bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNA methylation controls stress granule formation and function during erythropoiesis
Authors: Gunage Rajesh , Lin Shuibin , Wiley David , Choudhuri Avik , Smith Mackenzie , Han Tianxiao , Shah Arish , Coyne Steven , Koczirka Katherine , Chen Kenny Zhi Ming , Yu Chunjie , Drake Kyle , Yang Xin , Yang Song , Zhou Yi , Bauer Daniel , Qian Zhijian , Calo Eliezer , Gregory Richard I. , Zon Leonard I. 
Published: November 2024

AbstractStress granules (SGs) are crucial in RNA regulation, affecting cell fate and function. SGs contain RNAs, some of which can be methylated. We studied m6A RNA modifications during the human CD34+HSPCs (hCD34+) differentiating into erythroid cells and found that mRNAs encoding many erythroid-specific proteins had decreased methylation during differentiation. Increased levels ALKBH5 demethylase during erythropoiesis controls the levels of the 3’UTR methylation of these mRNAs. hCD34+carrying ALKBH5 mutations demonstrated a block in erythropoiesis, and mass-spectrometry studies of the mutant cells showed decreased levels of SG proteins, including the core granule protein ATXN2. ALKBH5 directly regulates the methylation of the mRNA ofATXN2.ATXN2overexpression accelerated the erythroid differentiation of HSPCs and rescued the erythroid differentiation ofALKBH5mutant cells. Very few SGs are found in normal human erythroid progenitors. SGs accumulated substantially inALKBH5mutant cells, and surprisingly overexpression ofATNX2reduced SG numbers to normal. Polysome analysis demonstrated m6A-modified RNAs to be enriched in the pre-polysome fractions that were less translated. This work establishes a mechanism by which during stress, ATXN2 facilitates the release of SG-stored m6A-modified RNAs including erythroid-specific and SG-enriched RNAs that are loaded onto functional ribosomes, allowing better translation and accelerated erythroid differentiation during stress.
Neuropeptides specify and reprogram division of labor in the leafcutter antAtta cephalotes
Authors: Gilbert Michael B. , Glastad Karl M. , Fioriti Maxxum , Sorek Matan , Gannon Tierney , Xu Daniel , Pino Lindsay K. , Korotkov Anatoly , Biashad Ali , Baeza Josue , Lauman Richard , Filippova Anastasiia , Kacsoh Balint Z. , Bonasio Roberto , Mathis Mackenzie W. , Garcia Benjamin A. , Seluanov Andrei , Gorbunova Vera , Berger Shelley L. 
Published: November 2024

ABSTRACTSocial insects offer powerful models to investigate the mechanistic foundation of elaborate individual behaviors comprising a cooperative community. Workers of the leafcutter ant genusAttaprovide an extreme example of behavioral segregation among many phenotypically distinct worker types. We utilize the complex worker system ofAtta cephalotesto test the molecular underpinnings of behavioral programming and, in particular, the extent of plasticity to reprogramming. We identify specific neuropeptides as mediators of worker division of labor inA. cephalotes, finding two neuropeptides associated with characteristic behaviors of leafcutting and of brood care. Manipulation via genetic knockdown or by injection of these neuropeptides led to stark loss or gain of each behavior and to transcriptomic shifts in the predicted direction, that is, towards gene pathways expressed in the natural caste. We also compare specificA. cephalotesworker transcriptomes with those of orthologous workers of the eusocial mammal, the naked mole ratH. gaber, revealing global similarities between caste-biased expression and link to specific roles of our studied neuropeptides in ants. This work underscores the essential function of neuropeptides in establishing complex social behavior and a remarkable plasticity among individual behavioral types.
IL-10 Targets IRFs to Suppress IFN and Inflammatory Response Genes by Epigenetic Mechanisms
Authors: Mishra Bikash , Bachu Mahesh , Wingert Claire , Yuan Ruoxi , Chaudhary Vidyanath , Brauner Caroline , Bell Richard , Ivashkiv Lionel B. 
Published: November 2024

AbstractInterleukin-10 (IL-10) is pivotal in suppressing inflammation and innate immune activation, in large part by suppressing induction of genes by potent inflammatory factors such as TLR ligands. Despite decades of research, molecular mechanisms underlying this inhibition have not been resolved. This study utilized an integrated epigenomic analysis of gene transcription, chromatin accessibility, histone modifications and transcription factor binding to investigate IL-10-mediated suppression of LPS and TNF responses in primary human monocytes. Instead of inhibiting core TLR4-activated pathways such as NF-κB, MAPK-AP-1 and TBK1-IRF3 signaling, IL-10 targeted IRF transcription factor activity and DNA binding, particularly IRF5 and an IRF1-mediated amplification loop that is operative in monocytes. This resulted in suppression of inflammatory NF-κB target genes, in whose activation IRFs play an amplifying role, and near-complete suppression of interferon-stimulated genes. Mechanisms of TLR4 and TNFR target gene inhibition included downregulation of chromatin accessibility, de novo enhancer formation, and IRF1-associated H3K27ac activating histone marks. These results provide a mechanism by which IL-10 suppresses inflammatory NF-κB target genes, highlight the role of IRF1 in inflammatory gene expression, and describe an underappreciated suppression of IFN responses by epigenetic mechanisms.
Gut Microbial Utilization of the Alternative Sweetener, D-Allulose, via AlsE
Authors: Ndjite Glory Minabou , Jiang Angela , Ravel Charlotte , Grant Maggie , Jiang Xiaofang , Hall Brantley 
Published: November 2024

AbstractD-allulose, a rare sugar with emerging potential as a low-calorie sweetener, has garnered attention as an alternative to other commercially available alternative sweeteners, such as sugar alcohols, which often cause severe gastrointestinal discomfort. D-allulose-6-phosphate 3-epimerase (AlsE) is a prokaryotic enzyme that converts D-allulose-6-phosphate into D-fructose-6-phopshate, enabling its use as a carbon source. However, the taxonomic breadth of AlsE across gut bacteria remains poorly understood, hindering insights into the utilization of D-allulose by microbial communities. In this study, we provide experimental evidence showing thatClostridium innocuumis capable of D-allulose metabolism via a homologous AlsE. A bioinformatics search of 85,202 bacterial genomes identified 116 bacterial species with AlsE homologs, suggesting a limited distribution of AlsE in bacteria. Additionally,Escherichia colicontains a copy ofalsE, but it does not grow on D-allulose as a sole carbon source unlessalsEis heterologously expressed. A metagenomic analysis revealed that 15.8% of 3,079 adult healthy human metagenomic samples that we analyzed containedalsE, suggesting a limited prevalence of the enzyme in the gut microbiome. These results suggest that the gut microbiome has limited capacity to metabolize D-allulose viaalsE, supporting its use as an alternative sweetener with minimal impact on microbial composition and gastrointestinal symptoms. This finding also enables personalized nutrition, allowing diabetic individuals to assess their gut microbiota foralsE, and manage glycemic response while reducing gastrointestinal distress.
Pathological tau alters head direction signaling and induces spatial disorientation
Authors: Jiang Shan , Hijazi Sara , Sarkany Barbara , Gautsch Verena G. , LaChance Patrick A. , Hasselmo Michael E. , Bannerman David , Viney Tim J. 
Published: November 2024

SummarySpatial disorientation, an early symptom of dementia, is emerging as an early and reliable cognitive biomarker predicting future memory problems associated with Alzheimer’s disease, but the underlying neural mechanisms have yet to be fully defined. The anterodorsal thalamic nucleus (ADn) exhibits early and selective vulnerability to pathological misfolded forms of tau, a major hallmark of Alzheimer’s disease and ageing. The ADn contains a high density of head direction (HD) cells, which contribute to spatial navigation and orientation. Hence, their disruption may contribute to spatial disorientation. To test this, we virally expressed human mutant tau (htau) in the ADn of adult mice. HD-tau mice were defined by phosphorylated and oligomeric forms of htau in ADn somata and in axon terminals in postsynaptic target regions. Compared to controls, HD-tau mice exhibited increased looping behavior during spatial learning, and made a greater number of head turns during memory recall, indicative of spatial disorientation. Usingin vivoextracellular recordings, we identified htau-expressing ADn cells and found a lower proportion of HD cells in the ADn from HD-tau mice, along with reduced directionality and altered burst firing. These findings provide evidence that expression of pathological human tau can alter HD signaling, leading to impairments in spatial orientation.
Effects of Soluble Electron Shuttles on Microbial Iron Reduction and Methanogenesis
Authors: Thapa Bhim Sen , Flynn Theodore M. , Jensvold Zena D. , Kemner Kenneth M. , Sladek Margaret F. , O’Loughlin Edward J. , Marshall Christopher W. 
Published: November 2024

AbstractIn many aquatic and terrestrial ecosystems, iron (Fe) reduction by microorganisms is a key part of biogeochemical cycling and energy flux. The presence of redox active electron shuttles in the environment potentially enables a phylogenetically diverse group of microbes to use insoluble iron as a terminal electron acceptor. We investigated the impact that different electron shuttles had on respiration, microbial physiology, and microbial ecology. We tested eight different electron shuttles, seven quinones and riboflavin, with redox potentials between 0.217 V and -0.340 V. Fe(III) reduction coupled to acetate oxidation was observed with all shuttles. Once Fe(III) reduction began to plateau, a rapid increase in acetate consumption was observed and coincided with the onset of methane production, except in the incubations with the shuttle 9,10-anthraquinone-2-carboxylic acid (AQC). The rates of iron reduction, acetate consumption, methanogenesis, and the microbial communities varied significantly across the different shuttles independent of redox potential. In general, shuttles appeared to reduce the overall diversity of the community compared to no shuttle controls, but certain shuttles were exceptions to this trend. Geobacteraceae were the predominant taxonomic family in all enrichments except in the presence of AQC or 1,2,-dihydroxyanthraquinone (AQZ), but each shuttle enriched a unique community significantly different from the no shuttle control conditions. This suggests that the presence of different redox-active electron shuttles can have a large influence on the microbial ecology and total carbon flux in the environment.ImportanceIron is the fourth most abundant element in the Earth’s crust and the reduction of iron by microbes is an important component of global biogeochemical cycles. A phylogenetically diverse group of microbes are capable of conserving energy with oxidized iron as a terminal electron acceptor, but the environmental conditions favoring certain taxonomic clades in iron-reducing environments is unclear. One complicating factor often overlooked in small-scale enrichments is the influence of soluble, redox-active electron shuttles on the rate and microbial ecology of iron reduction. We tested the effects of eight different electron shuttles on the microbial physiology and ecology in iron-reducing enrichments derived from a local wetland. Each electron shuttle varied the microbial activity and enriched for a microbial community distinct from the no shuttle control condition. Therefore, in complex subsurface environments with many redox-active compounds present, we propose electron shuttles as a reason for the coexistence of multiple clades of iron-reducing bacteria.
Electronic health records reveal variations in the use of blood units by hour and medical specialty
Authors: Turkulainen Esa , Peltola Elissa , Perola Markus , Koskinen Miika , Arvas Mikko , Ilmakunnas Minna 
Published: November 2024

ABSTRACTBACKGROUND AND OBJECTIVESEfficient blood supply chain requires accurate demand estimates. Blood demand is created by clinicians making transfusion decisions based on patient status. To better understand the use of blood units, we tracked their use hourly and across a large hospital organization.MATERIALS AND METHODSWe analyzed blood use in adult patients over 2021-2022 at HUS Helsinki University Hospital, serving a population of 1.7 million and consuming a third of blood units used in Finland. We utilized electronic health records (EHR) to map transfusions to patient demographics, diagnoses, medical specialties, treatment events, surgical procedures, and laboratory values. Data were matched to transfusion of red blood cells, platelets and plasma using timestamps and treatment episodes.RESULTSIn total, 107,331 units were transfused to 19,637 unique patients in 50,978 transfusion episodes. Most transfusions occurred in emergency settings, with 61.5% of use driven by emergency department admissions. The most common diagnoses were malignant neoplasms, anemias, and cardiovascular diseases. In total, 47.9% of transfusions were associated with a surgical procedure. Of these, 72.9% were for urgent surgery. Blood use peaked in the early evening and was lowest during morning office hours.CONCLUSIONThe study offers a comprehensive picture of blood use in one of the largest European hospital organizations. In addition to elective use, a significant portion of blood demand is driven by urgent and emergency needs, which introduces some uncertainty in predicting blood use. Future studies should aim to understand both elective and emergency blood use to help improve demand estimates.HighlightsThis study presents the first investigation into intraday blood use within a large hospital district, with precise transfusion timestamps enabling alignment with patient events.Over the past 25 years, blood demand has shifted from surgery to hematology in the HUS Helsinki University Hospital.The majority of blood is used in emergencies and urgent care, mostly outside office hours.
Association of hypotension with mortality among US adults: prospective cohort study
Authors: Han Yan , Tang Jing , Wu Na , Li Zhao , Cai Dachuan , Ren Hong , Hu Peng , Chen Zhiwei 
Published: November 2024

AbstractBackgroundThe associations of hypotension with mortality in general population remains incompletely understood. We aimed to investigate whether hypotension is associated with higher all-cause and cardiovascular disease (CVD) mortality in this population.MethodsIn this prospective analysis, we utilized data from the National Health and Nutrition Examination Survey (NHANES, 1999-2018), with mortality information linked until 2019. We used multivariable Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% CIs for the associations of different blood pressure (BP) with all-cause and CVD mortality.FindingsAmong the 37,832 participants, a total of 5261 deaths and 1664 deaths attributed to CVD causes were recorded over a median of 8.4 years of follow-up. The prevalence of hypotension was 7.6%. Both systolic BP and diastolic BP exhibited a J-shaped association with the all-cause and CVD mortality in restricted cubic spline modeling analysis (nonlinear-P <0.01). Compared to the normal BP group, the adjusted HRs for all-cause and CVD mortality in the hypotension group were 1.44 (1.20-1.74) and 1.57 (1.10-2.24), respectively. Subgroup analyses revealed that older individuals (age ≥60 years) and those with obesity exhibited more pronounced HRs for all-cause mortality, with HRs of 1.60 (1.28-2.00) and 1.95 (1.45-2.61), respectively (P for interaction <0.05).InterpretationIn this nationally representative cohort of US adults, hypotension demonstrated a significant association with both all-cause and cardiovascular disease mortality, particularly among elderly and obesity individuals. The findings underscore the significance of paying attention to and optimizing the management of hypotension in the general population.
Using a Bayesian network to classify time to return to sport based on football injury epidemiological data
Authors: Yung Kate K.Y. , Wu Paul P.Y. , aus der Fünten Karen , Hecksteden Anne , Meyer Tim 
Published: November 2024

AbstractObjectiveThe return-to-sport (RTS) process is multifaceted and complex, as multiple variables may interact and influence the time to RTS. These variables include intrinsic factors of the player, such as anthropometrics and playing position, or extrinsic factors, such as competitive pressure. Providing an individualised estimation is often challenging, and yet clinical decision support tools are often rare in the industry. This study aims to demonstrate the functions of a Bayesian network by the use of a set of basic epidemiological data.MethodsTo exemplify the use of Bayesian network in sports medicine, such as providing an individualised estimation time to RTS for individual players, we applied Bayesian network to a set of basic epidemiological data. Bayesian network was used as a decision support tool to model the epidemiological data and to integrate clinical data, non-clinical factors and expert knowledge. Specifically, we used the Bayesian network to capture the interaction between variables in order to 1) classify days to RTS and 2) injury severity (minimal, mild, moderate and severe).ResultsRetrospective injury data of 3374 player seasons and 6143 time-loss injuries from seven seasons of the professional German football league (Bundesliga, 2014/2015 through 2020/2021) were collected from public databases and media resources. A total of twelve variables from three main categories (player’s characteristics and anthropometrics, match information and injury information) were included. The key response variables are 1)days to RTS(1-3, 4-7, 8-14, 15-28, 29-60, >60, and 2)severity(minimal, mild, moderate and severe). As there are more than two categories, producer’s and user’s accuracy was used to reflect the sensitivity and specificity of the model. The producer’s accuracy of the model for days to RTS ranges from 0.24 to 0.97, while for severity categories range from 0.73 to 1.00. The user’s accuracy of the model for days to RTS ranges from 0.52 to 0.83, while for severity categories, it ranges from 0.67 to 1.00.ConclusionsThe Bayesian network can help to capture different types of data to model the probability of an outcome, such as days to return to sports. In our study, the result from the BN may support coaches and players in predicting days to RTS given an injury, 2) support team planning via assessment of scenarios based on player’s characteristics and injury risk and 3) provide evidence-based support of understanding relationships between factors and RTS. This study shows the key functions and applications of the Bayesian network in RTS, and we suggest further experimenting and developing the Bayesian network into a decision-supporting aid.
The effects of left vagus nerve block on postoperative nausea and vomiting in patients undergoing thoracic or abdominal laparoscopic surgery: A randomized controlled trial
Authors: Chen Chen , Yang Zhongyu , Zheng Qi , Ren Yanghao , Yang Tianyu , Zhen Xinyue , Ding Liang , Fan Bingqian , Wang Tianhai , Dai Hongyan 
Published: November 2024

AbstractPurposeTo explore the influence of preoperative vagus nerve block (VNB) on postoperative nausea and vomiting (PONV) in patients undergoing thoracic or abdominal laparoscopic surgery.MethodsPatients were randomly divided into the VNB group (V group, n=60) and the control group (C group, n=60). The V group received left VNB before anesthesia induction, while the C group did not receive any intervention. The incidence and severity of PONV within one day after surgery were compared between the two groups to evaluate the effect of left VNB on PONV in patients.ResultsThe incidence of PONV in the V group (25%) was significantly lower than that in the C group (60%) (χ2= 15.038,P< 0.001). The incidences of mild and severe PONV in the V group were 16.67% and 8.33%, respectively, while those in the C group were 36.67% and 23.33%, respectively. The differences between the two groups were significant (mild: χ2= 6.136,P= 0.013; severe: χ2= 5.065,P= 0.024).ConclusionLeft VNB can reduce the incidence and severity of PONV caused by thoracic or abdominal laparoscopic surgery.
Post-SARS-CoV-2 Onset Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Symptoms in Two Cohort Studies of COVID-19 Recovery
Authors: Jamal Armaan , Dalhuisen Thomas , Gallego Márquez Nuria , Dziarski Alisha D. , Uy Julian , Walch Samantha N. , Thomas Sean A. , Fehrman Emily A. , Romero Arianna E. , Zelaya Ashley S. , Akasreku Enam A. , Adeagbo Tamilore V. , Pasetes Elizabeth C. , Akbas Selin Y. , Azola Alba M. , Deeks Steven G. , Kelly J. Daniel , Martin Jeffrey N. , Henrich Timothy J. , Landay Alan L. , Peluso Michael J. , Antar Annukka A. R. 
Published: November 2024

ObjectiveTo determine how many people with long COVID also meet diagnostic criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).MethodsWe identified which participants with long COVID also met the Institute of Medicine (IOM) or the 2003 Canadian Consensus Criteria (CCC) for ME/CFS at approximately 6-8 months post-SARS-CoV-2 infection in two cohorts: (1) the JHU COVID Recovery cohort, which enrolled participants within 4 weeks of infection and (2) the Long-term Impact of Infection with Novel Coronavirus (LIINC) cohort, which enriched for participants with long COVID. Neither study administered ME/CFS-specific surveys, so available data elements were mapped onto each ME/CFS diagnostic criteria.ResultsOf 97 JHU participants with long COVID, 5 met IOM criteria and 2 met CCC criteria. Of 281 LIINC participants with long COVID, 51 met the IOM criteria and 29 met the CCC criteria. In LIINC, participants with long COVID meeting ME/CFS criteria were more likely to be female and report a greater number of post-COVID symptoms (p<0.001).ConclusionsThe co-occurrence of ME/CFS symptoms and long COVID suggests that SARS-CoV-2 is a cause of ME/CFS. ME/CFS-specific measures should be incorporated into studies of post-acute COVID-19 to advance studies of post-SARS-CoV-2 onset ME/CFS.