bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cholangiocyte glycocalyx degradation boosts primary sclerosing cholangitis
Authors: Klein Friederike , Wellhöner Freya , Freise Anika , Niculovic Kristina M. , Junca Howard , Vicente Manuel , Kats Elina , Luiz Gustavo dos Anjos Borges , Knegendorf Leonard , Cirksena Karsten , Triefenbach Antonia Marie , Woelfl Franziska , Abdullah Helin Fatma , Schulz Meike , Plumeier Iris , Kahl Silke , Albers Iris , Zoodsma Martijn , Vital Marius , Voigtländer Torsten , Lenzen Henrike , Schmitz Jessica , Saborowski Anna , Manns Michael P. , Solbach Philipp , Bräsen Jan Hinrich , Gerold Gisa , Xu Cheng-Jian , Wedemeyer Heiner , Münster-Kühnel Anja K. , Pieper Dietmar H. , Heidrich Benjamin 
Published: June 2024

SummaryPrimary sclerosing cholangitis (PSC) is an inflammatory disease of the biliary tract eventually leading to bile duct destruction, liver failure, cholangiocellular adenocarcinoma and/or death. No disease modifying treatments are available1. Especially cytotoxicity of bile acids, are discussed as potential driver of disease progression2. Cholangiocytes are protected by a bicarbonate umbrella formed by the glycocalyx, a dense layer of membrane bound polyglycans extending into the extracellular space3,4. Bile of PSC patients harbors a unique microbiome5. Here we identified a new factor in the pathogenesis of PSC. The bacterial degradation of sialic acid and galactose are associated with a poor event free survival of PSC patients and could identify bacterial liberation of sialic acid as crucial element in cholangiocyte damage using cell culture experiments, individualized organoid models and liver biopsies. With this study the view on bacteria-host interactions in bile duct associated diseases is widened. Functional patterns of the bacterial community are crucial for bile duct destruction in PSC patients. This opens a new field of diagnostic tools, disease modifying treatment options and identification of patients at risk.
Predictive Models for Secondary Epilepsy in Patients with Acute Ischemic Stroke Within One Year
Authors: Jinxin Liu , Haoyue He , Yanglingxi Wang , Jun Du , Kaixin Liang , Jun Xue , Yidan Liang , Peng Chen , Shanshan Tian , Yongbing Deng 
Published: June 2024

AbstractObjectivePost-stroke epilepsy (PSE) is a major complication that worsens both prognosis and quality of life in patients with ischemic stroke. This study aims to develop an interpretable machine learning model to predict PSE using medical records from four hospitals in Chongqing.MethodsWe collected and analyzed medical records, imaging reports, and laboratory test results from 21,459 patients diagnosed with ischemic stroke. Traditional univariable and multivariable statistical analyses were performed to identify key predictive factors. The dataset was divided into a 70% training set and a 30% testing set. To address class imbalance, the Synthetic Minority Oversampling Technique combined with Edited Nearest Neighbors was used. Nine widely applied machine learning algorithms were evaluated and compared using relevant prediction metrics. SHAP (SHapley Additive exPlanations) was used to interpret the model, assessing the contributions of different features.ResultsRegression analyses showed that complications such as hydrocephalus, cerebral hernia, and deep vein thrombosis, as well as brain regions (frontal, parietal, and temporal lobes), significantly contributed to PSE. Factors like age, gender, NIH Stroke Scale (NIHSS) scores, and laboratory results such as WBC count and D-dimer levels were associated with a higher risk of PSE. Among the machine learning models, tree-based methods such as Random Forest, XGBoost, and LightGBM demonstrated strong predictive performance, achieving an AUC of 0.99.ConclusionOur model successfully predicts PSE risk, with tree-based models showing superior performance. The NIHSS score, WBC count, and D-dimer were identified as the most important predictors.
HighMycobacterium bovisexposure but low IGRA positivity in UK farm workers
Authors: Thomas Amy , Halliday Alice , Clapp Genevieve , Symonds Ross , Hopewell-Kelley Noreen , McGrath Carmel , Wheeler Lucy , Dacey Anna , Noel Nigel , Turner Andrea , Oliver Isabel , Wood James , Moran Ed , Virgo Paul , Goenka Anu , Brooks-Pollock Ellen 
Published: June 2024

AbstractBackgroundBetween 1999 and 2021, 505 culture-confirmed cases ofM. bovisdisease in humans (zoonotic tuberculosis, TB) were identified in England. We aimed to estimate the prevalence ofM. bovisinfection in persons exposed to TB-infected cattle in England and identify any risk factors associated with latent TB infection (LTBI) in this population.MethodsWe co-developed a retrospective cohort study in southwest England, a bovine TB high risk area, with members of the UK farming community. A questionnaire captured participant characteristics, behaviours and farming practices. Linkage with historical herd testing data was used to categorise participants as low, medium or high risk for TB exposure. Interferon gamma release assay (IGRA) positivity with Quantiferon was used to determine LTBI status and linked to questionnaire data.ResultsWe recruited 90 participants at agricultural shows and a standalone event. Participants were farmers/farm workers (79/90) and veterinary professionals (11/90). Median age was 45.5 years (IQR: 19–77); 58% were male; 66% reported BCG vaccination.M. bovisexposure was via direct contact with infected cattle and consumption of raw milk. One participant in the high-risk group was IGRA positive, all other participants were IGRA negative. Estimated IGRA positivity rate was 1.1% (95% CI 0.058%–7.0%) in all participants and 4.0% (95%CI 0.21%–22%) in participants with high exposure levels.ConclusionsWe found limited LTBI in individuals in contact with TB-infected cattle in England, despite high and prolonged exposure. We identified a high-risk group of farmers who should be prioritised for future engagement.
Cost comparison of unplanned hospital admissions from care home and community settings: A retrospective cohort study using routinely collected linked data
Authors: Geue C , Ciminata G , Reddy Mukka G , Mackay D , Lewsey J , Friday JM , Dundas R , Tran QB , Brown D , Ho F , Hastie C , Fleming M , Stevenson A , du Toit C , Padmanabhan S , Pell JP 
Published: June 2024

ABSTRACTPeople living in care homes often have multiple morbidities and complex healthcare needs, potentially leading to more frequent healthcare utilisation (planned and unplanned) and increased costs. Unscheduled hospital attendance from a care home setting is often regarded as system failure, futile and inefficient in terms of resource use. However, there is a lack of evidence on the costs associated with these attendances. This retrospective cohort study aims to estimate these costs and provides a comparison by usual place of residence. Data were obtained from NHS Greater Glasgow and Clyde Safe Haven reference datasets. Individual-level record linkage between Trak ED, recording emergency admissions, and other routine healthcare datasets was carried out. Healthcare costs were estimated using a two-part model. The first part used a probit model to estimate the probability of positive healthcare resource utilisation, and the second part used a GLM to estimate costs, conditional on costs being positive. Annual mean costs were higher for care home residents than community-dwellers overall and in both men and women and all deprivation quintiles. No significant difference in costs was observed for care home residents who were younger than 65 years and those with no comorbidity. Our results indicate a notable increase in healthcare expenditure for individuals residing in care homes compared to those living in the community following unplanned acute care incidents, emphasising the importance of developing interventions that are specifically designed to meet the unique requirements of this demographic.
A unified genome constraint, pathogenicity, and pLoF model identifies new genes associated with epilepsy
Authors: Aguilar Oscar , Rivas Mijail , Rivas Manuel A. 
Published: June 2024

AbstractBackgroundEpilepsy is a highly heterogeneous disorder thought to have strong genetic components. However, identifying these risk factors using whole-exome sequencing studies requires very large sample sizes and good signal-to-noise ratio in order to assess the association between rare variants in any given gene and disease.MethodsWe present a novel approach for predicting constraint in the human genome – sections of the genome where any mutation can cause a severe disorder. Through application of a Hidden Markov Model (HMM) to the Regeneron Genetics Center Million Exome dataset and the AllofUs whole genome sequencing data, we predict the probability of observing no variants across the population for each position in the genome. Next, we aggregate the constraint predictions by gene and assess its association to epilepsy. Finally, we extend our analysis model to incorporate pathogenicity predictions from AlphaMissense (AM) and pLoFs, and compare against published results.ResultsWe identified a set of (p < 1×10−4) genes with stronger signals than previously published studies including KDM5B, KCNQ2, CACNA1A, CACNA1B, RYR2, and ATP2B2. Our models allow us to evaluate the contribution of constraint, protein structure based pathogenicity prediction from AM, and pLoFs jointly.ConclusionWe showed that relatively simple sequence-dependent constraint prediction models can complement structure-based missense variant pathogenicity predictions and pLoFs for population cohort studies which require additional statistical power in the identification of gene-based signals for neurogenetic and psychiatric disorders.
High-Throughput Genotyping ofPlasmodium vivaxin the Peruvian Amazon via Molecular Inversion Probes
Authors: Popkin-Hall Zachary R. , Niaré Karamoko , Crudale Rebecca , Simkin Alfred , Fola Abebe A. , Sanchez Juan F. , Pannebaker Danielle L. , Giesbrecht David J. , Kim Isaac E. , Aydemir Özkan , Bailey Jeffrey A. , Valdivia Hugo O. , Juliano Jonathan J. 
Published: June 2024

AbstractPlasmodium vivaxtransmission occurs throughout the tropics and is an emerging threat in areas ofPlasmodium falciparumdecline, causing relapse infections that complicate treatment and control. Targeted sequencing forP. falciparumhas been widely deployed to detect population structure and the geographic spread of antimalarial and diagnostic resistance. However, there are fewer such tools forP. vivax. Leveraging global variation data, we designed four molecular inversion probe (MIP) genotyping panels targeting geographically differentiating SNPs, neutral SNPs, putative antimalarial resistance genes, and vaccine candidate genes. We deployed these MIP panels on 866 infections from the Peruvian Amazon and identified transmission networks with clonality (IBD>0.99), copy number variation inPvdbpand multiplePvrbps, fixation of putative antimalarial resistance, and balancing selection in 13 vaccine candidate genes. Our MIP panels are the broadest genotyping panel currently available and are poised for successful deployment in other regions ofP. vivaxtransmission.
Diverging Patterns of Cognitive Decline by Sex and Race-Ethnicity in Seriously Ill Older Americans
Authors: Mejía-Guevara Iván , Periyakoil V.S. 
Published: June 2024

AbstractObjectivesDifferences in Cognitive decline are common in older adults in the last years of life, but differences across sex and race-ethnicity are poorly understood. This study investigated if sex and/or race-ethnicity moderated changes in cognitive function in older adults in the last years of life.MethodsData from the Health and Retirement Study (HRS) from 1993 to 2016 were used to analyze imputed cognition summary scores for total word recall and mental status of older adults aged 60-99. Loss of cognitive function was estimated using a multilevel mixed-effects model and accelerated cognitive decline was approximated by incorporating a change-point model using a restricted sample of decedent respondents who died aged 65-99.ResultsNotable disparities were seen in the rates of cognitive decline across sex and race-ethnic groups in the last years of life. Women consistently scored lower than men in word recall but higher in mental status, regardless of race-ethnicity. Non-Hispanic White respondents, men and women, consistently outperformed Hispanic and Black respondents in word recall tasks and mental status.ConclusionsOur study shows that sex and race-ethnicity moderate cognitive decline in older adults during the last years of life. Older adults from underserved communities are at higher risk of cognitive decline. Our study could inform clinical practice and policy focused on mitigating the adverse impact of cognitive decline experienced by marginalized populations of older adults in the last years of life.
Clinical characteristics and prognosis in patients with acute myocarditis or unexplained acute chest pain: a nationwide longitudinal cohort study
Authors: Björkenstam Marie , Bobbio Emanuele , Polte Christian L. , Hjalmarsson Clara , Bergh Niklas , Omerovic Elmir , Bollano Entela 
Published: June 2024

AbstractBackgroundAcute myocarditis is a disease with variable prognosis, ranging from complete recovery to end-stage heart failure (HF) and death. The aim of this study was to examine the risk of mortality and HF in patients with suspected acute myocarditis (AM) in comparison to patients hospitalized for unexplained acute chest pain (ACP).MethodsWe used the SWEDEHEART-registry to identify patients >16 years admitted to hospital between 1 January 1998 and 31 December 2018 with either AM or ACP. Risks of all-cause mortality and development of HF were calculated and compared by use of adjusted Cox regression analyses.ResultsA total of 3,792 patients with AM and 109,934 patients with ACP were included. Median follow-up time was 7.8 years (Q1, Q3; 3.4, 12.3). AM patients were younger compared to ACP patients, median age 37 years (Q1, Q3; 26, 52) vs 59 years (Q1, Q3; 49, 69), and more likely to be men (79.9% vs 51.4%, p <0.001). Comorbidity burden was lower within the AM cohort. Chest pain was the most common presenting symptom in both groups. Mortality rate at 30 days (OR 3.75, 95% CI 1.9-7.3, p<0,001) as well as long term (OR 2.0, 95% CI 1.69-2.39, p <0.001) were significantly higher among AM patients and AM patients were more likely to develop HF during follow-up (OR 2.3, 95% CI 1.81-2.93, p<0,001).ConclusionsAM patients had a worse short -and long-term outcome compared with ACP. The risk for development of HF was higher for AM patients even after the first year.
Relative Improvement in Language vs Motor Functions with Reperfusion Therapies for Acute Stroke due to Large Vessel Occlusion
Authors: Ahmad Zaka , Yedavalli Vivek , Sarmiento Gonzalez Wladimir , Hillis Argye E. 
Published: June 2024

AbstractBackgroundWhen weighing potential risks versus benefits of reperfusion therapy, the functions likely to recover if blood flow can be restored should be considered. Because deep and motor areas of the brain often infarct relatively early in acute stroke, we hypothesized that reperfusion therapies are more likely to improve language function and neglect (cortical functions) more than motor function.MethodsIn this retrospective review of a prospectively collected database, patients with acute stroke due to large vessel occlusion), we evaluated percent improvement (mean change in score/maximum score) for different items of the National Institutes of Health Score Scale with and without endovascular thrombectomy, and/or intravenous thrombolysis.ResultsIn total, 290 patients (mean age 61.8; SD 14.0; 47.9% female) met the inclusion criteria. For all outcome measures (percent change in language, total language, motor, and neglect) there were significant effects of treatment group (p<0.0001 for all), with the greatest change in the EVT +tPA group, then EVT only group, followed by tPA only, followed by no intervention. Differences between EVT + tPA and EVT only were not significant (p=.30 to 0.79 across outcomes). For patients with aphasia and/or right sided weakness before treatment, the percent change in language was significantly greater than the percent change in weakness (29.8% vs. 12.7%; t(93)=5.3;p<0.0001). Greater percent improvement in language was observed in all treatment groups (p=0.0003 to 0.03 across treatment groups).ConclusionsIn patients with acute ischemic stroke due to LVO, improvements in all neurological functions occur with tPA, and even more with EVT (with and without IV tPA). However, gains in language are even greater than gains in motor function with both interventions. Few patients had neglect before treatment, but of those who did, the majority improved, and most (92.8%) improved with EVT.
Summary of best evidence for interventions for nurse burnout
Authors: Wang Liping , Li Guixiang , Liu Jiayi , Diao Yanjun , Zhuo Yu 
Published: June 2024

AbstractObjectiveTo search, evaluate and summarize the best evidence on nurse burnout intervention at home and abroad, and provide evidence-based basis for clinical nursing staff.MethodsThe literature on nurse burnout intervention was searched in Chinese and English guideline websites and databases, including guidelines, evidence summaries, systematic reviews, clinical decision-making, expert consensus, and randomized controlled studies. The search period was from database establishment to December 31, 2023.Results16 articles were included, including 1 guideline, 1 consensus, 1 evidence summary, 1 randomized controlled study, and 12 systematic reviews. After comprehensive analysis and induction, we extracted five aspects, including effective communication, self-care, resource support, education and training, and social environment, with a total of 15 best evidence.ConclusionThe best evidence for evidence-based intervention for nurse burnout is scientific and practical, and can provide a certain reference for clinical practice in reducing nurse burnout.
Preclinical evaluation of tissue-selective gene therapies for congenital generalised lipodystrophy
Authors: Tiwari Mansi , Roumane Ahlima , Sommer Nadine , Han Weiping , Delibegović Mirela , Rochford Justin J. , Mcilroy George D. 
Published: June 2024

ABSTRACTLipodystrophy is a rare disorder which can be life-threatening. Here individuals fail to develop or maintain appropriate adipose tissue stores. This typically causes severe metabolic complications, including hepatic steatosis and lipoatrophic diabetes. There is no cure for lipodystrophy, and treatment options remain very limited. Here we evaluate whether tissue-selective adeno-associated virus (AAV) vectors can provide a targeted form of gene therapy for lipodystrophy, using a preclinical lipodystrophic mouse model ofBscl2deficiency. We designed AAV vectors containing the mini/aP2 or thyroxine-binding globulin promoter to selectively target adipose or liver respectively. The AAV-aP2 vectors also contained the liver-specific microRNA-122 target sequence, restricting hepatic transgene expression. Systemic delivery of AAV-aP2 vectors overexpressing humanBSCL2restored adipose tissue development and metabolic health in lipodystrophic mice without detectable expression in the liver. High doses (1×1012GCs) of liver-selective vectors led to off target expression and adipose tissue development, whilst low doses (1×1010GCs) expressed selectively and robustly in the liver but did not improve metabolic health. This reveals that adipose tissue-selective, but not liver directed, AAV-mediated gene therapy is sufficient to substantially recover metabolic health in generalised lipodystrophy. This provides an exciting potential new avenue for an effective, targeted, and thereby safer therapeutic intervention.
Inclusion of Hsp70 co-chaperone and RNA binding activities facilitate optimal function of spliceosomal disassembly factor Cwf23 in intron-richSchizosaccharomyces pombe
Authors: Yadav Kirpa , Raut Sandeep , Roy Meghna G , Gopika S , Desai Minita , Balashankar R. , Kumar Mishra Shravan , Sahi Chandan 
Published: June 2024

AbstractCwc23 is an essential J-domain protein that collaborates with the disassembly factor Ntr1 to facilitate spliceosomal disassembly. Although Cwc23 orthologs have been identified in spliceosomal extracts of many eukaryotes, their functionality in intron-rich eukaryotes remains largely unexplored. Here, we investigate the functionality of Cwf23, an ortholog of Cwc23 inSchizosaccharomyces pombe. Our study reveals that while the interaction between Cwf23 andSpNtr1 is conserved, it is not essential inS. pombe. Additionally, the RNA recognition motif (RRM) in Cwf23 is crucial for its function, as mutations in the RRM affect both growth and pre-mRNA splicing. Unlike its budding yeast counterpart, the J-domain of Cwf23 is indispensable, as J-domain mutants cannot support cell viability. These findings suggest a new paradigm in which the presence of a functional RRM and the essential nature of the J-domain underscore the increased requirements for an RNA-binding Hsp70 co-chaperone machinery in spliceosomal remodelling in “intron-rich” eukaryotes.
Long-term in vitro exposure ofTreponema pallidumto sub-bactericidal doxycycline did not induce resistance: Implications for doxy-PEP and syphilis
Authors: Tantalo Lauren C. , Luetkemeyer Ann , P. Lieberman Nicole A. , Nunley B. Ethan , Avendaño Carlos , Greninger Alexander L. , Celum Connie , Giacani Lorenzo 
Published: June 2024

ABSTRACTDoxycycline post-exposure prophylaxis (doxy-PEP) could significantly reduce syphilis incidence. However, the increase in intermittent doxycycline usage might select resistantTreponema pallidum(T. pallidum) strains. To assess whether resistance to doxycycline could be induced in this pathogen, we exposed the SS14 strain in vitro both intermittently and continuously to a sub-bactericidal doxycycline concentration that still exerts antibiotic pressure. During and after each exposure experiment, we assessed the doxycycline minimal inhibitory concentration in test and control treponemes and performed whole genome sequencing, concluding that no resistance developed. This work suggests that doxycycline-resistantT. pallidumis not an immediate threat for doxy-PEP implementation.
Highly synchronized inhibition from Purkinje cells entrains cerebellar output in zebrafish
Authors: Agarwal Vandana , Narayanan Sriram , Sengupta Mohini , Varma Aalok , Sarkar Sudeepta , Chinta Suma , Thirumalai Vatsala 
Published: June 2024

AbstractCerebellar function, known to be important for motor learning and motor coordination, is mediated by efferent neurons that project to diverse motor areas. To understand cerebellar function, it is imperative to study how these efferent neurons integrate inputs from the principal neurons of the cerebellar cortex, the inhibitory Purkinje neurons (PNs). In zebrafish, PNs are bistable and we show here that bistability influences spike synchrony among PNs. Bistability also alters spike correlation with motor bouts. We asked how PN population synchrony influences Eurydendroid cells (ECs), which are postsynaptic targets of PNs and are the cerebellar efferent cells in zebrafish. Using optogenetics, we artificially modulated population synchrony of PNs over millisecond time scales and showed that under conditions of high synchrony, EC firing is briefly suppressed and entrained by PN spiking. However, the magnitude of such modulation is relatively small and indicates a strong combined influence of other synaptic inputs on EC spiking.Key PointsCerebellar Purkinje neurons (PN) in larval zebrafish alter simple spike correlations with each other based on cellular state.They also alter simple spike correlations with motor bouts as a function of state.We altered PN population synchrony in a graded manner using optogenetics.PN targets are cerebellar efferent neurons, which in teleosts are called eurydendroid cells.When PN population is firing with high synchrony, eurydendroid cells are entrained better than when the PN input is asynchronous.This can explain how PNs use bistability to modulate their influence on cerebellar output and ultimately, motor behavior.