bluuebunny/crossref_metadata_2025_split huggingface dataset:
Occupational lead exposure in gasoline station forecourt attendants and other occupations in relation to ALS (amyotrophic lateral sclerosis) risk
Authors: Koski Lassi , Tshoni Unathi A. , Olowoyo Joshua O. , Kobyana Aprilia S. , Lion Ntebo G. , Mugivhisa Liziwe L. , Wärmländer Sebastian K.T.S. , Roos Per M. 
Published: June 2023

AbstractAmyotrophic lateral sclerosis (ALS) is an always fatal neurodegenerative disease characterised by a gradual death of motor neurons in the spinal cord and brain. The cause of ALS is unknown. There appears to be both a genetic and an environmental aspect of ALS disease causation. Multiple occupations are associated with an elevated ALS risk. Interestingly, many of these occupations involve exposure to lead, indicating a possible connection between ALS and lead exposure. Examples include mechanical workers, military service occupations, leather workers and tanners. Gasoline station forecourt attendants, also known as petrol station assistants, show a severely increased ALS risk, and our measurements on forecourt attendants in South Africa show that they display significantly elevated blood lead concentrations. Thus, forecourt attendants can be added to the list of occupations with overlapping risks for lead exposure and ALS incidence. These occupational risks for forecourt attendants are expected to decrease in the future, as leaded gasoline is being phased out worldwide. Nonetheless, the overlapping risks for ALS incidence and lead exposure among forecourt attendants and several other occupations strengthen the hypothesis that lead exposure contributes to ALS.
Hypoxic-Ischemic Encephalopathy Based on clinical biomarkers and associated risk factors in Neonates from Southern Ethiopian Public Hospitals: A Case Control Study
Authors: Ayele Getnet Melaku , Mergia Getachew , Getahun Senait Belay , Kebede Selamawit Semagn , Ferede Zemedu Awoke , Kabthymer Robel Hussien , Abebe Mesfin 
Published: June 2023

AbstractHypoxic ischemic encephalopathy (HIE) is a serious condition that results from reduced oxygen supply and blood flow to the brain, leading to brain injury and potential long-term neurodevelopmental impairments. This study aimed to identify the maternal and neonatal factors that are associated with HIE among newborns in Ethiopia. An unmatched-control study was conducted in fifteen public hospitals in Southern Nation Nationalities and the Peoples Regional State of Ethiopia. Data were collected from 515 newborns with their index mothers (175 cases and 340 controls) using a structured questionnaire and clinical records which were created and managed by Kobo software for mobile-assisted data collection. Clinical biomarkers were used to diagnose Hypoxic ischemic encephalopathy. Logistic regression analysis was performed to identify the factors associated with Hypoxic ischemic encephalopathy. Maternal education, ultrasound checkup status, gestational age at delivery, mode of delivery, and labor duration were significantly associated with Hypoxic ischemic encephalopathy. Newborns born to illiterate mothers (AOR= 1.913, 95%CI: 1.177, 3.109), those whose mothers did not have an ultrasound checkup during pregnancy (AOR= 1.859, 95%CI: 1.073, 3.221), those who were born preterm (AOR= 4.467, 95%CI: 1.993, 10.012) or post-term (AOR= 2.903, 95%CI: 1.325, 2.903), those who were delivered by cesarean section (AOR= 7.569, 95%CI: 4.169, 13.741), and those who were delivered after prolonged labor (AOR= 3.591, 95%CI: 2.067, 6.238) had higher odds of developing Hypoxic ischemic encephalopathy than their counterparts. This study provides valuable insights into the risk factors for Hypoxic ischemic encephalopathy among newborns in Southern Ethiopia. Improving maternal education and health care services during pregnancy and delivery may help reduce the incidence and severity of Hypoxic ischemic encephalopathy. Future research should use laboratory or imaging investigations, including private health institutions, and explore the mechanisms and outcomes of Hypoxic ischemic encephalopathy.
Plasma microbial cell-free DNA sequencing for the diagnosis and surveillance of fever following hematopoietic stem cell transplant
Authors: Fung Monica , Degner Nicholas , Sam Srey , Cleveland Hayley , Teraoka Justin , Pandey Shraddha , Shariff Dayana , Blauwkamp Timothy , Chin-Hong Peter 
Published: June 2023

ABSTRACTBackgrounFever is a common complication in hematopoietic stem-cell transplant recipients, yet an etiology is often not found. Plasma microbial cell-free DNA sequencing may improve diagnosis and management of fever in this population.MethodsThis prospective study (ClinicalTrials.gov;NCT02804464) enrolled 70 patients undergoing allogeneic HCT and followed them for one year. Plasma microbial cell-free DNA sequencing was collected within 24 hours of fever and for infection surveillance weekly after HCT through day 63 post-HCT followed by monthly until study end. Plasma mcfDNA sequencing results were compared with all standard microbiological testing results collected within 48 hours of fever onset.ResultsAmong 53 fevers eligible for analysis, clinical adjudication determined that a probable cause of fever was detected by blood culture in in 7 (13%), by all microbiology in 9 (17%), and by plasma microbial cell-free DNA sequencing in 12 (23%), including 5 in which microbiology was negative, increasing the diagnostic yield by 56%. The positive percent agreement with microbiology was 78% (7/9) and the negative percent agreement was 89% (39/44). Adjudication determined that plasma microbial cell-free DNA sequencing results would have led to a change in antimicrobial management in 55% (7/12) of fevers with detections. Weekly surveillance with plasma microbial cell-free DNA sequencing detected 8 of 15 causative pathogens prior to fever by a mean of 4.8 days (range 1-8 days).ConclusionsPlasma microbial cell-free DNA sequencing shows promise in the surveillance, diagnosis and management of fever in hematopoietic stem cell transplant recipients.Article SummaryPlasma microbial cell-free DNA sequencing increased the diagnostic yield for the infectious etiologies of fever in allogeneic hematopoietic stem-cell recipients by 56% when compared to standard microbiologic testing. Weekly surveillance detected pathogens prior to fever onset.
Reference-free multiplexed single-cell sequencing identifies genetic modifiers of the human immune response
Authors: Hartoularos George C. , Si Yichen , Zhang Fan , Kathail Pooja , Lee David S. , Ogorodnikov Anton , Sun Yang , Song Yun S. , Kang Hyun Min , Ye Chun Jimmie 
Published: June 2023

AbstractMultiplexed single-cell sequencing (mux-seq) using single-nucleotide polymorphisms (SNPs) has emerged as an efficient approach to perform expression quantitative trait loci (eQTL) studies that map interactions between genetic variants and cell types, cell states, or experimental perturbations. Here we introduce theclueframework, a novel approach to encode mux-seq experiments that eliminates the need for reference genotypes and experimental barcoding. Theclueframework is made possible by the development offreemuxlet, an algorithm that clusters cells based on SNPs called from single-cell RNA-seq or ATAC-seq data. To demonstrate the feasibility ofclue, we profiled the surface protein and RNA abundances of peripheral blood mononuclear cells from 64 individuals, stimulated with 5 distinct extracellular stimuli — all within a single day. Our analysis of the demultiplexed data identified rare immune cell types and cell type-specific responses to interferon and toll-like receptor stimulation. Furthermore, by integrating genotyping data, we mapped response eQTLs specific to certain cell types. These findings showcase the potential and scalability of theclueframework for reference-free multiplexed single-cell sequencing studies.
Neurogenetic and multi-omic sources of overlap among sensation seeking, alcohol consumption, and alcohol use disorder
Authors: Miller Alex P. , Gizer Ian R. 
Published: June 2023

AbstractSensation seeking is bidirectionally associated with levels of alcohol consumption in both adult and adolescent samples and shared neurobiological and genetic influences may in part explain this association. Links between sensation seeking and alcohol use disorder (AUD) may primarily manifest via increased alcohol consumption rather than through direct effects on increasing problems and consequences. Here the overlap between sensation seeking, alcohol consumption, and AUD was examined using multivariate modeling approaches for genome-wide association study (GWAS) summary statistics in conjunction with neurobiologically-informed analyses at multiple levels of investigation. Meta-analytic and genomic structural equation modeling (GenomicSEM) approaches were used to conduct GWAS of sensation seeking, alcohol consumption, and AUD. Resulting summary statistics were used in downstream analyses to examine shared brain tissue enrichment of heritability and genome-wide evidence of overlap (e.g., stratified GenomicSEM, RRHO, genetic correlations with neuroimaging phenotypes) and to identify genomic regions likely contributing to observed genetic overlap across traits (e.g., H-MAGMA, LAVA). Across approaches, results supported shared neurogenetic architecture between sensation seeking and alcohol consumption characterized by overlapping enrichment of genes expressed in midbrain and striatal tissues and variants associated with increased cortical surface area. Alcohol consumption and AUD evidenced overlap in relation to variants associated with decreased frontocortical thickness. Finally, genetic mediation models provided evidence of alcohol consumption mediating associations between sensation seeking and AUD. This study extends previous research by examining critical sources of neurogenetic and multi-omic overlap among sensation seeking, alcohol consumption, and AUD which may underlie observed phenotypic associations.
3D T2w fetal body MRI: automated organ volumetry, growth charts and population-averaged atlas
Authors: Uus Alena U. , Hall Megan , Grigorescu Irina , Zampieri Carla Avena , Collado Alexia Egloff , Payette Kelly , Matthew Jacqueline , Kyriakopoulou Vanessa , Hajnal Joseph V. , Hutter Jana , Rutherford Mary A. , Deprez Maria , Story Lisa 
Published: June 2023

ABSTRACTStructural fetal body MRI provides true 3D information required for volumetry of fetal organs. However, current clinical and research practice primarily relies on manual slice-wise segmentation of raw T2-weighted stacks, which is time consuming, subject to inter- and intra-observer bias and affected by motion-corruption. Furthermore, there are no existing standard guidelines defining a universal approach to parcellation of fetal organs. This work produces the first parcellation protocol of the fetal body organs for motion-corrected 3D fetal body MRI. It includes 10 organ ROIs relevant to fetal quantitative volumetry studies. We also introduce the first population-averaged T2w MRI atlas of the fetal body. The protocol was used as a basis for training of a neural network for automated organ segmentation. It showed robust performance for different gestational ages. This solution minimises the need for manual editing and significantly reduces time. The general feasibility of the proposed pipeline was also assessed by analysis of organ growth charts created from automated parcellations of 91 normal control 3T MRI datasets that showed expected increase in volumetry during 22-38 weeks gestational age range. In addition, the results of comparison between 60 normal and 12 fetal growth restriction datasets revealed significant differences in organ volumes.
Long-term clinical outcomes of bariatric surgery in adults with severe obesity: A population-based retrospective cohort study
Authors: Wiebe Natasha , Tonelli Marcello 
Published: June 2023

BackgroundBariatric surgery leads to sustained weight loss in a majority of recipients, and also reduces fasting insulin levels and markers of inflammation. We described the long-term associations between bariatric surgery and clinical outcomes including 30 morbidities.MethodsWe did a retrospective population-based cohort study of 304,157 adults with severe obesity, living in Alberta, Canada; 6,212 of whom had bariatric surgery. We modelled adjusted time to mortality, hospitalization, surgery and the adjusted incidence/prevalence of 30 morbidities after 5 years of follow-up.ResultsOver a median follow-up of 4.4 years (range 1 day-22.0 years), bariatric surgery was associated with increased risk of hospitalization (HR 1.46, 95% CI 1.41,1.51) and additional surgery (HR 1.42, 95% CI 1.32,1.52) but with a decreased risk of mortality (HR 0.76, 95% CI 0.64,0.91). After 5 years, bariatric surgery was associated with a lower risk of severe chronic kidney disease (HR 0.45, 95% CI 0.27,0.75), coronary disease (HR 0.49, 95% CI 0.33,0.72), diabetes (HR 0.51, 95% CI 0.47,0.56), inflammatory bowel disease (HR 0.55, 95% CI 0.37,0.83), hypertension (HR 0.70, 95% CI 0.66,0.75), chronic pulmonary disease (HR 0.75, 95% CI 0.66,0.86), asthma (HR 0.79, 95% 0.65,0.96), cancer (HR 0.79, 95% CI 0.65,0.96), and chronic heart failure (HR 0.79, 95% CI 0.64,0.96). In contrast, after 5 years, bariatric surgery was associated with an increased risk of peptic ulcer (HR 1.99, 95% CI 1.32,3.01), alcohol misuse (HR 1.55, 95% CI 1.25,1.94), frailty (HR 1.28, 95% 1.11,1.46), severe constipation (HR 1.26, 95% CI 1.07,1.49), sleep disturbance (HR 1.21, 95% CI 1.08,1.35), depression (HR 1.18, 95% CI 1.10,1.27), and chronic pain (HR 1.12, 95% CI 1.04,1.20).InterpretationBariatric surgery was associated with lower risks of death and certain morbidities. However, bariatric surgery was also associated with increased risk of hospitalization and additional surgery, as well as certain other morbidities. Since values and preferences for these various benefits and harms may differ between individuals, this suggests that comprehensive counselling should be offered to patients considering bariatric surgery.
CXCR4 signaling strength regulates hematopoietic multipotent progenitor fate through extrinsic and intrinsic mechanisms
Authors: Rondeau Vincent , Kalogeraki Maria , Roland Lilian , Nader Zeina Abou , Gourhand Vanessa , Bonaud Amélie , Lemos Julia , Khamyath Mélanie , Moulin Clémentine , Schell Bérénice , Delord Marc , Bidaut Ghislain , Lecourt Séverine , Freitas Christelle , Anginot Adrienne , Mazure Nathalie , McDermott David H. , Parietti Véronique , Setterblad Niclas , Dulphy Nicolas , Bachelerie Françoise , Aurrand-Lions Michel , Stockholm Daniel , Lobry Camille , Murphy Philip M. , Espéli Marion , Mancini Stéphane J.C. , Balabanian Karl 
Published: June 2023

ABSTRACTHow cell-extrinsic niche-related and cell-intrinsic cues drive lineage specification of hematopoietic multipotent progenitors (MPPs) in the bone marrow (BM) is partly understood. We show that CXCR4 signaling strength regulates localization and fate of MPPs. In mice phenocopying the BM myeloid skewing of patients with WHIM Syndrome (WS), a rare immunodeficiency caused by gain-of-functionCXCR4mutations, enhanced mTOR signaling and overactive Oxphos metabolism were associated with myeloid rewiring of lymphoid-primed MPPs (or MPP4). Fate decision of MPP4 was also affected by molecular changes established at the MPP1 level. Mutant MPP4 displayed altered BM localization relative to peri-arteriolar structures, suggesting that extrinsic cues contribute to their myeloid skewing. Chronic treatment with CXCR4 antagonist AMD3100 or mTOR inhibitor Rapamycin rescued lymphoid capacities of mutant MPP4, demonstrating a pivotal role for the CXCR4-mTOR axis in regulating MPP4 fate. Our study thus provides mechanistic insights into how CXCR4 signaling regulates the lymphoid potential of MPPs.
Phase-locking of neural activity to the envelope of speech in the delta frequency band reflects differences between word lists and sentences
Authors: Mohammadi Yousef , Graversen Carina , Østergaard Jan , Kaeseler Andersen Ole , Reichenbach Tobias 
Published: June 2023

AbstractThe envelope of a speech signal is tracked by neural activity in the cerebral cortex. The cortical tracking occurs mainly in two frequency bands, theta (4 - 8 Hz) and delta band (1 - 4 Hz). Tracking in the faster theta band has been mostly associated with lower-level acoustic processing, such as the parsing of syllables, whereas the slower tracking in the delta band relates to higher-level linguistic information of words and word sequences. However, much regarding the more specific association between cortical tracking and acoustic as well as linguistic processing remains to be uncovered. Here we recorded electroencephalographic (EEG) responses to both meaningful sentences as well as random word lists in different levels of signal-to-noise ratios (SNRs) that lead to different levels of speech comprehension as well as listening effort. We then related the neural signals to the acoustic stimuli by computing the phase-locking value (PLV) between the EEG recordings and the speech envelope. We found that the PLV in the delta band increases with increasing SNR for sentences but not for the random word lists, showing that the PLV in this frequency band reflects linguistic information. When attempting to disentangle the effects of SNR, speech comprehension, and listening effort, we observed a trend that the PLV in the delta band might reflect listening effort rather than the other two variables, although the effect was not statistically significant. In summary, our study shows that the PLV in the delta band reflects linguistic information and might be related to listening effort.
Leveraging information between multiple population groups and traits improves fine-mapping resolution
Authors: Zhou Feng , Soremekun Opeyemi , Chikowore Tinashe , Fatumo Segun , Barroso Inês , Morris Andrew P , Asimit Jennifer L 
Published: June 2023

AbstractStatistical fine-mapping helps to pinpoint likely causal variants underlying genetic association signals. Its resolution can be improved by (i) leveraging information between traits; and (ii) exploiting differences in linkage disequilibrium structure between diverse population groups. Using association summary statistics, MGflashfm jointly fine-maps signals from multiple traits and population groups; MGfm uses an analogous framework to analyse each trait separately. We also provide a practical approach to fine-mapping with out-of-sample reference panels. In simulation studies we show that MGflashfm and MGfm are well-calibrated and that the mean proportion of causal variants with PP>0.80 is above 0.75 (MGflashfm) and 0.70 (MGfm). In our analysis of four lipids traits across five population groups, MGflashfm gives a median 99% credible set reduction of 10.5% over MGfm. MGflashfm and MGfm only require summary level data, making them very useful fine-mapping tools in consortia efforts where individual-level data cannot be shared.
A TOPBP1 Allele Causing Male Infertility Uncouples XY Silencing Dynamics From Sex Body Formation
Authors: Ascencao Carolline F. R. , Sims Jennie R. , Dziubek Alexis , Comstock William , Fogarty Elizabeth A. , Badar Jumana , Freire Raimundo , Grimson Andrew , Weiss Robert S. , Cohen Paula E. , Smolka Marcus 
Published: June 2023

ABSTRACTMeiotic sex chromosome inactivation (MSCI) is a critical feature of meiotic prophase I progression in males. While the ATR kinase and its activator TOPBP1 are key drivers of MSCI within the specialized sex body (SB) domain of the nucleus, how they promote silencing remains unclear given their multifaceted meiotic functions that also include DNA repair, chromosome synapsis and SB formation. Here we report a novel mutant mouse harboring mutations in the TOPBP1-BRCT5 domain.Topbp1B5/B5males are infertile, with impaired MSCI despite displaying grossly normal events of early prophase I, including synapsis and SB formation. Specific ATR-dependent events are disrupted including phosphorylation and localization of the RNA:DNA helicase Senataxin.Topbp1B5/B5spermatocytes initiate, but cannot maintain ongoing, MSCI. These findings reveal a non-canonical role for the ATR-TOPBP1 signaling axis in MSCI dynamics at advanced stages in pachynema and establish the first mouse mutant that separates ATR signaling and MSCI from SB formation.
The macroevolutionary dynamics of mammalian sexual size dimorphism
Authors: Jones Megan E. , Sheard Catherine 
Published: June 2023

AbstractSexual size dimorphism (SSD) is a common phenomenon across the animal kingdom. Mammals are unusual in primarily displaying male-biased SSD, where males of a species are typically larger than females. The driving factors behind the evolution of this SSD have been much debated, with popular hypotheses including the influence of mating system and social organisation via sexual selection, dietary niche divergence, and the role of body size (Rensch’s rule). Here, we investigate the macroevolutionary origins and maintenance of SSD among mammals, using phylogenetic general mixed linear models and a comprehensive global dataset to evaluate correlations of diet, body mass, seasonality, social organisation, and mating system with SSD type. We find that SSD as a whole is lost at a greater rate than it is gained, with female-biased SSD being particularly unstable. Non-monogamy, vertebrate prey consumption, and temperature seasonality correlate with male-biased SSD, while polyandry correlates with female-biased SSD, and both types of SSD are positively correlated with body mass. This is in partial contrast to the predictions of Rensch’s rule, which predicts that female-biased SSD would correlate negatively with body size. Taken together, our results highlight the importance of considering multiple ecological and social drivers when evaluating the macroevolutionary trajectory of sex differences in body size.
Integrated modeling of the Nexin-dynein regulatory complex reveals its regulatory mechanism
Authors: Ghanaeian Avrin , Majhi Sumita , McCaffrey Caitie L. , Nami Babak , Black Corbin S. , Yang Shun Kai , Legal Thibault , Papoulas Ophelia , Janowska Martyna , Valente-Paterno Melissa , Marcotte Edward M. , Wloga Dorota , Bui Khanh Huy 
Published: June 2023

AbstractCilia are hairlike protrusions that project from the surface of eukaryotic cells and play key roles in cell signaling and motility. Ciliary motility is regulated by the conserved nexin-dynein regulatory complex (N-DRC), which links adjacent doublet microtubules and regulates and coordinates the activity of outer doublet complexes. Despite its critical role in cilia motility, the assembly and molecular basis of the regulatory mechanism are poorly understood. Here, utilizing cryo-electron microscopy in conjunction with biochemical cross-linking and integrative modeling, we localized 12 DRC subunits in the N-DRC structure ofTetrahymena thermophila. We also found that the CCDC96/113 complex is in close contact with the N-DRC. In addition, we revealed that the N-DRC is associated with a network of coiled-coil proteins that most likely mediates N-DRC regulatory activity.