bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quality of Life and Psychiatric Comorbidities Associated with Migraines in Medical Students: A Cross-Sectional Study
Authors: Hassan Nusaiba , Hassan Roaa , Mohammed Batoul , Elomeiri Leina 
Published: September 2024

AbstractObjectivesThis study aims to assess the health-related quality of life (HRQoL) and psychiatric comorbidities among medical students suffering from migraines at the University of Khartoum.Materials and MethodsA descriptive observational cross-sectional study was conducted on 78 medical students diagnosed with migraines. Participants completed a self-reported questionnaire that included the SF-12 Health Survey to assess HRQoL and the Hopkins Symptom Checklist (HSCL-25) to evaluate psychiatric symptoms.Results42.3% of students reported poor quality of life, particularly in the mental component (MCS) compared to the physical component (PCS). Psychiatric symptoms, including anxiety and depression, were prevalent in 70.5% of the participants. Gender was the only sociodemographic factor significantly affecting both HRQoL and psychiatric comorbidity, with females reporting poorer physical health and higher rates of psychiatric symptoms than males, consistent with findings from other studies.ConclusionQuality of life in regard to the mental aspect is significantly impaired in medical students suffering from migraine. Psychiatric comorbidities, namely depression and anxiety, are common in these patients. Universities should keep reports of students who are diagnosed with migraine and provide support programs and follow-up regarding medical treatment and psychiatric evaluation.
Erythrocyte Osmotic Fragility as A Diagnostic Marker in Glaucoma: A Comprehensive Analysis Using LASSO Regression
Authors: Yang Jialiang , Yang Fang , Gu Junming , Cheng Yilian , Luo Qian , Hao Fang , Gong Bo , Zhang Houbin 
Published: September 2024

AbstractObjectiveThis study investigates the potential of blood biomarkers in the early diagnosis of glaucoma, focusing on erythrocyte osmotic fragility (EOF) as a novel indicator. We used Least Absolute Shrinkage and Selection Operator (LASSO) regression to evaluate EOF’s predictive utility for glaucoma diagnosis.MethodsWe included 195 confirmed glaucoma patients and an equal number of age- and sex-matched healthy controls. Blood samples were analyzed for various parameters, including white blood cell count, neutrophil count, red blood cell (RBC) count, and EOF. Key differential markers were identified, and a predictive model was constructed using LASSO regression models.ResultsLASSO regression analysis identified HCT, NEUT, LYMPH, MCV, MCHC, and EOF as critical blood biomarkers discriminating glaucoma patients from healthy controls. Incorporating EOF into the model significantly enhanced its predictive performance, with EOF showing a positive correlation with the likelihood of glaucoma.ConclusionsEOF is a promising predictive biomarker for glaucoma. Combining EOF with other blood biomarkers significantly improves the accuracy of glaucoma diagnosis.
Large language models outperform traditional natural language processing methods in extracting patient-reported outcomes in IBD
Authors: Patel Perseus V. , Davis Conner , Ralbovsky Amariel , Tinoco Daniel , Williams Christopher Y.K. , Slatter Shadera , Naderalvojoud Behzad , Rosen Michael J. , Hernandez-Boussard Tina , Rudrapatna Vivek 
Published: September 2024

AbstractBackground and AimsPatient-reported outcomes (PROs) are vital in assessing disease activity and treatment outcomes in inflammatory bowel disease (IBD). However, manual extraction of these PROs from the free-text of clinical notes is burdensome. We aimed to improve data curation from free-text information in the electronic health record, making it more available for research and quality improvement. This study aimed to compare traditional natural language processing (tNLP) and large language models (LLMs) in extracting three IBD PROs (abdominal pain, diarrhea, fecal blood) from clinical notes across two institutions.MethodsClinic notes were annotated for each PRO using preset protocols. Models were developed and internally tested at the University of California San Francisco (UCSF), and then externally validated at Stanford University. We compared tNLP and LLM-based models on accuracy, sensitivity, specificity, positive and negative predictive value. Additionally, we conducted fairness and error assessments.ResultsInter-rater reliability between annotators was >90%. On the UCSF test set (n=50), the top-performing tNLP models showcased accuracies of 92% (abdominal pain), 82% (diarrhea) and 80% (fecal blood), comparable to GPT-4, which was 96%, 88%, and 90% accurate, respectively. On external validation at Stanford (n=250), tNLP models failed to generalize (61-62% accuracy) while GPT-4 maintained accuracies >90%. PaLM-2 and GPT-4 showed similar performance. No biases were detected based on demographics or diagnosis.ConclusionsLLMs are accurate and generalizable methods for extracting PROs. They maintain excellent accuracy across institutions, despite heterogeneity in note templates and authors. Widespread adoption of such tools has the potential to enhance IBD research and patient care.
Planar cell polarity coordination in a cnidarian embryo provides clues to animal body axis evolution
Authors: Uveira Julie , Donati Antoine , Léria Marvin , Lechable Marion , Lahaye François , Vesque Christine , Houliston Evelyn , Momose Tsuyoshi 
Published: September 2024

SummaryBody axis specification is a crucial event in animal embryogenesis and was an essential evolutionary innovation for founding the animal kingdom. It involves two distinct components that coordinate to establish the spatial organisation of the embryo: initiation of cascades of regionalised gene expression and orientation of morphogenetic processes such as body elongation. Intense interest in the first component has revealed Wnt/β-catenin signalling as ancestrally responsible for initiating regional gene expression, but the evolutionary origin of oriented morphogenesis has received little attention. Here, by addressing the cell and morphological basis of body axis development in embryos of the cnidarianClytia hemisphaerica,we have uncovered a simple and likely ancestral coordination mechanism between Wnt/β-catenin signalling and directed morphogenesis. We show that the ligand Wnt3, known to initiate oral gene expression via localised Wnt/β-catenin pathway activation, also has a key β-catenin-independent role in globally orienting planar cell polarity (PCP) to direct morphogenesis along the oral-aboral axis. This PCP orientation occurs in two distinct steps: local orientation by Wnt3 and global propagation by conserved core PCP protein interactions along the body axis. From these findings we propose novel scenarios for PCP-driven symmetry-breaking underlying the emergence of the animal body plan.
Next generation APOBEC3 inhibitors: Optimally designed for potency and nuclease stability
Authors: Hedger Adam K. , Myint Wazo , Lee Jeong Min , Suchenski-Loustaunau Diego , Balachandran Vanivilasini , Shaqra Ala M. , Kurt-Yilmaz Nese , Watts Jonathan K. , Matsuo Hiroshi , Schiffer Celia A. 
Published: September 2024

ABSTRACTAPOBEC3 (or A3) enzymes have emerged as potential therapeutic targets due to their role in introducing heterogeneity in viruses and cancer, often leading to drug resistance. Inhibiting these enzymes has remained elusive as initial phosphodiester (PO) linked DNA based inhibitors lack stability and potency. We have enhanced both potency and nuclease stability, of 2′-deoxy-zebularine (dZ), substrate-based oligonucleotide inhibitors for two critical A3’s: A3A and A3G. While replacing the phosphate backbone with phosphorothioate (PS) linkages increased nuclease stability, fully PS-modified inhibitors lost potency (1.4-3.7 fold) due to the structural constraints of the active site. For both enzymes, mixed PO/PS backbones enhanced potency (2.3-9.2 fold), while also vastly improving nuclease resistance. We also strategically introduced 2′-fluoro sugar modifications, creating the first nanomolar inhibitor of A3G-CTD2. With hairpin-structured inhibitors containing optimized PS patterns and LNA sugar modifications, we characterize the first single-digit nanomolar inhibitor targeting A3A. These extremely potent A3A inhibitors, were highly resistant to nuclease degradation in serum stability assays. Overall, our optimally designed A3 oligonucleotide inhibitors show improved potency and stability, compared to previous attempts to inhibit these critical enzymes, opening the door to realize the therapeutic potential of A3 inhibition.
Paramyxovirus matrix proteins modulate host cell translation via exon-junction complex interactions in the cytoplasm
Authors: Hung Chuan-Tien , Haas Griffin D , Watkinson Ruth E , Chiu Hsin-Ping , Kowdle Shreyas , Stevens Christian S , Park Arnold , Wohlschlegel James A , Thibault Patricia A , Lee Benhur 
Published: September 2024

ABSTRACTViruses have evolved myriad strategies to exploit the translation machinery of host cells to potentiate their replication. However, how paramyxovirus (PMVs) modulate cellular translation for their own benefit has not been systematically examined. Utilizing puromycylation labeling, overexpression of individual viral genes, and infection with wild-type virus versus its gene-deleted counterpart, we found that PMVs significantly inhibit host cells’ nascent peptide synthesis during infection, with the viral matrix being the primary contributor to this effect. Using the rNiV-NPL replicon system, we discovered that the viral matrix enhances viral protein translation without affecting viral mRNA transcription and suppresses host protein expression at the translational level. Polysome profile analysis revealed that the HPIV3 matrix promotes the association of viral mRNAs with ribosomes, thereby enhancing their translation efficiency during infection. Intriguingly, our NiV-Matrix interactome identified the core exon-junction complex (cEJC), critical for mRNA biogenesis, as a significant component that interacts with the paramyxoviral matrix predominantly in the cytoplasm. siRNA knockdown of eIF4AIII simulated the restriction of cellular functions by the viral matrix, leading to enhanced viral gene translation and a reduction in host protein synthesis. Moreover, siRNA depletion of cEJC resulted in a 2-3 log enhancement in infectious virus titer for various PMVs but not SARS-CoV-2, enterovirus D68, or influenza virus. Our findings characterize a host translational interference mechanism mediated by viral matrix and host cEJC interactions. We propose that the PMV matrix redirects ribosomes to translate viral mRNAs at the expense of host cell transcripts, enhancing viral replication, and thereby enhancing viral replication. These insights provide a deeper understanding of the molecular interactions between paramyxoviruses and host cells, highlighting potential targets for antiviral strategies.
Calpains Orchestrate Secretion of Annexin-containing Microvesicles during Membrane Repair
Authors: Williams Justin Krish , Ngo Jordan Matthew , Murugupandiyan Abinayaa , Croall Dorothy E. , Hartzell H Criss , Schekman Randy 
Published: September 2024

AbstractMicrovesicles (MVs) are membrane-enclosed, plasma membrane-derived particles released by cells from all branches of life. MVs have utility as disease biomarkers and may participate in intercellular communication; however, physiological processes that induce their secretion are not known. Here, we isolate and characterize annexin-containing MVs and show that these vesicles are secreted in response to the calcium influx caused by membrane damage. The annexins in these vesicles are cleaved by calpains. After plasma membrane injury, cytoplasmic calcium-bound annexins are rapidly recruited to the plasma membrane and form a scab-like structure at the lesion. In a second phase, recruited annexins are cleaved by calpains-1/2, disabling membrane scabbing. Cleavage promotes annexin secretion within MVs. Our data supports a new model of plasma membrane repair, where calpains relax annexin-membrane aggregates in the lesion repair scab, allowing secretion of damaged membrane and annexins as MVs. We anticipate that cells experiencing plasma membrane damage, including muscle and metastatic cancer cells, secrete these MVs at elevated levels.
Sex-Specific Cytokine, Chemokine, and Growth Factor Signatures in T1D Patients and Progressors
Authors: Girdhar Khyati , Mine Keiichiro , DaCosta Jeffrey M. , Atkinson Mark A. , Ludvigsson Johnny , Altindis Emrah 
Published: September 2024

ABSTRACTWhile studies have reported altered levels of cytokines in type 1 diabetes (T1D) patients, the results are inconsistent, likely because of variable factors. This study tests the hypothesis that there are sex-based differences in cytokine levels in T1D, prior to and after disease onset. We analyzed 48 blood cytokine, chemokine, and growth factor levels using a multiplex assay. We found only two cytokines, M-CSF and IL-6, with significant differences between T1D patients (n=25) versus controls overall (n=25). However, we identified notable alterations when comparing sex-age-matched controls and T1D samples. Inflammatory cytokines (TNF-α, IL-6, IL-1a), Th2 cytokines (IL-4, IL-13), and chemokines (MIP-1α, RANTES, MIP-3) were lower in female T1D patients compared to female controls, but not in males. IL-22 was lower in female T1D patients compared to female controls, while it was higher in male T1D patients compared to male controls. In contrast, growth factors (EGF, PDGF-AB/BB) were higher in male T1D patients compared to male controls. In T1D progressors (children who developed the disease years after the sample collection, n=16-21), GROa was lower compared to controls in both sexes. Our findings underscore the importance of understanding sex-specific differences in T1D pathogenesis and their implications for developing personalized treatments.
PI3K/AKT Signaling Mediates Stress-Inducible Amyloid Aggregation Through c-myc
Authors: Lacroix Emma , Momchilova Evgenia A. , Chandhok Sahil , Padavu Mythili , Zapf Richard , Audas Timothy E. 
Published: September 2024

SummaryIn response to environmental stress, eukaryotic cells reversibly form functional amyloid aggregates, called amyloid bodies (A-bodies). While these solid-like biomolecular condensates share many biophysical characteristics with pathological amyloids, A-body are non-toxic, and induce a protective state of cellular dormancy. As a recently identified structure, the modulators of A-body biogenesis remain uncharacterized, with the seeding noncoding RNA being the only known regulatory factor. Here, we use an image-based high-throughput screen to identify candidate pathways regulating A-body biogenesis. Our data demonstrates that the PI3K signaling axis meditates A-body formation during heat shock, by activating AKT and repressing GSK3-mediated degradation of c-myc. This enhances c-myc binding to regulatory elements of the seeding noncoding RNA, upregulating the transcripts that nucleate A-body formation. Identifying a link between PI3K signaling, c-myc, and physiological amyloid aggregates, extends the range of activity for these well-established regulators, while providing insight into cellular components whose dysregulation could underly amyloidogenic disorders.
A comprehensive comparative analysis of bacterial communities within cryoconite holes of Arctic and Antarctic glaciers as a response to global warming changes
Authors: Sasin-Kurowska Joanna , Golan Maciej , Piłsyk Sebastian , Sochacka-Piętal Marta 
Published: September 2024

AbstractCryoconite holes, water-filled ponds with sediment at the bottom, play a crucial role for glacial microbiological ecosystems. While they have been widely studied in various regions of the world (e.g., the Arctic, Antarctic, Alps, Himalayas, Central Andes), the novelty of the analyses presented here lies in their deeper exploration of metagenomic data. This study provides a comparative analysis of environmental factors influencing microbial biodiversity, with an additional focus on explaining the effects of pollution on bacterial communities.
The Parenting and Family Adjustment Scales (PAFAS) questionnaire: psychometric qualities of the parenting scale in two large Brazilian birth cohorts
Authors: Martins Rafaela Costa , Gomes Hugo S. , Bauer Andreas , Hoffmann Maurício Scopel , de Mola Christian Loret , Altafim Elisa Rachel Pisani , Domingues Marlos Rodrigues , Murray Joseph 
Published: September 2024

AbstractObjectiveAnalyse the psychometric properties of the Portuguese version of the PAFAS (Parenting and Family Adjustment Scales) parenting scale, using data from two large Brazilian birth cohorts.MethodsThe original PAFAS parenting scale, which consists of 18 items (parental inconsistency 5 items, coercive parenting 5 items, positive encouragement 3 items, and parent-child relationship 5 items) was applied in two Brazilian birth cohorts in Pelotas (ages 4 [n = 4010] and 6-7 [n = 3867]) and Rio Grande (age 3 [n = 992]). Confirmatory factor analysis was conducted, and internal consistency assessed, as well as construct validity in relation to maternal depression measured on the Edinburgh Postnatal Depression Scale.ResultsThe model with a structure of 4 subscales showed that the global scale of parenting on the PAFAS had a good fit, but certain items did not fit well on sub-scales and were removed (2 items from parental inconsistency, 1 from coercive parenting, and 1 from positive encouragement). The original form of the parent-child relationship sub-scale was maintained. Considering the total PAFAS parenting score, we found that mothers with maternal depression had a higher likelihood of more problematic parental practices than mothers without depression.ConclusionsA revised 14-item PAFAS parenting scale has good psychometric properties and we encourage its use in Brazilian populations.
Leveraging Machine Learning & Mobile Application Technology for Vitiligo Management: A Proof-of-Concept
Authors: Abdolahnejad Mahla , Jeong Hyerin , Lin Victoria , Ng Tiffany , Altaki Emad , Mo Anthea , Yildiz Burak , Chan Hannah O. , Hong Collin , Joshi Rakesh 
Published: September 2024

AbstractVitiligo, a dermatological condition characterized by depigmented patches on the skin, affects up to 2% of the global population. Its management is complex, often hindered by delayed diagnosis due to limited access to dermatologists and/ digital tools. Recent advancements in machine learning (ML) offer a potential solution by providing digital tools for early detection and management. This proof-of-concept study describes the development of a machine learning pipeline integrated into a mobile application for vitiligo assessment.Using a dataset of 1,309 images, including segmental and generalized vitiligo, the CNN was trained for binary classification with an accuracy of 95%. The model segments depigmented patches and conducts colorimetric analysis for precise evaluation. We compared traditional Wood’s lamp imaging with CNN-generated maps, showing comparable or superior results in detecting faint depigmentation.Developed using Flutter for cross-platform compatibility, the app enables patients to upload images for analysis and track disease progression. A Golang-based backend ensures robust data management, while a PostgreSQL database supports secure storage of patient information. The integration of Azure Active Directory enhances security and user authentication.This approach aims to bridge the gap in dermatological care by providing an accessible, ML-driven solution for vitiligo management. Future iterations will expand the applications’ capability to screen for other depigmentation disorders, incorporate automated scoring systems for more personalized patient management, and communication services.
Cardiac Cross-Reactivity of NaV Autoantibodies in Metastatic Breast Cancer: A Possible Trigger for Sudden Cardiac Death
Authors: Pappone Carlo , Tarantino Adriana , Melgari Dario , Piccoli Marco , Ciconte Giuseppe , Frosio Anthony , Micaglio Emanuele , Calamaio Serena , Vantellino Chiara , Cirillo Federica , Creo Pasquale , Castoldi Valerio , Prevostini Rachele , De Toma Alessandro , Boccellino Antonio , Negro Gabriele , Giannelli Luigi , Ćalović Žarko , Leocani Letizia , Santinelli Vincenzo , Toma Domenico De , Rivolta Ilaria , Anastasia Luigi 
Published: September 2024

AbstractBackground and AimsPatients with metastatic breast cancer have an increased risk of sudden cardiac death (SCD) that cannot be fully explained by cardiotoxic treatments. Recent evidence shows that autoantibodies targeting the cardiac NaV1.5 sodium channel in Brugada syndrome (BrS) can trigger arrhythmias and elevate SCD risk. Similarly, autoantibodies against the neonatal NaV1.5 isoform have been found in metastatic breast cancer patients. Given the high homology between these NaV1.5 isoforms, we investigated whether these autoantibodies cross-react with the cardiac isoform, potentially contributing to SCD in this population.MethodsPlasma from twenty metastatic breast cancer patients was analyzed for anti-NaV1.5 autoantibodies using HEK293A cells expressing the NaV1.5 protein, followed by Western blotting. The effects of these autoantibodies on sodium current density were assessed in cellular models and wild-type mice, with electrocardiographic monitoring after plasma infusion.ResultsFifteen plasma samples from metastatic breast cancer patients tested positive for anti-NaV1.5 autoantibodies, significantly reducing sodium current density in vitro. Mice injected with these plasma samples developed severe arrhythmias and a Brugada syndrome-like ECG pattern. In contrast, plasma samples either without the autoantibodies or with IgG depletion showed no such effects, underscoring the role of IgG in sodium current reduction and confirming the pathogenicity of the autoantibodies.ConclusionsThis study demonstrates that anti-NaV1.5 autoantibodies in metastatic breast cancer patients can cross-react with the cardiac NaV1.5 isoform, potentially leading to fatal arrhythmias. These findings highlight a novel mechanism for the high SCD rate in this population and suggest that therapies involving sodium blockers should be used with caution to avoid exacerbating this risk. Reliable diagnostic tests and targeted therapies are urgently needed to mitigate SCD risk in affected patients.
A Psychometric Examination of the Dimensional Obsessive Compulsive Scale in a Treatment-Seeking Youth Sample
Authors: Farrell Nicholas R. , MacDonald Catherine W. , Nuñez Mia , Rhode Andreas , Lume Nicholas , McGrath Patrick B. , Baskova Marina , Wilson Eli , Abramowitz Jonathan S. , Feusner Jamie D. 
Published: September 2024

AbstractThe Dimensional Obsessive Compulsive Scale (DOCS) was developed to address several limitations of existing self-report measures of obsessive compulsive disorder (OCD) symptoms, and has been found to be a psychometrically sound method of assessing OCD symptoms in adults. However, to date, the psychometric performance of the DOCS has not been studied in a youth sample. The present study addressed this gap in the literature by examining the psychometric properties of the DOCS in a large sample (n=182) of treatment-seeking youth diagnosed with OCD. Results indicated that the DOCS showed good convergent validity with a youth OCD assessment scale, as well as similar sensitivity to the effects of treatment-related change in symptom severity. The DOCS also maintained its original four-factor structure in the youth sample, similar to findings in adults, supporting the consistency of the four subscales included. Overall, the DOCS appears to represent a promising method for assessing OCD symptom severity and response to treatment of OCD in youth.