medRxiv : the preprint server for health sciences最新文献

{"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 microbiom","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}

{"title":"Consultation informs strategies to improve functional evidence use in variant classification.","authors":"Rehan M Villani, Bronwyn Terrill, Emma Tudini, Maddison E McKenzie, Corrina C Cliffe, Christopher N Hahn, Ben Lundie, Tessa Mattiske, Ebony Matotek, Abbye E McEwen, Sarah L Nickerson, James Breen, Douglas M Fowler, John Christodoulou, Lea Starita, Alan F Rubin, Amanda B Spurdle","doi":"10.1101/2024.12.04.24318523","DOIUrl":"https://doi.org/10.1101/2024.12.04.24318523","url":null,"abstract":"<p><p>To determine if a variant identified by diagnostic genetic testing is causal for disease, applied genetics professionals evaluate all available evidence to assign a clinical classification. Experimental assay data can provide strong functional evidence for or against pathogenicity in variant classification, but appears to be underutilised. We surveyed genetic diagnostic professionals in Australasia to assess their application of functional evidence in clinical practice. Results indicated that survey respondents are not confident to apply functional evidence, mainly due to uncertainty around practice recommendations. Respondents also identified need for support resources, educational opportunities, and in particular requested expert recommendations and updated practice guidelines to improve translation of experimental data to curation evidence. As an initial step, we have collated a list of functional assays recommended by 19 ClinGen Variant Curation Expert Panels as a source of international expert opinion on functional evidence evaluation. Additional support resources for diagnostic practice are in development.</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/PMC11643179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831576","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 striatum is an early, accurate indicator of amyloid burden using [ ¹¹ C]PiB in Down syndrome: comparison of two radiotracers.","authors":"Max McLachlan, Brecca Bettcher, Andrew McVea, Alexandra DiFillipo, Matthew Zammit, Lisette LeMerise, Jeremy Rouanet, Julie Price, Dana Tudorascu, Charles Laymon, David Keator, Patrick Lao, Adam M Brickman, Tim Fryer, Sigan Hartley, Beau M Ances, Sterling Johnson, Tobey Betthauser, Charles K Stone, Shahid Zaman, Benjamin Handen, Elizabeth Head, Mark Mapstone, Bradley T Christian","doi":"10.1101/2024.12.04.24318526","DOIUrl":"10.1101/2024.12.04.24318526","url":null,"abstract":"<p><strong>Introduction: </strong>Adults with Down syndrome demonstrate striatum-first amyloid accumulation with [ ¹¹ C]PiB PET imaging, which has not been replicated with [ ¹⁸ F]florbetapir (FBP). Early striatal accumulation has not been temporally quantified with respect to global cortical measures.</p><p><strong>Methods: </strong>Longitudinal PiB (n=175 participants) and FBP (n=92 participants) data from the Alzheimer Biomarkers Consortium-Down Syndrome were used to measure cortical and striatal binding. Generalized temporal models for cortical and striatal amyloid accumulation were created using the sampled iterative local approximation (SILA) method.</p><p><strong>Results: </strong>PiB demonstrated greater striatal-to-cortical ratios than FBP. SILA analysis revealed striatal amyloid burden occurs 3.40 (2.39) years earlier than the cortex in PiB. There was no difference between the cortex and striatum in FBP.</p><p><strong>Discussion: </strong>Among adults with Down syndrome, the striatum consistently accumulates amyloid earlier than the cortex when measured with PiB. This suggests the striatum is more sensitive to the onset of PiB PET-detectable amyloid in Down syndrome.</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/PMC11643166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831617","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":"Development of a novel transcriptomic measure of aging: Transcriptomic Mortality-risk Age (TraMA).","authors":"Eric T Klopack, Gokul Seshadri, Thalida Em Arpawong, Steve Cole, Bharat Thyagarajan, Eileen M Crimmins","doi":"10.1101/2024.12.04.24318517","DOIUrl":"10.1101/2024.12.04.24318517","url":null,"abstract":"<p><p>Increasingly, research suggests that aging is a coordinated multi-system decline in functioning that occurs at multiple biological levels. We developed and validated a transcriptomic (RNA-based) aging measure we call Transcriptomic Mortality-risk Age (TraMA) using RNA-seq data from the 2016 Health and Retirement Study using elastic net Cox regression analyses to predict 4-year mortality hazard. In a holdout test sample, TraMA was associated with earlier mortality, more chronic conditions, poorer cognitive functioning, and more limitations in activities of daily living. TraMA was also externally validated in the Long Life Family Study and several publicly available datasets. Results suggest that TraMA is a robust, portable RNAseq-based aging measure that is comparable, but independent from past biological aging measures (e.g., GrimAge). TraMA is likely to be of particular value to researchers interested in understanding the biological processes underlying health and aging, and for social, psychological, epidemiological, and demographic studies of health and aging.</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/PMC11643192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831385","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":"Alzheimer's Disease Sequencing Project Release 4 Whole Genome Sequencing Dataset.","authors":"Yuk Yee Leung, Wan-Ping Lee, Amanda B Kuzma, Heather Nicaretta, Otto Valladares, Prabhakaran Gangadharan, Liming Qu, Yi Zhao, Youli Ren, Po-Liang Cheng, Pavel P Kuksa, Hui Wang, Heather White, Zivadin Katanic, Lauren Bass, Naveen Saravanan, Emily Greenfest-Allen, Maureen Kirsch, Laura Cantwell, Taha Iqbal, Nicholas R Wheeler, John J Farrell, Congcong Zhu, Shannon L Turner, Tamil I Gunasekaran, Pedro R Mena, Jimmy Jin, Luke Carter, Xiaoling Zhang, Badri N Vardarajan, Arthur Toga, Michael Cuccaro, Timothy J Hohman, William S Bush, Adam C Naj, Eden Martin, Clifton Dalgard, Brian W Kunkle, Lindsay A Farrer, Richard P Mayeux, Jonathan L Haines, Margaret A Pericak-Vance, Gerard D Schellenberg, Li-San Wang","doi":"10.1101/2024.12.03.24317000","DOIUrl":"https://doi.org/10.1101/2024.12.03.24317000","url":null,"abstract":"<p><p>The Alzheimer's Disease Sequencing Project (ADSP) is a national initiative to understand the genetic architecture of Alzheimer's Disease and Related Dementias (AD/ADRD) by sequencing whole genomes of affected participants and age-matched cognitive controls from diverse populations. The Genome Center for Alzheimer's Disease (GCAD) processed whole-genome sequencing data from 36,361 ADSP participants, including 35,014 genetically unique participants of which 45% are from non-European ancestry, across 17 cohorts in 14 countries in this fourth release (R4). This sequencing effort identified 387 million bi-allelic variants, 42 million short insertions/deletions, and 2.2 million structural variants. Annotations and quality control data are available for all variants and samples. Additionally, detailed phenotypes from 15,927 participants across 10 domains are also provided. A linkage disequilibrium panel was created using unrelated AD cases and controls. Researchers can access and analyze the genetic data via NIAGADS Data Sharing Service, the VariXam tool, or NIAGADS GenomicsDB.</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/PMC11643159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831534","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}