bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of abnormal thyroid hormone levels in acute new-onset atrial fibrillation
Authors: Hytting Jakob , Celik Serkan , Bodeström Eriksson Linus , Mallios Panagiotis , Digerfeldt Christofer , Waldemar Annette , Wijkman Magnus , Singull Martin , Hubbert Laila 
Published: January 2025

IntroductionKnown risk factors for new-onset atrial fibrillation/flutter (NOAF) include thyrotoxicosis and subclinical hypothyroidism. While prior research has predominantly explored the link between thyrotoxicosis and NOAF, the presence of subclinical hypothyroidism among patients presenting with acute NOAF in the emergency department (ED) remains an underexplored area of inquiry. This study aimed to assess the prevalence of undiagnosed thyrotoxicosis and subclinical hypothyroidism in patients with acute NOAF diagnosed in the ED.MethodsThis registry-based cohort study was conducted in the ED at Vrinnevi Hospital in Sweden during the years 2018, 2020, and 2022, with a 1-year follow-up period. Patients ≥18 years diagnosed with NOAF in the ED, with no ongoing thyroid hormone substitution or previous documented thyroid abnormality within the past 2 years, were included. The primary outcome was the diagnosis of thyrotoxicosis or subclinical hypothyroidism either in the ED or during a 1-year follow-up period.Results486 patients with NOAF were included in the study (43.6% females). 329 (67.7%) underwent thyroid function testing in the ED or by the end of the 1-year follow-up. In total, 16 (4.9%) patients presented with subclinical hypothyroidism while 4 (1.2%) patients presented with clinical or subclinical thyrotoxicosis.DiscussionThis study found that subclinical hypothyroidism was more prevalent (4.9%) than thyrotoxicosis (1.2%) among patients presenting with acute NOAF. These findings contrast with previous research that has predominantly linked thyrotoxicosis with acute NOAF, suggesting the need for further studies including both subclinical hypothyroidism and thyrotoxicosis in patients with NOAF.
U-shaped association between the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and mortality risk in obese adults: evidence from NHANES 1999–2018
Authors: Lin Zi , Yi Tao , Hu Feng , Chen Jinhua , Chen Lianglong 
Published: January 2025

BackgroundObesity, often accompanied by dyslipidemia and increased cardiovascular risk, poses a significant threat to overall mortality. The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) has been identified as a valuable parameter for assessing dyslipidemia. The goal of the study was to elucidate the relationship between NHHR and mortality in obese populations.MethodsData for the study cohort were sourced from the National Health and Nutrition Examination Survey (1999–2018). The association between NHHR and mortality from all causes and cardiovascular disease was examined through multivariable Cox regression and restricted cubic splines (RCS). Segmented multivariable Cox regression and subgroup analyses were conducted when segmented effects were identified. The reliability of the results was confirmed through multiple sensitivity analyses.ResultsA total of 7,504 participants were included in the analysis. During a median follow-up of 119 months, 866 subjects died for all causes, of which 318 were related to cardiovascular diseases. A U-shaped association was found utilizing RCS analysis, with cardiovascular mortality and all-cause mortality exhibiting the lowest risk points at 3.409 and 3.369, respectively. The fully adjusted model revealed a negative relationship between the risk of cardiovascular mortality (HR = 0.68, 95% CI: 0.49–0.94) and all-cause mortality (HR = 0.82, 95% CI: 0.67–1.00) for per 1 mmol/L increase in NHHR levels below the cut-off value. On the other hand, above the cut-off point, NHHR was positively correlated with cardiovascular mortality (HR = 1.18, 95% CI: 1.02–1.36) and all-cause mortality (HR = 1.13, 95% CI: 1.01–1.28). The sensitivity results of this study were in accordance with earlier findings, and no significant interactions in NHHR levels were discovered across different subgroups.ConclusionsIn the obese adults, NHHR displayed a U-shaped relationship with cardiovascular and all-cause death. Monitoring and managing NHHR levels in obese population may help mitigate the risk of mortality.
A novel machine learning based framework for developing composite digital biomarkers of disease progression
Authors: Zhai Song , Liaw Andy , Shen Judong , Xu Yuting , Svetnik Vladimir , FitzGerald James J. , Antoniades Chrystalina A. , Holder Dan , Dockendorf Marissa F. , Ren Jie , Baumgartner Richard 
Published: January 2025

BackgroundCurrent methods of measuring disease progression of neurodegenerative disorders, including Parkinson's disease (PD), largely rely on composite clinical rating scales, which are prone to subjective biases and lack the sensitivity to detect progression signals in a timely manner. Digital health technology (DHT)-derived measures offer potential solutions to provide objective, precise, and sensitive measures that address these limitations. However, the complexity of DHT datasets and the potential to derive numerous digital features that were not previously possible to measure pose challenges, including in selection of the most important digital features and construction of composite digital biomarkers.MethodsWe present a comprehensive machine learning based framework to construct composite digital biomarkers for progression tracking. This framework consists of a marginal (univariate) digital feature screening, a univariate association test, digital feature selection, and subsequent construction of composite (multivariate) digital disease progression biomarkers using Penalized Generalized Estimating Equations (PGEE). As an illustrative example, we applied this framework to data collected from a PD longitudinal observational study. The data consisted of Opal™ sensor-based movement measurements and MDS-UPDRS Part III scores collected at 3-month intervals for 2 years in 30 PD and 10 healthy control participants.ResultsIn our illustrative example, 77 out of 235 digital features from the study passed univariate feature screening, with 11 features selected by PGEE to include in construction of the composite digital measure. Compared to MDS-UPDRS Part III, the composite digital measure exhibited a smoother and more significant increasing trend over time in PD groups with less variability, indicating improved ability for tracking disease progression. This composite digital measure also demonstrated the ability to classify between de novo PD and healthy control groups.ConclusionMeasures from DHTs show promise in tracking neurodegenerative disease progression with increased sensitivity and reduced variability as compared to traditional clinical scores. Herein, we present a novel framework and methodology to construct composite digital measure of disease progression from high-dimensional DHT datasets, which may have utility in accelerating the development and application of composite digital biomarkers in drug development.
Equity across the educational spectrum: innovations in educational access crosswise all levels
Authors: Naim Arshi 
Published: January 2025

IntroductionEducational equity remains a critical issue in the U.S., where disparities in access and outcomes exist across socioeconomic, racial, gender, and geographical areas. These inequities influence student success at all levels, from general education to higher education. The study aims to explore these disparities, identify their root causes, and examine their effects on educational opportunities and student outcomes. Current study addresses the gaps in resources, tuition affordability, and support mechanisms, this research highlights the urgent need for innovative solutions to bridge inequities. The study’s focus the importance of creating an inclusive and accessible educational framework that can benefit all learners.Research methodsThis study utilizes a quantitative approach to investigate educational inequities across various levels of education in the U.S. Data sources include national education databases, university records, standardized test scores, and financial aid statistics, providing a comprehensive view of the disparities. Regression analysis is employed to identify key indicators and assess the relationships between these factors and educational outcomes. By analyzing data across diverse contexts and demographics, the methodology ensures a clear understanding of the patterns and dynamics of inequality. This approach provides a data-driven groundwork for identifying effective strategies to enhance equity in education.ResultsThe findings reveal significant disparities in educational access and outcomes, with socioeconomic status, race, gender, and geography emerging as prominent factors. General education is marked by unequal resource distribution, while higher education faces challenges with high tuition costs and limited financial aid for marginalized groups. The analysis highlights how these inequities hinder student achievement and perpetuate systemic barriers. However, the study also identifies successful interventions, such as targeted scholarships, inclusive teaching practices, and comprehensive support systems. These initiatives demonstrate tangible progress in mitigating disparities and creating pathways for a more equitable educational experience across the spectrum.DiscussionThe study emphasizes the implications of the findings from quantitative results, linking observed disparities to systemic issues in policy and practice. It suggests the need for scalable solutions, such as equitable funding models, affordable tuition policies, and inclusive curricula, to address persistent inequities. This research highlights the success of targeted interventions, the study advocates for expanding programs like scholarships and support services to under-served communities. While progress has been made, significant work remains to ensure equity across all educational levels in U.S. The study concludes with recommendations for policymakers and educators to adopt evidence-based strategies that promote access and inclusion, fostering a fairer educational system for all.
From past to present: tracing the trends of diabetes drug trials in mainland China
Authors: Ma Zengqing , Zhao Xin , Lin Yu , Zhang Hong , Wu Lianping , Tao Yang , Shi Hongjun , Li Susu 
Published: January 2025

BackgroundThis study aimed to analyze the changing trend of diabetes drugs clinical trials in China during 2013-2023, and provided a reference for the research and development of diabetes drugs.MethodsDiabetes drug clinical trial data were obtained from the registration and information disclosure platform of the National Medical Products Administration (NMPA) between January 1, 2013, and December 31, 2023. Trends of clinical trials on diabetes drugs were systematically analyzed in terms of characteristics, trial design, time trends, drug type, and indications.ResultsFrom 2013 to 2023, a total of 1,256 diabetes drugs clinical trials have been registered on the NMPA platform, of which 1056 were chemical drugs and 184 were biological products. The indications are mainly type 2 diabetes mellitus (n=1237, 98.49%). Among them, 838 clinical trials have been completed, 379 were proceeding, and 39 have been terminated or suspended. There were 42 international multi-center clinical trials, and the remaining 1034 clinical trials were domestic. Bioequivalence trials were 691, accounting for 55.02%, followed by 340 phase I clinical trials and 169 phase III clinical trials. The leading units were mostly distributed in eastern China. The proportion of clinical trial sponsorship from domestic pharmaceutical companies is higher than that from overseas companies.ConclusionsChina has made significant advancements in diabetes drug research and development over the past decade. However, problems such as serious drug homogeneity, and insufficient innovation have become increasingly prominent. The government, clinical trial institutions, and pharmaceutical companies must collaborate to promote the high-quality development of drug clinical trials.
Global research hotspots and trends in oxidative stress-related diabetic nephropathy: a bibliometric study
Authors: Wang Xiao-rong , Wu Zeng , He Tong-tong , Chen Xiao-han , Jin Xiao-fei , Zuo Chun-yue , Yang Shao-ze , Gao Yu , Zhou Xiao-hong , Gao Wei-juan 
Published: January 2025

BackgroundOxidative stress is widely acknowledged as a key pathogenic mechanism in diabetic nephropathy (DN). In recent years, the role of oxidative stress in DN has garnered increasing attention. However, no bibliometric analysis has yet been conducted on the relationship between oxidative stress and DN. This study aims to systematically analyze the relevant literature, identify trends in research, assess current hotspots, and predict future directions.MethodsWe retrieved literature related to oxidative stress and DN from the Web of Science Core Collection database. We analyzed data on publication volume, countries/regions, institutions, journals, keywords, and other relevant metrics using VOSviewer, the Bibliometrix R package, and CiteSpace.ResultsFrom 2014 to 2024, a total of 4076 publications related to oxidative stress and DN were published across 755 journals, showing a consistent upward trend each year. China and the United States are the leading contributors in this field and demonstrate close collaborative efforts. The top contributors by country, institution, journal, and author include: China (1919 publications), Jilin University and Central South University (69 publications each), BIOMEDICINE &amp; PHARMACOTHERAPY (117 publications), and Prof. Sun Lin (33 publications). The most frequent keyword is “oxidative stress” (3683 occurrences). In the co-citation analysis, Alicic RZ’s 2017 study was the most cited (144 citations). These findings highlight the critical importance of investigating the pathogenesis of DN from the oxidative stress perspective.ConclusionThis study demonstrates a steady increase in research on oxidative stress in DN since 2014, highlighting its central role in the pathogenesis of DN. Future research should focus on the molecular mechanisms of oxidative stress in DN and explore its therapeutic potential, to provide new strategies for the prevention and treatment of DN.
Comprehensive analysis of ferroptosis-related genes reveals potential therapeutic targets in osteoporosis patients: a computational analysis and in vitro experiments
Authors: Chen Sihui , Jiang Yi , Xie Guoqin , Wu Peng , Zhu Jinyu 
Published: January 2025

BackgroundFerroptosis-related genes have been reported to play important roles in many diseases, but their molecular mechanisms in osteoporosis have not been elucidated.MethodsBased on two independent GEO datasets (GSE35956 and GSE35958), and GSE35959 as the validation dataset, we comprehensively elucidated the pathological mechanism of ferroptosis-related genes in osteoporosis by GO analyses, KEGG analyses and a PPI network. Then, We used Western Blot (WB) and Quantitative real-time polymerase chain reaction (qPCR) to verify the expression level of KMT2D, a ferroptosis-related hub gene, in clinical samples. Subsequently, we predicted the upstream miRNA of KMT2D gene and analyzed the mechanism of KMT2D in osteoporosis, the potential prognostic value and its immune invasion of KMT2D in pan-cancer.ResultsThis study identified KMT2D and MYCN, TP63, RELA, SOX2, and CDKN1A as key ferroptosis-related genes in osteoporotic cell aging. The independent dataset validated that the expression level of KMT2D was significantly upregulated in osteoporosis samples. The experimental verification results of qPCR and WB indicate that KMT2D is highly expressed in patients with osteoporosis. Further analysis revealed that the hsa-miR-204-5p-KMT2D axis may play an important role in the aging of osteoporotic cells. The analysis of KMT2D reveals that KMT2D may mainly play a role in the aging of osteoporotic cells through epigenetics and the value in pan-cancer.ConclusionThe study provides a theoretical basis for the treatment of osteoporosis.
Development and external validation of a model to predict recurrence in patients with non-muscle invasive bladder cancer
Authors: Tang Jiajia , Fan Longmei , Huang Tianyu , Yang Rongrong , Yang Xinqi , Liao Yuanjian , Zuo Mingshun , Zhang Neng , Zhang Jiangrong 
Published: January 2025

BackgroundMost patients initially diagnosed with non-muscle invasive bladder cancer (NMIBC) still have frequent recurrence after urethral bladder tumor electrodesiccation supplemented with intravesical instillation therapy, and their risk of recurrence is difficult to predict. Risk prediction models used to predict postoperative recurrence in patients with NMIBC have limitations, such as a limited number of included cases and a lack of validation. Therefore, there is an urgent need to develop new models to compensate for the shortcomings and potentially provide evidence for predicting postoperative recurrence in NMIBC patients.MethodsClinicopathologic characteristics and follow-up data were retrospectively collected from 556 patients with NMIBC who underwent transurethral resection of bladder tumors by electrocautery (TURBT) from January 2014 to December 2023 at the Affiliated Hospital of Zunyi Medical University and 167 patients with NMIBC who underwent the same procedure from January 2018 to April 2024 at the Third Affiliated Hospital of Zunyi Medical University. Independent risk factors affecting the recurrence of NMIBC were screened using the least absolute shrinkage and selection operator (Lasso) and Cox regression analysis. Cox risk regression models and randomized survival forest (RSF) models were developed. The optimal model was selected by comparing the area under the curve (AUC) of the working characteristics of the subjects in both and presented as a column-line graph.ResultsThe study included data from 566 patients obtained from the affiliated hospital of Zunyi Medical University and 167 patients obtained from the third affiliated hospital of Zunyi Medical University. Tumor number, urine leukocytes, urine occult blood, platelets, and red blood cell distribution width were confirmed as independent risk factors predicting RFS by Lasso-Cox regression analysis. The Cox proportional risk regression model and RSF model were constructed based on Lasso, which showed good predictive efficacy in both training and validation sets, especially the traditional Cox proportional risk regression model. In addition, the discrimination, consistency, and clinical utility of the column-line graph were assessed using C-index, area under the curve (AUC), calibration curve, and decision curve analysis (DCA). Patients at high risk of recurrence can be identified early based on risk stratification.ConclusionInternal and external validation has demonstrated that the model is highly discriminative and stable and can be used to assess the risk of early recurrence in NMIBC patients and to guide clinical decision-making.
Infiltrating lipid-rich macrophage subpopulations identified as a regulator of increasing prostate size in human benign prostatic hyperplasia
Authors: Lanman Nadia Atallah , Meco Era , Fitchev Philip , Kolliegbo Andree K. , Broman Meaghan M. , Filipovich Yana , Kothandaraman Harish , Cresswell Gregory M. , Talaty Pooja , Antoniak Malgorzata , Brumer Svetlana , Glaser Alexander P. , Higgins Andrew M. , Helfand Brian T. , Franco Omar E. , Wang Chi-Hsiung , Crawford Susan E. , Ratliff Timothy L. , Hayward Simon W. , Vickman Renee E. 
Published: January 2025

IntroductionMacrophages exhibit marked phenotypic heterogeneity within and across disease states, with lipid metabolic reprogramming contributing to macrophage activation and heterogeneity. Chronic inflammation has been observed in human benign prostatic hyperplasia (BPH) tissues, however macrophage activation states and their contributions to this hyperplastic disease have not been defined. We postulated that a shift in macrophage phenotypes with increasing prostate size could involve metabolic alterations resulting in prostatic epithelial or stromal hyperplasia.MethodsSingle-cell RNA-seq of CD45+ transition zone leukocytes from 10 large (&gt;90 grams) and 10 small (&lt;40 grams) human prostates was conducted. Macrophage subpopulations were defined using marker genes and evaluated by flow cytometry.ResultsBPH macrophages do not distinctly categorize into M1 and M2 phenotypes. Instead, macrophages with neither polarization signature preferentially accumulate in large versus small prostates. Specifically, macrophage subpopulations with altered lipid metabolism pathways, demarcated by TREM2 and MARCO expression, accumulate with increased prostate volume. TREM2high and MARCOhigh macrophage abundance positively correlates with patient body mass index and urinary symptom scores. TREM2high macrophages have a statistically significant increase in neutral lipid compared to TREM2low macrophages from BPH tissues. Lipid-rich macrophages were observed to localize within the stroma in BPH tissues. In vitro studies indicate that lipid-loaded macrophages increase prostate epithelial and stromal cell proliferation compared to control macrophages. DiscussionThese data define two new BPH immune subpopulations, TREM2high and MARCOhigh macrophages, and suggest that lipid-rich macrophages may exacerbate lower urinary tract symptoms in patients with large prostates. Further investigation is needed to evaluate the therapeutic benefit of targeting these cells in BPH.
Single-cell transcriptome analysis of medaka lymphocytes reveals absence of fully mature T cells in the thymus and the T-lineage commitment in the kidney
Authors: Sakaguchi Hiyori , Matsuda Masaru , Iwanami Norimasa 
Published: January 2025

The cellular and molecular mechanisms underlying lymphocyte development are diverse among teleost species. Although recent scRNA-seq analyses of zebrafish hematopoietic cells have advanced our understanding of teleost hematopoiesis, comparative studies using another genetic model, medaka, which is evolutionarily distant among teleosts, is useful for understanding commonality and species-specificity in teleosts. In order to gain insight into how different molecular and cellular mechanisms of lymphocyte development in medaka and zebrafish, we established a recombination activating gene 1 (rag1) mutant medaka, which exhibited defects in V(D)J rearrangement of lymphocyte antigen receptor genes, accordingly lacking mature B and T cells. scRNA-seq analysis of wild type and rag1 mutant lymphocytes in the thymus and kidney characterized the developing stages of T and B cells, and found that most developed cd4+cd8– and cd4–cd8+ single-positive (SP) T-cell populations are absent in the thymus, and identified lymphoid progenitor cells already committed to the T lineage in kidney, implying unique features of medaka lymphocyte development.