bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ambulance response times and 30-day mortality: a Copenhagen (Denmark) registry study
Authors: Mills Alexander Andrew Matthew , Mills Elisabeth Helen Anna , Blomberg Stig Nikolaj Fasmer , Christensen Helle Collatz , Møller Amalie Lykkemark , Gislason Gunnar , Køber Lars , Kragholm Kristian Hay , Lippert Freddy , Folke Frederik , Andersen Mikkel Porsborg , Torp-Pedersen Christian 
Published: October 2023

Background and importance
Ensuring prompt ambulance responses is complicated and costly. It is a general conception that short response times save lives, but the actual knowledge is limited.

Objective
To examine the association between the response times of ambulances with lights and sirens and 30-day mortality.

Design
A registry-based cohort study using data collected from 2014–2018.

Settings and participants
This study included 182 895 individuals who, during 2014–2018, were dispatched 266 265 ambulances in the Capital Region of Denmark.

Outcome measures and analysis
The primary outcome was 30-day mortality. Subgroup analyses were performed on out-of-hospital cardiac arrests, ambulance response priority subtypes, and caller-reported symptoms of chest pain, dyspnoea, unconsciousness, and traffic accidents. The relation between variables and 30-day mortality was examined with logistic regression.

Results
Unadjusted, short response times were associated with higher 30-day mortality rates across unadjusted response time quartiles (0–6.39 min: 9%; 6.40–8.60 min: 7.5%, 8.61–11.80 min: 6.6%, >11.80 min: 5.5%). This inverse relationship was consistent across subgroups, including chest pain, dyspnoea, unconsciousness, and response priority subtypes. For traffic accidents, no significant results were found. In the case of out-of-hospital cardiac arrests, longer response times of up to 10 min correlated with increased 30-day mortality rates (0–6.39 min: 84.1%; 6.40–8.60 min: 86.7%, 8.61–11.8 min: 87.7%, >11.80 min: 85.5%). Multivariable-adjusted logistic regression analysis showed that age, sex, Charlson comorbidity score, and call-related symptoms were associated with 30-day mortality, but response time was not (OR: 1.00 (95% CI [0.99–1.00])).

Conclusion
Longer ambulance response times were not associated with increased mortality, except for out-of-hospital cardiac arrests.
Deciphering the cell-intrinsic effect of DNMT3A clonal hematopoiesis in circulating monocytes: potential mechanistic insights into a protective role in Alzheimer’s disease
Authors: Abplanalp Wesley T. , Dimmeler Stefanie , Zeiher Andreas M. 
Published: October 2023

AbstractBackgroundRecent evidence showed an unforeseen connection between clonal hematopoiesis (CH) and protection against Alzheimer’s disease (AD) and found mutant bone marrow-derived cells infiltrate the brain and acquire a microglial-like phenotype, correlating with reduced neuritic plaques and neurofibrillary tangles in non-AD individuals. CH, characterized by somatic mutations in hematopoietic stem cells leading to clonal expansion of immune cells, has previously been associated with the exacerbation of various age-related diseases.Methods and ResultsAs the mechanism behind this protective effect remains unclear, our study introduces a novel method, MutDetect-Seq, capable of discerning cell-intrinsic effects of CH mutations. Single-cell RNA sequencing profiles in patients with DNMT3A CH mutations were assessed, hypothesizing that mutant cells might augment phagocytosis, potentially mitigating neurodegenerative processes. Indeed, DNMT3A mutant monocytes exhibited a distinct pro-phagocytic gene signature as demonstrated via upregulation of prototypical phagocytotic genes like CALR, FCGR1A, CYBA, S100A8, S100A9 and FCER1G. Upregulation was validated in vitro with DNMT3A silenced THP1 macrophages. Furthermore, upregulated gene pathways in mutant monocytes associated with phagocytosis, suggesting bone marrow-derived monocytic cells with CH DNMT3A mutations could replenish the brain’s phagocytic capacity, counteracting age-related declines in microglial phagocytosis, and thereby causatively reducing neurodegenerative processes in AD.ConclusionThis study reveals critical phenotypic disparities between DNMT3A CH driver harboring mutant and wild-type monocytes, shedding light on a potential mechanism underlying the unexpected protective role of CH in AD progression and offering insights into the effects of different CH mutations in disease contexts.
Suppressed IgG4 class switching in dupilumab- and TNF inhibitor-treated patients after repeated SARS-CoV-2 mRNA vaccination
Authors: Valk Anika M. , Keijser Jim B.D. , van Dam Koos P.J. , Stalman Eileen W. , Wieske Luuk , Steenhuis Maurice , Kummer Laura Y.L. , Spuls Phyllis I. , Bekkenk Marcel W. , Musters Annelie H. , Post Nicoline F. , Bosma Angela L. , Horváth Barbara , Hijnen DirkJan , Schreurs Corine R.G. , van Kempen Zoé L.E. , Killestein Joep , Volkers Adriaan G. , Tas Sander W. , Boekel Laura , Wolbink Gerrit J. , Keijzer Sofie , Derksen Ninotska I.L. , van Deelen Melanie , van Mierlo Gerard , Kuijpers Taco W. , Eftimov Filip , van Ham S. Marieke , Brinke Anja ten , Rispens Theo ,   T2B! Immunity against SARS-CoV-2 study group
Published: October 2023

AbstractBackgroundRepeated mRNA vaccination against SARS-CoV-2 has been shown to induce class switching to IgG4, a non-inflammatory human antibody subclass linked to tolerance. Although poorly understood, prolonged antigenic stimulation and IL-4 signalling may be instrumental in IgG4 switching. We and others have previously shown that widely used immunosuppressive drugs such as methotrexate (MTX) and TNF inhibitors (TNFi) have a minor inhibitory impact on humoral SARS-CoV-2 mRNA vaccination responses. However, the impact of such immunosuppressive drugs on IgG4 switching is unknown.AimTo study the impact of widely used immunosuppressive drugs (TNFi, MTX, or the IL-4 receptor-blocking antibody dupilumab on IgG4 skewing upon repeated SARS-CoV-2 mRNA vaccination.MethodsAntibody responses to the receptor-binding domain (RBD) of the spike protein upon repeated SARS-CoV-2 mRNA vaccination were measured in 604 individuals including patients with immune-mediated inflammatory diseases treated with TNFi and/or MTX, or dupilumab, as well as healthy controls and untreated patients.ResultsWe observed a substantial increase in the proportion of RBD-specific IgG4 antibodies (median 21%) in healthy/untreated controls after a third mRNA vaccination. This IgG4 skewing was absent when primary vaccination was adenoviral vector-based and was profoundly reduced in both dupilumab- and TNFi-treated patients (<1%), but only moderately in patients treated with MTX (7%).ConclusionOur results imply a major role for both IL-4/IL-13 as well as TNF in IgG4 class switching. These novel findings advance our understanding of IgG4 class switch dynamics, and may benefit future mRNA vaccine strategies, humoral tolerance induction, as well as treatment of IgG4 pathologies.
Evaluation of Measles Surveillance System, Bono Region, Ghana
Authors: Zumah Fidelis , Asem Livingstone , Debuo Der Amanda , Sackey Samuel 
Published: October 2023

AbstractBackgroundMeasles remains a global public health problem despite the availability of a safe and effective vaccine, it is one of the leading causes of childhood morbidity and mortality. Hence, this study assessed the performance of the measles surveillance system in the Bono Region of Ghana.MethodsA descriptive evaluation study was employed using the updated Centers for Disease Control (CDC) guideline for evaluating public health surveillance systems. The data collection methods employed were observation checklists, questionnaires, and measles records reviewResultsOut of the 12 districts, 83.3% had case definitions. Three-quarters had IDSR reporting forms while 66.7% could transport measles specimens for confirmation. The performance of the supportive functions of the system was sub-optimal. The study revealed that half of the districts were not able to meet most of the standards for the support function. Moreover, timeliness of weekly and monthly reports above 90% was found in the study to be 66.7% and 25% respectively, and just about half of the districts attained over 90% timeliness. Also, the measles surveillance system was simple, flexible, useful, and acceptable despite its low positive predictive value of 1.5%.ConclusionThe results of the study suggest that the general performance of the measles surveillance system in the Bono Region was sub-optimal. The performance of the core functions of the surveillance system is considered to be satisfactory. About half of the districts performed satisfactorily for the supportive functions. The completeness and timeliness of the reports were also satisfactory. Also, the Measles surveillance system was simple, flexible, useful, and quite acceptable despite its low positive predictive value. There is a need for capacity building on measles surveillance for surveillance officers and community volunteers, effective supportive supervision, and effective communication at all levels to improve the activities of the surveillance system and ultimately eliminate measles.
Simulation of COVID-19 Epidemic from Potential Viral Loads in Saudi Arabian Wastewater Treatment Plants
Authors: Meetei Mutum Zico , Msmali Ahmed H. , Ahmadini Abdullah Ali H. , Alshqaq Shokrya , Alna-shiri Hassien M 
Published: October 2023

AbstractSARS-CoV-2 is a contagious respiratory virus that has been discovered in sewage, human waste, and wastewater treatment facilities. Wastewater surveillance has been considered one of the lowest-cost means of testing for tracking the COVID-19 outbreak in communities. This paper highlights the dynamics of the virus’s infection, persistence, and occurrence in wastewater treatment plants. Our aim is to develop and implement a mathematical model to infer the epidemic dynamics from the possible density of SARS-CoV-2 viral load in wastewater. We present a log-normal model and fractional order of susceptible-exposed-infected-recovery (SEIR) epidemic model for predicting the spread of the COVID-19 disease from the wastewater data. We study the dynamic properties of the fractional order SEIR model with respect to the fractional ordered values. The model is used to comprehend how the coronavirus spreads through wastewater treatment plants in Saudi Arabia. Our modeling approach can help with wastewater surveillance for early prediction and cost-effective monitoring of the epidemic outbreak in a situation of low testing capacity.
Cardiac atrophy, dysfunction, and metabolic impairments: a cancer-induced heart failure phenotype
Authors: Ogilvie Leslie M. , Delfinis Luca J. , Coyle-Asbil Bridget , Vudatha Vignesh , Alshamali Razan , Garlisi Bianca , Pereira Madison , Matuszewska Kathy , Garibotti Madison C. , Gandhi Shivam , Brunt Keith R. , Trevino Jose G. , Perry Christopher G.R. , Petrik Jim , Simpson Jeremy A. 
Published: October 2023

ABSTRACTMuscle atrophy and weakness are prevalent features of cancer. While extensive research has characterized skeletal muscle wasting in cancer cachexia, limited studies have investigated how cardiac structure and function are affected by therapy-naïve cancer. In cell-based models of orthotopic, syngeneic epithelial ovarian cancer (EOC) and pancreatic ductal adenocarcinoma (PDAC), and a patient-derived pancreatic xenograft model (PDX), we evaluated cardiac structure, function, and metabolism. Tumor-bearing mice showed cardiac atrophy and intrinsic systolic and diastolic dysfunction; associated with hypotension and exercise intolerance. In hearts of ovarian tumor-bearing mice, fatty acid-supported mitochondrial respiration decreased and carbohydrate-supported respiration increased, establishing a substrate shift in cardiac metabolism that is characteristic of heart failure. EOC decreased cytoskeletal and cardioprotective gene expression, which was paralleled by downregulation of transcription factors that regulate cardiomyocyte size and function. PDX tumors altered myosin heavy chain isoform expression – a molecular phenotype observed in heart failure. Markers of autophagy and ubiquitin-proteasome system were upregulated with cancer, providing evidence of catabolic signaling that promotes cardiac wasting. Together, metabolic stress, cardiac gene dysregulation, and upregulation of catabolic pathways contribute to cardiac atrophy and failure during cancer. Finally, we demonstrate that pathological cardiac remodeling is induced by human cancer, providing translational evidence of cancer-induced cardiomyopathy.
Admix-kit: An Integrated Toolkit and Pipeline for Genetic Analyses of Admixed Populations
Authors: Hou Kangcheng , Gogarten Stephanie , Kim Joohyun , Hua Xing , Dias Julie-Alexia , Sun Quan , Wang Ying , Tan Taotao ,   Polygenic Risk Methods in Diverse Populations (PRIMED) Consortium Methods Working Group, Atkinson Elizabeth G. , Martin Alicia , Shortt Jonathan , Hirbo Jibril , Li Yun , Pasaniuc Bogdan , Zhang Haoyu 
Published: October 2023

AbstractSummaryAdmixed populations, with their unique and diverse genetic backgrounds, are often underrepresented in genetic studies. This oversight not only limits our understanding but also exacerbates existing health disparities. One major barrier has been the lack of efficient tools tailored for the special challenges of genetic study of admixed populations. Here, we present admix-kit, an integrated toolkit and pipeline for genetic analyses of admixed populations. Admix-kit implements a suite of methods to facilitate genotype and phenotype simulation, association testing, genetic architecture inference, and polygenic scoring in admixed populations.Availability and implementationAdmix-kit package is open-source and available athttps://github.com/KangchengHou/admix-kit. Additionally, users can use the pipeline designed for admixed genotype simulation available athttps://github.com/UW-GAC/admix-kit_workflow.
The neuronal chromatin landscape in adult schizophrenia brains is linked to early fetal development
Authors: Girdhar Kiran , Bendl Jaroslav , Baumgartner Andrew , Therrien Karen , Venkatesh Sanan , Mathur Deepika , Dong Pengfei , Rahman Samir , Kleopoulos Steven P. , Misir Ruth , Reach Sarah M. , Auluck Pavan K. , Marenco Stefano , Lewis David A. , Haroutunian Vahram , Funk Cory , Voloudakis Georgios , Hoffman Gabriel E. , Fullard John F. , Roussos Panos 
Published: October 2023

AbstractNon-coding variants increase risk of neuropsychiatric disease. However, our understanding of the cell-type specific role of the non-coding genome in disease is incomplete. We performed population scale (N=1,393) chromatin accessibility profiling of neurons and non-neurons from two neocortical brain regions: the anterior cingulate cortex and dorsolateral prefrontal cortex. Across both regions, we observed notable differences in neuronal chromatin accessibility between schizophrenia cases and controls. A per-sample disease pseudotime was positively associated with genetic liability for schizophrenia. Organizing chromatin intocis- andtrans-regulatory domains, identified a prominent neuronaltrans-regulatory domain (TRD1) active in immature glutamatergic neurons during fetal development. Polygenic risk score analysis using genetic variants within chromatin accessibility of TRD1 successfully predicted susceptibility to schizophrenia in the Million Veteran Program cohort. Overall, we present the most extensive resource to date of chromatin accessibility in the human cortex, yielding insights into the cell-type specific etiology of schizophrenia.
Walking Pace, Sport Genes, and the Lung Cancer
Authors: Wang Mengying , Meng Xiangqi , Tian Weiliang , Sun Ruinan , Wang Siyue , Qin Yilei , Ranson Janice M. , Peng Hexiang , Napolioni Valerio , Lau Patrick W. C. , Wu Tao , Huang Jie 
Published: October 2023

AbstractBackgroundTo investigate the association between walking pace and lung cancer risk, and explore whether any association is modified by endurance and power-related genes.MethodsWe followed up 449,890 UK Biobank participants free of cancer at baseline. Data on self-reported walking pace were collected by touchscreen questionnaire at baseline. Blood samples were obtained for genotyping. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for lung cancer incidence and mortality, with slow walking pace as the reference.Findings4,087 lung cancer incident cases and 2,245 lung cancer deaths were identified during a median follow-up period of 12.1 and 12.7 years, respectively. For incident lung cancer, HR (95% CI) were 0.71 (0.65- 0.78) and 0.55 (0.49-0.61) among participants with steady and brisk walking pace, respectively. For lung cancer mortality, steady and brisk walking paces were associated with 32% and 48% lower risks, respectively. Associations of walking pace with risks of lung cancer occurrence and mortality were modified by rs1815739 inACTN3and rs7191721 inRBFOX1. The protective effect of faster walking pace was more evident among participants carrying a higher number of T allele for rs1815739 inACTN3(Pinteraction=0.04 for both lung cancer incidence and mortality) and A allele for rs7191721 inRBFOX1(Pinteraction=0.01 for lung cancer incidence,Pinteraction=0.004 for lung cancer mortality).InterpretationFaster walking pace is associated with lower risks of both lung cancer occurrence and mortality, and this protective effect is modulated by polymorphisms in endurance geneRBFOX1and in power gene (ACTN3).FundingThis work was supported by grants from the China Postdoctoral Science Foundation (Grant No. BX2021021, 2022M710249), Fujian Provincial Health Technology Project (Grant No. 2020CXB009), and the Natural Science Foundation of Fujian Province, China (Grant No. 2021J01352).
A Large Language Model-Based Generative Natural Language Processing Framework Finetuned on Clinical Notes Accurately Extracts Headache Frequency from Electronic Health Records
Authors: Chiang Chia-Chun , Luo Man , Dumkrieger Gina , Trivedi Shubham , Chen Yi-Chieh , Chao Chieh-Ju , Schwedt Todd J. , Sarker Abeed , Banerjee Imon 
Published: October 2023

AbstractBackgroundHeadache frequency, defined as the number of days with any headache in a month (or four weeks), remains a key parameter in the evaluation of treatment response to migraine preventive medications. However, due to the variations and inconsistencies in documentation by clinicians, significant challenges exist to accurately extract headache frequency from the electronic health record (EHR) by traditional natural language processing (NLP) algorithms.MethodsThis was a retrospective cross-sectional study with human subjects identified from three tertiary headache referral centers-Mayo Clinic Arizona, Florida, and Rochester. All neurology consultation notes written by more than 10 headache specialists between 2012 to 2022 were extracted and 1915 notes were used for model fine-tuning (90%) and testing (10%). We employed four different NLP frameworks: (1)ClinicalBERT (Bidirectional Encoder Representations from Transformers) regression model(2) Generative Pre-Trained Transformer-2 (GPT-2) Question Answering (QA) Model zero-shot (3) GPT-2 QA model few-shot trainingfine-tuned on Mayo Clinic notes; and(4) GPT-2 generative model few-shot trainingfine-tuned on Mayo Clinic notes to generate the answer by considering the context of included text.ResultsThe GPT-2 generative model was the best-performing model with an accuracy of 0.92[0.91 – 0.93] and R2score of 0.89[0.87, 0.9], and all GPT2-based models outperformed the ClinicalBERT model in terms of the exact matching accuracy. Although the ClinicalBERT regression model had the lowest accuracy 0.27[0.26 – 0.28], it demonstrated a high R2score 0.88[0.85, 0.89], suggesting the ClinicalBERT model can reasonably predict the headache frequency within a range of ≤ ± 3 days, and the R2score was higher than the GPT-2 QA zero-shot model or GPT-2 QA model few-shot training fine-tuned model.ConclusionWe developed a robust model based on a state-of-the-art large language model (LLM)-a GPT-2 generative model that can extract headache frequency from EHR free-text clinical notes with high accuracy and R2score. It overcame several challenges related to different ways clinicians document headache frequency that were not easily achieved by traditional NLP models. We also showed that GPT2-based frameworks outperformed ClinicalBERT in terms of accuracy in extracting headache frequency from clinical notes. To facilitate research in the field, we released the GPT-2 generative model and inference code with open-source license of community use in GitHub.
Comparing Approaches to Specimen Identification using Neotropical Freshwater Fishes in the Barra del Colorado Wildlife Refuge, Costa Rica
Authors: Perez Taegan JM , Fontenelle JP , Kolmann Matthew A. , Angulo Arturo , López-Fernández Hernán , Lovejoy Nathan R. 
Published: October 2023

AbstractAs global biodiversity declines continue, conservation efforts are increasingly important in megadiverse areas such as the Neotropics where biodiversity is especially imperiled. The accurate identification of specimens is critical to successful conservation plans. However, in groups such as freshwater fishes, different identification methodologies have documented challenges. Using a biodiversity survey of fishes from the Barra del Colorado Wildlife Refuge in northeastern Costa Rica, we compared: (1) morphological identifications in the field, (2) morphological identifications in the lab by experts, (3) DNA barcode-based identifications, and (4) identifications based on an integrative approach. Our results suggest that both barcode-based identifications and field morphological identifications provided fewer correct species identifications than lab identifications performed by experts using morphology. We attribute shortfalls of DNA barcoding in this case to the misidentification of reference material, the use of outdated taxonomy for references sequences, and the non-uniform representation of groups in public databases across taxa. We suggest the use of an integrative approach to identify freshwater fishes in Costa Rica and other megadiverse areas of the Neotropics where similar issues with public barcode reference libraries exist. We also recommend the creation of regional curated barcode reference libraries to aid in the identification of traditionally difficult to identify species/specimens. We also provide the most up to date species list for the ichthyofauna of the Barra del Colorado Wildlife Refuge identifying 51 species from 42 genera, 21 families, and 17 orders. Generating accurate species lists for protected areas and areas of importance will provide conservation practitioners with effective tools for tracking diversity changes over time.