bluuebunny/crossref_metadata_2025_split huggingface dataset:
The valine-arginine dipeptide repeat protein encoded by mammalian telomeric RNA appears highly expressed in mitosis and may repress global translation
Authors: Al-Turki Taghreed M. , Mantri Venkata , Willcox Smaranda , Mills C. Allie , Herring Laura E. , Cho Su-Ji , Lee Hannah , Meyer Cailyn , Anton E. S. , Griffith Jack D. 
Published: July 2024

AbstractTranslation of mammalian telomeric G-rich RNA via the Repeat Associated non-AUG translation mechanism can produce two dipeptide repeat proteins: repeating valine-arginine (VR) and repeating glycine-leucine (GL). Their potentially toxic nature suggests that one or both must play a needed role in the cell. Using light microscopy combined with antibody staining we discovered that cultured human cells stain brightly for VR during mitosis with VR staining co-localizing with ribosomes.In vitro, VR protein represses translation in a firefly luciferase assay. Affinity purification combined with mass spectrometry identified ribosomal proteins as the major class of VR interacting proteins. Extension to mouse embryonic cerebral cortical development showed strong staining in the ventricular zone where high mitotic index neural progenitor cells proliferate and in the cortical plate where new neurons settle. These observations point to VR playing a key role in mitosis very possibly depressing global translation, a role mediated by the telomere.TeaserThe telomeric valine-arginine dipeptide repeat protein is highly expressed in mitotic cells in culture and in mouse embryonic neural tissue.
ThunderBolt: An interactive data sharing and analysis platform for large-omics experiments
Authors: Geddes Thomas Andrew , Chaudhuri Rima , Parker Benjamin L. , Yang Pengyi , Burchfield James G. 
Published: July 2024

AbstractSummaryMass-spectrometry (MS) datasets present a unique set of challenges that make in-depth bioinformatics analysis non-trivial, with analysis requiring both expertise and time. Often these datasets have unique structures that need to be dealt with on an individual basis. Currently, tools providing a fast, interactive and guided way of exploring and analysing these data sets are not readily available. To this end, we have developed ThunderBolt: a highly interactive, point-and-click web-based application providing both bioinformaticians and biologists with a platform for i) searching and comparing multiple omics datasets, ii) fast data exploration and quality control, iii) interactive visualization, iv) pre-processing, v) statistical analysis and vi) functional and network enrichment analysis of large proteomics datasets using the Shiny framework.AvailabilityThunderBolt is a shiny-application accessible athttps://thunderbolt.sydney.edu.au/Contactjames.burchfield@sydney.edu.auSupplementary information
Endoglin regulates the integrity of the bone marrow vasculature
Authors: Rodriguez Diego , Jaykar Mangesh , Watts Deepika , Sinha Anupam , Gaete Diana , Krüger Anja , Mirtschink Peter , Rauner Martina , Chavakis Triantafyllos , Arthur Helen M. , Wielockx Ben 
Published: July 2024

AbstractEndoglin (Eng) is an accessory receptor for transforming growth factor-β (TGF-β) that is critical for maintaining vascular integrity. Mutations in Eng cause hereditary hemorrhagic telangiectasia (HHT), resulting in arteriovenous malformations (AVMs) and blood abnormalities. Despite the known association between Eng deficiency and AVMs, the underlying mechanisms are unclear. In addition, the role of the bone marrow (BM), a major source of immune and blood cells, in endothelial Eng (EC-Eng) deficiency is unexplored. We show that BM blood vessels conditionally deficient in Eng (cKO) undergo a structured remodeling process over four weeks, with distinct proliferative and resolution phases. These phases involve angiogenic set points, the involvement of integrins, and the modulation of vascular integrity. In addition, we observe changes in hematopoietic stem and progenitor cells (HSPC) and circulating granulocytes, along with reduced red blood cells and platelets due to splenic sequestration. Using a conditional heterozygous EC-Eng deficient mouse model, reflecting the genetics of HHT patients, we identify vascular changes similar to those in the cKO model. Taken together, using multiplein vivoapproaches, we suggest that reduced Eng expression in the endothelium drives significant BM vascular remodeling, sharing mechanisms with early vascular processes associated with AVM formation.Explanation of NoveltyOur findings reveal that BM blood vessels deficient in endoglin undergo an orchestrated remodeling process with distinct proliferative and resolution phases over several weeks. We identify specific angiogenic set points and profound alterations in vascular integrity, along with hematopoietic changes starting at the level of hematopoietic stem and progenitor cells. These findings advance our understanding of the role of Eng in vascular remodeling and may provide novel therapeutic targets for HHT.Key PointsConditional EC-Eng deficiency leads to vascular remodeling in the BM of mice in a temporally orchestrated manner.EC-Eng facilitates vascular integrity, hematopoietic homeostasis, and immune cell mobilization.
Postnatal xanthine metabolism regulates cardiac regeneration in mammals
Authors: Saito Yuichi , Sugiura Yuki , Sakaguchi Akane , Sada Tai , Nishiyama Chihiro , Maeda Rae , Kaneko Mari , Kiyonari Hiroshi , Kimura Wataru 
Published: July 2024

AbstractPostnatal cardiomyocyte cell cycle withdrawal is a critical step wherein the mammalian heart loses regenerative potential after birth. Here, we conducted interspecies multi-omic comparisons between the mouse heart and that of the opossum, which have different postnatal time-windows for cardiomyocyte cell cycle withdrawal. Xanthine metabolism was activated in both postnatal hearts in parallel with cardiomyocyte cell cycle arrest. The pentose phosphate pathway (PPP) which produces NADPH was found to decrease simultaneously. Postnatal myocardial tissues became oxidized accordingly, and administration of antioxidants to neonatal mice altered the PPP and suppressed the postnatal activation of cardiac xanthine metabolism. These results suggest a redox-dependent postnatal switch from purine synthesis to degradation in the heart. Inhibition of xanthine metabolism in the postnatal heart extended postnatal duration of cardiomyocyte proliferation and maintained postnatal heart regeneration potential in mice. These findings highlight a novel role of xanthine metabolism as a metabolic regulator of cardiac regeneration potential.
The impact of antibiotics on the presence of the protozoan anaerobeBlastocystisand the surrounding microbiome: a case study
Authors: Newton Jamie M. , Edwards William JS. , Thompson Gary , Gentekaki Eleni , Tsaousis Anastasios D. 
Published: July 2024

AbstractBackgroundBlastocystis, the most prevalent eukaryotic gut microbe in humans, has a global distribution. Studies have linked its presence with distinct gut microbiome and metabolome profiles compared to those where the organism is absent. However, the in vivo effect of antibiotics onBlastocystisand the surrounding gut microbiome remains understudied. This case study aimed to explore how antibiotic consumption influences the presence ofBlastocystisand the subsequent changes in the gut microbiome and metabolome of an individual with irritable bowel syndrome (IBS).MethodsStool samples from an IBS patient, collected at various time points, were tested forBlastocystispresence using RT-PCR targeting theSSUrRNAgene, followed by sequencing of positive samples. Illumina sequencing determined the gut microbiome composition, while one-dimensional proton NMR spectroscopy analysed the metabolome composition. Statistical analyses were conducted to identify relationships between antibiotic consumption, bacterial diversity, metabolome composition, andBlastocystispresence.ResultsAntibiotics significantly impacted the gut microbiome, with diversity declining early in the antibiotic course, then recovering later and post-course.Blastocystiswas detected early, late, and post-course but not mid-course, coinciding with the decline in bacterial diversity. No significant differences were observed betweenBlastocystis-positive andBlastocystis-negative samples. However, bacterial composition significantly differed between samples collected before, early, and after the antibiotic course compared to those collected mid-course. Metabolite groups, including short-chain fatty acids, amino acids, and succinate, exhibited changes throughout the antibiotic course, indicating that gut metabolite composition is affected by antibiotic consumption.Discussion/ConclusionWhile antibiotics did not significantly impactBlastocystiscolonisation, they did cause a mid-course decline in microbial diversity andBlastocystispresence. The study also revealed significant alterations in important metabolites such as SCFAs and amino acids throughout the antibiotic course, with an altered metabolome observed post-course. This case study underscores the complex interactions between antibiotics, gut microbiota, and metabolites, highlighting the resilience ofBlastocystisin the gut ecosystem.
Trends in syphilis prevalence by race and ethnicity among people who are pregnant in the United States 2016–2023
Authors: Liang Yizhi , Menzies Nicolas A , Rönn Minttu M 
Published: July 2024

AbstractBackgroundThis study aimed to estimate syphilis prevalence among people who are pregnant with live births by race and ethnicity 2016–2023.MethodsWe analyzed data on syphilis infection from U.S. birth certificates using a Bayesian mathematical model, adjusting for test sensitivity, specificity, and screening coverage. We calibrated the model under two scenarios: (1) assuming screening coverage is as estimated in Medicaid claims data and (2) assuming higher screening coverage than observed in Medicaid claims data. We compared the estimates to stillbirths attributable to syphilis reported through routine surveillance. We examined racial and ethnic disparities using the index of disparity.ResultsIn Scenario 1, syphilis prevalence among people who are pregnant with live births increased from 101.1 (95% uncertainty interval [UI]: 87.5–120.5) per 100,000 live births in 2016 to 533.4 (95% UI: 496.6–581.0) per 100,000 live births in 202. In Scenario 2, prevalence increased from 73.9 (95% UI: 51.2–130.0) per 100,000 live births to 378.1 (95% UI: 295.5–592.0) per 100,000 live births over the same period. With rising prevalence, relative racial and ethnic disparities narrowed over time. Prevalence was estimated to be higher among women with stillbirths compared to women with live births.ConclusionsIn the United States, improved estimates of screening coverage are needed to understand the gaps in congenital syphilis prevention and to inform estimates of syphilis prevalence among pregnant persons.One sentence summary lineIn the United States, we estimated an increasing syphilis prevalence among people who are pregnant, reaching 533 per 100,000 live births in 2023, with notable racial and ethnic disparities.
Impact of active case finding for tuberculosis with mass chest X-ray screening in Glasgow, Scotland, 1950-1963: an epidemiological analysis of historical data
Authors: MacPherson Peter , Stagg Helen R , Schwalb Alvaro , Henderson Hazel , Taylor Alice E , Burke Rachael M , Rickman Hannah M , Miller Cecily , Houben Rein MGJ , Dodd Peter J , Corbett Elizabeth L 
Published: July 2024

AbstractBackgroundCommunity active case finding for tuberculosis was widely implemented in Europe and North America between 1940-1970, when incidence was comparable to many present-day high-burden countries. Using an interrupted time series analysis, we analysed the effect of the 1957 Glasgow mass chest X-ray campaign to inform contemporary approaches to screening.Methods and findingsCase notifications for 1950-1963 were extracted from public health records and linked to demographic data. We fitted Bayesian multilevel regression models to estimate annual relative case notification rates (CNR) during and after a mass screening intervention implemented over five weeks in 1957 compared to the counterfactual scenario where the intervention had not occurred. We additionally estimated case detection ratios and incidence. From 11/3/1957-12/4/1957, 714,915 people (622,349 of 819,301 [76.0%] resident adults ≥15 years) were screened with miniature chest X-ray; 2,369 (0.4%) were diagnosed with tuberculosis. Pre-intervention (1950-1956), pulmonary CNRs were declining at 2.3% per year from a CNR of 222/100,000 in 1950. With the intervention in 1957, there was a doubling in the pulmonary CNR (RR: 1.95, 95% uncertainty interval [UI]: 1.80-2.11), and 36% decline in the year after (RR: 0.64, 95%UI: 0.59-0.71). Post-intervention (1958-1963) annual rates of decline (5.4% per year) were greater (RR: 0.77, 95%UI: 0.69-0.85), and there were an estimated 4,656 (95%UI: 3,670-5,725) pulmonary case notifications averted due to the intervention. Effects were consistent across all city wards and notifications declined substantially in young children (0-5 years) with the intervention.ConclusionsA single, rapid round of mass screening with chest X-ray (probably the largest ever conducted) resulted in a major and sustained reduction in tuberculosis case notifications. Contemporary high-burden settings may achieve similar benefits with high-intensity screening.
Protein signatures associated with loneliness and social isolation: plasma proteome analyses in the English Longitudinal Study of Ageing, with causal evidence from Mendelian randomization
Authors: Gong Jessica , Preminger Zohar , Steptoe Andrew , Fancourt Daisy 
Published: July 2024

ABSTRACTThe understanding of biological pathways related to loneliness and social isolation remains incomplete. Cutting-edge population-based proteomics offers opportunities to uncover novel biological pathways linked to social deficits. This study employed a proteome-wide and data-driven approach to estimate the cross-sectional associations between objective measures of social connections (i.e., social isolation) and subjective measures (i.e., loneliness) with protein abundance, using the English Longitudinal Study of Ageing. Greater social isolation was associated with higher levels of 11 proteins (TNFRSF10A, MMP12, TRAIL-R2, SKR3, TNFRSF11A, VSIG2, PRSS8, FGFR2, KIM1, REN, and NEFL) after minimal adjustments; and three proteins were significantly associated after full adjustments (TNFRSF10A, TNFRSF11A, and HAOX1). Findings from two-sample Mendelian randomization indicated that a lower frequency of in-person social contact with friends or family causally increased levels of TNFRSF10A, TRAIL-R2, TNFRSF11A, and KIM1, and decreased the level of NEFL. The study also highlighted several enriched biological pathways, including necrosis and cell death regulation, dimerization of procaspase-8, and inhibition of caspase-8 pathways, which have previously not been linked to social deficits. These findings could help explain the relationship between social deficits and disease, confirming the importance of continuing to explore novel biological pathways associated with social deficits.
Long-term neurological and gastrointestinal sequelae of SARS-CoV-2, influenza, and other neurotropic infections with and without vaccination
Authors: Konings Bo , Villatoro Luisa , Burns Robert , Barahona Guillermo , McKnight Megan , Hui Ken , Tack Jan , Pasricha Pankaj Jay 
Published: July 2024

ABSTRACTCOVID-19 increases the risk of neurological and gastrointestinal sequelae, but it is unclear if it does so more than other infections. Using a multicenter record network, we matched 649,478 COVID-19 patients to negative controls (NCs) and patients infected with influenza, human herpesvirusses, and lyme’s disease (LD) to compare new-onset gastrointestinal (GISx), autonomic (ANSx), sensory (SNSx), and motor (MNSx) symptoms 3-12 months after infection. ANSx showed significant increases compared to NCs (odds ratio (OR) 1.34; confidence interval (CI) 1.31-1.36) and most other investigated infections (LD, influenza, infectious mononucleosis, and herpes zoster; OR 1.40, 1.13, 1.11, and 1.05, respectively). SNSx (OR 1.35; CI 1.31-1.39), MNSx (OR 1.32; CI 1.28-1.36) and GISx (OR 1.36; CI 1.33-1.38) were increased but varied more compared with other infections. COVID-19 vaccination reduced the risk of GISx, ANSx, and SNSx. Sequelae frequently ascribed to COVID-19 may manifest with similar or higher frequency after other infections, except ANSx.
Understanding Opportunities for Prescribing Pre-exposure Prophylaxis (PrEP) at Two Academic Medical Centers in a High Priority Jurisdiction for Ending the HIV Epidemic
Authors: McNulty Moira C. , McGuckin Katherine , Friedman Eleanor E. , Caputo Matthew , Mason Joseph A. , Devlin Samantha A. , Giurcanu Mihai , Hazra Anu , Ridgway Jessica P. , Achenbach Chad J. 
Published: July 2024

AbstractIntroductionPre-exposure prophylaxis (PrEP) is an effective, yet underutilized tool for HIV prevention. We sought to understand practice patterns and opportunities for prescribing PrEP across two large, urban, academic healthcare institutions in Chicago, Illinois.MethodsWe analyzed electronic medical record data from two institutions including encounters for persons ≥18 years of age with ≥1 negative HIV test between 1/1/2015-12/31/2021 who had indications for PrEP. Eligible encounters were those within a six-month window after STI diagnosis, or as long as injection drug use (IDU) was documented. We categorized encounters as inpatient, emergency department (ED), primary care, infectious disease (ID), obstetrics and gynecology/women’s health (OBGYN) and other outpatient settings. We performed bivariable and multivariable mixed effects regression models to examine associations, reporting odds ratios (or adjusted odds ratios) and 95% confidence intervals (OR, aOR, 95% CI).ResultsIn total, 9644 persons contributed 53031 encounters that resulted in 4653 PrEP prescriptions. The two healthcare institutions had differing patient demographics; institution A had more 18–24 year-olds (58.3% vs 31.3%), more African Americans (83.8% vs 27.9%), and more women (65.7% vs 46.3%). Institution B had more White (40.6% vs 7.1%) and Hispanic persons (14.0% vs 4.2%), and more men who have sex with men (MSM) (15.2% vs 3.3%). Institution A had more eligible encounters in the ED (30.8% vs 7.3%) as well as in infectious disease, inpatient, OBYGN, and primary care settings. Institution B accounted for the majority of PrEP prescriptions (97.0%).Adjusted models found lower odds of PrEP prescriptions in non-Hispanic Black (aOR 0.23 [0.16, 0.32]) and Latino (aOR 0.62 [0.44, 0.89]) patients, those with injection drug use (aOR 0.01 [0.00, 0.09]), men who have sex with women (aOR 0.36 [0.23, 0.56]), women who have sex with men (aOR 0.11 [0.06, 0.19]), and in the ED (ref) or OBGYN (0.11 [0.04, 0.27]) settings; while increased odds of PrEP prescription were associated with non-Hispanic White (ref) and MSM (aOR 24.87 [15.79, 39.15]) patients, and encounters at Institution B (aOR 1.78 [1.25, 2.53]) and in infectious disease (aOR [11.92 [7.65, 18.58]), primary care (aOR 2.76 [1.90, 4.01]), and other outpatient subspecialty settings (aOR 2.67 [1.84, 3.87]).ConclusionsInstitution A contained persons historically underrepresented in PrEP prescriptions, while institution B accounted for most PrEP prescriptions. Opportunities exist to improve equity in PrEP prescribing and across ED and OBGYN settings.
LDAK-KVIK performs fast and powerful mixed-model association analysis of quantitative and binary phenotypes
Authors: Hof Jasper P. , Speed Doug 
Published: July 2024

ABSTRACTMixed-model association analysis (MMAA) is the preferred tool for performing a genome-wide association study, because it enables robust control of type 1 error and increased statistical power to detect trait-associated loci. However, existing MMAA tools often suffer from long runtimes and high memory requirements. We present LDAK-KVIK, a novel MMAA tool for analyzing quantitative and binary phenotypes. Using simulated phenotypes, we show that LDAK-KVIK produces well-calibrated test statistics, both for homogeneous and heterogeneous datasets. LDAK-KVIK is computationally-efficient, requiring less than 20 CPU hours and 8Gb memory to analyse genome-wide data for 350k individuals. These demands are similar to those of REGENIE, one of the most efficient existing MMAA tools, and up to 30 times less than those of BOLT-LMM, currently the most powerful MMAA tool. When applied to real phenotypes, LDAK-KVIK has the highest power of all tools considered. For example, across 40 quantitative phenotypes from the UK Biobank (average sample size 349k), LDAK-KVIK finds 16% more significant loci than classical linear regression, whereas BOLT-LMM and REGENIE find 15% and 11% more, respectively. LDAK-KVIK can also perform gene-based tests; across the 40 quantitative UK Biobank phenotypes, LDAK-KVIK finds 18% more significant genes than the leading existing tool.
Seroprevalence of HumanBrucellaAntibodies and associated Among Patients Seeking Medical Attention at Community Hospitals in Selected Districts of Western Province in Zambia
Authors: Mambote Armand Mayindu , Muma John Bwalya , Mubiana Mary , Mudenda Steward , Daka Victor , Mubanga Melai , Bumbangi Flavien Nsoni , Chitalu Chanda , Mfune Ruth Lindizyani 
Published: July 2024

ABSTRACTIntroductionBrucellosis is a neglected zoonotic disease that affects humans and animals and can lead to severe illness in humans and financial losses for households that rear livestock. The study aimed to investigate the seroprevalence of humanBrucellaantibodies and associated risk factors among patients seeking medical attention at community hospitals.MethodsA cross-sectional seroepidemiological study was conducted from 21stApril 2021 to 21stApril 2024 among patients seeking medical attention at community hospitals in selected districts of Western province in Zambia. 225 blood samples were collected from consenting participants. Sera were separated and analysed for anti-Brucellaantibodies using the Rose Bengal Test (RBT) and Competitive enzyme-linked immunosorbent assay (c-ELISA) in parallel. A questionnaire was administered to obtain epidemiological data related to exposure to theBrucellapathogen. The data obtained were coded and entered in the Micro-Soft Excel 2013® and analysed using STATA version 15®.Results197 sera samples were found acceptable for testing and analysis for this study, out of these, the seroprevalence ofBrucellaantibodies was 18.3% (n=36, 95% CI=0.13-0.24) and 4.57% (n=9, 95% CI=-0.68-0.28) on RBT and c-ELISA respectively.Among the risk factors considered, the number of animals was statistically significantly associated withBrucellaseropositivity (OR 6.49, 95% CI=1.10-38.13, p-value = 0.039).ConclusionsBrucellaantibodies are prevalent among patients attending health facilities in the Western province of Zambia. The number of animals were significantly associated with theBrucellaseropositivity.