bluuebunny/crossref_metadata_2025_split huggingface dataset:
The radiation of Austral teals and the evolution of flightlessness
Authors: Rosinger Hanna S. , Kardialsky Olga , Kennedy Martyn , Spencer Hamish G. , Steiner Florian M. , Schlick-Steiner Birgit C. , Rawlence Nicolas J. , Knapp Michael 
Published: October 2023

AbstractThe origin and evolution in the Southern Hemisphere of the Austral teals, consisting of the grey-teal and brown-teal species complexes, remains poorly understood due to limited molecular data. With the group containing multiple independent examples of flight loss, understanding the evolutionary history of the group is of significant interest for functional genomic studies into the evolution of flightlessness. Here we present the first whole mitogenome-based phylogeny of the Austral teals. We show that the group diverged from a common ancestor with mallards in the late Miocene and soon after radiated into the brown-teal and grey-teal lineages, as well as the widely distributed pintails and green-winged ducks. The brown-teal species complex, which includes the volant brown and Chatham Island teals as well as the flightless, sub-Antarctic Auckland and Campbell Island teals, radiated within the past 0.9 - 2.2 million years. The divergence of the extinct Chatham Island teal, and the stepping-stone colonisation of the Auckland and Campbell Islands occurred from mainland New Zealand. Morphological changes towards flightlessness are also present in the volant brown teal on mainland New Zealand, suggesting that this group was on the pathway to flightlessess, which accelerated in some insular island lineages.
Acquisition of auditory discrimination mediated by different processes through two distinct circuits linked to the lateral striatum
Authors: Setogawa Susumu , Okauchi Takashi , Hu Di , Wada Yasuhiro , Hikishima Keigo , Onoe Hirotaka , Nishizawa Kayo , Sakayori Nobuyuki , Miyawaki Hiroyuki , Kitanishi Takuma , Mizuseki Kenji , Cui Yilong , Kobayashi Kazuto 
Published: October 2023

AbstractThe striatum, the central hub of cortico-basal ganglia loops, contains functionally heterogeneous subregions distinguished by the topographic patterns of structural connectivity. These subregions mediate various processes of procedural learning. However, it remains unclear when and how striatal subregions engage in the acquisition of sensory stimulus-based decision-making. A neuroimaging of regional brain activity shows that the anterior dorsolateral striatum (aDLS) and posterior ventrolateral striatum (pVLS) in rats are activated in a different temporal pattern during the acquisition phase of auditory discrimination. Chronic and transient pharmacologic manipulations show that the aDLS promotes the behavioral strategy driven by the stimulus-response association while suppressing that by the response-outcome association, and that the pVLS contributes to forming and maintaining the stimulus-response strategy. Electrophysiological recording indicates that subpopulations of aDLS neurons predominantly represent the outcome of specific behaviors at the initial period of discrimination learning, and that pVLS subpopulations encode the beginning and ending of each behavior according to the progress of learning. In addition, other subpopulations of striatal neurons indicate sustained activation after obtaining reward with distinct patterns reflecting the stimulus-response associations. Our findings demonstrate that aDLS and pVLS neurons integrate the new learning of auditory discrimination in spatiotemporally and functionally different manners.
Virological characteristics of the SARS-CoV-2 Omicron EG.5.1 variant
Authors: Tsujino Shuhei , Deguchi Sayaka , Nomai Tomo , Padilla-Blanco Miguel , Plianchaisuk Arnon , Wang Lei , Begum MST Monira , Uriu Keiya , Mizuma Keita , Nao Naganori , Kojima Isshu , Tsubo Tomoya , Li Jingshu , Matsumura Yasufumi , Nagao Miki , Oda Yoshitaka , Tsuda Masumi , Anraku Yuki , Kita Shunsuke , Yajima Hisano , Sasaki-Tabata Kaori , Guo Ziyi , Hinay Alfredo A , Yoshimatsu Kumiko , Yamamoto Yuki , Nagamoto Tetsuharu , Asakura Hiroyuki , Nagashima Mami , Sadamasu Kenji , Yoshimura Kazuhisa , Nasser Hesham , Jonathan Michael , Putri Olivia , Kim Yoonjin , Chen Luo , Suzuki Rigel , Tamura Tomokazu , Maenaka Katsumi ,   The Genotype to Phenotype Japan (G2P-Japan) Consortium, Irie Takashi , Matsuno Keita , Tanaka Shinya , Ito Jumpei , Ikeda Terumasa , Takayama Kazuo , Zahradnik Jiri , Hashiguchi Takao , Fukuhara Takasuke , Sato Kei 
Published: October 2023

AbstractIn middle-late 2023, a sublineage of SARS-CoV-2 Omicron XBB, EG.5.1 (a progeny of XBB.1.9.2), is spreading rapidly around the world. Here, we performed multiscale investigations to reveal virological features of newly emerging EG.5.1 variant. Our phylogenetic-epidemic dynamics modeling suggested that two hallmark substitutions of EG.5.1, S:F456L and ORF9b:I5T, are critical to the increased viral fitness. Experimental investigations addressing the growth kinetics, sensitivity to clinically available antivirals, fusogenicity and pathogenicity of EG.5.1 suggested that the virological features of EG.5.1 is comparable to that of XBB.1.5. However, the cryo-electron microscopy reveals the structural difference between the spike proteins of EG.5.1 and XBB.1.5. We further assessed the impact of ORF9b:I5T on viral features, but it was almost negligible at least in our experimental setup. Our multiscale investigations provide the knowledge for understanding of the evolution trait of newly emerging pathogenic viruses in the human population.
Knowledge, attitude and practices on intermittent preventive treatment in pregnant women with malaria: a mixed method facility-based study in Western Kenya
Authors: Mukala Joseph , Mogere Dominic , Kirira Peter , Kanoi Bernard N. , Akinyi Violet , Kobia Francis , Waweru Harrison , Gitaka Jesse 
Published: October 2023

AbstractIntermittent preventive treatment remains a core strategy for malaria prevention in pregnancy. Sulfadoxine-pyrimethamine is recommended for all pregnant women in malaria prone zones. It is scheduled monthly at each antenatal care visit up to 36 weeks. Here, we sought to assess the knowledge, attitude and practices on intermittent preventive treatment in pregnant women with malaria in Webuye hospital. Prior to the enrollment, ethical approval and permissions were sought from relevant institutions, as well as consents obtained from 140 participants aged between 18-49 years with gestation about 16 weeks. Malaria test was conducted via either microscopy or rapid test and participants were split into malaria positive and negative cohorts. Closed and open-ended questionnaire were administered to the participants and two focus group discussions were organized to collect their views. The results were expressed in percentage and Chi-square of association at a p-value equal or less than 0.05 (95%). Qualitative data were analyzed by the means of MAXQDA software. Our analysis revealed that there was a significant difference between the proportion of negative and positive groups among mothers’ knowledgeable on the side effects (p-value = 0.001), different doses (p-value = 0.012). Those who were informed about intermittent preventive treatment before administration (p-value = 0.003). The proportion of mothers knowledgeable about side effects and different doses were higher among the malaria positive group as compare to the negative with 52.9% versus 25.7% and 20.0% versus 5.7% respectively. Moreover, 76.3% of respondents reported that intermittent preventive treatment prevents malaria, 30.9% had the opinion that it causes abortion. Expectant women who were aware of the benefits of this strategy had this to say; “This medicine helps to reduce the effects of malaria and prevents mother to contract malaria”.However, those unaware had this to say;“I have never been told about something like that but it prevents diseases”. Those whoknew about the schedule and side effects said“It is given three doses during each antenatal visit”.Therefore, good knowledge, attitude and practices of intermittent preventive treatment are key for control and prevention of malaria in endemic prone areas.
Effects of the maternal and fetal proteome on birth weight: a Mendelian randomization analysis
Authors: McBride Nancy , Fernández-Sanlés Alba , Al Arab Marwa , Bond Tom A. , Zheng Jie , Magnus Maria C. , Corfield Elizabeth C. , Clayton Gemma L , Hwang Liang-Dar , Beaumont Robin N. , Evans David M. , Freathy Rachel M. , Gaunt Tom R. , Lawlor Deborah A , Borges Maria Carolina 
Published: October 2023

AbstractBackgroundFetal growth is an important indicator of survival, regulated by maternal and fetal genetic and environmental factors. However, little is known about the underlying molecular mechanisms. Proteins play a major role in a wide range of biological processes and could provide key insights into maternal and fetal molecular mechanisms regulating fetal growth.MethodWe used intergenerational two-sample Mendelian randomization to explore the effects of 1,139 maternal and fetal genetically-instrumented plasma proteins on birth weight. We used genome-wide association summary data from the Early Growth Genetics (EGG) consortium (n=406,063 with maternal and/or fetal genotype), with independent replication in the Norwegian Mother, Father and Child Cohort Study (MoBa; n=74,932 mothers and n=62,108 offspring). Maternal and fetal data were adjusted for the correlation between fetal and maternal genotype, to distinguish their independent genetic effects.ResultsWe found that higher genetically-predicted maternal levels of NEC1 increased birth weight (mean-difference: 12g (95% CI [6g, 18g]) per 1 standard deviation protein level) as did PRS57 (20g [10g, 31g]) and ULK3 (140g [81g, 199g]). Higher maternal levels of Galectin_4 decreased birth weight (-206g [-299g, -113g]). In contrast, in the offspring, higher genetically-predicted offspring levels of NEC1 decreased birth weight (-10g [-16g, -5g]), alongside sLeptin_R (-8g [-12g, -4g]), and UBS3B (-78g [-116g, -41g]). Higher fetal levels of Galectin_4 increased birth weight (174g [89g, 258g]). We replicated these results in MoBa, and found supportive evidence for shared causal variants from genetic colocalization analyses and protein-protein network associations.ConclusionsWe find strong evidence for causal effects, sometimes in opposing directions, of maternal and fetal genetically-instrumented proteins on birth weight. These provide new insights into maternal and fetal molecular mechanisms regulating fetal growth, involving glucose metabolism, energy balance, and vascular function that could be used to identify new intervention targets to reduce the risk of fetal growth disorders, and their associated adverse maternal and fetal outcomes.
A Genome-Wide Association Study (GWAS) meta-analysis of post-traumatic osteoarthritis of the knee (GO-PTOA): Protocol for Analysis Plan
Authors: McDonald Merry-Lynn , Richman Joshua , Boer Cindy , Kalsoum Raneem , Dochtermann Daniel , Barker Tyler , Briem Kristin , Hatzikotoulas Konstantinos , Hollis Benjamin , Jostins-Dean Luke , Magi Reedik , Reimann Ene ,   EstBB Research Team, Southam Lorraine , Styrkarsdottir Unnur , Tiwari Hemant , Van Meurs Joyce , Zeggini Eleftheria , Singh Jasvinder , Watt Fiona E. 
Published: October 2023

ABSTRACTPost Traumatic Osteoarthritis (PTOA) of the knee is osteoarthritis (OA) occurring specifically after a significant acute injury to the joint. Approximately 50% of people with significant knee joint injuries, such as anterior cruciate ligament (ACL) rupture, develop symptomatic radiographic OA within 10 years. Although impacts of the disease are well-described, there is little known about the genetic risk of developing OA after a knee injury relative to idiopathic OA. There is an unmet clinical need to understand the aetiology of PTOA, which will help us to understand, predict and prevent PTOA.In this Analysis Plan, we describe our methodological approach to performing a Genome Wide Association Study (GWAS) meta-analysis, developed by the Genetics of Osteoarthritis consortium (GO)-PTOA working group. We aim to determine if genetic variants associate with PTOA following a knee joint injury and understand whether these variants are similar to or different from those associated with idiopathic knee OA (iOA).Summary statistics from six international cohorts and biobanks will be included in the meta-analysis. We have harmonized an approach to identify cases of acute knee injury, knee PTOA cases as well as controls. Our three main objectives are to identify genetic variation associated with:knee PTOA independent of knee iOAknee PTOA compared with knee injured controls without OAknee PTOA compared with controls over 40 years of age without injury or OA Although not part of our primary analysis, we also plan to identify genetic variation associated with the onset of knee PTOA in a time-to-event analysis in the future.Where resources allow, sensitivity analyses for all aims will be carried out, adjusting for body mass index (BMI). For case-control analyses, either a logistic regression or linear mixed model (LMM) will be used. For later time-to-event analysis, a matched case-control Cox Proportion Hazards (PH) regression model will be applied. Cohorts will share their summary statistics with the central analysis site conducting the single meta-analysis for each GWAS, which is likely to be carried out in either METAL or GWAMA.Findings from this work will potentially improve our understanding of PTOA pathogenesis and aetiology. Better understanding of genetic determinants could contribute to more accurate prognostic modelling and precision medicine in the future.
Is Recovery Just the Beginning? Persistent Symptoms and Health and Performance Deterioration in Post-COVID-19, non-hospitalised University Students - A Cross-Sectional Study
Authors: Latifi Ashkan , Flegr Jaroslav 
Published: October 2023

AbstractMany individuals experience persistent symptoms such as deteriorated physical and mental health, increased fatigue, and reduced cognitive performance months after recovering from COVID-19. Current data are limited on the long-term trajectory of these symptoms and their prevalence in milder cases. Our study aimed to assess the persistent effects of COVID-19 on physical and mental health, fatigue, and cognitive performance in a cohort of 214 students, averaging 21.8 years of age. Of these, 148 had contracted COVID-19 but were not hospitalized, with the time since infection ranging from 1 to 39 months. We utilized a comprehensive panel of cognitive tests to measure intelligence, memory, and psychomotor skills, and a detailed anamnestic questionnaire to evaluate physical and mental health. While contracting COVID-19 did not significantly impact overall health and performance, it was associated with increased reports of fatigue. However, the reported severity of the disease had a pronounced negative influence on physical health, mental well-being, fatigue, and reaction time. Trends of improvement in physical and mental health, as well as error rate, were observed within the first two years post-infection. However, fatigue and reaction time showed a trend of deterioration. Beyond the two-year mark, physical health and error rate continued to improve, while mental health began to deteriorate. Fatigue and reaction time continued to decline. Overall, our findings suggest that some effects of contracting COVID-19 can persist or even deteriorate over time, even in younger individuals who had mild cases that did not require hospitalization.
Ancestry-specific regulatory and disease architectures are likely due to cell-type-specific gene-by-environment interactions
Authors: Wang Juehan , Gazal Steven 
Published: October 2023

AbstractMulti-ancestry genome-wide association studies (GWAS) have highlighted the existence of variants with ancestry-specific effect sizes. Understanding where and why these ancestry-specific effects occur is fundamental to understanding the genetic basis of human diseases and complex traits. Here, we characterized genes differentially expressed across ancestries (ancDE genes) at the cell-type level by leveraging single-cell RNA-seq data in peripheral blood mononuclear cells for 21 individuals with East Asian (EAS) ancestry and 23 individuals with European (EUR) ancestry (172K cells); then, we tested if variants surrounding those genes were enriched in disease variants with ancestry-specific effect sizes by leveraging ancestry-matched GWAS of 31 diseases and complex traits (averageN= 90K and 267K in EAS and EUR, respectively). We observed that ancDE genes tend to be cell-type-specific, to be enriched in genes interacting with the environment, and in variants with ancestry-specific disease effect sizes, suggesting the impact of shared cell-type-specific gene-by-environment (GxE) interactions between regulatory and disease architectures. Finally, we illustrated how GxE interactions might have led to ancestry-specificMCL1expression in B cells, and ancestry-specific allele effect sizes in lymphocyte count GWAS for variants surroundingMCL1. Our results imply that large single-cell and GWAS datasets in diverse populations are required to improve our understanding on the effect of genetic variants on human diseases.
Determinants of mosaic chromosomal alteration fitness
Authors: Pershad Yash , Mack Taralynn , Poisner Hannah , Jakubek Yasminka A , Stilp Adrienne M , Mitchell Braxton D , Lewis Joshua P , Boerwinkle Eric , Loos Ruth J , Chami Nathalie , Wang Zhe , Barnes Kathleen , Pankratz Nathan , Fornage Myriam , Redline Susan , Psaty Bruce M , Bis Joshua C , Shojaie Ali , Silverman Edwin K , Cho Michael H , Yun Jeong , DeMeo Dawn , Levy Daniel , Johnson Andrew , Mathias Rasika , Taub Margaret , Arnett Donna , North Kari , Raffield Laura M , Carson April , Doyle Margaret F , Rich Stephen S. , Rotter Jerome I. , Guo Xiuqing , Cox Nancy , Roden Dan M , Franceschini Nora , Desai Pinkal , Reiner Alex , Auer Paul L , Scheet Paul , Jaiswal Siddhartha , Weinstock Joshua S , Bick Alexander G 
Published: October 2023

AbstractClonal hematopoiesis (CH) is characterized by the acquisition of a somatic mutation in a hematopoietic stem cell that results in a clonal expansion. These driver mutations can be single nucleotide variants in cancer driver genes or larger structural rearrangements called mosaic chromosomal alterations (mCAs). The factors that influence the variations in mCA fitness and ultimately result in different clonal expansion rates are not well-understood. We used the Passenger-Approximated Clonal Expansion Rate (PACER) method to estimate clonal expansion rate for 6,381 individuals in the NHLBI TOPMed cohort with gain, loss, and copy-neutral loss of heterozygosity mCAs. Our estimates of mCA fitness were correlated (R2= 0.49) with an alternative approach that estimated fitness of mCAs in the UK Biobank using a theoretical probability distribution. Individuals with lymphoid-associated mCAs had a significantly higher white blood cell count and faster clonal expansion rate. In a cross-sectional analysis, genome-wide association study of estimates of mCA expansion rate identifiedTCL1A,NRIP1, andTERTlocus variants as modulators of mCA clonal expansion rate.
Understanding the variant landscape, and genetic epidemiology of Multiple Endocrine Neoplasia in India
Authors: Vatsyayan Aastha , Bhardwaj Juhi , Agrawal Srashti Jyoti , Saikia Bhaskar Jyoti , Arvinden VR , Senthivel Vigneshwar , Trehan Suruchi , Pandhare Kavita , Imran Mohamed , Bhoyar Rahul C , Divakar Mohit Kumar , Mishra Anushree , Jolly Bani , Sivasubbu Sridhar , Scaria Vinod 
Published: October 2023

AbstractAimMultiple Endocrine Neoplasia (MEN) is a familial cancer syndrome that encompasses several different types of endocrine tumors. The disease has three main types, namely MEN1, MEN2 and MEN4 that may or may not overlap phenotypically, but are caused by genetic mutations in three different genes, namelyRET, MEN1andCDKN1Brespectively. Genetic testing for effective diagnosis, improved prognosis, and treatment is recommended as part of of clinical practice guidelines, which makes establishment of accurate pathogenicity classification of variants across the three genes essential. However, few resources offer such classification, especially in a population specific manner.Materials and MethodsUsing the gold-standard ACMG/AMP guidelines for variant classification, we have systematically classified variants reported across theRET, MEN1andCDKN1Bgenes reported in the IndiGen dataset, and established the genetic epidemiology of MEN in the Indian population. We have additionally classified variants from ClinVar and Mastermind, and made all variant classifications freely accessible in the form of a database called MAPVar. Finally, we have designed a primer panel for accurate, cost-effective diagnosis of the three MEN types.ResultsWe have established the genetic prevalence of MEN in the Indian population to be the following: 1 in nearly 341 individuals is a likely carrier of MEN linked pathogenicRETmutations in the Indian population.We have compiled ACMG-classified variants from three large datasets to create an exhaustive compendium of MEN-linked variants called MEN-Associated Pathogenic Variants (MAPVar). The database is available at:https://clingen.igib.res.in/MAPVar/We have also designed an NGS primer panel across two pools covering all 33 exonic regions of the three genes through 38 amplicons.ConclusionOur work establishes that MEN is prevalent disorder in India, with MEN2 variants being the most reported of the three types. This indicates the need of more genomic studies of MEN variants to establish a more comprehensive variant landscape specific to Indian populations.Additionally, genetic testing is an effective tool used against MEN. Our panel offers a means of swift testing, and the MAPVar resource offers an exhaustive compendium of ACMG-classified MEN variants, that can act as a ready reference to aid in interpretation of genetic testing results, as well as better understanding genetic variants in clinical as well as research settings.