bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of antihypertensive medications use and survival in patients with ovarian cancer: a population-based retrospective cohort study
Authors: Everatt Rūta , Kuzmickienė Irena , Brasiūnienė Birutė , Vincerževskienė Ieva , Intaitė Birutė , Cicėnas Saulius , Lisauskienė Ingrida 
Published: March 2024

Abstract
Background
Despite declining mortality in most countries and in Lithuania, ovarian cancer burden has remained high. Studies have indicated that antihypertensive medications use may help to improve ovarian cancer survival, however findings remain controversial. The aim of the study was to analyse the association between post-diagnosis antihypertensive medications intake and cancer-specific survival in ovarian cancer patients.

Methods
This retrospective cohort study included 588 ovarian cancer cases diagnosed between 2013 and 2015. Hazard ratios (HR) and corresponding 95% confidence intervals (95%CI) were estimated using multivariable Cox proportional hazards models to assess associations between antihypertensive medications and ovarian cancer-specific mortality.

Results
In total, 279 (47%) patients died during the follow-up; 242 (87%) of them died due to ovarian cancer. The risk of ovarian cancer death was reduced in angiotensin-converting enzyme inhibitors (ACE inhibitors) users vs. non-users (HR 0.55, 95% CI: 0.36–0.83). Subgroup analysis showed better ovarian cancer survival in higher dose ACE inhibitors users (HR 0.46, 95% CI: 0.28–0.77, p for trend 0.002); the effect was also stronger in age 51–65 years, stage I–III, surgery or chemotherapy treatment, pre-diagnosis ACE inhibitor users’ and pre-diagnosis hypertension subgroups. The risk of cancer-specific death was slightly lower among calcium-channel blocker and angiotensin-receptor blocker users and higher among beta-blocker users as compared to non-users, however chance and confounding could not be ruled out. We found no association between the use of centrally and peripherally acting antiadrenergic agents and diuretics and risk of ovarian cancer-specific mortality.

Conclusions
Our findings imply that post-diagnosis use of ACE inhibitors may be associated with reduced ovarian cancer-specific mortality; however, further research is needed for the comprehensive assessment.
A national survey on current state and development needs of clinical and academic emergency medicine in China
Authors: du Lanfang , Li Yan , wang Zhenjie , Zhang Guoqiang , Chen Xiaohui , Tian Yingping , Zhu Changju , Zhang Jinsong , Wu Lidong , Li Peiwu , Chen Yuguo , Ji Bing , Pan Shuming , Zeng Jun , Chai Yanfen , Mu Yesai , Zhang Mao , Ma Yu , Lv Chuanzhu , Ma Qingbian 
Published: March 2024

Abstract
Background
To characterize the current state of emergency medicine (EM) and the requirements for advancing EM clinical practice, education and research in China.

Methods
An anonymous electronic survey was conducted by Chinese Society of Emergency Medicine during September to October 2021. The survey contained 30 questions divided into 2 sections: the current state of EM development and the requirements for EM growth.

Results
722 hospitals were included, of 487 were Level III and 235 were Level II hospitals. We found that after 40 years of development, EM had established a mature disciplinary system and refined sub-specialties including critical care, cardiopulmonary resuscitation, toxicology, disaster and emergency rescue. In Level III hospitals, 70.8% of EDs were standardized training centers for EM residents, but master’s degree program, Doctor Degree program and post-doctoral degree program was approved in only 37.8%, 8.4% and 2.9% of EDs respectively and postgraduate curriculum was available in 1/4 of EDs. Only 8% have national or provincial key laboratories. In addition to advance clinical practice, there was also a high demand to improve teaching and research capacities, mainly focusing on literature review, research design and delivery, paper writing, residency training.

Conclusions
EM has built a mature discipline system and refined sub-specialties in China. Teaching and research developed parallel with clinical practice. However, there was still a lack of EM master’s and doctoral programs and research capacities need to be improved. More outstanding clinical and academic training should be provided to promote the rapid growth of EM in China.
Seasonally adjusted laboratory reference intervals to improve the performance of machine learning models for classification of cardiovascular diseases
Authors: Muse Victorine P. , Placido Davide , Haue Amalie D. , Brunak Søren 
Published: March 2024

Abstract
Background
Variation in laboratory healthcare data due to seasonal changes is a widely accepted phenomenon. Seasonal variation is generally not systematically accounted for in healthcare settings. This study applies a newly developed adjustment method for seasonal variation to analyze the effect seasonality has on machine learning model classification of diagnoses.

Methods
Machine learning methods were trained and tested on ~ 22 million unique records from ~ 575,000 unique patients admitted to Danish hospitals. Four machine learning models (adaBoost, decision tree, neural net, and random forest) classifying 35 diseases of the circulatory system (ICD-10 diagnosis codes, chapter IX) were run before and after seasonal adjustment of 23 laboratory reference intervals (RIs). The effect of the adjustment was benchmarked via its contribution to machine learning models trained using hyperparameter optimization and assessed quantitatively using performance metrics (AUROC and AUPRC).

Results
Seasonally adjusted RIs significantly improved cardiovascular disease classification in 24 of the 35 tested cases when using neural net models. Features with the highest average feature importance (via SHAP explainability) across all disease models were sex, C- reactive protein, and estimated glomerular filtration. Classification of diseases of the vessels, such as thrombotic diseases and other atherosclerotic diseases consistently improved after seasonal adjustment.

Conclusions
As data volumes increase and data-driven methods are becoming more advanced, it is essential to improve data quality at the pre-processing level. This study presents a method that makes it feasible to introduce seasonally adjusted RIs into the clinical research space in any disease domain. Seasonally adjusted RIs generally improve diagnoses classification and thus, ought to be considered and adjusted for in clinical decision support methods.
Do healthcare providers consider the social determinants of health? Results from a nationwide cross-sectional study in the United States
Authors: Glenn Jeffrey , Kleinhenz Gwen , Smith Jenna M.S. , Chaney Robert A. , Moxley Victor B.A. , Donoso Naranjo Paola G. , Stone Sarah , Hanson Carl L. , Redelfs Alisha H. , Novilla M. Lelinneth B. 
Published: March 2024

Abstract
Background
While the social determinants of health (SDOH) have a greater impact on individual health outcomes than the healthcare services a person receives, healthcare providers face barriers to addressing these factors in clinical settings. Previous studies have shown that providers often lack the necessary knowledge and resources to adequately screen for and otherwise assist patients with unmet social needs. This study explores the perceptions and behaviors related to SDOH among healthcare providers in the United States (US).

Methods
This cross-sectional study analyzed data from a 22-item online survey using Reaction Data’s research platform of healthcare professionals in the US. Survey items included demographic questions as well as Likert scale questions about healthcare providers’ perceptions and behaviors related to SDOH. Descriptive statistics were calculated, and further analyses were conducted using t-tests and analysis of variance.

Results
A total of 563 respondents completed the survey, with the majority being male (72.6%), White (81%), and located in urban areas (82.2%). In terms of perceptions, most providers agreed or strongly agreed that SDOH affect the health outcomes of all patients (68.5%), while only 24.1% agreed or strongly agreed that their healthcare setting was set up to address SDOH. In terms of behavior, fewer than half currently screened for SDOH (48.6%) or addressed (42.7%) SDOH in other ways. Most providers (55.7%) wanted additional resources to focus on SDOH. Statistical analyses showed significant differences by gender, with females being more likely than males to prioritize SDOH, and by specialty, with psychiatrists, pediatricians, and family/general medicine practitioners being more likely to prioritize SDOH.

Conclusion
Most healthcare providers understand the connection between unmet social needs and their patients’ health, but they also feel limited in their ability to address these issues. Ongoing efforts to improve medical education and shift the healthcare system to allow for payment and delivery of more holistic care that considers SDOH will likely provide new opportunities for healthcare providers. In addition to what they can do at the institutional and patient levels, providers have the potential to advocate for policy and system changes at the societal level that can better address the root causes of social issues.
Transmembrane protein 176B regulates amino acid metabolism through the PI3K-Akt-mTOR signaling pathway and promotes gastric cancer progression
Authors: Li Jing , Fang ZiQing , Dal Emre , Zhang Hao , Yu KeXun , Ma MengDi , Wang MingLiang , Sun Ruochuan , Lu MingDian , Wang HuiZhen , Li YongXiang 
Published: March 2024

Abstract
Background
The present study aimed to investigate the expression level, biological function, and underlying mechanism of transmembrane protein 176B (TMEM176B) in gastric cancer (GC).

Methods
TMEM176B expression was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting (WB). The function of TMEM176B was determined by various in vitro assays including colony formation, 5-ethynyl-2ʹ-deoxyuridine (EdU), Transwell, and flow cytometry. Bioinformatics techniques were then used to elucidate the signaling pathways associated with TMEM176B activity. Tumor formation experiments were conducted on nude mice for in vivo validation of the preceding findings. TMEM176B expression was cross-referenced to clinicopathological parameters and survival outcomes.

Results
It was observed that TMEM176B was overexpressed in GC cells and tissues. Targeted TMEM176B abrogation inhibited colony formation, proliferation, migration, and invasion but promoted apoptosis in GC cell lines while TMEM176B overexpression had the opposite effects. Subsequent experimental validation disclosed an association between TMEM176B and the phosphatidylinositol 3-carboxykinase (PI3K)-protein kinase B (Akt)-mammalian target of rapamycin (mTOR) signaling axis. Moreover, TMEM176B affects GC cancer progression by regulating asparagine synthetase (ASNS). The in vivo assays confirmed that TMEM176B is oncogenic and the clinical data revealed a connection between TMEM176B expression and the clinicopathological determinants of GC.

Conclusion
The foregoing results suggest that TMEM176B significantly promotes the development of gastric cancer and is an independent prognostic factor of it.
Keratinocyte-derived circulating microRNAs in extracellular vesicles: a novel biomarker of psoriasis severity and potential therapeutic target
Authors: Park Young Joon , Kim Dong Chan , Lee Soo-Jin , Kim Han Seul , Pak Ji Young , Kim Junho , Cheong Jae Youn , Lee Eun-So 
Published: March 2024

Abstract
Background
Psoriasis is a chronic inflammatory disorder characterized by pathogenic hyperproliferation of keratinocytes and immune dysregulation. Currently, objective evaluation tools reflecting the severity of psoriasis are insufficient. MicroRNAs in extracellular vesicles (EV miRNAs) have been shown to be potential biomarkers for various inflammatory diseases. Our objective was to investigate the possibility of plasma-derived EV miRNAs as a marker for the psoriasis disease severity.

Methods
EVs were extracted from the plasma of 63 patients with psoriasis and 12 with Behçet’s disease. We performed next-generation sequencing of the plasma-derived EV miRNAs from the psoriasis patients. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to validate the level of EV miRNA expression. In situ hybridization was used to discern the anatomical location of miRNAs. qRT-PCR, western blotting, and cell counting kits (CCKs) were used to investigate IGF-1 signaling in cells transfected with miRNA mimics.

Results
We identified 19 differentially expressed EV miRNAs and validated the top three up-and down-regulated EV miRNAs. Among these, miR-625-3p was significantly increased in patients with severe psoriasis in both plasma and skin and most accurately distinguished moderate-to-severe psoriasis from mild-to-moderate psoriasis. It was produced and secreted by keratinocytes upon stimulation. We also observed a significant intensification of IGF-1 signalling and increased cell numbers in the miR-625-3p mimic transfected cells.

Conclusions
We propose keratinocyte-derived EV miR-625-3p as a novel and reliable biomarker for estimating the severity of psoriasis. This biomarker could objectively evaluate the severity of psoriasis in the clinical setting and might serve as a potential therapeutic target.
Trial registration None.
Effect of exercise training on heath, quality of life, exercise capacity in juvenile idiopathic arthritis: a meta-analysis of randomized controlled trials
Authors: Liu Wen-yu , Li Hui-min , Jiang Hao , Zhang Wen-kui 
Published: March 2024

Abstract
Objective
Little is known about the efficacy and safety of exercise training on juvenile idiopathic arthritis (JIA). This study aims to investigate the effect of exercise on health, quality of life, and different exercise capacities in individuals with JIA.

Method
A comprehensive search of Medline, Embase, Web of Science, and the Cochrane Library was conducted from database inception to October, 2023. Included studies were randomized controlled trials (RCTs) reporting the effects of exercise on JIA patients. Two independent reviewers assessed the literature quality using the Cochrane Collaboration’s risk of bias tool. Standardized mean differences (SMD) were combined using random or fixed effects models. The level of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.

Result
Five RCTs met the inclusion criteria, containing 216 female participants and 90 males. The meta-analysis results showed that exercise had no significant effect on JIA patients based on the Child Health Assessment Questionnaire (CHAQ) (SMD=-0.32, 95%CI: -0.83, 0.19; I2 = 73.2%, P = 0.011) and Quality of Life (QoL) (SMD = 0.27, 95%CI: -0.04, 0.58; I2 = 29.4%, P = 0.243) and no significant effect on peak oxygen uptake (VO2peak). However, exercise significantly reduced visual analog scale (VAS) pain scores in JIA patients (SMD = 0.50, 95%CI: -0.90, -0.10; I2 = 50.2%, P = 0.134). The quality of evidence assessed by GRADE was moderate to very low.

Conclusion
Exercise does not significantly affect the quality of life and exercise capacity in JIA patients but may relieve pain. More RCTs are needed in the future to explore the effects of exercise on JIA.
Structural and practical identifiability analysis in bioengineering: a beginner’s guide
Authors: Wanika Linda , Egan Joseph R. , Swaminathan Nivedhitha , Duran-Villalobos Carlos A. , Branke Juergen , Goldrick Stephen , Chappell Mike 
Published: March 2024

AbstractAdvancements in digital technology have brought modelling to the forefront in many disciplines from healthcare to architecture. Mathematical models, often represented using parametrised sets of ordinary differential equations, can be used to characterise different processes. To infer possible estimates for the unknown parameters, these models are usually calibrated using associated experimental data. Structural and practical identifiability analyses are a key component that should be assessed prior to parameter estimation. This is because identifiability analyses can provide insights as to whether or not a parameter can take on single, multiple, or even infinitely or countably many values which will ultimately have an impact on the reliability of the parameter estimates. Also, identifiability analyses can help to determine whether the data collected are sufficient or of good enough quality to truly estimate the parameters or if more data or even reparameterization of the model is necessary to proceed with the parameter estimation process. Thus, such analyses also provide an important role in terms of model design (structural identifiability analysis) and the collection of experimental data (practical identifiability analysis). Despite the popularity of using data to estimate the values of unknown parameters, structural and practical identifiability analyses of these models are often overlooked. Possible reasons for non-consideration of application of such analyses may be lack of awareness, accessibility, and usability issues, especially for more complicated models and methods of analysis. The aim of this study is to introduce and perform both structural and practical identifiability analyses in an accessible and informative manner via application to well established and commonly accepted bioengineering models. This will help to improve awareness of the importance of this stage of the modelling process and provide bioengineering researchers with an understanding of how to utilise the insights gained from such analyses in future model development.
Efficacy of home phototherapy versus inpatient phototherapy for neonatal hyperbilirubinemia: a systematic review and meta-analysis
Authors: Li Rui , Li Tingting , Yan Xudong , Feng Jing , Yu Zhangbin , Chen Cheng 
Published: March 2024

Abstract
Background
Home phototherapy (HPT) remains a contentious alternative to inpatient phototherapy (IPT) for neonatal hyperbilirubinemia. To guide evidence-based clinical decision-making, we conducted a meta-analysis of randomized clinical trials (RCTs) and cohort studies and assessed the comparative risks and benefits of HPT and IPT.

Methods
PubMed, Embase, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure Database, Wanfang Database, Chinese Science and Technique Journals Database, ClinicalTrials.gov, and International Clinical Trial Registry Platform trial were searched from inception until June 2, 2023. We included RCTs and cohort studies and adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Study quality was assessed with the Cochrane Collaboration Risk of Bias tool and the Newcastle–Ottawa scale. The outcome measures were phototherapy duration, daily bilirubin level reduction, exchange transfusion, hospital readmission, parental stress scale, and complications. We used fixed- or random-effects meta-analysis models, assessed heterogeneity (I2), conducted subgroup analyses, evaluated publication bias, and graded evidence quality.

Results
Nine studies (998 patients) were included (four RCTs, five cohort studies). HPT was associated with longer phototherapy duration (SMD = 0.55, 95% CI: 0.06–1.04, P = 0.03). Cohort study subgroup analysis yielded consistent results (SMD = 0.90; 95% CI: 0.69 to 1.11, P < 0.001, I2 = 39%); the RCTs were not significantly different (SMD = -0.04; 95% CI: -0.15 to 0.08, P = 0.54, I2 = 0%). Hospital readmission was higher with HPT (RR = 4.61; 95% CI: 1.43–14.86, P = 0.01). Daily bilirubin reduction (WMD = -0.12, 95% CI: -0.68 to 0.44, P = 0.68) or complications were not significantly different (RR = 2.29; 95% CI: 0.31–16.60, P = 0.41). The evidence quality was very low. HPT was associated with lower parental stress (SMD = -0.44, 95% CI: -0.71 to -0.16, P = 0.002). None of three included studies reported exchange transfusion.

Conclusions
The current evidence does not strongly support HPT efficacy for neonatal hyperbilirubinemia, as high-quality data on long-term outcomes are scarce. Future research should prioritize well-designed, large-scale, high-quality RCTs to comprehensively assess HPT risks and benefits.
Early-life ruminal microbiome-derived indole-3-carboxaldehyde and prostaglandin D2 are effective promoters of rumen development
Authors: Sun Daming , Bian Gaorui , Zhang Kai , Liu Ning , Yin Yuyang , Hou Yuanlong , Xie Fei , Zhu Weiyun , Mao Shengyong , Liu Junhua 
Published: March 2024

Abstract
Background
The function of diverse ruminal microbes is tightly linked to rumen development and host physiology. The system of ruminal microbes is an excellent model to clarify the fundamental ecological relationships among complex nutrient–microbiome–host interactions. Here, neonatal lambs are introduced to different dietary regimes to investigate the influences of early-life crosstalk between nutrients and microbiome on rumen development.

Results
We find starchy corn-soybean starter-fed lambs exhibit the thickest ruminal epithelia and fiber-rich alfalfa hay-fed lambs have the thickest rumen muscle. Metabolome and metagenome data reveal that indole-3-carboxaldehyde (3-IAld) and prostaglandin D2 (PGD2) are the top characteristic ruminal metabolites associated with ruminal epithelial and muscular development, which depend on the enhanced ruminal microbial synthesis potential of 3-IAld and PGD2. Moreover, microbial culture experiment first demonstrates that Bifidobacterium pseudolongum is able to convert tryptophan into 3-IAld and Candida albicans is a key producer for PGD2. Transcriptome sequencing of the ruminal epithelia and smooth muscle shows that ruminal epithelial and muscular development is accompanied by Wnt and Ca2+ signaling pathway activation. Primary cell cultures further confirm that 3-IAld promotes ruminal epithelial cell proliferation depending on AhR-wnt/β-catenin signaling pathway and PGD2 accelerates ruminal smooth muscle cell proliferation via Ca2+ signaling pathway. Furthermore, we find that 3-IAld and PGD2 infusion promote ruminal epithelial and musculature development in lambs.

Conclusions
This study demonstrates that early-life ruminal microbiome-derived 3-IAld and PGD2 are effective promoters of rumen development, which enhances our understanding of nutrient–microbiome–host interactions in early life.