bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Study of Patient-Reported Dry Eye Disease in Diabetes Mellitus in Indonesia
Authors: Mokoagow Md Ikhsan , Noor Nina Asrini , Rahayu Tri , Andalia Damara , Ramandari Niluh Archi Sri , Epriliawati Marina 
Published: December 2024

ABSTRACTBackgroundDiabetes mellitus (DM), one of the most common metabolic diseases in the world, is a chronic metabolic disorder characterized by persistent hyperglycemia. In diabetic patients, ocular symptoms can develop. One commonly found ocular disease is dry eye disease (DED). DED is a multifactorial disease characterized by instability of the tear layer that causes various symptoms and/or visual impairment, usually accompanied by damage to the ocular surface.ObjectiveThis study aims to determine the prevalence of dry eye disease (DED) in type 2 DM patients and to assess the correlation between DED and various type 2 DM-related conditions in Indonesia.MethodologyThis study is a cross-sectional observational study. The study population includes all consecutive patients diagnosed with type 2 DM between Feb 5 and Mar 26, 2024, at three hospitals and two clinics in Jakarta. The DED assessment was conducted using the DEQ-5 questionnaire, translated and validated in Bahasa, Indonesia. The Kolmogorov-Smirnov normality test and Spearman correlation test were performed on all data sets to determine the correlation between DEQ-5 outcome and the patient’s age, disease duration, fasting blood glucose (FBG) levels, and HbA1c levels.ResultA total of 309 patients were recruited in this study. The patients’ age varies from 23 to 84 years old, and the majority of them have had type 2 DM for five years or less. From 309 patients, 264 FBG and 72 HbA1c test results were recorded. Through the DEQ-5 questionnaire, 64 (20.71%) scored higher than 6, indicating they are experiencing DED. Among the factors considered, including age, gender, duration of disease, FBG level, and HbA1c level, only the FBG level correlated with DED (rs= .186, n = 263, p < .002).ConclusionThere’s a positive correlation between the FBG level and DED. Elevating FBG levels are associated with an increased likelihood of developing DED.
Exploring current and potential roles of informal healthcare providers in tuberculosis care in West Bengal, India: a qualitative content analysis
Authors: Thapa Poshan , Narasimhan Padmanesan , Hall John J. , Jayasuriya Rohan , Mukherjee Partha Sarathi , Das Dipesh Kr , Beek Kristen 
Published: December 2024

AbstractIndia accounts for 27 percent of global Tuberculosis (TB) cases, the highest among the 30 high-burden countries. Despite growing evidence highlighting the significance and potential of Informal Healthcare Providers (IPs) in TB care, their role remains ambiguous in India’s TB policies and guidelines, in contrast to the well-defined roles of the formal private sector. Considering such gaps, this study explores the perspectives of IPs and Formal Providers (FPs) regarding IPs’ current and potential roles in TB care. The study was conducted in West Bengal, India. We adopted a qualitative approach and conducted in-depth interviews with 23 IPs and 11 FPs. The study data was analysed using a content analysis approach. The study’s findings identified four current roles of IPs in TB care, two of which were corroborated by FPs: 1) Passive case finding and referral and 2) Treatment supporter. As for potential roles, an alignment was observed between the two groups of providers for the majority of the roles (5/7 roles). However, both IPs and FPs expressed reservations about assigning IPs the roles of 1) Clinical evaluation of TB cases and 2) Initiation of treatment for confirmed TB patients. The findings highlight the active involvement of IPs in various TB care roles, acknowledged by FPs, and also demonstrate significant potential for their expanded engagement under the National TB Elimination Program (NTEP) of India.
EXaCT-2: An augmented and customizable oncology-focused whole exome sequencing platform
Authors: Waltman Peter , Chandra Pooja , Eng Ken W , Wilkes David C , Park Hyeon , Pabon Carlos , Delpe Princesca , Bhinder Bhavneet , Manohar Jyothi , Kane Troy , Fernandez Evan , Gorski Kathryn , Greco Noah , Simi Manuele , Tang Jeffrey M , Zisimopoulos Pantelis , King Abigail , Assaad Majd Al , Teneyck Theresa , Roberts Douglas , Monge Jorge , Demichelis Francesca , Tam Wayne , Ouseph Madhu M , Sigaras Alexandros , Beltran Himisha , Rennert Hannah , Lindeman Neal , Song Wei , Solomon James , Mosquera Juan Miguel , Kim Rob , Catalano Jeffrey , Hassane Duane C , Sigouros Michael , Elemento Olivier , Alonso Alicia , Sboner Andrea 
Published: December 2024

AbstractWith the rapid advances in cancer research, the list of variants and genes that drive human diseases is constantly expanding. Moreover, the FDA has approved more cancer therapies that incorporate a broader set of genomic features than simple gene variants such as Tumor Mutation Burden (TMB), microsatellite instability status (MSI), and fusion events in gene families such as the NTRK receptors. These features currently require multiple testing methods (IHC/FISH/etc.). With the cost of NGS testing dropping, it is now possible to envision an NGS assay capable of reliably detecting these features without the need for additional testing. The EIPM multidisciplinary team has developed EXaCT-2: a whole exome sequencing (WES) assay that gives the coverage of a targeted assay on cancer genes and the breadth to detect copy number events, cancer-related fusions, and viruses, which can facilitate diagnostic and therapeutic decisions for cancer patients.We evaluated EXaCT-2 on 250 matched tumor/normal pairs and compared its performance with orthogonally validated results. We show the assay achieves the expected coverage of critical cancer genes, provides a better characterization of somatic copy number alterations, detects common cancer rearrangements and viruses, and enables the accurate estimation of global molecular metrics, such as tumor mutational burden and microsatellite instability.
Uncovering Phenotypic Expansion in AXIN2-Related Disorders through Precision Animal Modeling
Authors: Aceves-Ewing Nathalie M. , Lanza Denise G. , Marcogliese Paul C. , Lu Di , Hsu Chih-Wei , Gonzalez Matthew , Christiansen Audrey E. , Rasmussen Tara L. , Ho Alex J. , Gaspero Angelina , Seavitt John , Dickinson Mary E. , Yuan Bo , Shayota Brian J. , Pachter Stephanie , Hu Xiaolin , Day-Salvatore Debra Lynn , Mackay Laura , Kanca Oguz , Wangler Michael F. , Potocki Lorraine , Rosenfeld Jill A. , Lewis Richard Alan , Chao Hsiao-Tuan , Lee Brendan , Lee Sukyeong ,   Undiagnosed Diseases Network,   Baylor College of Medicine Center for Precision Medicine Models, Yamamoto Shinya , Bellen Hugo J. , Burrage Lindsay C. , Heaney Jason D. 
Published: December 2024

AbstractHeterozygous pathogenic variants inAXIN2are associated with oligodontia-colorectal cancer syndrome (ODCRCS), a disorder characterized by oligodontia, colorectal cancer, and in some cases, sparse hair and eyebrows. We have identified four individuals with one of twode novo, heterozygous variants (NM_004655.4:c.196G>A, p.(Glu66Lys) and c.199G>T, p.(Gly67Arg)) inAXIN2whose presentations expand the phenotype of AXIN2-related disorders. In addition to ODCRCS features, these individuals have global developmental delay, microcephaly, and limb, ophthalmologic, and renal abnormalities. Structural modeling of these variants suggests that they disrupt AXIN2 binding to tankyrase, which regulates AXIN2 levels through PARsylation and subsequent proteasomal degradation. To test whether these variants produce a phenotypein vivo, we utilized an innovative prime editing N1 screen to phenotype heterozygous (p.E66K) mouse embryos, which were perinatal lethal with short palate and skeletal abnormalities, contrary to published viableAxin2null mouse models. Modeling of the p.E66K variant in theDrosophilawing revealed gain-of-function activity compared to reference AXIN2. However, the variant showed loss-of-function activity in the fly eye compared to reference AXIN2, suggesting that the mechanism by which p.E66K affects AXIN2 function is cell context-dependent. Together, our studies in humans, mice, and flies demonstrate that specific variants in the tankyrase-binding domain of AXIN2 are pathogenic, leading to phenotypic expansion with context-dependent effects on AXIN2 function and WNT signaling. Moreover, the modeling strategies used to demonstrate variant pathogenicity may be beneficial for the resolution of otherde novoheterozygous variants of uncertain significance associated with congenital anomalies in humans.
Emergence and transmission dynamics of the FY.4 Omicron variant in Kenya
Authors: Musundi Sebastian , Mwanga Mike J. , Lambisia Arnold W. , Morobe John Mwita , Murunga Nickson , Moraa Edidah , Ndwiga Leonard , Cheruyoit Robinson , Musyoki Jennifer , Mutunga Martin , Guzman-Rincon Laura M , Sande Charles , Mwangangi Joseph , Bejon Philip , Ochola-Oyier Lynette Isabella , Nokes D James , Agoti Charles N. , Nyiro Joyce , Githinji George 
Published: December 2024

AbstractThe recombinant FY.4 SARS-CoV-2 variant was first reported in Kenya in March 2023 and was the dominant circulating variant between April and July 2023. The variant was characterised by two important mutations: Y451H in the receptor binding domain of the spike protein and P42L in open reading frame 3a. Using phylogenetics and phylodynamic approaches, we investigated the emergence and spread of the FY.4 in Kenya and the rest of the world. Our findings suggest FY.4 circulated early in Kenya before export to North America and Europe. Early circulation of FY.4 in Kenya was predominantly observed in the coastal part of the country and the estimated time to the most recent common ancestor suggests FY.4 circulated as early as December 2022. The collected genomic and epidemiological data show that the FY.4 variant led to a large local outbreak in Kenya and resulted in localised outbreaks in Europe, North America and Asia-pacific. These findings underscore the importance of sustained genomic surveillance especially in under sampled regions in deepening our understanding of the evolution and spread of SARS-CoV-2 variants.
Inflammatory Bowel Disease Drivers Revealed in Human Organ Chips
Authors: Özkan Alican , Merry Gwenn , Chou David B. , Posey Ryan R. , Stejskalova Anna , Calderon Karina , Sperry Megan , Horvath Viktor , Ferri Lorenzo E. , Carlotti Emanuela , McDonald Stuart A. C. , Winton Douglas J. , Riccardi Rocco , Bordeianou Lilianna , Hall Sean , Goyal Girija , Ingber Donald E. 
Published: December 2024

AbstractInflammatory bowel disease (IBD) patients exhibit compromised intestinal barrier function and decreased mucus accumulation, as well as increased inflammation, fibrosis, and cancer risk, with symptoms often being exacerbated in women during pregnancy. Here, we show that these IBD hallmarks can be replicated using human Organ Chips lined by IBD patient-derived colon epithelial cells interfaced with matched fibroblasts cultured under flow. Use of heterotypic tissue recombinants revealed that IBD fibroblasts are the primary drivers of multiple IBD symptoms. Inflammation and fibrosis are accentuated by peristalsis-like motions in IBD Chips and when exposed to pregnancy-associated hormones in female IBD Chips. Carcinogen exposure also increases inflammation, gene mutations, and chromosome duplication in IBD Chips, but not in Healthy Chips. These data enabled by human Organ Chip technology suggest that the intestinal stroma and peristalsis-associated mechanical deformations play a key role in driving inflammation and disease progression in male and female IBD patients.
Vaccination exemptions among Kindergartners by state-level 2024 Presidential election result
Authors: Faust Jeremy Samuel , Renton Benjamin K. 
Published: December 2024

AbstractImportancePediatric vaccine exemptions have increased in recent years. How political environments influence these trends is unknown.ObjectiveTo analyze state-level kindergarten vaccination exemption rates from 2009-2024, stratified by 2024 Presidential election results, to assess changes over time.Design, Setting, and ParticipantsThis cross-sectional study used publicly available CDC data on kindergarten vaccination exemptions across all U.S. states and Washington, DC. States were categorized as Donald Trump or Kamala Harris states based on 2024 election results. Previous elections were also assessed.Main Outcomes and MeasuresIncident rates (IRs) of vaccination exemptions (all, medical, and non-medical) were calculated yearly. Incident rate ratios (IRRs) comparing vaccination exemption rates in Harris versus Trump win states were calculated. and Spearman correlations assessed associations between exemption rates and Republican vote share in the four most recent Presidential elections.ResultsAnalysis included 53,997,748 person-years of kindergarten data. By 2023-2024, non-medical exemptions were permitted in 90.2% of states. Exemption rates increased in Trump states but decreased in Harris states during the study period. Most exemptions were non-medical.Conclusions and RelevanceKindergarten vaccination exemptions now diverge by political environment, increasing over time in states won by Trump in 2024 and decreasing in states won by Harris. The findings suggest growing politicization of vaccination practices, warranting targeted public health interventions.
Global analysis of protein and small-molecule substrates of ubiquitin-like proteins (UBLs)
Authors: Shao Guang-Can , Chen Zhen-Lin , Lu Shan , Wu Qing-Cui , Sheng Yao , Wang Jing , Ma Yan , Sui Jian-Hua , Chi Hao , Qi Xiang-Bing , He Si-Min , Du Li-Lin , Dong Meng-Qiu 
Published: December 2024

AbstractUbiquitin-like proteins (UBLs) constitute a family of evolutionarily conserved proteins that share similarities with ubiquitin in 3D structures and modification mechanisms. For most UBLs including Small-Ubiquitin-like Modifiers (SUMO), their modification sites on substrate proteins cannot be identified using the mass spectrometry-based method that has been successful for identifying ubiquitination sites, unless a UBL protein is mutated accordingly. To identify UBL modification sites without having to mutate UBL, we have developed a dedicated search engine pLink-UBL on the basis of pLink, a software tool for identification of cross-linked peptide pairs. pLink-UBL exhibited superior precision, sensitivity, and speed than “make-do” search engines such as MaxQuant, pFind, and pLink. For example, compared to MaxQuant, pLink-UBL increased the number of identified SUMOylation sites by 50 ∼ 300% from the same datasets. Additionally, we present a method for identifying small-molecule modifications of UBLs. This method involves antibody enrichment of a UBL C-terminal peptide following enrichment of a UBL protein, followed by LC-MS/MS analysis and a pFind 3 blind search to identify unexpected modifications. Using this method, we have discovered non-protein substrates of SUMO, of which spermidine is the major one for fission yeast SUMO Pmt3. Spermidine can be conjugated to the C-terminal carboxylate group of Pmt3 through its N1or also likely, N8amino group in the presence of SUMO E1, E2, and ATP. Pmt3-spermidine conjugation does not require E3 and can be reversed by SUMO isopeptidase Ulp1. SUMO-spermidine conjugation is present in mice and humans. Also, spermidine can be conjugated to ubiquitinin vitroby E1 and E2 in the presence of ATP. The above observations suggest that spermidine may be a common small molecule substrate of SUMO and possibly ubiquitin across eukaryotic species.HighlightsA specialized software pLink-UBL enables precise identification of UBL modification sites on protein substrates.pFind 3 blind search enables identification of unexpected small-molecule substrates of a UBL protein.Spermidine is a small molecule substrate of fission yeast SUMO Pmt3 as well as mammalian SUMO proteins.The C-terminal carboxyl group of Pmt3 can be attached to the N1or likely also the N8amino group of spermidine in the presence of E1, E2, and ATP, and can be detached by SUMO isopeptidase.
First Detection of Oropouche Virus inCulicoides insignisin the Ucayali Region, Peru: Evidence of a Possible New Vector
Authors: Requena-Zúñiga Edwin , Palomino-Salcedo Miriam , García-Mendoza María P. , Figueroa-Romero Maribel D. , Merino-Sarmiento Nancy S. , Escalante-Maldonado Oscar , Cornelio-Santos Ana L. , Cárdenas-Garcia Patricia , Jiménez Carlos Augusto , Cabezas-Sanchez César 
Published: December 2024

AbstractThis report details the first detection of the Oropouche virus (OROV) inCulicoides insignisin the Ucayali region (Peruvian Amazon) during an outbreak study in 2024. Captures conducted in peri-urban and rural areas showed thatC. insignisaccounted for 96.7% of the collectedCulicoidesspecimens. RT-qPCR testing confirmed the presence of the virus in twoC. insignispools, establishing this species as a potential OROV vector in the study area, thereby contributing to the understanding of the virus’s epidemiology in the Amazon region.
Quality Improvement (QI) Project: Enhancing Surgical Safety Checklist Utilization at a Rural Primary Hospital
Authors: Gemechu Melaku Teshale , Adinew Anteneh Cheru , Ledamo Elias Ermias 
Published: December 2024

AbstractBackgroundDespite evidence demonstrating various benefits of the World Health Organization (WHO) Surgical Safety Checklist (SSC), its utilization is less frequent in low and middle income countries. This quality improvement project was conducted at a Primary Hospital, a rural facility in Ethiopia, to address suboptimal utilization of the SSC. At baseline, an average SSC utilization rate was 50% and a completion rate was 80% over the prior 6 months.MethodsA single cycle Plan-Do-Study-Act (PDSA) approach was employed to enhance adherence. Key interventions included translating the SSC into Amharic, conducting a two-day training session, introducing pre- and post-operative briefings, and requiring surgeons to remain in the operating room until checklist completion. Bi-weekly audits and regular supervision were conducted to monitor progress. Key performance indicators were SSC utilization and completion rates, while secondary indicators included rate of prophylactic antibiotic administration and surgical site infection. Trend analysis using run charts and Interrupted Time Series (ITS) analysis evaluated changes over time, while staff interviews provided insights into behavioral and attitudinal shifts.ResultsThe quality improvement project demonstrated a significant and sustained improvement in the utilization and completion rates of the WHO Surgical Safety Checklist (SSC). Baseline measurements in October 2023 showed a utilization rate of 53% and a completion rate of 65%. Following targeted interventions, both metrics steadily improved, reaching 100% by June 2024 and maintaining this level through September 2024.ConclusionThe QI project demonstrated that achieving 100% utilization and completion of the WHO Surgical Safety Checklist (SSC) is feasible even in rural hospitals of low- and middle-income countries (LMICs). Formal training proved crucial for improving adherence, addressing gaps seen with informal approaches, and fostering better team communication and culture. This underscores the value of structured, localized interventions for improving surgical safety practices and encourages broader adoption in similar contexts. To sustain the results, ongoing supportive trainings, monthly supervision, and staff recognition initiatives were initiated.
Lumbar Spine Degenerative Classification Using YOLO v8 and DeepScoreNet
Authors: Mousavi Amir 
Published: December 2024

AbstractDegenerative conditions of the lumbar spine, such as neural foraminal narrowing, subarticular stenosis, and spinal canal stenosis, are common and can lead to chronic pain and disability. Detecting and assessing the severity of these conditions is a key task in radiology, often requiring considerable expertise. In this work, we aim to develop automated models that aid radiologists in diagnosing these conditions using lumbar spine MR images. We utilize state-of-the-art deep learning methods for both detection and classification tasks, focusing on severity classification across five intervertebral disc levels and three different imaging modalities. The dataset and methodology used in this study are part of the RSNA 2024 Lumbar Spine Degenerative Classification competition. Our approach involves a two-step process, combining object detection with YOLO v8 and severity classification using a DeepScoreNet architecture. Through careful cross-validation and model evaluation, we demonstrate the potential of these models to improve diagnostic accuracy and efficiency. The DeepScoreNet model, introduced in this article, comprises 2,787,651 parameters and achieved accuracies of 81% for score(severity) prediction in cases of Neural Foraminal Narrowing, 89% for Spinal Canal Stenosis, and 74% for Subarticular Stenosis.The code for this approach is available in the GitHub repository.(https://github.com/liamirpy/Lumbar-Spine-Degenerative-Classification)
Cigarette Smoking Across Life from 1946 to 2018: Harmonisation of Four British Birth Cohort Studies
Authors: Wright Liam , Kock Loren , Tattan-Birch Harry , Bann David 
Published: December 2024

AbstractBackground and AimsTobacco smoking has declined dramatically in the many high-income countries over the past seventy years. Studies that have mapped this trend have relied on repeat cross-sectional or retrospectively measured smoking data which has limitations regarding accurate measurement, inclusion of early smokers, and capturing of within-person change over time. Here, we (1) introduce a new resource detailing harmonisable smoking data in four British birth cohort studies spanning 1946-2018 and (2) use this data to document age and cohort changes in smoking.MethodsWe used prospectively and longitudinally measured smoking data in four British Birth Cohort Studies, born 1946, 1958, 1970 and 2000/02, respectively, to examine changes in the prevalence of daily smoking and cigarettes smoked per day between cohorts and within cohorts over the life course in males and females combined and stratified by sex.ResultsThe prevalence of smoking and the average number of cigarettes smoked by daily smokers declined between each successive cohort. Males smoked more and with greater intensity than females, on average, though sex differences were smaller in latter cohorts. Within a cohort, the prevalence and intensity of smoking peaked in early adulthood (< age 30y) and declined thereafter; participants who continued to smoke daily, smoked fewer cigarettes as they grew older.ConclusionSmoking prevalence and cigarette consumption declined substantially between cohorts born across the latter half of the twentieth and early twenty-first centuries. The British Birth Cohorts represent a unique and largely underutilized resource for investigating trends in smoking across life (prenatal to old age) and by year of birth (1946-2001), including changes in the determinants, correlates, and consequences of smoking. We provide syntax and information on items on smoking in these cohorts to catalyse future research, also available at:osf.io/54w6q.