bluuebunny/crossref_metadata_2025_split huggingface dataset:
A review of menopause in transgender and gender diverse individuals
Authors: Kelley Carly E. , Ariel Danit 
Published: February 2025

Purpose of review
This review aims to provide a comprehensive overview of the specific challenges, health considerations, and healthcare needs of transgender and gender diverse (TGD) people navigating menopause, highlighting the intersection of gender identity, hormone treatment, and age-related changes.

Recent findings
Research on menopause in TGD individuals is lacking, without guidelines to support clinical management. This is the first review of its type to summarize the described impact of the menopausal transition on TGD individuals, the potential long-term risks associated with both gender-affirming hormone therapy and the intersectionality with aging, and how these risks may impact hormone management and overall comprehensive care.

Summary
By drawing on the shared principles of cisgender menopausal hormone therapy and gender-affirming hormone therapy, providers are well positioned to apply their expertise to support the TGD population during menopause. We recommend using shared decision-making, culturally competent care, and a strong understanding of the biological, personal, and social experiences of TGD people that do not necessarily conform to stereotypically ciswoman experiences.
GLP-1 receptor agonists for weight loss for perimenopausal and postmenopausal women: current evidence
Authors: Mikdachi Hana , Dunsmoor-Su Rebecca 
Published: February 2025

Purpose of review
Glucagon-like peptide-1 receptor agonists (GLP-1 RA) have emerged as a leading pharmacologic for managing weight gain across most populations, including peri and postmenopausal women who frequently suffer from weight gain. There is a paucity of data about this specific population and how they respond to these medications. This review aims to discuss the data available about the use and effects of GLP-1 RAs in the peri and postmenopausal populations.

Recent findings
GLP-1 RAs are consistently the most effective pharmacologic for weight loss and can be a valuable tool for use in peri and postmenopausal women.

Summary
Additional research is needed to determine the risks and benefits and ideal use of GLP-1 RAs in peri and postmenopausal women.
State-Level Hospital Quality in the United States: Analyzing Variation and Trends From 2013 to 2021
Authors: Teotia Arjun , Fulton Brent D. , Arnold Dan R. , Scheffler Richard M. 
Published: February 2025

ABSTRACT

Objective:
This study develops a hospital quality index to analyze state-level variations in hospital quality in the United States from 2013 to 2021, using data from 3,000 hospitals from the Centers for Medicare & Medicaid Services (CMS) Hospital Compare data set.

Design:
The quality index combines three risk-adjusted measures from the CMS Hospital Compare: 30-day readmission rate, 30-day mortality rate, and patient experience. Each measure is converted into a z-score, weighted by hospital beds, and averaged to form the final index, which has a mean of 0 and a standard deviation of 1.

Results:
In 2021, the average U.S. hospital quality measures were 15.1% for readmissions, 11.2% for mortality, and 69.7% for patient experience. There was significant state-level heterogeneity. The quality index ranged from −0.54 to 0.57. Eight states notably outperformed the U.S. average, with Utah leading. Conversely, 14 states underperformed. From 2013 to 2021, there was an average annual improvement in readmissions (0.08pp) and mortality (0.12pp), but a decline in patient experience (0.27pp).

Conclusions:
The study highlights improvements in hospital quality over time but underscores disparities at the state level. The quality index provides a valuable tool for understanding and addressing these variations in hospital care quality.
The Influence of Emotional Intelligence on Shared Governance Councils Effectiveness Among Nurses Participating in Shared Governance Councils in an Oncology Setting
Authors: AL-Ruzzieh Majeda A. , AL-Helih Yahia M. , Ayaad Omar , Hess Robert G. 
Published: February 2025

OBJECTIVE
This study aimed to assess the influence of emotional intelligence (EI) on shared governance councils' effectiveness among oncology nurses who participate in these councils.

BACKGROUND
Literature suggests that EI enhances job satisfaction, caring behavior, communication, and patient outcomes.

METHODS
This study used a cross-sectional design. The study took place at a large cancer hospital in Jordan. A convenience sample of 176 was used. The data were collected using self-administered questionnaires, the Wong and Law Emotional Intelligence Scale, and the Council Health Survey (CHS).

RESULTS
The findings indicated a significantly elevated degree of EI among oncology nurses, with a mean (SD) score of 5.8 (0.73) out of 7. The CHS score was 4.15 out of 5. The multiple regression analysis yielded a significant result, with an F statistic of 12.617 and degrees of freedom of 4 and 157. The P value was <0.001.

CONCLUSION
Findings support integrating more EI initiatives into nursing education and professional development.
Animal tracking with particle algorithms for conservation
Authors: Lavender Edward , Scheidegger Andreas , Albert Carlo , Biber Stanisław W. , Brodersen Jakob , Aleynik Dmitry , Cole Georgina , Dodd Jane , Wright Peter J. , Illian Janine , James Mark , Smout Sophie , Thorburn James , Moor Helen 
Published: February 2025

AbstractThe movements of aquatic animals affect their exposure to threats and the efficacy of conservation measures, such as Marine Protected Areas (MPAs). However, many species’ movements remain poorly understood and difficult to reconstruct from available datasets, hampering conservation efforts. This is especially the case for species that rarely surface, for which data are often limited to observations from acoustic telemetry (detections) and ancillary sensors, such as archival tags. Here, we pioneer the use of state-of-the-art particle algorithms to model animal movement, integrate datasets and assess MPA design, using a case study of the Critically Endangered flapper skate (Dipturus intermedius) in Scotland. Our algorithms led to 5-fold improvements in maps of space use and 30-fold improvements in residency estimates (lower mean error) compared to prevailing heuristic methods. By formally integrating tracking datasets, we were uniquely able to examine movements beyond receivers into fished zones, MPA-scale residency and specific habitats beyond protected areas that may warrant protection. This work showcases a probabilistically sound modelling framework that is sufficiently fast, flexible and accessible to meet the demands of modern animal-tracking datasets in acoustic telemetry systems. This represents a marked advance for analyses of animal movements and MPA efficacy worldwide.
CFTRGene Variant Detection in Moroccan Individuals via Nanopore Long-Read Sequencing
Authors: El Makhzen Nada , Nater Alexander , Rougier Jean-Sébastien , Bokhobza Alexandre , Sanz Javier , Zweier Christiane , Hämmerli Anne-Flore , Bruggmann Rémy , Bouguenouch Laila , Lakhdar Idrissi Mounia , Abriel Hugues 
Published: February 2025

AbstractBackgroundCystic fibrosis (CF) is an autosomal recessive disease resulting from pathogenic CF transmembrane conductance regulator (CFTR) pathogenic gene variants. While CF’s frequency varies among ethnicities, its epidemiology, clinical manifestations, and mutational profiles in Africa still must be explored due to the absence of a comprehensive public health strategy there. This study postulates that complete sequencing ofCFTRusing Oxford Nanopore Technology (ONT)-based long-read sequencing enhances the diagnostic yield.MethodsTo amplify ∼25-kb fragments covering the wholeCFTRgene (NM_000492.4), we designed 11 primer pairs, and barcoded libraries were prepared and sequenced on ONT flow cells (R10.4.1) using an Mk1C device. Variant pathogenicity was assessed by expressing the variant channel in HEK293 cells and examining expression through immuno-blotting.ResultsWith sequencing data obtained from 9 Moroccan individuals (6 probands with suspected CF diagnoses and 3 parents), we identified the following variants: c.680T>G p.Leu227Arg, c.1521_1523del p.Phe508del, c.3484C>T p.Arg1162*, c.1090T>C p.Ser364Pro, c.3233T>C p.Phe1078Ser and c.2991G>C p.Leu997Phe. The analytical pipeline we developed allowed the phasing of the variants. Sanger sequencing confirmed all these results. The previously uncharacterisedCFTRvariants p.Ser364Pro and p.Phe1078Ser exhibit diminished expression in HEK293 cells, substantiating their pathogenic nature, with p.Phe1078Ser responding positively to thein vitrotreatment with CFTR-modulator molecules.ConclusionsThis study demonstrates the potential of long-read sequencing using ONT as an efficient means to detect CF-causing variants in African populations. Given the significant genetic heterogeneity in Africa, this technique can serve as an affordable molecular screening tool for CF, especially in areas with constrained access to genetic screening.HighlightsHere, we demonstrate the efficiency of sequencing the completeCFTRgene using Oxford Nanopore Technology, an information-rich and accurate method.Not-yet-reportedCFTRvariants of unknown significance were identified from a small cohort of nine cystic fibrosis patients and parents from Fez, Morocco.The biochemical characterisation of theCFTRvariants p.Ser364Pro, p.Phe1078Ser, and p.Leu997Phe highlights the importance of conducting expression studies when genetic variants are identified.Our proposed approach will enhance diagnostic outcomes, particularly in populations with significant genetic diversity, such as those in Africa.
Extracellular alpha satellite DNA in human plasma as a novel molecular biomarker for early diagnosis of bladder cancer
Authors: Đermić D. , Feliciello I. 
Published: February 2025

AbstractAlthough bladder cancer (BC) is a common urological disease, there are deficiencies in current methods used for its detection, hence the research on the identification of non- invasive biomarkers is given a high priority. Alpha satellite DNA is a major human satellite DNA (hASAT), which is important for genome stability and whose aberrant overexpression is a hallmark of many human cancers. Here we identified and quantified its release into the circulation of BC patients, demonstrating its increased copy number with respect to healthy controls.Absolute quantification of extracellular alpha satellite DNA (ecASAT) repeats was performed by nanoplate-based digital PCR using few microliters of blood plasma from cancer patients as well as from BC negative controls. We found that copy number of ecASAT repeats is significantly higher in blood plasma of BC patients than in healthy controls.The results suggest that the ec-hASAT copy number variation in human plasma could act as a reliable biomarker for early detection of BC.
RTBES Radiological Index for Quantitative Assessment of Tuberculosis Evolution: Development and Validation
Authors: Cuadras Patrícia , Rafart Gerard , Català Martí , Arias Lilibeth , Pérez Ricard , Martinson Neil , Rosenthal Alex , Gabrielian Andrei , Vashakidze Sergo , Tenesa Montserrat , Bechini Jordi , Vilaplana Cristina 
Published: February 2025

AbstractQuestion addressed by the studyA radiological index capable of quantifying pulmonary tuberculosis (TB) disease progression on standard Chest X-Ray (CXR) could enhance clinical management and inform therapeutic decision-making. Our objectives were: to develop a radiological index that quantitatively assesses the progression of pulmonary TB in patients over the course of treatment and follow-up, to evaluate its usefulness by using CXRs from a cohort of TB patients, and to validate it with CXRs from an independent cohort of TB patients.Materials/patients and methodsAn index was developed to identify and classify patterns of radiological findings of both active and inactive pulmonary TB. This index was evaluated in a first cohort comprising a pseudonymized sample of serial CXRs from 21 TB patients at the Perinatal HIV Research Unit (PHRU) in South Africa and validated in a second, larger, independent cohort comprising 50 treated TB patients from the National Institute of Allergy and Infectious Diseases (NIAID) TB Data Portals. The relationship between index values for activity markers and patients’ clinical characteristics was also analysed.ResultsA radiological index, the RUTI-TB Evolution Score (RTBES), was created and validated in two cohorts, achieving 95.96% interobserver agreement (±2 points). In both cohorts, RTBES for active TB signs decreased over follow-up. Higher baseline RTBES correlated with male sex, higher bacterial loads, and extensive pulmonary involvement (including cavitation and pleural effusions). Baseline RTBES≥2 predicted unfavourable outcomes; 80% of failures/deaths occurred above this threshold.Answer to the questionRTBES effectively quantified pulmonary TB severity and tracked treatment evolution on standard CXRs, showing promise as a prognostic tool to inform clinical decision-making.
Characterizing meniscal calcifications with photon counting-based dual-energy computed tomography
Authors: Nevanranta Eeva , Karjalainen Ville-Pauli , Brix Mikael , Hellberg Iida , Turkiewicz Aleksandra , Shakya Bijay , Önnerfjord Patrik , Ylisiurua Sampo , Sjögren Amanda , Elkhouly Khaled , Hughes Velocity , Tjörnstrand Jon , Saarakkala Simo , Englund Martin , Finnilä Mikko A.J 
Published: February 2025

ABSTRACTMeniscal calcifications are associated with meniscal degeneration and osteoarthritis (OA). However, differentiating between calcification types, such as basic calcium phosphate (BCP) and calcium pyrophosphate (CPP), remains challengingin vivo. Therefore, assessing new imaging possibilities is crucial in understanding the calcification pathologies and their relationship with OA. This study investigated dual-energy computed tomography combined with a photon counting detector (PCD-DECT) to identify calcifications in human meniscal samplesex vivo, using Raman spectroscopy as reference. 82 meniscus samples from 41 donors were imaged using PCD-DECT at 120kVp. Data were collected in two energy bins (20-50keV and 50-120keV) with an isotropic resolution of 37µm. Raman spectroscopy was used to classify the calcifications as BCP or CPP. Among 82 samples, Raman spectroscopy identified 36 samples with only either BCP or CPP calcifications, that were included in the subsequent analysis. Regression models were used to compare the dual-energy index (DEI) and to assess the low energy values for corresponding high energy values between calcification types. The highest difference observed between BCP and CPP in comparison of low energy values for corresponding high energy values was 166HU (95%CI: 73, 259) at high energy value of 500HU and the difference between DEI values was 0.035 (95%CI: 0.011, 0.059), suggesting a potential difference in the measured parameters of calcification types. To conclude, PCD-DECT allowed the measurement of BCP and CPP calcificationsex vivo, offering new potentialin vivoapplications in the future, which could help understand calcification processes and evaluate the efficacy of disease-modifying drugs targeting calcification inhibition.
Ensemble Post-hoc Explainable AI in Multivariate Time Series: Identifying Medical Features Driving Disease Prediction
Authors: Metsch Jacqueline Michelle , Hempel Philip , Maurer Miriam Cindy , Spicher Nicolai , Hauschild Anne-Christin 
Published: February 2025

ABSTRACTDespite the growing success of deep learning (DL) in multivariate time-series classification, such as 12-lead electrocardiography (ECG), widespread integration into clinical practice has yet to be achieved. The limited transparency of DL hinders clinical adoption, where understanding model decisions is crucial for trust and compliance with regulations such as the General Data Protection Regulation (GDPR) or the EU AI Act.To tackle this challenge, we implemented a state-of-the-art 1D-ResNet in Pytorch that was trained on the large-scale Brazilian CODE dataset to classify six different ECG abnormalities. We employed the model on the German PTB-XL dataset, and evaluated its decision-making processes using 16 post-hoc explainable AI (XAI) methods. To assess the clinical relevance of the model’s attributions, we conducted a Wilcoxon signed-rank test to identify features with significantly higher relevance for each XAI method. We used an ensemble majority vote approach to validate whether the model has learned clinically meaningful features for each abnormality. Additionally, a Mann–Whitney U test was employed to detect significant differences in relevance attributions between correctly and incorrectly classified ECGs.Overall, the model achieved sensitivity scores above 0.9 for most abnormalities in the PTB-XL dataset. However, our XAI analysis showed that the model struggled to capture clinically relevant features for some diseases. Certain XAI methods, including DeepLift, DeepLiftShap, and Occlusion, consistently highlighted clinically meaningful features across abnormalities, while others, such as LIME, KernelShap, and LRP, failed to do so. Moreover, some XAI methods demonstrated significant differences in attributions between correctly and incorrectly classified ECGs, highlighting their potential for enhancing model robustness and interpretability.In conclusion, our findings underscore the importance of selecting suitable XAI methods tailored to specific model architectures and data types to ensure transparency and reliability. By identifying effective XAI techniques, this study contributes to closing the gap between DL advancements and their clinical implementation, paving the way for more trustworthy AI-driven healthcare solutions.
Fructose-1,6-bisphosphatase (FBPase) fine-tunes heterotrophic growth in cyanobacteria
Authors: Caliebe Frauke , Ojha Ravi Shankar , Gruber Marco , Boehm Marko , Shen Lu , Bräsen Christopher , Snoep Jacky L. , Forchhammer Karl , Hagemann Martin , Siebers Bettina , Gutekunst Kirstin 
Published: February 2025

AbstractCyanobacteria switch their carbon metabolism between photoautotrophy and heterotrophy during diurnal cycles. In cyanobacteria, the classical glycolytic control point is characterized by two catabolic phosphofructokinases (PFKs) and a bifunctional anabolic fructose-1,6-biphosphatase/sedoheptulose-1,7-biphosphatase (F/SBPase;slr2094) catalyzing two key reactions in the Calvin-Benson-Bassham (CBB) cycle. In addition,Synechocystispossesses a fructose-1,6-bisphosphatase (FBPase;slr0952) with yet unknown physiological function and biochemical properties. Hence, our aim was to investigate the FBPase and the interplay of the four enzymes in photoautotrophic and heterotrophic carbon metabolism.We discovered that FBPase is specific for FBP, showing no SBPase activity, and unlike F/SBPase does not exhibit any biochemical regulatory properties. Growth studies with deletion mutants revealed that FBPase and PFKs play a major role under heterotrophic conditions. In contrast to F/SBPase, FBPase is not involved in the CBB cycle, but instead fine-tunes heterotrophic growth. Transaldolase cannot replace the function of SBPase in the CBB cycle.In conclusion, the classical Embden-Meyerhoff-Parnass pathway control point, which is known to be mediated by the antagonistic enzyme pair PFK and FBPase in heterotrophic bacteria and eukaryotes, is also present inSynechocystis. We found redox-insensitive FBPases from plant chloroplasts to be closely related toSynechocystisFBPase, indicating that they might serve a similar function.HighlightSynechocystisfructose-1,6-bisphosphatase (slr0952) is unlike fructose-1,6-biphosphatase/sedoheptulose-1,7-biphosphatase (slr2094) monofunctional, not redox-regulated, and supports heterotrophy in darkness, despite catalyzing an anabolic reaction. Thus, presumably Slr2094 alone drives two Calvin-Benson-Bassham cycle key reactions.
Scoping review protocol- Scoping review Vitamin B12deficiency in long term metformin use and clinician awareness
Authors: Parsonage Ian , Wainwright David , Barratt Julian 
Published: February 2025

AbstractIntroductionA relationship between long-term metformin use and vitamin B12deficiency has been long discussed in literature. Nonetheless, prior to 2022, there was no official guidance. In June 2022, the MHRA published advice, stating that low vitamin B12is now considered to be a common side effect. It advises checking levels in patients with symptoms of B12deficiency, as well as monitoring those at risk of B12deficiency.Despite efforts to promote evidence-based practice, there is still a gap in the translation of research findings into policies and clinical practice. The above research has been shared widely in the academic and specialist Diabetes literature over a prolonged period. The purpose of the scoping review is to explore what evidence is available regarding clinicians’ awareness of the association between metformin use and vitamin B12deficiency in patients with T2DM and how this evidence is implemented into frontline clinical practice and what screening processes are recommended or exist?Methods and analysisThis is a protocol for a scoping review to be guided by the Joanna Briggs Institute (JBI) methodology for scoping reviews20. The databases to be searched will include CINAHL, MEDLINE, EMBASE, British Nursing Index, via EBSCOhost. Sources of unpublished studies, policies and grey literature will include Google Scholar, the Cochrane Library, ProQuest Dissertations and Theses Open. Titles and abstracts of articles were reviewed by the authors. If articles were representative of the inclusion criteria, the articles went through a full-text review by the authors The results of the search and study inclusion/exclusion process will be reported and presented in a Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) flow diagram. Data will be extracted from papers, using the recommended JBI data extraction tool.Strengths and limitations of this studyTo the authors’ knowledge, this is the first scoping review to look at clinician awareness of Vitamin B12deficiency in long term metformin use.Strengths include an extensive search of multiple databases, including grey literature.As this is a scoping review, the quality of the evidence and risk of bias will not be evaluated.The review is also limited to selected languages which may bias the evidence.
Single-cell multiomics of neuronal activation reveals context-dependent genetic control of brain disorders
Authors: Liang Lifan , Zhang Siwei , Wang Zicheng , Zhang Hanwen , Li Chuxuan , Duhe Alexandra C. , Sun Xiaotong , Zhong Xiaoyuan , Kozlova Alena , Jamison Brendan , Wood Whitney , Pang Zhiping P. , Sanders Alan R. , He Xin , Duan Jubao 
Published: February 2025

AbstractDespite hundreds of genetic risk loci identified for neuropsychiatric disorders (NPD), most causal variants/genes remain unknown. A major hurdle is that disease risk variants may act in specific biological contexts, e.g., during neuronal activation, which is difficult to studyin vivoat the population level. Here, we conducted a single-cell multiomics study of neuronal activation (stimulation) in human iPSC-induced excitatory and inhibitory neurons from 100 donors, and uncovered abundant neuronal stimulation-specific causal variants/genes for NPD. We surveyed NPD-relevant transcriptomic and epigenomic landscape of neuronal activation and identified thousands of genetic variants associated with activity-dependent gene expression (i.e., eQTL) and chromatin accessibility (i.e., caQTL). These caQTL explained considerably larger proportions of NPD heritability than the eQTL. Integrating the multiomic data with GWAS further revealed NPD risk variants/genes whose effects were only detected upon stimulation. Interestingly, multiple lines of evidence support a role of activity-dependent cholesterol metabolism in NPD. Our work highlights the power of cell stimulation to reveal context-dependent “hidden” genetic effects.