bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends in occupational respiratory conditions with short latency from 1999 to 2019 in the UK - evidence from the Surveillance of Work-related and Occupational Respiratory Disease (SWORD) reporting scheme
Authors: Barradas Ana , Iskandar Ireny , Carder Melanie , Gittins Matthew , Byrne Laura , Taylor Susan , Daniels Sarah , Wiggans Ruth E. , Fishwick David , Seed Martin , van Tongeren Martie 
Published: May 2023

AbstractBackgroundOccupational short-latency respiratory disease (SLRD; predominantly asthma, rhinitis, hypersensitivity pneumonitis, and occupational infections) prevalence is difficult to determine but certain occupations may be associated with increased susceptibility.AimsThis study aimed to examine which occupations and industries are currently at high risk for SLRD and determine their respective suspected causal agents based on cases reported by physicians to the Surveillance of Work-related and Occupational Respiratory Disease (SWORD) scheme in the UK.MethodsSLRD cases reported to the SWORD scheme between 1999 and 2019 were analysed to determine directly standardised rate ratios (SRR) by occupation against the average rate for all other occupations combined.ResultsBakers and flour confectioners showed significantly raised SRR for occupational rhinitis (234.4 [95% CI, 200.5 - 274.0]) and asthma (59.9 [95% CI, 51.6 - 69.5]). Chemical and related process operatives also presented raised SRR values for these two conditions, with SRR of 29.5 [95% CI, 24.3 - 35.7] and 21.0 [95% CI, 16.9 - 26.1] for rhinitis and asthma, respectively. SRR were also significantly raised for vehicle spray painters when considering occupational asthma (63.5 [95% CI, 51.5 - 78.3]) alone, and laboratory technicians were also amongst the top three increased SRR for rhinitis (18.7 [95% CI, 15.1 - 23.1]). The suspected agents most frequently associated with these occupations and conditions were flour, isocyanates, and laboratory animals and insects. Metal machining setters and setter-operators showed increased SRR for occupational hypersensitivity pneumonitis (42.0 [95% CI, 29.3 - 60.3]), largely due to cutting/soluble oils. The occupation mostly affected by infectious disease was welding trades (12.9 [95% CI, 5.7 - 29.3]) and the suspected causal agent predominantly reported for this condition was pathogens and microorganisms, with a predominance ofMycobacterium tuberculosis.ConclusionsThis study identified the occupational groups at increased risk of developing a SLRD based on data recorded over a recent two-decade period in the UK. Asthma and rhinitis were identified as the prevailing conditions and hypersensitivity pneumonitis as a potentially rising respiratory problem in the metalworking industry.
Drug Overdose Mortality Rates by Educational Attainment and Sex for Adults Aged 25–64 in the United States Before and During the COVID-19 Pandemic, 2015–2021
Authors: Xu Jay J. , Seamans Marissa J. , Friedman Joseph R. 
Published: May 2023

AbstractIntroductionDramatic increases in U.S. drug overdose deaths involving synthetic opioids, especially fentanyl, beginning around 2014 have driven a marked progression in overall drug overdose deaths in the U.S., sharply rising after the onset of the COVID-19 pandemic. Disparities in drug overdose deaths by educational attainment (EA) during the fentanyl era of the drug overdose epidemic and its intersection with the COVID-19 pandemic have not been widely scrutinized.MethodsUtilizing restricted-use mortality data from the National Vital Statistics System and population estimates from the American Community Survey, we estimated annual national age-adjusted mortality rates (AAMRs) from drug overdoses jointly stratified by EA and sex for adults aged 25–64 from 2015 to 2021. State-level AAMRs in 2015 and 2021 were also estimated to examine the geographic variation in the cumulative evolution of EA-related disparities over the course of the analysis period.ResultsNationally, AAMRs rose fastest among persons with at most a high school-level education, whereas little to no change was observed for bachelor’s degree holders, widening pre-existing disparities. During the analysis period, the difference in national AAMRs between persons with at most a high school-level education and bachelor’s degree holders increased from less than 8-fold (2015) to approximately 13-fold (2021). The national widening of EA-related disparities accelerated amid the COVID-19 pandemic, and they widened in nearly every state. Among non-bachelor’s degree holders, national AAMRs increased markedly faster for males.ConclusionsThe widening disparities in drug overdose deaths by EA are a likely indicator of a rapidly increasing socioeconomic divide in drug overdose mortality more broadly. Policy strategies should address upstream socioeconomic drivers of drug use and overdose, particularly among males.
Gene prediction and evolutionary characterization of heat shock transcription factors inSalvia miltiorrhiza
Authors: Meng Xianwen , Yan Xiang 
Published: May 2023

AbstractBackgroundHeat shock transcription factors (HSFs) serve as central regulators in plants and enable adaptations to dynamic environmental changes, such as heat stress.Salvia miltiorrhizais an important medicinal plant model. However, various biotic and abiotic stresses, pathogen infections, and degeneration of elite cultivars limit the yield and quality of S. miltiorrhiza. Therefore, it is important to predict and characterize the stress resistance genes ofS. miltiorrhizaand clarify potential molecular mechanisms for genetic improvement. However, the knowledge of HSF genes inS. miltiorrhizais limited.MethodsThus, we performed a genome-wide analysis of HSF genes inS. miltiorrhiza.ResultsUsing high-quality genome sequences, we predicted 34 HSF genes distributed unevenly across eight chromosomes. Twenty-three genes were segmentally duplicated, suggesting that inS. miltiorrhiza, segmental duplications have significantly contributed to the expansion of the HSF gene family. The predicted genes were divided into 15 phylogenetic groups, among which the sequence characteristics were relatively well conserved. The Ka/Ks ratios indicated that duplicated HSF genes underwent negative selection. Most of the HSF genes displayed different expression characteristics under drought stress and salicylic acid induction. This study provides valuable data that may inform further functional studies of HSF genes inS. miltiorrhiza.
Brain Connectivity Correlates of Breathing and Cardiac Irregularities in SUDEP: A Resting-State fMRI Study
Authors: Kassinopoulos Michalis , Rolandi Nicolo , Alphan Laren , Harper Ronald M. , Oliveira Joana , Scott Catherine , Kozák Lajos R. , Guye Maxime , Lemieux Louis , Diehl Beate 
Published: May 2023

AbstractSudden unexpected death in epilepsy (SUDEP) is the leading cause of premature mortality among people with epilepsy. Evidence from witnessed and monitored SUDEP cases indicate seizure-induced cardiovascular and respiratory failures; yet, the underlying mechanisms remain obscure. SUDEP occurs often during the night and early morning hours, suggesting that sleep or circadian rhythm-induced changes in physiology contribute to the fatal event. Resting-state fMRI studies have found altered functional connectivity between brain structures involved in cardiorespiratory regulation in later SUDEP cases and in individuals at high-risk of SUDEP. However, those connectivity findings have not been related to changes in cardiovascular or respiratory patterns. Here, we compared fMRI patterns of brain connectivity associated with regular and irregular cardiorespiratory rhythms in SUDEP cases with those of living epilepsy patients of varying SUDEP risk, and healthy controls. We analysed resting-state fMRI data from 98 patients with epilepsy (9 who subsequently succumbed to SUDEP, 43 categorized as low SUDEP risk (no tonic-clonic seizures (TCS) in the year preceding the fMRI scan), and 46 as high SUDEP risk (>3 TCS in the year preceding the scan)) and 25 healthy controls. The global signal amplitude (GSA), defined as the moving standard deviation of the fMRI global signal, was used to identify periods with regular (‘low state’) and irregular (‘high state’) cardiorespiratory rhythms. Correlation maps were derived from seeds in twelve regions with a key role in autonomic or respiratory regulation, for the low and high states. Following principal component analysis, component weights were compared between the groups. We found widespread alterations in connectivity of precuneus/posterior cingulate cortex in epilepsy compared to controls, in the low state (regular cardiorespiratory activity). In the low state, and to a lesser degree in the high state, reduced anterior insula connectivity (mainly with anterior and posterior cingulate cortex) in epilepsy appeared, relative to healthy controls. For SUDEP cases, the insula connectivity differences were inversely related to the interval between the fMRI scan and death. The findings suggest that anterior insula connectivity measures may provide a biomarker of SUDEP risk. The neural correlates of autonomic brain structures associated with different cardiorespiratory rhythms may shed light on the mechanisms underlying terminal apnea observed in SUDEP.
The fallacy of global comparisons based onper capitameasures
Authors: Kratochvíl Lukáš , Havlíček Jan 
Published: May 2023

ABSTRACTSocial and environmental scientists often present comparisons across countries and policy makers use such comparisons to take evidence-based action. For a meaningful comparison among countries, one often needs to normalize the measure for differences in the population size. The first choice is usually to calculateper capitaratios. Such ratios, however, normalize the measure for differences in population size directly only under proportional increase of the measure with population size. Violation of this assumption frequently leads to misleading conclusions. To illustrate this issue, we compareper capitaratios with an approach based on regression, which eliminates many of the problems with ratios and allows for a straightforward data interpretation. Theper capitameasures in three global datasets (GDP, COVID-related mortality, and CO2production) systematically overestimate values in countries with small populations, while countries with large populations tend to have misleadingly lowper capitaratios due to the large denominators. Despite their biases, comparisons based onper capitaratios are still ubiquitous and are used for influential recommendations by various global institutions. Their continued use can cause significant damage when employed as evidence for policy actions and should be replaced by a more scientifically substantiated method, such as a regression-based approach.
Naked mole rats have distinctive cardiometabolic and genetic adaptations to their underground low-oxygen lifestyles
Authors: Faulkes Chris G. , Eykyn Thomas R. , Miljkovic Jan Lj. , Charles Rebecca L. , Prag Hiran A. , Patel Nikayla , Hart Daniel W. , Murphy Michael P. , Bennett Nigel C. , Aksentijevic Dunja 
Published: May 2023

AbstractThe naked mole-ratHeterocephalus glaberis a eusocial mammal exhibiting extreme longevity (37-year lifespan), extraordinary resistance to hypoxia and absence of cardiovascular disease. To identify the mechanisms behind these exceptional traits, RNAseq and metabolomics of cardiac tissue from naked mole-rats was compared to other African mole-rat genera. We identified metabolic and genetic adaptations unique to naked mole-rats including elevated glycogen, thus enabling glycolytic ATP generation during cardiac ischemia. Elevated normoxic expression of HIF-1α was observed while downstream hypoxia responsive-genes were down regulated, suggesting adaptation to low oxygen environments. Naked mole-rat hearts showed reduced succinate build-up during ischemia and negligible tissue damage following ischemia-reperfusion injury. These adaptive evolutionary traits reflect a unique hypoxic and eusocial lifestyle that collectively may contribute to their longevity and health span.One Sentence SummaryNaked mole-rats have metabolic adaptations distinct from other subterranean genera rendering them resistant to cardiovascular pathology.
Uracil-DNA Glycosylase of Murine Gammaherpesvirus 68 Binds Cognate Viral Replication Factors Independently of its Catalytic Residues
Authors: Smith Kyle R. , Paul Somnath , Dong Qiwen , Anannya Orchi , Oldenburg Darby G. , Forrest J. Craig , McBride Kevin M. , Krug Laurie T. 
Published: May 2023

ABSTRACTHerpesviruses are large double-stranded DNA viruses that encode core replication proteins and accessory factors involved in nucleotide metabolism and DNA repair. Mammalian Uracil-DNA glycosylases (UNG) excise deleterious uracil residues from their genomic DNA. Each herpesvirus UNG studied to date has demonstrated conservation of the enzymatic function to excise uracil residues from DNA. We previously reported that a murine gammaherpesvirus (MHV68) with a stop codon inORF46(ORF46.stop) that encodes for vUNG was defective in lytic replication and latencyin vivo.However, a mutant virus that expressed a catalytically inactive vUNG (ORF46.CM) had no replication defect, unless coupled with additional mutations in the catalytic motif of the viral dUTPase (ORF54.CM). The disparate phenotypes observed in the vUNG mutants led us to explore the non-enzymatic properties of vUNG. Immunoprecipitation of vUNG followed by mass spectrometry in MHV68-infected fibroblasts identified a complex comprised of the cognate viral DNA polymerase, vPOL encoded byORF9, and the viral DNA polymerase processivity factor, vPPF encoded byORF59. MHV68 vUNG colocalized with vPOL and vPPF in subnuclear structures consistent with viral replication compartments. In reciprocal co-immunoprecipitations, the vUNG formed a complex with the vPOL and vPPF upon transfection with either factor alone, or in combination. Last, we determined that key catalytic residues of vUNG are not required for interactions with vPOL and vPPF upon transfection or in the context of infection. We conclude that the vUNG of MHV68 associates with vPOL and vPPF independently of its catalytic activity.IMPORTANCEGammaherpesviruses encode a uracil-DNA glycosylase (vUNG) that is presumed to excise uracil residues from viral genomes. We previously identified the vUNG enzymatic activity, but not the protein itself, as dispensable for gammaherpesvirus replicationin vivo. In this study, we report a non-enzymatic role for the viral UNG of a murine gammaherpesvirus to form a complex with two key components of the viral DNA replication machinery. Understanding the role of the vUNG in this viral DNA replication complex may inform the development of antiviral drugs that combat gammaherpesvirus associated cancers.
Altered grid-like coding in early blind people
Authors: Sigismondi Federica , Xu Yangwen , Silvestri Mattia , Bottini Roberto 
Published: May 2023

AbstractSpatial navigation in humans relies heavily on vision. However, the impact of early blindness on the brain navigation network and on the hippocampal-entorhinal system supporting cognitive maps, in particular, remains elusive. Here, we tested sighted and early blind individuals in both imagined navigation in fMRI and real-world navigation. During imagined navigation, the Human Navigation Network was reliably activated in both groups, showing resilience to visual deprivation. However, neural geometry analyses highlighted crucial differences between groups. A 60° rotational symmetry, characteristic of grid-like coding, emerged in the entorhinal cortex of sighted but not blind people, who instead showed a 4-fold (90°) symmetry. Moreover, higher parietal cortex activity during navigation in the blind was correlated with the magnitude of 4-fold symmetry and real-word navigation abilities. In sum, early blindness can alter the geometry of entorhinal cognitive maps, possibly as a consequence of higher reliance on parietal egocentric coding during navigation.
Fibroblasts as an in vitro model of circadian genetic and genomic studies: A temporal analysis
Authors: Francia Marcelo , Bot Merel , Boltz Toni , De la Hoz Juan F. , Boks Marco , Kahn René , Ophoff Roel 
Published: May 2023

ABSTRACTBipolar disorder (BD) is a heritable disorder characterized by shifts in mood that manifest in manic or depressive episodes. Clinical studies have identified abnormalities of the circadian system in BD patients as a hallmark of underlying pathophysiology. Fibroblasts are a well-establishedin vitromodel for measuring circadian patterns. We set out to examine the underlying genetic architecture of circadian rhythm in fibroblasts, with the goal to assess its contribution to the polygenic nature of BD disease risk. We collected, from primary cell lines of 6 healthy individuals, temporal genomic features over a 48 hour period from transcriptomic data (RNA-seq) and open chromatin data (ATAC-seq). The RNA-seq data showed that only a limited number of genes, primarily the known core clock genes such asARNTL,CRY1,PER3,NR1D2andTEFdisplay circadian patterns of expression consistently across cell cultures. The ATAC-seq data identified that distinct transcription factor families, like those with the basic helix-loop-helix motif, were associated with regions that were increasing in accessibility over time. Whereas known glucocorticoid receptor target motifs were identified in those regions that were decreasing in accessibility. Further evaluation of these regions using stratified linkage disequilibrium score regression (sLDSC) analysis failed to identify a significant presence of them in the known genetic architecture of BD, and other psychiatric disorders or neurobehavioral traits in which the circadian rhythm is affected. In this study, we characterize the biological pathways that are activated in thisin vitrocircadian model, evaluating the relevance of these processes in the context of the genetic architecture of BD and other disorders, highlighting its limitations and future applications for circadian genomic studies.
Novel mechanism ofMYCderegulation in Multiple Myeloma
Authors: Rahmat Mahshid , Clement Kendell , Alberge Jean-Baptiste , Sklavenitis-Pistofidis Romanos , Kodgule Rohan , Fulco Charles P. , Heilpern-Mallory Daniel , Nilsson Katarina , Dorfman David , Engreitz Jesse M. , Getz Gad , Pinello Luca , Ryan Russell , Ghobrial Irene M. 
Published: May 2023

ABSTRACTMYCderegulation occurs in 67% of multiple myeloma (MM) cases and associates with progression and worse prognosis in MM. EnhancedMYCexpression is known to be driven by translocation or amplification events, but it only occurs in 40% of MM patients. Here, we describe a new mechanism ofMYCregulation, whereby epigenetic regulation ofMYCby increased accessibility of a cell-type specific enhancer leads to increasedMYCexpression. We found enhancer activity does not associate with enhancer hijacking events. We identified specific binding of c-MAF, IRF4, and SPIB transcription factors to the enhancer can activateMYC. In addition, we discovered focal amplification of this specific enhancer in approximately 4% of MM patients. Together, our findings define a new epigenetic mechanism ofMYCderegulation in MM beyond known translocations or amplifications and point to the importance of non-coding regulatory elements and their associated transcription factor networks as drivers of MM progression.
A coarse-grained DNA model to study protein-DNA interactions and liquid-liquid phase separation
Authors: Kapoor Utkarsh , Kim Young C. , Mittal Jeetain 
Published: May 2023

AbstractRecent advances in coarse-grained (CG) computational models for DNA have enabled molecular- level insights into the behavior of DNA in complex multiscale systems. However, most existing CG DNA models are not compatible with CG protein models, limiting their applications for emerging topics such as protein-nucleic acid assemblies. Here, we present a new computationally efficient CG DNA model. We first use experimental data to establish the model’s ability to predict various aspects of DNA behavior, including melting thermodynamics and relevant local structural properties such as the major and minor grooves. We then employ an all-atom hydropathy scale to define non-bonded interactions between protein and DNA sites, to make our DNA model compatible with an existing CG protein model (HPS-Urry), that is extensively used to study protein phase separation, and show that our new model reasonably reproduces the experimental binding affinity for a prototypical protein-DNA system. To further demonstrate the capabilities of this new model, we simulate a full nucleosome with and without histone tails, on a microsecond timescale, generating conformational ensembles and provide molecular insights into the role of histone tails in influencing the liquid-liquid phase separation (LLPS) of HP1α proteins. We find that histone tails interact favorably with DNA, influencing the conformational ensemble of the DNA and antagonizing the contacts between HP1α and DNA, thus affecting the ability of DNA to promote LLPS of HP1α. These findings shed light on the complex molecular framework that fine-tunes the phase transition properties of heterochromatin proteins and contributes to heterochromatin regulation and function. Overall, the CG DNA model presented here is suitable to facilitate micron-scale studies with sub-nm resolution in many biological and engineering applications and can be used to investigate protein-DNA complexes, such as nucleosomes, or LLPS of proteins with DNA, enabling a mechanistic understanding of how molecular information may be propagated at the genome level.
WhACC: Whisker Automatic Contact Classifier with Expert Human-Level Performance
Authors: Maire Phillip , King Samson G. , Cheung Jonathan Andrew , Walker Stef , Hires Samuel Andrew 
Published: May 2023

AbstractThe rodent vibrissal system remains pivotal in advancing neuroscience research, particularly for studies of cortical plasticity, learning, decision-making, sensory encoding and sensorimotor integration. While this model system provides notable advantages for quantifying active tactile input, it is hindered by the labor-intensive process of curating touch events across millions of video frames. Even with the aid of automated tools like the Janelia Whisker Tracker, millisecond-accurate touch curation often requires >3 hours of manual review / million video frames. We address this limitation by introducing Whisker Automatic Contact Classifier (WhACC), a python package designed to identify touch periods from high-speed videos of head-fixed behaving rodents with human-level performance. For our model design, we train ResNet50V2 on whisker images and extract features. Next, we engineer features to improve performance with an emphasis on temporal consistency. Finally, we select only the most important features and use them to train a LightGBM classifier. Classification accuracy is assessed against three expert human curators on over one million frames. WhACC shows pairwise touch classification agreement on 99.5% of video frames, equal to between-human agreement. Additionally, comparison between an expert curator and WhACC on a holdout dataset comprising nearly four million frames and 16 single-unit electrophysiology recordings shows negligible differences in neural characterization metrics. Finally, we offer an easy way to select and curate a subset of data to adaptively retrain WhACC. Including this retraining step, we reduce human hours required to curate a 100 million frame dataset from ∼333 hours to ∼6 hours.