bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oral Health, Inflammation, and Cardiometabolic Factors in the VA Million Veteran Program
Authors: Yu Y.H. , Pridgen K.M. , Nelson T.J. , Miller D.R. , Wells J.M. , Assimes T.L. , O’Donnell C.J. , Tsao P.S. , Chang K.M. , Lynch J.A. 
Published: December 2024

Introduction: Associations between cardiometabolic comorbidities and self-reported oral health (OH) are often underexplored in large biobank datasets. While these associations are unaffected by dental care access, they could be mediated by immune responses and inflammation. Objectives: This study assessed the associations between cardiometabolic comorbidities and self-reported OH, periodontitis, and tooth loss using the International Classification of Diseases (ICD) codes in participants from the U.S. Veterans Affairs Million Veteran Program (MVP), adjusting for immune and inflammatory covariates. Methods: Data from 154,167 MVP participants were extracted from January 2011 to September 2021, including lifetime cardiometabolic comorbidities, self-reported OH, ICD-coded periodontitis and tooth loss, and laboratory measurements. Multivariate logistic regression analysis was used to calculate the odds ratios of cardiometabolic comorbidities for self-reported OH, periodontitis, and tooth loss, adjusting for demographic, socioeconomic, cardiovascular, and inflammatory (neutrophil and lymphocyte cell counts) risk factors. A separate dataset was used for additional sensitivity analyses, adjusting for serum levels of C-reactive protein and albumin. Results: Complete data were analyzed for 154,167 participants (19%). Most participants (92%) were male and from European ancestry (94%). The mean age was 65.5 y (SD 11.4 y). Ten percent of participants had excellent self-reported OH. Fourteen percent had any periodontitis, and 17% had any tooth loss. Significant associations were found between tooth loss and congestive heart failure (odds ratio [OR], 1.74, P < 0.001) and peripheral vascular diseases (OR, 1.82, P < 0.001). There were also significant associations between congestive heart failure and self-reported OH (excellent versus “poor/fair/good/very good”), with increasing odds as self-reported OH declined ( P < 0.001 for trend). These associations remained significant even after sensitivity analyses, albeit with slight attenuation. Conclusion: This study of veterans underscores the important cardiometabolic links of self-reported poor OH and tooth loss, akin to those observed with periodontitis, even after adjusting for potential confounders related to demographics, lifestyle, and inflammation. Knowledge Transfer Statement: Exploring cardiometabolic associations with self-reported OH, clinically diagnosed periodontitis, and tooth loss using the ICD in the Veterans Affairs Million Veteran Program, we found significant associations. These associations persisted after adjustment for inflammatory confounders. These findings emphasized the benefit of assessing OH as a vital indicator of overall cardiometabolic health in large-scale biobank studies.
BRAFV600E induces key features of LCH in iPSCs with cell type–specific phenotypes and drug responses
Authors: Abagnale Giulio , Schwentner Raphaela , Ben Soussia-Weiss Philipp , van Midden Wouter , Sturtzel Caterina , Pötschger Ulrike , Rados Magdalena , Taschner-Mandl Sabine , Simonitsch-Klupp Ingrid , Hafemeister Christoph , Halbritter Florian , Distel Martin , Eder Sebastian K. , Hutter Caroline 
Published: December 2024

Abstract
Langerhans cell histiocytosis (LCH) is a clonal hematopoietic disorder defined by tumorous lesions containing CD1a+/CD207+ cells. Two severe complications of LCH are systemic hyperinflammation and progressive neurodegeneration. The scarcity of primary samples and lack of appropriate models limit our mechanistic understanding of LCH pathogenesis and affect patient care. We generated a human in vitro model for LCH using induced pluripotent stem cells (iPSCs) harboring the BRAFV600E mutation, the most common genetic driver of LCH. We show that BRAFV600E/WT iPSCs display myelomonocytic skewing during hematopoiesis and spontaneously differentiate into CD1a+/CD207+ cells that are similar to lesional LCH cells and are derived from a CD14+ progenitor. We show that BRAFV600E modulates the expression of key transcription factors regulating monocytic differentiation and leads to an upregulation of proinflammatory molecules and LCH marker genes early during myeloid differentiation. In vitro drug testing revealed that BRAFV600E-induced transcriptomic changes are reverted upon treatment with mitogen-activated protein kinase (MAPK) pathway inhibitors (MAPKis). Importantly, MAPKis do not affect myeloid progenitors but reduce only the mature CD14+ cell population. Furthermore, iPSC-derived neurons (iNeurons) cocultured with BRAFV600E/WT iPSC-derived microglia-like cells, differentiated from iPSC-derived CD34+ progenitors, exhibit signs of neurodegeneration with neuronal damage and release of neurofilament light chain. In summary, the iPSC-based model described here provides a platform to investigate the effects of BRAFV600E in different hematopoietic cell types and provides a tool to compare and identify novel approaches for the treatment of BRAFV600E-driven diseases.
Impact of measurable residual disease clearance kinetics in patients with AML undergoing intensive chemotherapy
Authors: Jen Wei-Ying , Sasaki Koji , Ravandi Farhad , Kadia Tapan M. , Wang Sa A. , Wang Wei , Loghavi Sanam , Daver Naval G. , DiNardo Courtney D. , Issa Ghayas C. , Abbas Hussein A. , Nasnas Cedric , Bataller Alex , Urrutia Samuel , Karrar Omer S. , Pierce Sherry , Kantarjian Hagop M. , Short Nicholas J. 
Published: December 2024

Abstract
The prognostic impact of measurable residual disease (MRD) in acute myeloid leukemia (AML) is unequivocal; however, the optimal time point for achieving undetectable MRD is unclear. We retrospectively studied patients with newly diagnosed (ND) AML who achieved remission with frontline intensive chemotherapy and had MRD assessed by flow cytometry after induction (time point 1 [TP1]) and after cycles 2 or 3 (TP2). Cases were grouped into MRD negative (Neg)/Neg, positive (Pos)/Neg, or Pos/Pos at TP1 and TP2, respectively. Of 1980 patients with ND AML, 277 met the inclusion criteria and were included in this analysis. The median relapse-free survival (RFS) was 73 months, 22 months, and 5 months for the MRD Neg/Neg, Pos/Neg, and Pos/Pos groups, respectively (P &lt; .01). There was a significant difference between the Neg/Neg and Pos/Neg groups (P = .05), suggesting benefit to early MRD negativity. The median overall survival (OS) was 81 months, 40 months, and 9 months, respectively (P &lt; .01), but the difference between Neg/Neg and Pos/Neg was not statistically significant (P = .19). Landmark analysis demonstrated the benefit of stem cell transplant (SCT), particularly in Neg/Neg intermediate-risk AML (median RFS, not reached vs 15 months; P &lt; .01). On multivariable analysis, MRD Pos/Neg was independently associated with a worse RFS than Neg/Neg (hazard ratio, 1.73; 95% confidence interval, 1.09-2.75; P = .02) but not for OS (P = .15). In conclusion, undetectable flow MRD after induction is associated with better RFS than undetectable MRD achieved later during consolidation. SCT benefited patients with intermediate-risk AML, regardless of MRD kinetics.
Sarcopenia in interstitial lung disease
Authors: Sheehy Robert , McCormack Samuel , Fermoyle Caitlin , Corte Tamera 
Published: December 2024

BackgroundInterstitial lung disease (ILD) encompasses a heterogeneous group of chronic lung conditions with considerable variability in prognosis and response to treatment. People with reduced muscle mass and function, known as sarcopenia, have a higher risk of mortality and adverse clinical outcomes both in the general population and in other chronic disease states. The importance of sarcopenia across the spectrum of patients with ILD is not well established.ObjectivesIn this narrative review, we explore the prevalence and clinical implications of sarcopenia in patients with ILD, evaluate the optimal methods to diagnose sarcopenia in this patient population and review treatment interventions.FindingsAlmost one third of patients with chronic forms of ILD have evidence of sarcopenia. Sarcopenia is associated with adverse clinical outcomes and increased risk of mortality in select populations with ILD. Screening tests such as the SARC-F (strength, assistance walking, rise from a chair, climb stairs, falls) questionnaire and clinical assessment tools (including grip strength dynamometry) are well validated. Medical imaging modalities, including computed tomography, are hampered by lack of a gold standard and normative values, but have been used in patients with ILD in acute care and research settings. If sarcopenia is identified, multidimensional interventions such as pulmonary rehabilitation are beneficial.ConclusionSarcopenia is common in patients with ILD and is associated with poorer outcomes. Accordingly, if identified, targeted interventions should be considered. Validated diagnostic criteria exist, but the optimal use of medical imaging techniques in this patient cohort remains an area of uncertainty.
Revisiting the follicle-stimulation hormone receptor expression and function in human myometrium and adipose tissue
Authors: Palak Ewelina , Ponikwicka-Tyszko Donata , Pulawska-Moon Kamila , Sztachelska Maria , Milewska Gabriela , Modzelewska Beata , Kleszczewski Tomasz , Koivukoski Maria L. , Bernaczyk Piotr , Hady Hady Razak , Gołaszewski Piotr , Lupinska Aleksandra N. , Kulikowski Marek , Lemancewicz Adam , Huhtaniemi Ilpo T. , Wolczynski Slawomir , Rahman Nafis A. 
Published: December 2024

Abstract
Background
Extragonadal follicle-stimulating hormone receptor (FSHR) expression at low levels has been shown in several normal and tumor tissues, including myometrium and adipose tissue. FSH-FSHR signaling in the myometrium has been suggested to regulate uterine contractile activity and the timing of labor. In contrast, FSH-FSHR has been linked to the activation of brown/beige fat thermogenesis in adipose tissue. The issue of extragonadal FSHR expression and its functionality remains contentious within the scientific community, as contradictory findings necessitate further independent and critical analyses. Hereby, we re-investigated the FSHR expression and its functionality in normal non-pregnant (M-NP) and pregnant (N-P) human myometrium, as well as in human visceral (VAT) and subcutaneous (SCAT) adipose tissue (AT).

Methods
FSHR expression at mRNA (real-time qPCR, RNAscope in situ hybridization) and protein (immunohistochemical staining) levels in adipose tissue, myometrium, and adipocytes were evaluated. Myometrium and adipocytes were treated with recombinant (rh)FSH to study its effects on functional pathways. Myometrium contractile activity was measured using a force transducer with digital output and the DASYLab software unit. Cyclic adenosine monophosphate (cAMP) production by myometrium explants and adipocytes was measured using a cAMP ELISA Kit. The activation of the AKT pathway in myometrium and adipocytes was analyzed by Western blot analysis.

Results
Contrary to previous observations, we found no expression of FSHR at either mRNA or protein levels in M-NP, N-P, VAT, and SCAT. Treatment with recombinant human FSH (rhFSH) showed no effect on cAMP production or phosphorylation of AKT in M-NP, N-P, as well as in VAT and SCAT. rhFSH treatment did not influence contractile activity in M-NP, N-P.

Conclusions
These findings suggest that the FSHR signaling pathway does not regulate myometrial contractility during pregnancy. Additionally, the absence of FSHR expression in both VAT and SCAT implied that FSHR does not play a role in the functional signaling pathways in adipose tissues. In conclusion, our findings contradict earlier data on the involvement of FSH-FSHR signaling in regulating myometrial contractility near term, as well as in adipose tissue function.
Exercise promotes skeletal muscle growth in adolescents via modulating Mettl3-mediated m6A methylation of MyoD in muscle satellite cells
Authors: Feng Shujing , Zhou Hao , Lin Xingzuan , Zhu Siyuan , Chen Huifang , Zhou Han , Wang Ru , Wang Peng , Shao Xiexiang , Wang Jianhua 
Published: December 2024

Abstract
Background
Exercise exerts positive impacts on skeletal muscle health and homeostasis. Emerging evidence suggests that m6A methylation is involved in various physiological processes. However, the impact of exercise on adolescent skeletal muscle growth and the underlying epigenetic mechanisms remain poorly understood.

Methods
The lower-limb skeletal muscles were harvested from exercise and control groups to compare the skeletal muscle growth in adolescents. mRNA sequencing was conducted to explore the mechanisms underlying enhanced skeletal muscle growth following exercise. The effects and mechanisms of Mettl3-mediated m6A methylation on adolescent skeletal muscle growth were investigated using muscle satellite cell (MuSC)-specific Mettl3 knockout (KO) mice. The potential function of MyoD for skeletal muscle growth in adolescents was explored by phenotypes after overexpression and evaluation of in vivo myogenesis. Additionally, the effects of the methyl donor betaine on adolescent skeletal muscle growth were investigated in vitro and in vivo.

Results
Exercise could promote skeletal muscle growth in adolescents. Sequencing data analysis and confirmation assays uncovered that exercise significantly increased Mettl3-mediated m6A methylation and elevated the expression levels of activation marker MyoD in MuSCs. Establishment of MuSC-specific Mettl3 KO mice further demonstrated that Mettl3-mediated m6A methylation in MyoD contributed to skeletal muscle growth during adolescence. Mettl3-mediated m6A methylation regulated MyoD mRNA stability at the posttranscriptional level in MuSCs, with a functional site at 234 bp A. Increased expression of MyoD could contribute to myogenesis of adolescent MuSCs. Furthermore, the methyl donor betaine could enhance MyoD expression, contributing to MuSCs activation and skeletal muscle growth in adolescents by boosting m6A methylation levels.

Conclusions
Exercise promoted skeletal muscle growth in adolescents through facilitating MyoD mRNA stability of MuSCs in a Mettl3-mediated m6A-dependent manner. The methyl donor betaine could be a potential alternative to exercise for promoting adolescent skeletal muscle growth by directly augmenting the global levels of m6A methylation. These findings may provide a theoretical foundation for encouraging daily fitness exercise and ensuring healthy growth in adolescents.
Pheno-Ranker: a toolkit for comparison of phenotypic data stored in GA4GH standards and beyond
Authors: Leist Ivo C. , Rivas-Torrubia María , Alarcón-Riquelme Marta E. , Barturen Guillermo , Consortium PRECISESADS Clinical , Gut Ivo G. , Rueda Manuel 
Published: December 2024

Abstract
Background
Phenotypic data comparison is essential for disease association studies, patient stratification, and genotype–phenotype correlation analysis. To support these efforts, the Global Alliance for Genomics and Health (GA4GH) established Phenopackets v2 and Beacon v2 standards for storing, sharing, and discovering genomic and phenotypic data. These standards provide a consistent framework for organizing biological data, simplifying their transformation into computer-friendly formats. However, matching participants using GA4GH-based formats remains challenging, as current methods are not fully compatible, limiting their effectiveness.

Results
Here, we introduce Pheno-Ranker, an open-source software toolkit for individual-level comparison of phenotypic data. As input, it accepts JSON/YAML data exchange formats from Beacon v2 and Phenopackets v2 data models, as well as any data structure encoded in JSON, YAML, or CSV formats. Internally, the hierarchical data structure is flattened to one dimension and then transformed through one-hot encoding. This allows for efficient pairwise (all-to-all) comparisons within cohorts or for matching of a patient’s profile in cohorts. Users have the flexibility to refine their comparisons by including or excluding terms, applying weights to variables, and obtaining statistical significance through Z-scores and p-values. The output consists of text files, which can be further analyzed using unsupervised learning techniques, such as clustering or multidimensional scaling (MDS), and with graph analytics. Pheno-Ranker’s performance has been validated with simulated and synthetic data, showing its accuracy, robustness, and efficiency across various health data scenarios. A real data use case from the PRECISESADS study highlights its practical utility in clinical research.

Conclusions
Pheno-Ranker is a user-friendly, lightweight software for semantic similarity analysis of phenotypic data in Beacon v2 and Phenopackets v2 formats, extendable to other data types. It enables the comparison of a wide range of variables beyond HPO or OMIM terms while preserving full context. The software is designed as a command-line tool with additional utilities for CSV import, data simulation, summary statistics plotting, and QR code generation. For interactive analysis, it also includes a web-based user interface built with R Shiny. Links to the online documentation, including a Google Colab tutorial, and the tool’s source code are available on the project home page: https://github.com/CNAG-Biomedical-Informatics/pheno-ranker.
Transforming community-based primary health care delivery through comprehensive performance measurement and reporting: examining the influence of context
Authors: Wong Sabrina T. , Thandi Manpreet , Martin-Misener Ruth , Johnston Sharon , Hogg William , Burge Fred 
Published: December 2024

Abstract
Background
Community-based primary health care represents various community-based health care (CBPHC) models that incorporate health promotion and community development to deliver first-contact health services. Learning health systems (LHSs) are essential for improving CBPHC in which feedback from relevant stakeholders is used to continuously improve health systems with the goal of achieving population health and health equity. Performance reporting is one way to present data to clinicians and decision makers to facilitate a process of reflection, participation, and collaboration among partners to improve CBPHC.

Methods
Our objective was to obtain feedback on a regional CBPHC performance portrait through key informant interviews. We used purposive convenience sampling to recruit participants who were clinicians in primary care and/or decision-makers in primary care at a regional level. The performance portrait summarized results of survey questions asked of patients, providers, and primary care organizations. The portrait was organized by the 10 pillars of the Patient’s Medical Home (PMH) model. Interview questions specifically asked about portrait content, formatting, interpretability, utility, and dissemination strategies. Content analysis was used to analyze interview data.

Results
We completed 19 interviews with key informants from the Canadian provinces of Nova Scotia (n = 8), Ontario (n = 6) and British Columbia (n = 5). We coded transcripts into four content areas: (1) Usability as influenced by content and interpretability, (2) Formatting, (3) Utility, and (4) Dissemination. Using data and reporting back to clinicians and decision-makers about how their practices and jurisdictions are performing in primary care in meaningful ways is important. Our results suggest having available methodology notes, including the analysis used to develop any scoring, sampling and sample sizes, and interpretation of the statistics is necessary.

Conclusions
This research was the first to create a comprehensive performance portrait using data driven by factors that are important to primary care partners. We obtained important feedback on the portrait in the context of usability, formatting, utility, and dissemination. This data needs to be used to provide feedback in continuous cycles to evaluate and improve CBPHC models as part of a LHS.
Ethics practices associated with reusing health data: an assessment of patient registries
Authors: van den Akker Olmo R. , Stark Susanne , Strech Daniel 
Published: December 2024

Abstract
Background
As routinely collected patient data have become increasingly accessible over the years, more attention has been directed at the ethics of using such data for research. Patient data is often available to researchers through patient registries that typically collect data of patients with a specific condition. While ethical guidelines for using patient data are presented frequently in the literature, it is currently unknown how patient registries implement the recommendations from these guidelines in practice and how they communicate their practices. In this project, we assessed to what extent a sample of 51 patient registries provides information about a range of ethics practices.

Methods
We searched for patient registries in the resource database of the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP). Our ethics reporting checklist was based on three sources: the Registry Evaluation and Quality Standards Tool (REQueST), the Agency for Healthcare Research and Quality (AHRQ) guide for good registry practices, and a systematic review of the principles and norms related to health data sharing by Kalkman and colleagues. The checklist includes 26 questions about five ethics components: governance, conflicts of interest, informed consent, privacy and data protection, and use-and-access.

Results
We found substantial heterogeneity in the way patient registries provide information about ethics practices. Patient registries often mentioned their governance structure and any potential conflicts of interests but typically did not describe the responsibilities and rights allocated to their funders. Information about informed consent was often provided to patients, but the available documents often lacked relevant information like the benefits and risks of participation. Privacy and data protection and use-and-access policies were typically discussed but not very concretely.

Conclusions
We conclude that registries typically provide information about key ethics practices such as governance, conflicts of interest, informed consent, privacy and data protection, and use-and-access procedures, but this information is often not as detailed as recommended in existing guidelines. The ethics reporting checklist we designed could be helpful for the ethical assessments of patient registries and other types of registries in the future as well as for self-assessment of registries aiming to improve their ethics practices.