi200086-4"><h3 class="BHead" id="nov000-1">Importance</h3><p class="para" id="N65543">The sensitivity of dried blood spots (DBS) to identify newborns with congenital cytomegalovirus (cCMV) infection has not been evaluated in screening studies using the current, higher-sensitivity methods for DBS processing.</p></div><div class="section" id="ab-poi200086-5"><h3 class="BHead" id="nov000-2">Objective</h3><p class="para" id="N65549">To assess the sensitivity of DBS polymerase chain reaction (PCR) for newborn screening for cCMV infection using saliva as the reference standard for screening, followed by collection of a urine sample for confirmation of congenital infection.</p></div><div class="section" id="ab-poi200086-6"><h3 class="BHead" id="nov000-3">Design, Setting, and Participants</h3><p class="para" id="N65555">This population-based cohort study took place at 5 newborn nurseries and 3 neonatal intensive care units in the Minneapolis/Saint Paul area in Minnesota from April 2016 to June 2019. Newborns enrolled with parental consent were screened for cCMV using DBS obtained for routine newborn screening and saliva collected 1 to 2 days after birth. Dried blood spots were tested for CMV DNA by PCR at both the University of Minnesota (UMN) and the US Centers for Disease Control and Prevention (CDC). Saliva swabs were tested by CMV DNA PCR at the UMN laboratory only. Newborns who screened positive by saliva or DBS had a diagnostic urine sample obtained by primary care professionals, tested by PCR within 3 weeks of birth. Analysis began July 2019.</p></div><div class="section" id="ab-poi200086-7"><h3 class="BHead" id="nov000-4">Exposures</h3><p class="para" id="N65561">Detection of CMV from a saliva swab using a PCR assay.</p></div><div class="section" id="ab-poi200086-8"><h3 class="BHead" id="nov000-5">Main Outcomes and Measures</h3><p class="para" id="N65567">Number of children with urine-confirmed cCMV and the proportion of them who were CMV positive through DBS screening.</p></div><div class="section" id="ab-poi200086-9"><h3 class="BHead" id="nov000-6">Results</h3><p class="para" id="N65573">Of 12 554 individuals enrolled through June 2019 (of 25 000 projected enrollment), 56 newborns were confirmed to have cCMV (4.5 per 1000 [95% CI, 3.3-5.7]). Combined DBS results from either UMN or CDC had a sensitivity of 85.7% (48 of 56; 95% CI, 74.3%-92.6%), specificity of 100.0% (95% CI, 100.0%-100.0%), positive predictive value (PPV) of 98.0% (95% CI, 89.3%-99.6%), and negative predictive value (NPV) of 99.9% (95% CI, 99.9%-100.0%). Dried blood spot results from UMN had a sensitivity of 73.2% (95% CI, 60.4%-83.0%), specificity of 100.0% (100.0%-100.0%), PPV of 100.0% (95% CI, 91.4%-100.0%), and NPV of 99.9% (95% CI, 99.8%-99.9%). Dried blood spot results from CDC had a sensitivity of 76.8% (95% CI, 64.2%-85.9%), specificity of 100.0% (95% CI, 100.0%-100.0%), PPV of 97.7% (95% CI, 88.2%-99.6%), and NPV of 99.9% (95% CI, 99.8%-99.9%). Saliva swab results had a sensitivity of 92.9% (52 of 56; 95% CI, 83.0%-97.2%), specificity of 99.9% (95% CI, 99.9%-100.0%), PPV of 86.7% (95% CI, 75.8%-93.1%), and NPV of 100.0% (95% CI, 99.9%-100.0%).</p></div><div class="section" id="ab-poi200086-10"><h3 class="BHead" id="nov000-7">Conclusions and Relevance</h3><p class="para" id="N65579">This study demonstrates relatively high analytical sensitivity for DBS compared with previous studies that performed population-based screening. As more sensitive DNA extraction and PCR methods continue to emerge, DBS-based testing should remain under investigation as a potential low-cost, high-throughput option for cCMV screening.</p></div>]]></description>
            <pubDate><![CDATA[2021-02-01T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Effect of Enteral Lipid Supplement on Severe Retinopathy of Prematurity]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765834397984-e0ad57ea-8720-4092-b0fe-42044c5a551b/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1001/jamapediatrics.2020.5653</link>
            <description><![CDATA[<div class="section" id="ab-poi200091-1"><h3 class="BHead" id="nov000-1">Question</h3><p class="para" id="N65546">Does enteral fatty acid supplementation with arachidonic acid (AA) and docosahexaenoic acid (DHA) from birth to 40 weeks’ postmenstrual age reduce severe retinopathy of prematurity (ROP) in extremely preterm infants?</p></div><div class="section" id="ab-poi200091-2"><h3 class="BHead" id="nov000-2">Findings</h3><p class="para" id="N65552">This randomized clinical trial found that enteral AA and DHA supplementation lowered the risk of severe ROP by 50%. In addition, the group that received enteral AA and DHA supplementation showed higher serum levels of both AA and DHA compared with controls.</p></div><div class="section" id="ab-poi200091-3"><h3 class="BHead" id="nov000-3">Meaning</h3><p class="para" id="N65558">Supplementing the diet of the most immature infants born at less than 27 weeks’ gestational age with an enteral lipid solution with AA:DHA had no significant adverse effects and seems to be a promising intervention to prevent sight-threatening ROP and thereby reduce visual impartment and blindness.</p></div><div class="section" id="ab-poi200091-4"><h3 class="BHead" id="nov000-1">Importance</h3><p class="para" id="N65543">Lack of arachidonic acid (AA) and docosahexaenoic acid (DHA) after extremely preterm birth may contribute to preterm morbidity, including retinopathy of prematurity (ROP).</p></div><div class="section" id="ab-poi200091-5"><h3 class="BHead" id="nov000-2">Objective</h3><p class="para" id="N65549">To determine whether enteral supplementation with fatty acids from birth to 40 weeks’ postmenstrual age reduces ROP in extremely preterm infants.</p></div><div class="section" id="ab-poi200091-6"><h3 class="BHead" id="nov000-3">Design, Setting, and Participants</h3><p class="para" id="N65555">The Mega Donna Mega trial, a randomized clinical trial, was a multicenter study performed at 3 university hospitals in Sweden from December 15, 2016, to December 15, 2019. The screening pediatric ophthalmologists were masked to patient groupings. A total of 209 infants born at less than 28 weeks’ gestation were tested for eligibility, and 206 infants were included. Efficacy analyses were performed on as-randomized groups on the intention-to-treat population and on the per-protocol population using as-treated groups. Statistical analyses were performed from February to April 2020.</p></div><div class="section" id="ab-poi200091-7"><h3 class="BHead" id="nov000-4">Interventions</h3><p class="para" id="N65561">Infants received either supplementation with an enteral oil providing AA (100 mg/kg/d) and DHA (50 mg/kg/d) (AA:DHA group) or no supplementation within 3 days after birth until 40 weeks’ postmenstrual age.</p></div><div class="section" id="ab-poi200091-8"><h3 class="BHead" id="nov000-5">Main Outcomes and Measures</h3><p class="para" id="N65567">The primary outcome was severe ROP (stage 3 and/or type 1). The secondary outcomes were AA and DHA serum levels and rates of other complications of preterm birth.</p></div><div class="section" id="ab-poi200091-9"><h3 class="BHead" id="nov000-6">Results</h3><p class="para" id="N65573">A total of 101 infants (58 boys [57.4%]; mean [SD] gestational age, 25.5 [1.5] weeks) were included in the AA:DHA group, and 105 infants (59 boys [56.2%]; mean [SD] gestational age, 25.5 [1.4] weeks) were included in the control group. Treatment with AA and DHA reduced severe ROP compared with the standard of care (16 of 101 [15.8%] in the AA:DHA group vs 35 of 105 [33.3%] in the control group; adjusted relative risk, 0.50 [95% CI, 0.28-0.91]; <i>P</i> = .02). The AA:DHA group had significantly higher fractions of AA and DHA in serum phospholipids compared with controls (overall mean difference in AA:DHA group, 0.82 mol% [95% CI, 0.46-1.18 mol%]; <i>P</i> &lt; .001; overall mean difference in control group, 0.13 mol% [95% CI, 0.01-0.24 mol%]; <i>P</i> = .03). There were no significant differences between the AA:DHA group and the control group in the rates of bronchopulmonary dysplasia (48 of 101 [47.5%] vs 48 of 105 [45.7%]) and of any grade of intraventricular hemorrhage (43 of 101 [42.6%] vs 42 of 105 [40.0%]). In the AA:DHA group and control group, respectively, sepsis occurred in 42 of 101 infants (41.6%) and 53 of 105 infants (50.5%), serious adverse events occurred in 26 of 101 infants (25.7%) and 26 of 105 infants (24.8%), and 16 of 101 infants (15.8%) and 13 of 106 infants (12.3%) died.</p></div><div class="section" id="ab-poi200091-10"><h3 class="BHead" id="nov000-7">Conclusions and Relevance</h3><p class="para" id="N65588">This study found that, compared with standard of care, enteral AA:DHA supplementation lowered the risk of severe ROP by 50% and showed overall higher serum levels of both AA and DHA. Enteral lipid supplementation with AA:DHA is a novel preventive strategy to decrease severe ROP in extremely preterm infants.</p></div><div class="section" id="ab-poi200091-11"><h3 class="BHead" id="nov000-8">Trial Registration</h3><p class="para" id="N65594">ClinicalTrials.gov Identifier: NCT03201588</p></div><p class="para" id="N65540">This randomized clinical trial examines whether enteral supplementation with arachidonic acid and docosahexaenoic acid from birth to 40 weeks’ postmenstrual age reduces retinopathy of prematurity in extremely preterm infants.</p>]]></description>
            <pubDate><![CDATA[2021-02-01T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Effect of Enteral Lipid Supplement on Severe Retinopathy of Prematurity]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765834397984-e0ad57ea-8720-4092-b0fe-42044c5a551b/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1001/jamapediatrics.2020.5653</link>
            <description><![CDATA[<div class="section" id="ab-poi200091-1"><h3 class="BHead" id="nov000-1">Question</h3><p class="para" id="N65546">Does enteral fatty acid supplementation with arachidonic acid (AA) and docosahexaenoic acid (DHA) from birth to 40 weeks’ postmenstrual age reduce severe retinopathy of prematurity (ROP) in extremely preterm infants?</p></div><div class="section" id="ab-poi200091-2"><h3 class="BHead" id="nov000-2">Findings</h3><p class="para" id="N65552">This randomized clinical trial found that enteral AA and DHA supplementation lowered the risk of severe ROP by 50%. In addition, the group that received enteral AA and DHA supplementation showed higher serum levels of both AA and DHA compared with controls.</p></div><div class="section" id="ab-poi200091-3"><h3 class="BHead" id="nov000-3">Meaning</h3><p class="para" id="N65558">Supplementing the diet of the most immature infants born at less than 27 weeks’ gestational age with an enteral lipid solution with AA:DHA had no significant adverse effects and seems to be a promising intervention to prevent sight-threatening ROP and thereby reduce visual impartment and blindness.</p></div><div class="section" id="ab-poi200091-4"><h3 class="BHead" id="nov000-1">Importance</h3><p class="para" id="N65543">Lack of arachidonic acid (AA) and docosahexaenoic acid (DHA) after extremely preterm birth may contribute to preterm morbidity, including retinopathy of prematurity (ROP).</p></div><div class="section" id="ab-poi200091-5"><h3 class="BHead" id="nov000-2">Objective</h3><p class="para" id="N65549">To determine whether enteral supplementation with fatty acids from birth to 40 weeks’ postmenstrual age reduces ROP in extremely preterm infants.</p></div><div class="section" id="ab-poi200091-6"><h3 class="BHead" id="nov000-3">Design, Setting, and Participants</h3><p class="para" id="N65555">The Mega Donna Mega trial, a randomized clinical trial, was a multicenter study performed at 3 university hospitals in Sweden from December 15, 2016, to December 15, 2019. The screening pediatric ophthalmologists were masked to patient groupings. A total of 209 infants born at less than 28 weeks’ gestation were tested for eligibility, and 206 infants were included. Efficacy analyses were performed on as-randomized groups on the intention-to-treat population and on the per-protocol population using as-treated groups. Statistical analyses were performed from February to April 2020.</p></div><div class="section" id="ab-poi200091-7"><h3 class="BHead" id="nov000-4">Interventions</h3><p class="para" id="N65561">Infants received either supplementation with an enteral oil providing AA (100 mg/kg/d) and DHA (50 mg/kg/d) (AA:DHA group) or no supplementation within 3 days after birth until 40 weeks’ postmenstrual age.</p></div><div class="section" id="ab-poi200091-8"><h3 class="BHead" id="nov000-5">Main Outcomes and Measures</h3><p class="para" id="N65567">The primary outcome was severe ROP (stage 3 and/or type 1). The secondary outcomes were AA and DHA serum levels and rates of other complications of preterm birth.</p></div><div class="section" id="ab-poi200091-9"><h3 class="BHead" id="nov000-6">Results</h3><p class="para" id="N65573">A total of 101 infants (58 boys [57.4%]; mean [SD] gestational age, 25.5 [1.5] weeks) were included in the AA:DHA group, and 105 infants (59 boys [56.2%]; mean [SD] gestational age, 25.5 [1.4] weeks) were included in the control group. Treatment with AA and DHA reduced severe ROP compared with the standard of care (16 of 101 [15.8%] in the AA:DHA group vs 35 of 105 [33.3%] in the control group; adjusted relative risk, 0.50 [95% CI, 0.28-0.91]; <i>P</i> = .02). The AA:DHA group had significantly higher fractions of AA and DHA in serum phospholipids compared with controls (overall mean difference in AA:DHA group, 0.82 mol% [95% CI, 0.46-1.18 mol%]; <i>P</i> &lt; .001; overall mean difference in control group, 0.13 mol% [95% CI, 0.01-0.24 mol%]; <i>P</i> = .03). There were no significant differences between the AA:DHA group and the control group in the rates of bronchopulmonary dysplasia (48 of 101 [47.5%] vs 48 of 105 [45.7%]) and of any grade of intraventricular hemorrhage (43 of 101 [42.6%] vs 42 of 105 [40.0%]). In the AA:DHA group and control group, respectively, sepsis occurred in 42 of 101 infants (41.6%) and 53 of 105 infants (50.5%), serious adverse events occurred in 26 of 101 infants (25.7%) and 26 of 105 infants (24.8%), and 16 of 101 infants (15.8%) and 13 of 106 infants (12.3%) died.</p></div><div class="section" id="ab-poi200091-10"><h3 class="BHead" id="nov000-7">Conclusions and Relevance</h3><p class="para" id="N65588">This study found that, compared with standard of care, enteral AA:DHA supplementation lowered the risk of severe ROP by 50% and showed overall higher serum levels of both AA and DHA. Enteral lipid supplementation with AA:DHA is a novel preventive strategy to decrease severe ROP in extremely preterm infants.</p></div><div class="section" id="ab-poi200091-11"><h3 class="BHead" id="nov000-8">Trial Registration</h3><p class="para" id="N65594">ClinicalTrials.gov Identifier: NCT03201588</p></div><p class="para" id="N65540">This randomized clinical trial examines whether enteral supplementation with arachidonic acid and docosahexaenoic acid from birth to 40 weeks’ postmenstrual age reduces retinopathy of prematurity in extremely preterm infants.</p>]]></description>
            <pubDate><![CDATA[2021-02-01T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Japanese quail (<i>Coturnix japonica</i>) as a novel model to study the relationship between the avian microbiome and microbial endocrinology-based host-microbe interactions]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765834184306-e1e55678-2b78-406a-a130-c9319790fd6e/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-020-00962-2</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">Microbial endocrinology, which is the study of neuroendocrine-based interkingdom signaling, provides a causal mechanistic framework for understanding the bi-directional crosstalk between the host and microbiome, especially as regards the effect of stress on health and disease. The importance of the cecal microbiome in avian health is well-recognized, yet little is understood regarding the mechanisms underpinning the avian host-microbiome relationship. Neuroendocrine plasticity of avian tissues that are focal points of host-microbiome interaction, such as the gut and lung, has likewise received limited attention. Avian in vivo models that enable the study of the neuroendocrine dynamic between host and microbiome are needed. As such, we utilized Japanese quail <i>(Coturnix japonica)</i> that diverge in corticosterone response to stress to examine the relationship between stress-related neurochemical concentrations at sites of host-microbe interaction, such as the gut, and the cecal microbiome.</p></div><div class="section" id="N65549"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">Our results demonstrate that birds which contrast in corticosterone response to stress show profound separation in cecal microbial community structure as well as exhibit differences in tissue neurochemical concentrations and structural morphologies of the gut. Changes in neurochemicals known to be affected by the microbiome were also identified in tissues outside of the gut, suggesting a potential relationship in birds between the cecal microbiome and overall avian physiology.</p></div><div class="section" id="N65555"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">The present study provides the first evidence that the structure of the avian cecal microbial community is shaped by selection pressure on the bird for neuroendocrine response to stress. Identification of unique region-dependent neurochemical changes in the intestinal tract following stress highlights environmental stressors as potential drivers of microbial endocrinology-based mechanisms of avian host-microbiome dialogue. Together, these results demonstrate that tissue neurochemical concentrations in the avian gut may be related to the cecal microbiome and reveal the Japanese quail as a novel avian model in which to further examine the mechanisms underpinning these relationships.</p><p class="para" id="Par110">
<div class="imageVideo"><img src="/dataresources/secured/content-1765834184306-e1e55678-2b78-406a-a130-c9319790fd6e/assets/40168_2020_962_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65570"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65573">The online version contains supplementary material available at 10.1186/s40168-020-00962-2.</p></div>]]></description>
            <pubDate><![CDATA[2021-02-02T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Antimicrobial-specific response from resistance gene carriers studied in a natural, highly diverse microbiome]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765832705739-7fe40e7a-f04f-4f93-b4d9-0d400b52a64d/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-020-00982-y</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">Antimicrobial resistance (AMR) is a major threat to public health. Microorganisms equipped with AMR genes are suggested to have partially emerged from natural habitats; however, this hypothesis remains inconclusive so far. To understand the consequences of the introduction of exogenic antimicrobials into natural environments, we exposed lichen thalli of <i>Peltigera polydactylon</i>, which represent defined, highly diverse miniature ecosystems, to clinical (colistin, tetracycline), and non-clinical (glyphosate, alkylpyrazine) antimicrobials. We studied microbiome responses by analysing DNA- and RNA-based amplicon libraries and metagenomic datasets.</p></div><div class="section" id="N65549"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">The analyzed samples consisted of the thallus-forming fungus that is associated with cyanobacteria as well as other diverse and abundant bacterial communities (up to 10<sup>8</sup> 16S rRNA gene copies ng<sup>-1</sup> DNA) dominated by <i>Alphaproteobacteria</i> and <i>Bacteroidetes</i>. Moreover, the natural resistome of this meta-community encompassed 728 AMR genes spanning 30 antimicrobial classes. Following 10 days of exposure to the selected antimicrobials at four different concentrations (full therapeutic dosage and a gradient of sub-therapeutic dosages), we observed statistically significant, antimicrobial-specific shifts in the structure and function but not in bacterial abundances within the microbiota. We observed a relatively lower response after the exposure to the non-clinical compared to the clinical antimicrobial compounds. Furthermore, we observed specific bacterial responders, e.g., <i>Pseudomonas</i> and <i>Burkholderia</i> to clinical antimicrobials. Interestingly, the main positive responders naturally occur in low proportions in the lichen holobiont. Moreover, metagenomic recovery of the responders’ genomes suggested that they are all naturally equipped with specific genetic repertoires that allow them to thrive and bloom when exposed to antimicrobials. Of the responders, <i>Sphingomonas</i>, <i>Pseudomonas</i>, and <i>Methylobacterium</i> showed the highest potential.</p></div><div class="section" id="N65582"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">Antimicrobial exposure resulted in a microbial dysbiosis due to a bloom of naturally low abundant taxa (positive responders) with specific AMR features. Overall, this study provides mechanistic insights into community-level responses of a native microbiota to antimicrobials and suggests novel strategies for AMR prediction and management.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1765832705739-7fe40e7a-f04f-4f93-b4d9-0d400b52a64d/assets/40168_2020_982_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65598"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65601">The online version contains supplementary material available at 10.1186/s40168-020-00982-y.</p></div>]]></description>
            <pubDate><![CDATA[2021-01-27T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[The pleiotropic effects of prebiotic galacto-oligosaccharides on the aging gut]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765822177538-091b87db-41c1-4e84-8b4e-58cee3f9087a/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-020-00980-0</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">Prebiotic galacto-oligosaccharides (GOS) have an extensively demonstrated beneficial impact on intestinal health. In this study, we determined the impact of GOS diets on hallmarks of gut aging: microbiome dysbiosis, inflammation, and intestinal barrier defects (“leaky gut”). We also evaluated if short-term GOS feeding influenced how the aging gut responded to antibiotic challenges in a mouse model of <i>Clostridioides difficile</i> infection. Finally, we assessed if colonic organoids could reproduce the GOS responder—non-responder phenotypes observed in vivo.</p></div><div class="section" id="N65549"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">Old animals had a distinct microbiome characterized by increased ratios of non-saccharolytic versus saccharolytic bacteria and, correspondingly, a lower abundance of β-galactosidases compared to young animals. GOS reduced the overall diversity, increased the abundance of specific saccharolytic bacteria (species of <i>Bacteroides</i> and <i>Lactobacillus</i>), increased the abundance of β-galactosidases in young and old animals, and increased the non-saccharolytic organisms; however, a robust, homogeneous bifidogenic effect was not observed. GOS reduced age-associated increased intestinal permeability and increased <i>MUC2</i> expression and mucus thickness in old mice. Clyndamicin reduced the abundance <i>Bifidobacterium</i> while increasing <i>Akkermansia</i>, <i>Clostridium</i>, <i>Coprococcus</i>, <i>Bacillus</i>, <i>Bacteroides</i>, and <i>Ruminococcus</i> in old mice. The antibiotics were more impactful than GOS on modulating serum markers of inflammation. Higher serum levels of IL-17 and IL-6 were observed in control and GOS diets in the antibiotic groups, and within those groups, levels of IL-6 were higher in the GOS groups, regardless of age, and higher in the old compared to young animals in the control diet groups. RTqPCR revealed significantly increased gene expression of TNFα in distal colon tissue of old mice, which was decreased by the GOS diet. Colon transcriptomics analysis of mice fed GOS showed increased expression of genes involved in small-molecule metabolic processes and specifically the respirasome in old animals, which could indicate an increased oxidative metabolism and energetic efficiency. In young mice, GOS induced the expression of binding-related genes. The galectin gene <i>Lgals1</i>, a β-galactosyl-binding lectin that bridges molecules by their sugar moieties and is an important modulator of the immune response, and the PI3K-Akt and ECM-receptor interaction pathways were also induced in young mice. Stools from mice exhibiting variable bifidogenic response to GOS injected into colon organoids in the presence of prebiotics reproduced the response and non-response phenotypes observed in vivo suggesting that the composition and functionality of the microbiota are the main contributors to the phenotype.</p></div><div class="section" id="N65588"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">Dietary GOS modulated homeostasis of the aging gut by promoting changes in microbiome composition and host gene expression, which was translated into decreased intestinal permeability and increased mucus production. Age was a determining factor on how prebiotics impacted the microbiome and expression of intestinal epithelial cells, especially apparent from the induction of galectin-1 in young but not old mice.</p><p class="para" id="Par555">
<div class="imageVideo"><img src="/dataresources/secured/content-1765822177538-091b87db-41c1-4e84-8b4e-58cee3f9087a/assets/40168_2020_980_MOESM8_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65604"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65607">The online version contains supplementary material available at 10.1186/s40168-020-00980-0.</p></div>]]></description>
            <pubDate><![CDATA[2021-01-28T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Gut microbiota-derived propionate mediates the neuroprotective effect of osteocalcin in a mouse model of Parkinson’s disease]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765821874902-e1bb6acf-171a-4edd-a297-cfbf0e097b50/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-020-00988-6</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">Parkinson’s disease (PD) is a neurodegenerative disorder with no absolute cure. The evidence of the involvement of gut microbiota in PD pathogenesis suggests the need to identify certain molecule(s) derived from the gut microbiota, which has the potential to manage PD. Osteocalcin (OCN), an osteoblast-secreted protein, has been shown to modulate brain function. Thus, it is of interest to investigate whether OCN could exert protective effect on PD and, if yes, whether the underlying mechanism lies in the subsequent changes in gut microbiota.</p></div><div class="section" id="N65546"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">The intraperitoneal injection of OCN can effectively ameliorate the motor deficits and dopaminergic neuronal loss in a 6-hydroxydopamine-induced PD mouse model. The further antibiotics treatment and fecal microbiota transplantation experiments confirmed that the gut microbiota was required for OCN-induced protection in PD mice. OCN elevated <i>Bacteroidetes</i> and depleted <i>Firmicutes</i> phyla in the gut microbiota of PD mice with elevated potential of microbial propionate production and was confirmed by fecal propionate levels. Two months of orally administered propionate successfully rescued motor deficits and dopaminergic neuronal loss in PD mice. Furthermore, AR420626, the agonist of FFAR3, which is the receptor of propionate, mimicked the neuroprotective effects of propionate and the ablation of enteric neurons blocked the prevention of dopaminergic neuronal loss by propionate in PD mice.</p></div><div class="section" id="N65558"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">Together, our results demonstrate that OCN ameliorates motor deficits and dopaminergic neuronal loss in PD mice, modulating gut microbiome and increasing propionate level might be an underlying mechanism responsible for the neuroprotective effects of OCN on PD, and the FFAR3, expressed in enteric nervous system, might be the main action site of propionate.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1765821874902-e1bb6acf-171a-4edd-a297-cfbf0e097b50/assets/40168_2020_988_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65573"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65576">The online version contains supplementary material available at 10.1186/s40168-020-00988-6.</p></div>]]></description>
            <pubDate><![CDATA[2021-01-31T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Specialized metabolic functions of keystone taxa sustain soil microbiome stability]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765820736614-43d5b805-b37e-4473-96c3-7560f1c4eaae/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-020-00985-9</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">The relationship between biodiversity and soil microbiome stability remains poorly understood. Here, we investigated the impacts of bacterial phylogenetic diversity on the functional traits and the stability of the soil microbiome. Communities differing in phylogenetic diversity were generated by inoculating serially diluted soil suspensions into sterilized soil, and the stability of the microbiome was assessed by detecting community variations under various pH levels. The taxonomic features and potential functional traits were detected by DNA sequencing.</p></div><div class="section" id="N65546"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">We found that bacterial communities with higher phylogenetic diversity tended to be more stable, implying that microbiomes with higher biodiversity are more resistant to perturbation. Functional gene co-occurrence network and machine learning classification analyses identified specialized metabolic functions, especially “nitrogen metabolism” and “phosphonate and phosphinate metabolism,” as keystone functions. Further taxonomic annotation found that keystone functions are carried out by specific bacterial taxa, including <i>Nitrospira</i> and <i>Gemmatimonas</i>, among others.</p></div><div class="section" id="N65558"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">This study provides new insights into our understanding of the relationships between soil microbiome biodiversity and ecosystem stability and highlights specialized metabolic functions embedded in keystone taxa that may be essential for soil microbiome stability.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1765820736614-43d5b805-b37e-4473-96c3-7560f1c4eaae/assets/40168_2020_985_MOESM6_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65573"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65576">The online version contains supplementary material available at 10.1186/s40168-020-00985-9.</p></div>]]></description>
            <pubDate><![CDATA[2021-01-31T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Antibiotic-associated dysbiosis affects the ability of the gut microbiota to control intestinal inflammation upon fecal microbiota transplantation in experimental colitis models]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765820106453-55a8f7f8-a1db-4318-a579-b4f5536a0fcf/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-020-00991-x</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">The gut microbiota plays a central role in host physiology and in several pathological mechanisms in humans. Antibiotics compromise the composition and functions of the gut microbiota inducing long-lasting detrimental effects on the host. Recent studies suggest that the efficacy of different clinical therapies depends on the action of the gut microbiota. Here, we investigated how different antibiotic treatments affect the ability of the gut microbiota to control intestinal inflammation upon fecal microbiota transplantation in an experimental colitis model and in ex vivo experiments with human intestinal biopsies.</p></div><div class="section" id="N65546"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">Murine fecal donors were pre-treated with different antibiotics, i.e., vancomycin, streptomycin, and metronidazole before FMT administration to colitic animals. The analysis of the gut microbiome, fecal metabolome, and the immunophenotyping of colonic lamina propria immune cells revealed that antibiotic pre-treatment significantly influences the capability of the microbiota to control intestinal inflammation. Streptomycin and vancomycin-treated microbiota failed to control intestinal inflammation and were characterized by the blooming of pathobionts previously associated with IBD as well as with metabolites related to the presence of oxidative stress and metabolism of simple sugars. On the contrary, the metronidazole-treated microbiota retained its ability to control inflammation co-occurring with the enrichment of <i>Lactobacillus</i> and of innate immune responses involving iNKT cells. Furthermore, ex vivo cultures of human intestinal lamina propria mononuclear cells and iNKT cell clones from IBD patients with vancomycin pre-treated sterile fecal water showed a Th1/Th17 skewing in CD4<sup>+</sup> T-cell populations; metronidazole, on the other hand, induced the polarization of iNKT cells toward the production of IL10.</p></div><div class="section" id="N65558"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">Diverse antibiotic regimens affect the ability of the gut microbiota to control intestinal inflammation in experimental colitis by altering the microbial community structure and microbiota-derived metabolites.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1765820106453-55a8f7f8-a1db-4318-a579-b4f5536a0fcf/assets/40168_2020_991_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65573"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65576">The online version contains supplementary material available at 10.1186/s40168-020-00991-x.</p></div>]]></description>
            <pubDate><![CDATA[2021-02-06T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Microbiome dynamics during the HI-SEAS IV mission, and implications for future crewed missions beyond Earth]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765799800140-75cecbe1-9d31-41a5-b16c-18c1e15443c2/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-020-00959-x</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">Human health is closely interconnected with its microbiome. Resilient microbiomes in, on, and around the human body will be key for safe and successful long-term space travel. However, longitudinal dynamics of microbiomes inside confined built environments are still poorly understood. Herein, we used the Hawaii Space Exploration Analog and Simulation IV (HI-SEAS IV) mission, a 1 year-long isolation study, to investigate microbial transfer between crew and habitat, in order to understand adverse developments which may occur in a future outpost on the Moon or Mars.</p></div><div class="section" id="N65546"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">Longitudinal 16S rRNA gene profiles, as well as quantitative observations, revealed significant differences in microbial diversity, abundance, and composition between samples of the built environment and its crew. The microbiome composition and diversity associated with abiotic surfaces was found to be rather stable, whereas the microbial skin profiles of individual crew members were highly dynamic, resulting in an increased microbiome diversity at the end of the isolation period. The skin microbiome dynamics were especially pronounced by a regular transfer of the indicator species <i>Methanobrevibacter</i> between crew members within the first 200 days. Quantitative information was used to track the propagation of antimicrobial resistance in the habitat. Together with functional and phenotypic predictions, quantitative and qualitative data supported the observation of a delayed longitudinal microbial homogenization between crew and habitat surfaces which was mainly caused by a malfunctioning sanitary facility.</p></div><div class="section" id="N65555"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">This study highlights main routes of microbial transfer, interaction of the crew, and origins of microbial dynamics in an isolated environment. We identify key targets of microbial monitoring, and emphasize the need for defined baselines of microbiome diversity and abundance on surfaces and crew skin. Targeted manipulation to counteract adverse developments of the microbiome could be a highly important strategy to ensure safety during future space endeavors.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1765799800140-75cecbe1-9d31-41a5-b16c-18c1e15443c2/assets/40168_2020_959_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65570"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65573">The online version contains supplementary material available at 10.1186/s40168-020-00959-x.</p></div>]]></description>
            <pubDate><![CDATA[2021-01-24T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Unmasking viral sequences by metagenomic next-generation sequencing in adult human blood samples during steroid-refractory/dependent graft-versus-host disease]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765799563352-dba420da-eebb-4caa-bc38-f6009cd62f11/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-020-00953-3</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">Viral infections are common complications following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Allo-HSCT recipients with steroid-refractory/dependent graft-versus-host disease (GvHD) are highly immunosuppressed and are more vulnerable to infections with weakly pathogenic or commensal viruses. Here, twenty-five adult allo-HSCT recipients from 2016 to 2019 with acute or chronic steroid-refractory/dependent GvHD were enrolled in a prospective cohort at Geneva University Hospitals. We performed metagenomics next-generation sequencing (mNGS) analysis using a validated pipeline and de novo analysis on pooled routine plasma samples collected throughout the period of intensive steroid treatment or second-line GvHD therapy to identify weakly pathogenic, commensal, and unexpected viruses.</p></div><div class="section" id="N65546"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">Median duration of intensive immunosuppression was 5.1 months (IQR 5.5). GvHD-related mortality rate was 36%. mNGS analysis detected viral nucleotide sequences in 24/25 patients. Sequences of ≥ 3 distinct viruses were detected in 16/25 patients; <i>Anelloviridae</i> (24/25) and human pegivirus-1 (9/25) were the most prevalent. In 7 patients with fatal outcomes, viral sequences not assessed by routine investigations were identified with mNGS and confirmed by RT-PCR. These cases included Usutu virus (1), rubella virus (1 vaccine strain and 1 wild-type), novel human astrovirus (HAstV) MLB2 (1), classic HAstV (1), human polyomavirus 6 and 7 (2), cutavirus (1), and bufavirus (1).</p></div><div class="section" id="N65555"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">Clinically unrecognized viral infections were identified in 28% of highly immunocompromised allo-HSCT recipients with steroid-refractory/dependent GvHD in consecutive samples. These identified viruses have all been previously described in humans, but have poorly understood clinical significance. Rubella virus identification raises the possibility of re-emergence from past infections or vaccinations, or re-infection.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1765799563352-dba420da-eebb-4caa-bc38-f6009cd62f11/assets/40168_2020_953_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65570"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65573">The online version contains supplementary material available at 10.1186/s40168-020-00953-3.</p></div>]]></description>
            <pubDate><![CDATA[2021-01-24T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Seasonal shifts in the gut microbiome indicate plastic responses to diet in wild geladas]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765798838344-3d1c68bc-8edf-48aa-b3b3-b9cee40b620c/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-020-00977-9</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">Adaptive shifts in gut microbiome composition are one route by which animals adapt to seasonal changes in food availability and diet. However, outside of dietary shifts, other potential environmental drivers of gut microbial composition have rarely been investigated, particularly in organisms living in their natural environments.</p></div><div class="section" id="N65546"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">Here, we generated the largest wild nonhuman primate gut microbiome dataset to date to identify the environmental drivers of gut microbial diversity and function in 758 samples collected from wild Ethiopian geladas (<i>Theropithecus gelada</i>). Because geladas live in a cold, high-altitude environment and have a low-quality grass-based diet, they face extreme thermoregulatory and energetic constraints. We tested how proxies of food availability (rainfall) and thermoregulatory stress (temperature) predicted gut microbiome composition of geladas. The gelada gut microbiome composition covaried with rainfall and temperature in a pattern that suggests distinct responses to dietary and thermoregulatory challenges. Microbial changes were driven by differences in the main components of the diet across seasons: in rainier periods, the gut was dominated by cellulolytic/fermentative bacteria that specialized in digesting grass, while during dry periods the gut was dominated by bacteria that break down starches found in underground plant parts. Temperature had a comparatively smaller, but detectable, effect on the gut microbiome. During cold and dry periods, bacterial genes involved in energy, amino acid, and lipid metabolism increased, suggesting a stimulation of fermentation activity in the gut when thermoregulatory and nutritional stress co-occurred, and potentially helping geladas to maintain energy balance during challenging periods.</p></div><div class="section" id="N65555"><h3 class="BHead" id="nov000-3">Conclusion</h3><p class="para" id="Par3">Together, these results shed light on the extent to which gut microbiota plasticity provides dietary and metabolic flexibility to the host, and might be a key factor to thriving in changing environments. On a longer evolutionary timescale, such metabolic flexibility provided by the gut microbiome may have also allowed members of <i>Theropithecus</i> to adopt a specialized diet, and colonize new high-altitude grassland habitats in East Africa.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1765798838344-3d1c68bc-8edf-48aa-b3b3-b9cee40b620c/assets/40168_2020_977_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65573"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65576">The online version contains supplementary material available at 10.1186/s40168-020-00977-9.</p></div>]]></description>
            <pubDate><![CDATA[2021-01-23T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Quantifying fluorescent glycan uptake to elucidate strain-level variability in foraging behaviors of rumen bacteria]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765793849001-2c312a3f-0e38-4276-9198-be10af31b256/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-020-00975-x</link>
            <description><![CDATA[<p class="para" id="Par1">Gut microbiomes, such as the microbial community that colonizes the rumen, have vast catabolic potential and play a vital role in host health and nutrition. By expanding our understanding of metabolic pathways in these ecosystems, we will garner foundational information for manipulating microbiome structure and function to influence host physiology. Currently, our knowledge of metabolic pathways relies heavily on inferences derived from metagenomics or culturing bacteria in vitro. However, novel approaches targeting specific cell physiologies can illuminate the functional potential encoded within microbial (meta)genomes to provide accurate assessments of metabolic abilities. Using fluorescently labeled polysaccharides, we visualized carbohydrate metabolism performed by single bacterial cells in a complex rumen sample, enabling a rapid assessment of their metabolic phenotype. Specifically, we identified bovine-adapted strains of <i>Bacteroides thetaiotaomicron</i> that metabolized yeast mannan in the rumen microbiome ex vivo and discerned the mechanistic differences between two distinct carbohydrate foraging behaviors, referred to as “medium grower” and “high grower.” Using comparative whole-genome sequencing, RNA-seq, and carbohydrate-active enzyme fingerprinting, we could elucidate the strain-level variability in carbohydrate utilization systems of the two foraging behaviors to help predict individual strategies of nutrient acquisition. Here, we present a multi-faceted study using complimentary next-generation physiology and “omics” approaches to characterize microbial adaptation to a prebiotic in the rumen ecosystem.</p><p class="para" id="Par2">
<div class="imageVideo"><img src="/dataresources/secured/content-1765793849001-2c312a3f-0e38-4276-9198-be10af31b256/assets/40168_2020_975_MOESM1_ESM.mp4" alt=""/></div></p><div class="section" id="N65556"><h3 class="BHead" id="nov000-1">Supplementary Information</h3><p class="para" id="N65559">The online version contains supplementary material available at 10.1186/s40168-020-00975-x.</p></div>]]></description>
            <pubDate><![CDATA[2021-01-22T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Identification of microbial signatures linked to oilseed rape yield decline at the landscape scale]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765793569014-50537f86-f4d6-48c8-8490-2efc1b96e51e/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-020-00972-0</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">The plant microbiome plays a vital role in determining host health and productivity. However, we lack real-world comparative understanding of the factors which shape assembly of its diverse biota, and crucially relationships between microbiota composition and plant health. Here we investigated landscape scale rhizosphere microbial assembly processes in oilseed rape (OSR), the UK’s third most cultivated crop by area and the world's third largest source of vegetable oil, which suffers from yield decline associated with the frequency it is grown in rotations. By including 37 conventional farmers’ fields with varying OSR rotation frequencies, we present an innovative approach to identify microbial signatures characteristic of microbiomes which are beneficial and harmful to the host.</p></div><div class="section" id="N65546"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">We show that OSR yield decline is linked to rotation frequency in real-world agricultural systems. We demonstrate fundamental differences in the environmental and agronomic drivers of protist, bacterial and fungal communities between root, rhizosphere soil and bulk soil compartments. We further discovered that the assembly of fungi, but neither bacteria nor protists, was influenced by OSR rotation frequency. However, there were individual abundant bacterial OTUs that correlated with either yield or rotation frequency. A variety of fungal and protist pathogens were detected in roots and rhizosphere soil of OSR, and several increased relative abundance in root or rhizosphere compartments as OSR rotation frequency increased. Importantly, the relative abundance of the fungal pathogen <i>Olpidium brassicae</i> both increased with short rotations and was significantly associated with low yield. In contrast, the root endophyte <i>Tetracladium</i> spp. showed the reverse associations with both rotation frequency and yield to <i>O. brassicae</i>, suggesting that they are signatures of a microbiome which benefits the host. We also identified a variety of novel protist and fungal clades which are highly connected within the microbiome and could play a role in determining microbiome composition.</p></div><div class="section" id="N65561"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">We show that at the landscape scale, OSR crop yield is governed by interplay between complex communities of both pathogens and beneficial biota which is modulated by rotation frequency. Our comprehensive study has identified signatures of dysbiosis within the OSR microbiome, grown in real-world agricultural systems, which could be used in strategies to promote crop yield.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1765793569014-50537f86-f4d6-48c8-8490-2efc1b96e51e/assets/40168_2020_972_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65576"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65579">The online version contains supplementary material available at 10.1186/s40168-020-00972-0.</p></div>]]></description>
            <pubDate><![CDATA[2021-01-22T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[A mixed community of skin microbiome representatives influences cutaneous processes more than individual members]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765793162414-3ae8cd33-c701-4263-be04-43c6d7d216e4/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-020-00963-1</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">Skin, the largest organ of the human body by weight, hosts a diversity of microorganisms that can influence health. The microbial residents of the skin are now appreciated for their roles in host immune interactions, wound healing, colonization resistance, and various skin disorders. Still, much remains to be discovered in terms of the host pathways influenced by skin microorganisms, as well as the higher-level skin properties impacted through these microbe-host interactions. Towards this direction, recent efforts using mouse models point to pronounced changes in the transcriptional profiles of the skin in response to the presence of a microbial community. However, there is a need to quantify the roles of microorganisms at both the individual and community-level in healthy human skin. In this study, we utilize human skin equivalents to study the effects of individual taxa and a microbial community in a precisely controlled context. Through transcriptomics analysis, we identify key genes and pathways influenced by skin microbes, and we also characterize higher-level impacts on skin processes and properties through histological analyses.</p></div><div class="section" id="N65546"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">The presence of a microbiome on a 3D skin tissue model led to significantly altered patterns of gene expression, influencing genes involved in the regulation of apoptosis, proliferation, and the extracellular matrix (among others). Moreover, microbiome treatment influenced the thickness of the epidermal layer, reduced the number of actively proliferating cells, and increased filaggrin expression. Many of these findings were evident upon treatment with the mixed community, but either not detected or less pronounced in treatments by single microorganisms, underscoring the impact that a diverse skin microbiome has on the host.</p></div><div class="section" id="N65552"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">This work contributes to the understanding of how microbiome constituents individually and collectively influence human skin processes and properties. The results show that, while it is important to understand the effect of individual microbes on the host, a full community of microbes has unique and pronounced effects on the skin. Thus, in its impacts on the host, the skin microbiome is more than the sum of its parts.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1765793162414-3ae8cd33-c701-4263-be04-43c6d7d216e4/assets/40168_2020_963_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65567"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65570">The online version contains supplementary material available at 10.1186/s40168-020-00963-1.</p></div>]]></description>
            <pubDate><![CDATA[2021-01-22T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Coexistence patterns of soil methanogens are closely tied to methane generation and community assembly in rice paddies]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765793063062-d16e4515-6bb6-472d-bfdf-a6f06389d9be/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-020-00978-8</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">Soil methanogens participate in complex interactions, which determine the community structures and functions. Studies continue to seek the coexistence patterns of soil methanogens, influencing factors and the contribution to methane (CH<sub>4</sub>) production, which are regulated primarily by species interactions, and the functional significance of these interactions. Here, methane emissions were measured in rice paddies across the Asian continent, and the complex interactions involved in coexistence patterns of methanogenic archaeal communities were represented as pairwise links in co-occurrence networks.</p></div><div class="section" id="N65549"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">The network topological properties, which were positively correlated with mean annual temperature, were the most important predictor of CH<sub>4</sub> emissions among all the biotic and abiotic factors. The methanogenic groups involved in commonly co-occurring links among the 39 local networks contributed most to CH<sub>4</sub> emission (53.3%), much higher than the contribution of methanogenic groups with endemic links (36.8%). The potential keystone taxa, belonging to <i>Methanobacterium, Methanocella</i>, <i>Methanothrix</i>, and <i>Methanosarcina</i>, possessed high linkages with the methane generation functional genes <i>mcrA</i>, <i>fwdB</i>, <i>mtbA,</i> and <i>mtbC</i>. Moreover, the commonly coexisting taxa showed a very different assembly pattern, with ~ 30% determinism and ~ 70% stochasticity. In contrast, a higher proportion of stochasticity (93~99%) characterized the assembly of endemically coexisting taxa.</p></div><div class="section" id="N65582"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">These results suggest that the coexistence patterns of microbes are closely tied to their functional significance, and the potential importance of common coexistence further imply that complex networks of interactions may contribute more than species diversity to soil functions.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1765793063062-d16e4515-6bb6-472d-bfdf-a6f06389d9be/assets/40168_2020_978_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65597"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65600">The online version contains supplementary material available at 10.1186/s40168-020-00978-8.</p></div>]]></description>
            <pubDate><![CDATA[2021-01-22T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Microdiversity and phylogeographic diversification of bacterioplankton in pelagic freshwater systems revealed through long-read amplicon sequencing]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765792906006-9b2a5930-d88f-4ec3-8ae8-d1a0c6e473cb/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-020-00974-y</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">Freshwater ecosystems are inhabited by members of cosmopolitan bacterioplankton lineages despite the disconnected nature of these habitats. The lineages are delineated based on &gt; 97% 16S rRNA gene sequence similarity, but their intra-lineage microdiversity and phylogeography, which are key to understanding the eco-evolutional processes behind their ubiquity, remain unresolved. Here, we applied long-read amplicon sequencing targeting nearly full-length 16S rRNA genes and the adjacent ribosomal internal transcribed spacer sequences to reveal the intra-lineage diversities of pelagic bacterioplankton assemblages in 11 deep freshwater lakes in Japan and Europe.</p></div><div class="section" id="N65546"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">Our single nucleotide-resolved analysis, which was validated using shotgun metagenomic sequencing, uncovered 7–101 amplicon sequence variants for each of the 11 predominant bacterial lineages and demonstrated sympatric, allopatric, and temporal microdiversities that could not be resolved through conventional approaches. Clusters of samples with similar intra-lineage population compositions were identified, which consistently supported genetic isolation between Japan and Europe. At a regional scale (up to hundreds of kilometers), dispersal between lakes was unlikely to be a limiting factor, and environmental factors or genetic drift were potential determinants of population composition. The extent of microdiversification varied among lineages, suggesting that highly diversified lineages (e.g., Iluma-A2 and acI-A1) achieve their ubiquity by containing a consortium of genotypes specific to each habitat, while less diversified lineages (e.g., CL500-11) may be ubiquitous due to a small number of widespread genotypes. The lowest extent of intra-lineage diversification was observed among the dominant hypolimnion-specific lineage (CL500-11), suggesting that their dispersal among lakes is not limited despite the hypolimnion being a more isolated habitat than the epilimnion.</p></div><div class="section" id="N65552"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">Our novel approach complemented the limited resolution of short-read amplicon sequencing and limited sensitivity of the metagenome assembly-based approach, and highlighted the complex ecological processes underlying the ubiquity of freshwater bacterioplankton lineages. To fully exploit the performance of the method, its relatively low read throughput is the major bottleneck to be overcome in the future.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1765792906006-9b2a5930-d88f-4ec3-8ae8-d1a0c6e473cb/assets/40168_2020_974_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65567"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65570">The online version contains supplementary material available at 10.1186/s40168-020-00974-y.</p></div>]]></description>
            <pubDate><![CDATA[2021-01-22T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Feasibility of using alternative swabs and storage solutions for paired SARS-CoV-2 detection and microbiome analysis in the hospital environment]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765789363427-94a6e0a3-16d0-4426-85a5-42e4e9f2792c/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-020-00960-4</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">Determining the role of fomites in the transmission of SARS-CoV-2 is essential in the hospital setting and will likely be important outside of medical facilities as governments around the world make plans to ease COVID-19 public health restrictions and attempt to safely reopen economies. Expanding COVID-19 testing to include environmental surfaces would ideally be performed with inexpensive swabs that could be transported safely without concern of being a source of new infections. However, CDC-approved clinical-grade sampling supplies and techniques using a synthetic swab are expensive, potentially expose laboratory workers to viable virus and prohibit analysis of the microbiome due to the presence of antibiotics in viral transport media (VTM). To this end, we performed a series of experiments comparing the diagnostic yield using five consumer-grade swabs (including plastic and wood shafts and various head materials including cotton, synthetic, and foam) and one clinical-grade swab for inhibition to RNA. For three of these swabs, we evaluated performance to detect SARS-CoV-2 in twenty intensive care unit (ICU) hospital rooms of patients including COVID-19+ patients. All swabs were placed in 95% ethanol and further evaluated in terms of RNase activity. SARS-CoV-2 was measured both directly from the swab and from the swab eluent.</p></div><div class="section" id="N65546"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">Compared to samples collected in VTM, 95% ethanol demonstrated significant inhibition properties against RNases. When extracting directly from the swab head as opposed to the eluent, RNA recovery was approximately 2–4× higher from all six swab types tested as compared to the clinical standard of testing the eluent from a CDC-approved synthetic (SYN) swab. The limit of detection (LoD) of SARS-CoV-2 from floor samples collected using the consumer-grade plastic (CGp) or research-grade plastic The Microsetta Initiative (TMI) swabs was similar or better than the SYN swab, further suggesting that swab type does not impact RNA recovery as measured by the abundance of SARS-CoV-2. The LoD for TMI was between 0 and 362.5 viral particles, while SYN and CGp were both between 725 and 1450 particles. Lastly microbiome analyses (16S rRNA gene sequencing) of paired samples (nasal and floor from same patient room) collected using different swab types in triplicate indicated that microbial communities were not impacted by swab type, but instead driven by the patient and sample type.</p></div><div class="section" id="N65552"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">Compared to using a clinical-grade synthetic swab, detection of SARS-CoV-2 from environmental samples collected from ICU rooms of patients with COVID was similar using consumer-grade swabs, stored in 95% ethanol. The yield was best from the swab head rather than the eluent and the low level of RNase activity and lack of antibiotics in these samples makes it possible to perform concomitant microbiome analyses.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1765789363427-94a6e0a3-16d0-4426-85a5-42e4e9f2792c/assets/40168_2020_960_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65567"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65570">The online version contains supplementary material available at 10.1186/s40168-020-00960-4.</p></div>]]></description>
            <pubDate><![CDATA[2021-01-22T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Bacterial community assemblages in classroom floor dust of 50 public schools in a large city: characterization using 16S rRNA sequences and associations with environmental factors]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765789253071-c60f46f3-c893-43aa-bf95-bf7ad86a8f54/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-020-00954-2</link>
            <description><![CDATA[<p class="para" id="Par1">Characterizing indoor microbial communities using molecular methods provides insight into bacterial assemblages present in environments that can influence occupants’ health. We conducted an environmental assessment as part of an epidemiologic study of 50 elementary schools in a large city in the northeastern USA. We vacuumed dust from the edges of the floor in 500 classrooms accounting for 499 processed dust aliquots for 16S Illumina MiSeq sequencing to characterize bacterial assemblages. DNA sequences were organized into operational taxonomic units (OTUs) and identified using a database derived from the National Center for Biotechnology Information. Bacterial diversity and ecological analyses were performed at the genus level. We identified 29 phyla, 57 classes, 148 orders, 320 families, 1193 genera, and 2045 species in 3073 OTUs. The number of genera per school ranged from 470 to 705. The phylum <i>Proteobacteria</i> was richest of all while <i>Firmicutes</i> was most abundant. The most abundant order included <i>Lactobacillales</i>, <i>Spirulinales</i>, and <i>Clostridiales</i>. <i>Halospirulina</i> was the most abundant genus, which has never been reported from any school studies before. Gram-negative bacteria were more abundant and richer (relative abundance = 0.53; 1632 OTUs) than gram-positive bacteria (0.47; 1441). Outdoor environment-associated genera were identified in greater abundance in the classrooms, in contrast to homes where human-associated bacteria are typically more abundant. Effects of school location, degree of water damage, building condition, number of students, air temperature and humidity, floor material, and classroom’s floor level on the bacterial richness or community composition were statistically significant but subtle, indicating relative stability of classroom microbiome from environmental stress. Our study indicates that classroom floor dust had a characteristic bacterial community that is different from typical house dust represented by more gram-positive and human-associated bacteria. Health implications of exposure to the microbiomes in classroom floor dust may be different from those in homes for school staff and students.</p><p class="para" id="Par2">
<div class="imageVideo"><img src="/dataresources/secured/content-1765789253071-c60f46f3-c893-43aa-bf95-bf7ad86a8f54/assets/40168_2020_954_MOESM1_ESM.mp4" alt=""/></div></p><div class="section" id="N65571"><h3 class="BHead" id="nov000-1">Supplementary Information</h3><p class="para" id="N65574">The online version contains supplementary material available at 10.1186/s40168-020-00954-2.</p></div>]]></description>
            <pubDate><![CDATA[2021-01-20T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Whole microbial community viability is not quantitatively reflected by propidium monoazide sequencing approach]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765789192476-9bb1f6d1-14c4-4e14-a312-3ef7bfffef63/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-020-00961-3</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">High-throughput sequencing provides a powerful window into the structural and functional profiling of microbial communities, but it is unable to characterize only the viable portion of microbial communities at scale. There is as yet not one best solution to this problem. Previous studies have established viability assessments using propidium monoazide (PMA) treatment coupled with downstream molecular profiling (e.g., qPCR or sequencing). While these studies have met with moderate success, most of them focused on the resulting “viable” communities without systematic evaluations of the technique. Here, we present our work to rigorously benchmark “PMA-seq” (PMA treatment followed by 16S rRNA gene amplicon sequencing) for viability assessment in synthetic and realistic microbial communities.</p></div><div class="section" id="N65546"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">PMA-seq was able to successfully reconstruct simple synthetic communities comprising viable/heat-killed <i>Escherichia coli</i> and <i>Streptococcus sanguinis</i>. However, in realistically complex communities (computer screens, computer mice, soil, and human saliva) with <i>E. coli</i> spike-in controls, PMA-seq did not accurately quantify viability (even relative to variability in amplicon sequencing), with its performance largely affected by community properties such as initial biomass, sample types, and compositional diversity. We then applied this technique to environmental swabs from the Boston subway system. Several taxa differed significantly after PMA treatment, while not all microorganisms responded consistently. To elucidate the “PMA-responsive” microbes, we compared our results with previous PMA-based studies and found that PMA responsiveness varied widely when microbes were sourced from different ecosystems but were reproducible within similar environments across studies.</p></div><div class="section" id="N65561"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">This study provides a comprehensive evaluation of PMA-seq exploring its quantitative potential in synthetic and complex microbial communities, where the technique was effective for semi-quantitative purposes in simple synthetic communities but provided only qualitative assessments in realistically complex community samples.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1765789192476-9bb1f6d1-14c4-4e14-a312-3ef7bfffef63/assets/40168_2020_961_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65576"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65579">The online version contains supplementary material available at 10.1186/s40168-020-00961-3.</p></div>]]></description>
            <pubDate><![CDATA[2021-01-21T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Decoding the RNA viromes in rodent lungs provides new insight into the origin and evolutionary patterns of rodent-borne pathogens in Mainland Southeast Asia]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765782533531-3461e765-ecc0-4012-94e7-5f9196ee4848/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-020-00965-z</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">As the largest group of mammalian species, which are also widely distributed all over the world, rodents are the natural reservoirs for many diverse zoonotic viruses. A comprehensive understanding of the core virome of diverse rodents should therefore assist in efforts to reduce the risk of future emergence or re-emergence of rodent-borne zoonotic pathogens.</p></div><div class="section" id="N65546"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">This study aimed to describe the viral range that could be detected in the lungs of rodents from Mainland Southeast Asia. Lung samples were collected from 3284 rodents and insectivores of the orders Rodentia, Scandentia, and Eulipotyphla in eighteen provinces of Thailand, Lao PDR, and Cambodia throughout 2006–2018. Meta-transcriptomic analysis was used to outline the unique spectral characteristics of the mammalian viruses within these lungs and the ecological and genetic imprints of the novel viruses. Many mammalian- or arthropod-related viruses from distinct evolutionary lineages were reported for the first time in these species, and viruses related to known pathogens were characterized for their genomic and evolutionary characteristics, host species, and locations.</p></div><div class="section" id="N65552"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">These results expand our understanding of the core viromes of rodents and insectivores from Mainland Southeast Asia and suggest that a high diversity of viruses remains to be found in rodent species of this area. These findings, combined with our previous virome data from China, increase our knowledge of the viral community in wildlife and arthropod vectors in emerging disease hotspots of East and Southeast Asia.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1765782533531-3461e765-ecc0-4012-94e7-5f9196ee4848/assets/40168_2020_965_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65568"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65571">The online version contains supplementary material available at 10.1186/s40168-020-00965-z.</p></div>]]></description>
            <pubDate><![CDATA[2021-01-21T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Polinton-like viruses are abundant in aquatic ecosystems]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765767952326-f4ca6dd3-4bc4-4eef-99c6-c7320fd9bc1e/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-020-00956-0</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">Polintons are large mobile genetic elements found in the genomes of eukaryotic organisms that are considered the ancient ancestors of most eukaryotic dsDNA viruses. Originally considered as transposons, they have been found to encode virus capsid genes, suggesting they may actually be integrated viruses; however, an extracellular form has yet to be detected. Recently, circa 25 Polinton-like viruses have been discovered in environmental metagenomes and algal genomes, which shared distantly related genes to both Polintons and virophages (<i>Lavidaviridae</i>). These entities could be the first members of a major class of ancient eukaryotic viruses; however, owing to the lack of available genomes for analysis, information on their global diversity, evolutionary relationships, eukaryotic hosts, and status as free virus particles is limited.</p></div><div class="section" id="N65549"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">Here, we analysed the metaviromes of an alpine lake to show that Polinton-like virus genome sequences are abundant in the water column. We identify major capsid protein genes belonging to 82 new Polinton-like viruses and use these to interrogate publicly available metagenomic datasets, identifying 543 genomes and a further 16 integrated into eukaryotic genomes. Using an analysis of shared gene content and major capsid protein phylogeny, we define large groups of Polinton-like viruses and link them to diverse eukaryotic hosts, including a new group of viruses, which possess all the core genes of virophages and infect oomycetes and Chrysophyceae.</p></div><div class="section" id="N65555"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">Our study increased the number of known Polinton-like viruses by 25-fold, identifying five major new groups of eukaryotic viruses, which until now have been hidden in metagenomic datasets. The large enrichment (&gt; 100-fold) of Polinton-like virus sequences in the virus-sized fraction of this alpine lake and the fact that their viral major capsid proteins are found in eukaryotic host transcriptomes support the hypothesis that Polintons in unicellular eukaryotes are viruses. In summary, our data reveals a diverse assemblage of globally distributed viruses, associated with a wide range of unicellular eukaryotic hosts. We anticipate that the methods we have developed for Polinton-like virus detection and the database of over 20,000 genes we present will allow for continued discovery and analysis of these new viral groups.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1765767952326-f4ca6dd3-4bc4-4eef-99c6-c7320fd9bc1e/assets/40168_2020_956_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65571"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65574">The online version contains supplementary material available at 10.1186/s40168-020-00956-0.</p></div>]]></description>
            <pubDate><![CDATA[2021-01-12T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Low-dosage ozonation in gas-phase biofilter promotes community diversity and robustness]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765767335475-c0ff88b9-6033-4b0e-8bec-72e33d412c52/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-020-00944-4</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">The ozonation of biofilters is known to alleviate clogging and pressure drop issues while maintaining removal performances in biofiltration systems treating gaseous volatile organic compounds (VOCs). The effects of ozone on the biofilter microbiome in terms of biodiversity, community structure, metabolic abilities, and dominant taxa correlated with performance remain largely unknown.</p></div><div class="section" id="N65546"><h3 class="BHead" id="nov000-2">Methods</h3><p class="para" id="Par2">This study investigated two biofilters treating high-concentration toluene operating in parallel, with one acting as control and the other exposed to low-dosage (200 mg/m<sup>3</sup>) ozonation. The microbial community diversity, metabolic rates of different carbon sources, functional predictions, and microbial co-occurrence networks of both communities were examined.</p></div><div class="section" id="N65555"><h3 class="BHead" id="nov000-3">Results</h3><p class="para" id="Par3">Consistently higher biodiversity of over 30% was observed in the microbiome after ozonation, with increased overall metabolic abilities for amino acids and carboxylic acids. The relative abundance of species with reported stress-tolerant and biofilm-forming abilities significantly increased, with a consortium of changes in predicted biological pathways, including shifts in degradation pathways of intermediate compounds, while the correlation of top ASVs and genus with performance indicators showed diversifications in microbiota responsible for toluene degradation. A co-occurrence network of the community showed a decrease in average path distance and average betweenness with ozonation.</p></div><div class="section" id="N65561"><h3 class="BHead" id="nov000-4">Conclusion</h3><p class="para" id="Par4">Major degrading species highly correlated with performance shifted after ozonation. Increases in microbial biodiversity, coupled with improvements in metabolizing performances of multiple carbon sources including organic acids could explain the consistent performance commonly seen in the ozonation of biofilters despite the decrease in biomass, while avoiding acid buildup in long-term operation. The increased presence of stress-tolerant microbes in the microbiome coupled with the decentralization of the co-occurrence network suggest that ozonation could not only ameliorate clogging issues but also provide a microbiome more robust to loading shock seen in full-scale biofilters.</p><p class="para" id="Par5">
<div class="imageVideo"><img src="/dataresources/secured/content-1765767335475-c0ff88b9-6033-4b0e-8bec-72e33d412c52/assets/40168_2020_944_MOESM6_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65577"><h3 class="BHead" id="nov000-5">Supplementary Information</h3><p class="para" id="N65580">The online version contains supplementary material available at 10.1186/s40168-020-00944-4.</p></div>]]></description>
            <pubDate><![CDATA[2021-01-12T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[A semi-tryptic peptide centric metaproteomic mining approach and its potential utility in capturing signatures of gut microbial proteolysis]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765767183057-42eb30db-e66d-4327-a86c-215b81e8c269/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-020-00967-x</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">Proteolysis regulation allows gut microbes to respond rapidly to dynamic intestinal environments by fast degradation of misfolded proteins and activation of regulatory proteins. However, alterations of gut microbial proteolytic signatures under complex disease status such as inflammatory bowel disease (IBD, including Crohn’s disease (CD) and ulcerative colitis (UC)), have not been investigated. Metaproteomics holds the potential to investigate gut microbial proteolysis because semi-tryptic peptides mainly derive from endogenous proteolysis.</p></div><div class="section" id="N65546"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">We have developed a semi-tryptic peptide centric metaproteomic mining approach to obtain a snapshot of human gut microbial proteolysis signatures. This approach employed a comprehensive meta-database, two-step multiengine database search, and datasets with high-resolution fragmentation spectra to increase the confidence of semi-tryptic peptide identification. The approach was validated by discovering altered proteolysis signatures of <i>Escherichia coli</i> heat shock response. Utilizing two published large-scale metaproteomics datasets containing 623 metaproteomes from 447 fecal and 176 mucosal luminal interface (MLI) samples from IBD patients and healthy individuals, we obtain potential signatures of altered gut microbial proteolysis at taxonomic, functional, and cleavage site motif levels. The functional alterations mainly involved microbial carbohydrate transport and metabolism, oxidative stress, cell motility, protein synthesis, and maturation. Altered microbial proteolysis signatures of CD and UC mainly occurred in terminal ileum and descending colon, respectively. Microbial proteolysis patterns exhibited low correlations with β-diversity and moderate correlations with microbial protease and chaperones levels, respectively. Human protease inhibitors and immunoglobulins were mainly negatively associated with microbial proteolysis patterns, probably because of the inhibitory effects of these host factors on gut microbial proteolysis events.</p></div><div class="section" id="N65555"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">This semi-tryptic peptide centric mining strategy offers a label-free approach to discover signatures of in vivo gut microbial proteolysis events if experimental conditions are well controlled. It can also capture in vitro proteolysis signatures to facilitate the evaluation and optimization of experimental conditions. Our findings highlight the complex and diverse proteolytic events of gut microbiome, providing a unique layer of information beyond taxonomic and proteomic abundance.</p><p class="para" id="Par4">
<div class="imageVideo"><img src="/dataresources/secured/content-1765767183057-42eb30db-e66d-4327-a86c-215b81e8c269/assets/40168_2020_967_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65570"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65573">The online version contains supplementary material available at 10.1186/s40168-020-00967-x.</p></div>]]></description>
            <pubDate><![CDATA[2021-01-12T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[High-dose saccharin supplementation does not induce gut microbiota changes or glucose intolerance in healthy humans and mice]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765762142858-a18c0bf5-e250-4a30-a7d2-3ab907cf2b9a/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1186/s40168-020-00976-w</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">Non-caloric artificial sweeteners (NCAS) are widely used as a substitute for dietary sugars to control body weight or glycemia. Paradoxically, some interventional studies in humans and rodents have shown unfavorable changes in glucose homeostasis in response to NCAS consumption. The causative mechanisms are largely unknown, but adverse changes in gut microbiota have been proposed to mediate these effects. These findings have raised concerns about NCAS safety and called into question their broad use, but further physiological and dietary considerations must be first addressed before these results are generalized. We also reasoned that, since NCAS are bona fide ligands for sweet taste receptors (STRs) expressed in the intestine, some metabolic effects associated with NCAS use could be attributed to a common mechanism involving the host.</p></div><div class="section" id="N65546"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">We conducted a double-blind, placebo-controlled, parallel arm study exploring the effects of pure saccharin compound on gut microbiota and glucose tolerance in healthy men and women. Participants were randomized to placebo, saccharin, lactisole (STR inhibitor), or saccharin with lactisole administered in capsules twice daily to achieve the maximum acceptable daily intake for 2 weeks. In parallel, we performed a 10-week study administering pure saccharin at a high dose in the drinking water of chow-fed mice with genetic ablation of STRs (T1R2-KO) and wild-type (WT) littermate controls. In humans and mice, none of the interventions affected glucose or hormonal responses to an oral glucose tolerance test (OGTT) or glucose absorption in mice. Similarly, pure saccharin supplementation did not alter microbial diversity or composition at any taxonomic level in humans and mice alike. No treatment effects were also noted in readouts of microbial activity such as fecal metabolites or short-chain fatty acids (SCFA). However, compared to WT, T1R2-KO mice were protected from age-dependent increases in fecal SCFA and the development of glucose intolerance.</p></div><div class="section" id="N65552"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">Short-term saccharin consumption at maximum acceptable levels is not sufficient to alter gut microbiota or induce glucose intolerance in apparently healthy humans and mice.</p></div><div class="section" id="N65558"><h3 class="BHead" id="nov000-4">Trial registration</h3><p class="para" id="Par4">Trial registration number NCT03032640, registered on January 26, 2017.</p><p class="para" id="Par5">
<div class="imageVideo"><img src="/dataresources/secured/content-1765762142858-a18c0bf5-e250-4a30-a7d2-3ab907cf2b9a/assets/40168_2020_976_MOESM1_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65578"><h3 class="BHead" id="nov000-5">Supplementary Information</h3><p class="para" id="N65581">The online version contains supplementary material available at 10.1186/s40168-020-00976-w.</p></div>]]></description>
            <pubDate><![CDATA[2021-01-12T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Translation of a Host Blood RNA Signature Distinguishing Bacterial From Viral Infection Into a Platform Suitable for Development as a Point-of-Care Test]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765758496633-ce32f181-5593-447f-b4cb-3ac0ae2d4f6d/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1001/jamapediatrics.2020.5227</link>
            <description><![CDATA[<p class="para" id="N65540">This study assesses a 2-gene RNA signature that can be translated into a rapid (&lt;25 minutes) and portable laboratory-on-a-chip platform suitable for development as a point-of-care test.</p>]]></description>
            <pubDate><![CDATA[2021-01-04T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Prevalence and Childhood Precursors of Opioid Use in the Early Decades of Life]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765739280262-e36bb885-c951-4066-b1e4-deb5f81a41e5/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1001/jamapediatrics.2020.5205</link>
            <description><![CDATA[<div class="section" id="ab-poi200082-1"><h3 class="BHead" id="nov000-1">Question</h3><p class="para" id="N65546">How common is opioid use in the early decades of life, and which childhood risk factors are associated with opioid use in young adulthood?</p></div><div class="section" id="ab-poi200082-2"><h3 class="BHead" id="nov000-2">Findings</h3><p class="para" id="N65552">This cohort study assessed opioid use among 1252 non-Hispanic White individuals and American Indian individuals in rural counties in the central Appalachia region of North Carolina from January 1993 to December 2015. By age 30 years, approximately one-quarter of participants had used opioids, and the findings revealed that childhood tobacco use and depression were associated with later nonheroin opioid use in general, weekly nonheroin opioid use, and heroin use.</p></div><div class="section" id="ab-poi200082-3"><h3 class="BHead" id="nov000-3">Meaning</h3><p class="para" id="N65558">Childhood tobacco use and depression may be associated with impaired reward system functioning, which may increase young adults’ vulnerability to opioid-associated euphoria.</p></div><p class="para" id="N65540">This cohort study documents age-related changes in opioid use and analyzes childhood antecedents of opioid use among non-Hispanic White individuals and American Indian individuals.</p><div class="section" id="ab-poi200082-4"><h3 class="BHead" id="nov000-1">Importance</h3><p class="para" id="N65543">Opioid use disorder and opioid deaths have increased dramatically in young adults in the US, but the age-related course or precursors to opioid use among young people are not fully understood.</p></div><div class="section" id="ab-poi200082-5"><h3 class="BHead" id="nov000-2">Objective</h3><p class="para" id="N65549">To document age-related changes in opioid use and study the childhood antecedents of opioid use by age 30 years in 6 domains of childhood risk: sociodemographic characteristics; school or peer problems; parental mental illness, drug problems, or legal involvement; substance use; psychiatric illness; and physical health.</p></div><div class="section" id="ab-poi200082-6"><h3 class="BHead" id="nov000-3">Design, Setting, and Participants</h3><p class="para" id="N65555">This community-representative prospective longitudinal cohort study assessed 1252 non-Hispanic White individuals and American Indian individuals in rural counties in the central Appalachia region of North Carolina from January 1993 to December 2015. Data were analyzed from January 2019 to January 2020.</p></div><div class="section" id="ab-poi200082-7"><h3 class="BHead" id="nov000-4">Exposures</h3><p class="para" id="N65561">Between ages 9 and 16 years, participants and their parents were interviewed up to 7 times using the Child and Adolescent Psychiatric Assessment and reported risk factors in 6 risk domains.</p></div><div class="section" id="ab-poi200082-8"><h3 class="BHead" id="nov000-5">Main Outcomes and Measures</h3><p class="para" id="N65567">Participants were assessed again at ages 19, 21, 25, and 30 years for nonheroin opioid use (any and weekly) and heroin use using the structured Young Adult Psychiatric Assessment.</p></div><div class="section" id="ab-poi200082-9"><h3 class="BHead" id="nov000-6">Results</h3><p class="para" id="N65573">Of 1252 participants, 342 (27%) were American Indian. By age 30 years, 322 participants had used a nonheroin opioid (24.2%; 95% CI, 21.8-26.5), 155 had used a nonheroin opioid weekly (8.8%; 95% CI, 7.2-10.3), and 95 had used heroin (6.6%; 95% CI, 5.2-7.9). Childhood risk markers for later opioid use included male sex, tobacco use, depression, conduct disorder, cannabis use, having peers exhibiting social deviance, parents with legal involvement, and elevated systemic inflammation. In final models, childhood tobacco use, depression, and cannabis use were most robustly associated with opioid use in young adulthood (ages 19 to 30 years). Chronic depression and dysthymia were strongly associated with any nonheroin opioid use (OR. 5.43; 95% CI, 2.35-12.55 and OR, 7.13; 95% CI, 1.99-25.60, respectively) and with weekly nonheroin opioid use (OR, 8.89; 95% CI, 3.61-21.93 and OR, 11.51; 95% CI, 3.05-42.72, respectively). Among young adults with opioid use, those with heroin use had the highest rates of childhood psychiatric disorders and comorbidities.</p></div><div class="section" id="ab-poi200082-10"><h3 class="BHead" id="nov000-7">Conclusions and Relevance</h3><p class="para" id="N65579">Childhood tobacco use and chronic depression may be associated with impaired reward system functioning, which may increase young adults’ vulnerability to opioid-associated euphoria. Preventing and treating early substance use and childhood mental illness may help prevent later opioid use.</p></div>]]></description>
            <pubDate><![CDATA[2020-12-28T00:00]]></pubDate>
        </item><item>
            <title><![CDATA[Prevalence and Childhood Precursors of Opioid Use in the Early Decades of Life]]></title>
            <media:thumbnail url="https://storage.googleapis.com/nova-demo-unsecured-files/unsecured/content-1765739280262-e36bb885-c951-4066-b1e4-deb5f81a41e5/cover.png"></media:thumbnail>
            <link>https://www.novareader.co/book/isbn/10.1001/jamapediatrics.2020.5205</link>
            <description><![CDATA[<div class="section" id="ab-poi200082-1"><h3 class="BHead" id="nov000-1">Question</h3><p class="para" id="N65546">How common is opioid use in the early decades of life, and which childhood risk factors are associated with opioid use in young adulthood?</p></div><div class="section" id="ab-poi200082-2"><h3 class="BHead" id="nov000-2">Findings</h3><p class="para" id="N65552">This cohort study assessed opioid use among 1252 non-Hispanic White individuals and American Indian individuals in rural counties in the central Appalachia region of North Carolina from January 1993 to December 2015. By age 30 years, approximately one-quarter of participants had used opioids, and the findings revealed that childhood tobacco use and depression were associated with later nonheroin opioid use in general, weekly nonheroin opioid use, and heroin use.</p></div><div class="section" id="ab-poi200082-3"><h3 class="BHead" id="nov000-3">Meaning</h3><p class="para" id="N65558">Childhood tobacco use and depression may be associated with impaired reward system functioning, which may increase young adults’ vulnerability to opioid-associated euphoria.</p></div><p class="para" id="N65540">This cohort study documents age-related changes in opioid use and analyzes childhood antecedents of opioid use among non-Hispanic White individuals and American Indian individuals.</p><div class="section" id="ab-poi200082-4"><h3 class="BHead" id="nov000-1">Importance</h3><p class="para" id="N65543">Opioid use disorder and opioid deaths have increased dramatically in young adults in the US, but the age-related course or precursors to opioid use among young people are not fully understood.</p></div><div class="section" id="ab-poi200082-5"><h3 class="BHead" id="nov000-2">Objective</h3><p class="para" id="N65549">To document age-related changes in opioid use and study the childhood antecedents of opioid use by age 30 years in 6 domains of childhood risk: sociodemographic characteristics; school or peer problems; parental mental illness, drug problems, or legal involvement; substance use; psychiatric illness; and physical health.</p></div><div class="section" id="ab-poi200082-6"><h3 class="BHead" id="nov000-3">Design, Setting, and Participants</h3><p class="para" id="N65555">This community-representative prospective longitudinal cohort study assessed 1252 non-Hispanic White individuals and American Indian individuals in rural counties in the central Appalachia region of North Carolina from January 1993 to December 2015. Data were analyzed from January 2019 to January 2020.</p></div><div class="section" id="ab-poi200082-7"><h3 class="BHead" id="nov000-4">Exposures</h3><p class="para" id="N65561">Between ages 9 and 16 years, participants and their parents were interviewed up to 7 times using the Child and Adolescent Psychiatric Assessment and reported risk factors in 6 risk domains.</p></div><div class="section" id="ab-poi200082-8"><h3 class="BHead" id="nov000-5">Main Outcomes and Measures</h3><p class="para" id="N65567">Participants were assessed again at ages 19, 21, 25, and 30 years for nonheroin opioid use (any and weekly) and heroin use using the structured Young Adult Psychiatric Assessment.</p></div><div class="section" id="ab-poi200082-9"><h3 class="BHead" id="nov000-6">Results</h3><p class="para" id="N65573">Of 1252 participants, 342 (27%) were American Indian. By age 30 years, 322 participants had used a nonheroin opioid (24.2%; 95% CI, 21.8-26.5), 155 had used a nonheroin opioid weekly (8.8%; 95% CI, 7.2-10.3), and 95 had used heroin (6.6%; 95% CI, 5.2-7.9). Childhood risk markers for later opioid use included male sex, tobacco use, depression, conduct disorder, cannabis use, having peers exhibiting social deviance, parents with legal involvement, and elevated systemic inflammation. In final models, childhood tobacco use, depression, and cannabis use were most robustly associated with opioid use in young adulthood (ages 19 to 30 years). Chronic depression and dysthymia were strongly associated with any nonheroin opioid use (OR. 5.43; 95% CI, 2.35-12.55 and OR, 7.13; 95% CI, 1.99-25.60, respectively) and with weekly nonheroin opioid use (OR, 8.89; 95% CI, 3.61-21.93 and OR, 11.51; 95% CI, 3.05-42.72, respectively). Among young adults with opioid use, those with heroin use had the highest rates of childhood psychiatric disorders and comorbidities.</p></div><div class="section" id="ab-poi200082-10"><h3 class="BHead" id="nov000-7">Conclusions and Relevance</h3><p class="para" id="N65579">Childhood tobacco use and chronic depression may be associated with impaired reward system functioning, which may increase young adults’ vulnerability to opioid-associated euphoria. Preventing and treating early substance use and childhood mental illness may help prevent later opioid use.</p></div>]]></description>
            <pubDate><![CDATA[2020-12-28T00:00]]></pubDate>
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            <title><![CDATA[Roundup causes embryonic development failure and alters metabolic pathways and gut microbiota functionality in non-target species]]></title>
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            <link>https://www.novareader.co/book/isbn/10.1186/s40168-020-00943-5</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">Research around the weedkiller Roundup is among the most contentious of the twenty-first century. Scientists have provided inconclusive evidence that the weedkiller causes cancer and other life-threatening diseases, while industry-paid research reports that the weedkiller has no adverse effect on humans or animals. Much of the controversial evidence on Roundup is rooted in the approach used to determine safe use of chemicals, defined by outdated toxicity tests. We apply a system biology approach to the biomedical and ecological model species <i>Daphnia</i> to quantify the impact of glyphosate and of its commercial formula, Roundup, on fitness, genome-wide transcription and gut microbiota, taking full advantage of clonal reproduction in <i>Daphnia.</i> We then apply machine learning-based statistical analysis to identify and prioritize correlations between genome-wide transcriptional and microbiota changes.</p></div><div class="section" id="N65552"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">We demonstrate that chronic exposure to ecologically relevant concentrations of glyphosate and Roundup at the approved regulatory threshold for drinking water in the US induce embryonic developmental failure, induce significant DNA damage (genotoxicity), and interfere with signaling. Furthermore, chronic exposure to the weedkiller alters the gut microbiota functionality and composition interfering with carbon and fat metabolism, as well as homeostasis. Using the “Reactome,” we identify conserved pathways across the Tree of Life, which are potential targets for Roundup in other species, including liver metabolism, inflammation pathways, and collagen degradation, responsible for the repair of wounds and tissue remodeling.</p></div><div class="section" id="N65558"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">Our results show that chronic exposure to concentrations of Roundup and glyphosate at the approved regulatory threshold for drinking water causes embryonic development failure and alteration of key metabolic functions via direct effect on the host molecular processes and indirect effect on the gut microbiota. The ecological model species <i>Daphnia</i> occupies a central position in the food web of aquatic ecosystems, being the preferred food of small vertebrates and invertebrates as well as a grazer of algae and bacteria. The impact of the weedkiller on this keystone species has cascading effects on aquatic food webs, affecting their ability to deliver critical ecosystem services.</p><p class="para" id="Par60">
<div class="imageVideo"><img src="/dataresources/secured/content-1765609196068-94f3d387-63f3-4414-b451-d656ead2ec26/assets/40168_2020_943_MOESM2_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65576"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65579">The online version contains supplementary material available at 10.1186/s40168-020-00943-5.</p></div>]]></description>
            <pubDate><![CDATA[2020-12-15T00:00]]></pubDate>
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            <title><![CDATA[Sensitive universal detection of blood parasites by selective pathogen-DNA enrichment and deep amplicon sequencing]]></title>
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            <link>https://www.novareader.co/book/isbn/10.1186/s40168-020-00939-1</link>
            <description><![CDATA[<div class="section" id="N65540"><h3 class="BHead" id="nov000-1">Background</h3><p class="para" id="Par1">Targeted amplicon deep sequencing (TADS) has enabled characterization of diverse bacterial communities, yet the application of TADS to communities of parasites has been relatively slow to advance. The greatest obstacle to this has been the genetic diversity of parasitic agents, which include helminths, protozoa, arthropods, and some acanthocephalans. Meanwhile, universal amplification of conserved loci from all parasites without amplifying host DNA has proven challenging. Pan-eukaryotic PCRs preferentially amplify the more abundant host DNA, obscuring parasite-derived reads following TADS. Flaherty et al. (2018) described a pan-parasitic TADS method involving amplification of eukaryotic 18S rDNA regions possessing restriction sites only in vertebrates. Using this method, host DNA in total DNA extracts could be selectively digested prior to PCR using restriction enzymes, thereby increasing the number of parasite-derived reads obtained following NGS. This approach showed promise though was only as sensitive as conventional PCR.</p></div><div class="section" id="N65546"><h3 class="BHead" id="nov000-2">Results</h3><p class="para" id="Par2">Here, we expand on this work by designing a second set of pan-eukaryotic primers flanking the priming sites already described, enabling nested PCR amplification of the established 18S rDNA target. This nested approach facilitated introduction of a second restriction digestion between the first and second PCR, reducing the proportional mass of amplifiable host-derived DNA while increasing the number of PCR amplification cycles. We applied this method to blood specimens containing <i>Babesia</i>, <i>Plasmodium</i>, various kinetoplastids, and filarial nematodes and confirmed its limit of detection (LOD) to be approximately 10-fold lower than previously described, falling within the range of most qPCR methods.</p></div><div class="section" id="N65558"><h3 class="BHead" id="nov000-3">Conclusions</h3><p class="para" id="Par3">The assay detects and differentiates the major malaria parasites of humans, along with several other clinically important blood parasites. This represents an important step towards a TADS-based universal parasite diagnostic (UPDx) test with a sufficient LOD for routine applications.</p><p class="para" id="Par060">
<div class="imageVideo"><img src="/dataresources/secured/content-1765477381039-e2a34ffe-a62d-4b07-9e6f-c633e8bd85d2/assets/40168_2020_939_MOESM2_ESM.mp4" alt=""/></div></p></div><div class="section" id="N65573"><h3 class="BHead" id="nov000-4">Supplementary Information</h3><p class="para" id="N65576">The online version contains supplementary material available at 10.1186/s40168-020-00939-1.</p></div>]]></description>
            <pubDate><![CDATA[2021-01-02T00:00]]></pubDate>
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