medRxiv : the preprint server for health sciences最新文献

{"title":"Strengthening evidence for text-based telehealth in post-operative care: A pragmatic study of the reach and effectiveness of two-way, text-based follow-up after voluntary medical male circumcision in South Africa.","authors":"Caryl Feldacker, Isabella Fabens, Tracy Dong, Khumbulani Moyo, Calsile Makhele, Motshana Phohole, Nelson Igaba, Sizwe Hlongwane, Jacqueline Pienaar, Maria Sardini, Felex Ndebele, Hannock Tweya, Marrianne Holec, Evelyn Waweru, Geoffrey Setswe","doi":"10.1101/2024.12.05.24317906","DOIUrl":"10.1101/2024.12.05.24317906","url":null,"abstract":"<p><p>Building upon evidence of safety and efficiency gains from a randomized control trial (RCT) in South Africa, we further scaled implementation of two-way, short message service (SMS), text-based (2wT) follow-up after voluntary medical male circumcision (VMMC). We aimed to determine if gains in adverse event (AE) identification and reduced follow-up visits could be maintained when 2wT was implemented in routine VMMC settings. A pragmatic, stepped wedge design (SWD) study was implemented across three districts in South Africa. Men ages 15 and older could opt into the 2wT telehealth follow-up approach when their facility was in the intervention period. Men in routine periods were offered the standard of care (SoC): in-person post-operative visits on days 2 and 7 as per national VMMC guidelines. 2wT participants were not required to attend any postoperative visits but could return for care if desired or referred. Two quality of care markers, safety (AE ascertainment rate) and efficiency (# in-person follow-up visits), were compared between groups. We aimed for at least 200 men per step to have 80% power to detect a change in AE rate from before to after 2wT was implemented. Secondary analysis explored response rates; client and site uptake; and AE details. Among 6842 clients in the intervention period, 2856 opted into 2wT (37.8%) across three intervention waves and two platforms (SMS or WhatsApp). Among those with post-operative follow-up, the AE ascertainment rate was higher among 2wT (0.60%) than SoC (0.13%) clients (p = 0.0018), demonstrating safety gains. On average, 2wT participants had 2.1 fewer visits compared to SoC clients (p<0.001), demonstrating gains in follow-up efficiency. Among 2wT men, 2069/2586 (80%) responded via 2wT over 14 days, demonstrating engagement in post-operative care. Of all intervention clients, 93 2wT (3.6%) and 342 (8.0%) SoC were considered lost to follow-up. In this expansion trial, we provided additional evidence that the 2wT approach maintains the quality of post-operative care for adult VMMC clients. 2wT should be scaled to augment in-person, post-operative visits after VMMC for eligible, interested males ages 15 and older. To achieve potential impact, effort is needed to improve access and uptake to 2wT among providers and sites, expanding the 2wT approach for other acute follow-up care especially among men.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11643153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammatory Bowel Disease Drivers Revealed in Human Organ Chips.","authors":"Alican Özkan, Gwenn Merry, David B Chou, Ryan R Posey, Anna Stejskalova, Karina Calderon, Megan Sperry, Viktor Horvath, Lorenzo E Ferri, Emanuela Carlotti, Stuart A C McDonald, Douglas J Winton, Rocco Riccardi, Lilianna Bordeianou, Sean Hall, Girija Goyal, Donald E Ingber","doi":"10.1101/2024.12.05.24318563","DOIUrl":"10.1101/2024.12.05.24318563","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD) patients exhibit compromised intestinal barrier function and decreased mucus accumulation, as well as increased inflammation, fibrosis, and cancer risk, with symptoms often being exacerbated in women during pregnancy. Here, we show that these IBD hallmarks can be replicated using human Organ Chips lined by IBD patient-derived colon epithelial cells interfaced with matched fibroblasts cultured under flow. Use of heterotypic tissue recombinants revealed that IBD fibroblasts are the primary drivers of multiple IBD symptoms. Inflammation and fibrosis are accentuated by peristalsis-like motions in IBD Chips and when exposed to pregnancy-associated hormones in female IBD Chips. Carcinogen exposure also increases inflammation, gene mutations, and chromosome duplication in IBD Chips, but not in Healthy Chips. These data enabled by human Organ Chip technology suggest that the intestinal stroma and peristalsis-associated mechanical deformations play a key role in driving inflammation and disease progression in male and female IBD patients.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11643285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Analysis of Psychosis Biotypes: Shared Ancestry-Adjusted Polygenic Risk and Unique Genomic Associations.","authors":"Cuihua Xia, Ney Alliey-Rodriguez, Carol A Tamminga, Matcheri S Keshavan, Godfrey D Pearlson, Sarah K Keedy, Brett Clementz, Jennifer E McDowell, David Parker, Rebekka Lencer, S Kristian Hill, Jeffrey R Bishop, Elena I Ivleva, Cindy Wen, Rujia Dai, Chao Chen, Chunyu Liu, Elliot S Gershon","doi":"10.1101/2024.12.05.24318404","DOIUrl":"10.1101/2024.12.05.24318404","url":null,"abstract":"<p><p>The Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) created psychosis Biotypes based on neurobiological measurements in a multi-ancestry sample. These Biotypes cut across DSM diagnoses of schizophrenia, schizoaffective disorder and bipolar disorder with psychosis. Two recently developed <i>post hoc</i> ancestry adjustment methods of Polygenic Risk Scores (PRSs) generate Ancestry-Adjusted PRSs (AAPRSs), which allow for PRS analysis of multi-ancestry samples. Applied to schizophrenia PRS, we found the Khera AAPRS method to show superior portability and comparable prediction accuracy as compared with the Ge method. The three Biotypes of psychosis disorders had similar AAPRSs across ancestries. In genomic analysis of Biotypes, 12 genes and isoforms showed significant genomic associations with specific Biotypes in Transcriptome-Wide Association Study (TWAS) of genetically regulated expression (GReX) in adult brain and fetal brain. TWAS inflation was addressed by inclusion of genotype principal components in the association analyses. Seven of these 12 genes/isoforms satisfied Mendelian Randomization (MR) criteria for putative causality, including four genes <i>TMEM140</i>, <i>ARTN</i>, <i>C1orf115</i>, <i>CYREN</i>, and three transcripts ENSG00000272941, ENSG00000257176, ENSG00000287733. These genes are enriched in the biological pathways of Rearranged during Transfection (RET) signaling, Neural Cell Adhesion Molecule 1 (NCAM1) interactions, and NCAM signaling for neurite out-growth. The specific associations with Biotypes suggest that pharmacological clinical trials and biological investigations might benefit from analyzing Biotypes separately.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11643284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leveraging DNA methylation to create Epigenetic Biomarker Proxies that inform clinical care: A new framework for Precision Medicine.","authors":"Natàlia Carreras-Gallo, Qingwen Chen, Laura Balagué-Dobón, Andrea Aparicio, Ilinca M Giosan, Rita Dargham, Daniel Phelps, Tao Guo, Kevin M Mendez, Yulu Chen, Athena Carangan, Srikar Vempaty, Sayf Hassouneh, Michael McGeachie, Tavis Mendez, Florence Comite, Karsten Suhre, Ryan Smith, Varun B Dwaraka, Jessica A Lasky-Su","doi":"10.1101/2024.12.06.24318612","DOIUrl":"10.1101/2024.12.06.24318612","url":null,"abstract":"<p><p>The lack of accurate, cost-effective, and clinically relevant biomarkers remains a major barrier to incorporating omic data into clinical practice. Previous studies have shown that DNA methylation algorithms have utility as surrogate measures for selected proteins and metabolites. We expand upon this work by creating DNAm surrogates, termed epigenetic biomarker proxies (EBPs), across clinical laboratories, the metabolome, and the proteome. After screening >2,500 biomarkers, we trained and tested 1,694 EBP models and assessed their incident relationship with 12 chronic diseases and mortality, followed up to 15 years. We observe broad clinical relevance: 1) there are 1,292 and 4,863 FDR significant incident and prevalent associations, respectively; 2) most of these associations are replicated when looking at the lab-based counterpart, and > 62% of the shared associations have higher odds and hazard ratios to disease outcomes than their respective observed measurements; 3) EBPs of current clinical biochemistries detect deviations from normal with high sensitivity and specificity. Longitudinal EBPs also demonstrate significant changes corresponding to the changes observed in lab-based counterparts. Using two cohorts and > 30,000 individuals, we found that EBPs validate across healthy and sick populations. While further study is needed, these findings highlight the potential of implementing EBPs in a simple, low-cost, high-yield framework that benefits clinical medicine.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11643242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peritraumatic C-reactive protein levels predict pain outcomes following traumatic stress exposure in a sex-dependent manner.","authors":"Lauren A McKibben, Miranda N Layne, Liz Marie Albertorio-Sáez, Ying Zhao, Erica M Branham, Stacey L House, Francesca L Beaudoin, Xinming An, Jennifer S Stevens, Thomas C Neylan, Gari D Clifford, Laura T Germine, Kenneth A Bollen, Scott L Rauch, John P Haran, Alan B Storrow, Christopher Lewandowski, Paul I Musey, Phyllis L Hendry, Sophia Sheikh, Christopher W Jones, Brittany E Punches, Robert A Swor, Lauren A Hudak, Jose L Pascual, Mark J Seamon, Elizabeth M Datner, David A Peak, Roland C Merchant, Robert M Domeier, Niels K Rathlev, Brian J O'Neil, Leon D Sanchez, Steven E Bruce, John F Sheridan, Steven E Harte, Ronald C Kessler, Karestan C Koenen, Kerry J Ressler, Samuel A McLean, Sarah D Linnstaedt","doi":"10.1101/2024.12.03.24318221","DOIUrl":"10.1101/2024.12.03.24318221","url":null,"abstract":"<p><strong>Background: </strong>Chronic pain following traumatic stress exposure (TSE) is common. Increasing evidence suggests inflammatory/immune mechanisms are induced by TSE, play a key role in the recovery process versus development of post-TSE chronic pain, and are sex specific. In this study, we tested the hypothesis that the inflammatory marker C-reactive protein (CRP) is associated with chronic pain after TSE in a sex-specific manner.</p><p><strong>Methods: </strong>We utilized blood-plasma samples and pain questionnaire data from men (n=99) and (n=223) women enrolled in <i>AURORA</i>, a multi-site emergency department (ED)-based longitudinal study of TSE survivors. We measured CRP using Ella/ELISA from plasma samples collected in the ED ('peritraumatic CRP', n=322) and six months following TSE (n=322). Repeated measures mixed-effects models were used to assess the relationship between peritraumatic CRP and post-TSE chronic pain.</p><p><strong>Results: </strong>Peritraumatic CRP levels significantly predicted post-TSE chronic pain, such that higher levels of CRP were associated with lower levels of pain over time following TSE, but only in men (men:β=-0.24, <i>p</i>=0.037; women:β=0.05, <i>p</i>=0.470). By six months, circulating CRP levels had decreased by more than half in men, but maintained similar levels in women (t(290)=1.926, <i>p</i>=0.055). More men with a decrease in CRP levels had decreasing pain over time versus women (men:83% women:65%; Z=2.21, <i>p</i>=0.027).</p><p><strong>Conclusions: </strong>In men but not women, we found circulating peritraumatic CRP levels predict chronic pain outcomes following TSE and resolution of CRP levels in men over time might be associated with increased pain recovery. Further studies are needed to validate these results.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11643190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The mouth of America: the oral microbiome profile of the US population.","authors":"Anil K Chaturvedi, Emily Vogtmann, Jianxin Shi, Yukiko Yano, Martin J Blaser, Nicholas A Bokulich, J Gregory Caporaso, Maura L Gillison, Barry I Graubard, Xing Hua, Autumn G Hullings, Lisa Kahle, Rob Knight, Shilan Li, Jody McLean, Vaishnavi Purandare, Yunhu Wan, Neal D Freedman, Christian C Abnet","doi":"10.1101/2024.12.03.24318415","DOIUrl":"10.1101/2024.12.03.24318415","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;The oral microbiome is increasingly recognized to play key roles in human health and disease; yet, population-representative characterizations are lacking.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;Characterize the composition, diversity, and correlates of the oral microbiome among US adults.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design: &lt;/strong&gt;Cross-sectional population-representative survey.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Setting: &lt;/strong&gt;The National Health and Nutrition Examination Survey (NHANES, 2009-2012), a stratified multistage probability sample of the US population.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants: &lt;/strong&gt;NHANES participants aged 18-69 years (n=8,237, representing 202,314,000 individuals).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Exposures: &lt;/strong&gt;Demographic, socioeconomic, behavioral, anthropometric, metabolic, and clinical characteristics.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main outcomes: &lt;/strong&gt;Oral microbiome, characterized through 16S rRNA sequencing. Microbiome metrics were alpha diversity (number of observed Amplicon Sequence Variants [ASV], Faith's Phylogenetic diversity, Shannon-Weiner Index, and Simpson Index); beta diversity (unweighted UniFrac, weighted UniFrac, and Bray-Curtis dissimilarity); and prevalence and relative abundance at taxonomic levels (phylum through genus). Analyses accounted for the NHANES complex sample design.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Among US adults aged 18-69 years, the oral microbiome encompassed 37 bacterial phyla, 99 classes, 212 orders, 446 families, and 1,219 genera. Five phyla-&lt;i&gt;Firmicutes, Actinobacteria, Bacteroidetes, Proteobacteria,&lt;/i&gt; and &lt;i&gt;Fusobacteria&lt;/i&gt; and six genera-&lt;i&gt;Veillonella, Streptococcus, Prevotella7, Rothia, Actinomyces, and Gemella&lt;/i&gt;, were present in nearly all US adults (weighted-prevalence &gt;99%). These genera also were the most abundant, accounting for 65.7% of abundance. Observed ASVs showed a quadratic pattern with age (peak at 30 years), was similar by sex, significantly lower among non-Hispanic White individuals, and increased with higher body mass index (BMI) categories, alcohol use, and periodontal disease severity. All covariates together accounted for a modest proportion of oral microbiome variability, as measured by beta diversity (unweighted UniFrac=8.7%, weighted UniFrac=7.2%, and Bray-Curtis=6.3%). By contrast, relative abundance of a few genera explained a high percentage of variability in beta diversity (weighted UniFrac: &lt;i&gt;Aggregatibacter&lt;/i&gt;=22.4%, &lt;i&gt;Lactococcus&lt;/i&gt;=21.6%, &lt;i&gt;Haemophilus&lt;/i&gt;=18.4%). Prevalence and relative abundance of numerous genera were significantly associated (Bonferroni-corrected Wald-p&lt;0.0002) with age, race and ethnicity, smoking, BMI categories, alcohol use, and periodontal disease severity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;We provide a contemporary reference standard for the oral microbiome of the US adult population. Our results indicate that a few genera were universally present in US adults and a different set of genera explained a high percentage of oral microbiome dive","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11643230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NIAGADS: A Comprehensive National Data Repository for Alzheimer's Disease and Related Dementia Genetics and Genomics Research.","authors":"Amanda Kuzma, Otto Valladares, Emily Greenfest-Allen, Heather Nicaretta, Maureen Kirsch, Youli Ren, Zivadin Katanic, Heather White, Andrew Wilk, Lauren Bass, Jascha Brettschneider, Luke Carter, Jeffrey Cifello, Wei-Hsuan Chuang, Kaylyn Clark, Prabhakaran Gangadharan, Jacob Haut, Pei-Chuan Ho, Wenhwai Horng, Taha Iqbal, Yumi Jin, Peter Keskinen, Alexis Lerro Rose, Michelle K Moon, Joseph Manuel, Liming Qu, Flawless Robbins, Naveensri Saravanan, Jin Sha, Sam Tate, Yi Zhao, Laura Cantwell, Jake Gardner, Shin-Yi Chou, Jung-Ying Tzeng, William Bush, Adam Naj, Pavel Kuksa, Wan-Ping Lee, Yuk Yee Leung, Gerard Schellenberg, Li-San Wang","doi":"10.1101/2024.10.07.24315029","DOIUrl":"10.1101/2024.10.07.24315029","url":null,"abstract":"<p><p>NIAGADS is the National Institute on Aging (NIA) designated national data repository for human genetics research on Alzheimer's Disease and related dementia (ADRD). NIAGADS maintains a high-quality data collection for ADRD genetic/genomic research and supports genetics data production and analysis. NIAGADS hosts whole genome and exome sequence data from the Alzheimer's Disease Sequencing Project (ADSP) and other genotype/phenotype data, encompassing 209,000 samples. NIAGADS shares these data with hundreds of research groups around the world via the Data Sharing Service, a FISMA moderate compliant cloud-based platform that fully supports the NIH Genome Data Sharing Policy. NIAGADS Open Access consists of multiple knowledge bases with genome-wide association summary statistics and rich annotations on the biological significance of genetic variants and genes across the human genome. NIAGADS stands as a keystone in promoting collaborations to advance the understanding and treatment of Alzheimer's disease.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11483014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic-avoiding Chlamydia trachomatis variants detected in cervical and endometrial specimens from women during 16S microbiome profiling.","authors":"Sangmi Jeong, Tammy Tollison, Hayden Brochu, Hsuan Chou, Tammy Yu, Priyanka Baghaie, Kacy S Yount, Toni Darville, Harold C Wiesenfeld, Sharon L Hillier, Xinxia Peng, Catherine M O'Connell","doi":"10.1101/2024.11.13.24316066","DOIUrl":"10.1101/2024.11.13.24316066","url":null,"abstract":"<p><strong>Background: </strong>Performance of a 16S rRNA analysis of the cervicovaginal microbiome of 220 participants recruited into the T Cell Response against Chlamydia (TRAC) cohort between February 2011 and August 2014 in Allegheny County, Pennsylvania USA detected DNA encoding chlamydial 16S rRNA in samples from seven participants whose tests were negative for Chlamydia trachomatis (CT) and DNA encoding gonococcal 16S rRNA from five participants whose tests were negative for Neisseria gonorrhoeae (NG) infection with the Aptima Combo2 assay (Hologic).</p><p><strong>Methods: </strong>We used targeted PCR amplification followed by sequencing to characterize the chlamydial 23S rRNA locus and qPCR to detect gonococcal DNA in residual diagnostic swab eluates or DNA used to generate 16S rRNA libraries.</p><p><strong>Results: </strong>Discrepant specimens that contained chlamydial DNA carried a diagnostic-avoidant, G1526A variant in the 23S rRNA locus identical to variants previously detected in Finland, Denmark, and the UK. PCR validation of gonococcal DNA was confirmed for all participants whose tests were negative, with stochastic effects consistent with infection levels close to the limit of detection by the diagnostic assay.</p><p><strong>Conclusions: </strong>These data indicate that this probe-avoidant CT mutant, and possibly others, were circulating in the northeastern US prior to their detection and characterization in 2019. Although infrequent, documentation of false negative results for CT indicates a need for clinicians to consider performance of a second test that uses alternate PCR targets if patients have persistent symptoms or have known contact to an infected sex partner and their initial NAAT is negative.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11601777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142740473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating Whole Genome and Transcriptome Sequencing to Characterize the Genetic Architecture of Isoform Variation and its Implications for Health and Disease.","authors":"Chunyu Liu, Roby Joehanes, Jiantao Ma, Jiuyong Xie, Jian Yang, Mengyao Wang, Tianxiao Huan, Shih-Jen Hwang, Jia Wen, Quan Sun, Demirkale Y Cumhur, Nancy L Heard-Costa, Peter Orchard, April P Carson, Laura M Raffield, Alexander Reiner, Yun Li, George O'Connor, Joanne M Murabito, Peter Munson, Daniel Levy","doi":"10.1101/2024.12.04.24318434","DOIUrl":"10.1101/2024.12.04.24318434","url":null,"abstract":"<p><p>We created a comprehensive whole blood splice variation quantitative trait locus (sQTL) resource by analyzing isoform expression ratio (isoform-to-gene) in Framingham Heart Study (FHS) participants (discovery: n=2,622; validation: n=1,094) with whole genome (WGS) and transcriptome sequencing (RNA-seq) data. External replication was conducted using WGS and RNA-seq from the Jackson Heart Study (JHS, n=1,020). We identified over 3.5 million <i>cis</i> -sQTL-isoform pairs ( <i>p</i> <5e-8), comprising 1,176,624 <i>cis</i> -sQTL variants and 10,883 isoform transcripts from 4,971 sGenes, with significant change in isoform-to-gene ratio due to allelic variation. We validated 61% of these pairs in the FHS validation sample ( <i>p</i> <1e-4). External validation ( <i>p</i> <1e-4) in JHS for the top 10,000 and 100,000 most significant <i>cis</i> -sQTL-isoform pairs was 88% and 69%, respectively, while overall pairs validated at 23%. For 20% of <i>cis</i> -sQTLs in the FHS discovery sample, allelic variation did not significantly correlate with overall gene expression. sQTLs are enriched in splice donor and acceptor sites, as well as in GWAS SNPs, methylation QTLs, and protein QTLs. We detailed several sentinel <i>cis</i> -sQTLs influencing alternative splicing, with potential causal effects on cardiovascular disease risk. Notably, rs12898397 (T>C) affects splicing of <i>ULK3</i> , lowering levels of the full-length transcript ENST00000440863.7 and increasing levels of the truncated transcript ENST00000569437.5, encoding proteins of different lengths. Mendelian randomization analysis demonstrated that a lower ratio of the full-length isoform is causally associated with lower diastolic blood pressure and reduced lymphocyte percentages. This sQTL resource provides valuable insights into how transcriptomic variation may influence health outcomes.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11643148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary Central Nervous System Lymphoma Tumor Biopsies Show Heterogeneity in Gene Expression Profiles, Genetic Subtypes, and in vitro Drug Sensitivity to Kinase Inhibitors.","authors":"Yuan Xiao Zhu, Jasper Ch Wong, Talal Hilal, Alanna Maguire, Jon Ocal, Katie Zellner, Xianfeng Chen, Brian K Link, Thomas M Habermann, Matthew J Maurer, James R Cerhan, Patrick B Johnston, Andrew L Feldman, David W Scott, Allison Rosenthal, Lisa Rimsza","doi":"10.1101/2024.11.11.24316310","DOIUrl":"10.1101/2024.11.11.24316310","url":null,"abstract":"<p><p>Primary central nervous system lymphoma (PCNSL) is clinically challenging due to its location and small biopsy size, leading to a lack of comprehensive molecular and biologic description. We previously demonstrated that 91% of PCNSL belong to the activated B-cell-like (ABC) molecular subtype of diffuse large B-cell lymphoma (DLBCL). Here we investigated the expression of 739 cancer related genes in HIV (-) patients using NanoString digital gene expression profiling in 25 ABC-PCNSL and 43 ABC-systemic DLBCL, all tumors were EBV (-). We found that two-thirds of ABC-PCNSL samples had a transcriptional landscape distinct from ABC-systemic DLBCL samples. Of the 739 genes measured, 135 were identified as differentially expressed between these ABC-PCNSL and ABC-systemic DLBCL (p<0.05). Compared with ABC-systemic DLBCL, ABC-PCNSL showed higher gene expression in several cancer related gene sets including genes related to Hedgehog, DNA damage repair, Wnt and MAPK signaling. Hierarchical clustering 28 PCNSL samples (25 ABC and 3 GCB subtypes) identified two transcriptional subgroups, P1 (n=9) and P2 (n=19). P2 showed higher activities across most of the cancer related pathways and had a significantly shorter patient survival time (p<0.01). Whole exome sequencing showed that some distinct genetic features of PCNSL compared to DLBCL. The genetic subtypes (\"LymphGen\") of PCNSL consisted mainly of \"MCD\" and \"Other\" subtypes, which did not correlate with clinical survival. These data provide more information about unique characters of PCNSL, which may help to identify novel drug targets for developing therapeutic strategies.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11643165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}