bluuebunny/crossref_metadata_2025_split huggingface dataset:
Undergraduate ultrasound training: prospective comparison of two different peer assisted course models on national standards
Authors: Weimer Johannes , Dionysopoulou Anna , Strelow Kai-Uwe , Buggenhagen Holger , Weinmann-Menke Julia , Dirks Klaus , Weimer Andreas , Künzel Julian , Börner Norbert , Ludwig Michael , Yang Yang , Lorenz Liv , Ille Carlotta , Müller Lukas 
Published: July 2023

Abstract
Background
A thorough knowledge of sonography is essential in clinical practice. Therefore, sonography training is increasingly incorporated into the medical school curriculum, entailing different course models. The question arises which model is most effective to convey sustained sonographic skills.

Methods
Two different peer-assisted learning (PAL) sonography course models were developed as part of a clinical prospective study. The course content was based on the national resident curriculum of the German Society for Ultrasound in Medicine (DEGUM). Model A consists of a 10-week course and model B of a two-day compact course. Each model entailed 20 teaching units (TU). A script was used to prepare for each unit. Two modified OSCE exams of the ultrasound skills (max = 50 points per exam) were performed during the last teaching unit to assess the competence level. For subjective self-assessment and model evaluation, a questionnaire with a 7-point Likert scale was employed.

Results
A total of 888 students of the 3rd year participated as part of a voluntary elective in the study (744 in model A and 144 in model B). In the exams, participants in model A (median 43 points) scored significantly higher than those in model B (median 39; p < 0.01). Participants in model A (mean 1.71 points) obtained significantly higher mean competency gain scores in subject knowledge than model B (mean 1.43 points; p < 0.01) participants. All participants were satisfied with the course concept (A: mean 1.68 vs. B: mean 1.78 points; p = 0.05), the teaching materials (A: mean 1.81 vs. B: mean 1.69 points; p = 0.52), and the tutor’s didactic skills (A: mean 1.24 vs. B: mean 1.15 points; p < 0.05).

Conclusion
These results suggest that sonography-specific competency may be obtained through different course models, with a model stretching over several weeks leading to a higher competence level. Further research should assess the long-term retention of the skills obtained in different models.
Development and validation of prediction model for overall survival in patients with lymphoma: a prospective cohort study in China
Authors: Li Xiaosheng , Chen Yue , Sun Anlong , Wang Ying , Liu Yao , Lei Haike 
Published: July 2023

Abstract
Objective
The survival of patients with lymphoma varies greatly among individuals and were affected by various factors. The aim of this study was to develop and validate a prognostic model for predicting overall survival (OS) in patients with lymphoma.

Methods
We conducted a prospective longitudinal cohort study in China between January 2014 and December 2018 (n = 1,594). After obtaining the follow-up data, we randomly split the cohort into the training cohort (n = 1,116) and the validation cohort (n = 478). The least absolute shrinkage and selection operator (LASSO) regression analysis was used to select the predictors of the model. Cox stepwise regression analysis was used to identify independent prognostic factors, which were finally displayed as static nomogram and web-based dynamic nomogram. We calculated the concordance index(C-index) to describe how the predicted survival of objectively confirmed prognosis. The calibration plot is used to evaluate the prediction accuracy and discrimination ability of the model. Net reclassification index (NRI) and decision curve analysis (DCA) curves were also used to evaluate the prediction ability and net benefit of the model.

Results
Nine variables in the training cohort were considered to be independent risk factors for patients with lymphoma in the final model: age, Ann Arbor Stage, pathologic type, B symptoms, chemotherapy, targeted therapy, lactate dehydrogenase (LDH), β2-microglobulin and C-reactive protein (CRP). The C-indices of OS were 0.749 (95% CI, 0.729–0.769) in the training cohort and 0.731 (95% CI, 0.762–0.700) in the validation cohort. A good agreement between prediction by nomogram and actual observation was shown in the calibration curve for the probability of survival in both the training cohort and validation cohorts. The areas under curve (AUC) of the area under the receiver operating characteristic (ROC) curves for 1-year, 3-year, and 5-year OS were 0.813, 0.800, and 0.762, respectively, in the training cohort, and 0.802, 0.768, and 0.721, respectively, in the validation cohort. Compared with the Ann Arbor Stage system, NRI and DCA showed that the model had a higher predictive capacity and net benefit.

Conclusion
The prediction models reliably estimate the outcome of patients with lymphoma. The model had high discrimination and calibration, which provided a simple and reliable tool for the survival prediction of the patients, and it might help patients benefit from personalized intervention.
How effectively are social accountability mechanisms being applied in mental health services within the newly federalized health system of Nepal? A multi-stakeholder qualitative study
Authors: Devkota Hridaya Raj , Baral Yuba Raj , Khanal Bindu , Adhikary Pratik 
Published: July 2023

Abstract
Background
The burden of mental health problems and inequalities in healthcare has emerged as critical issues, in Nepal. Strengthened citizen-driven social accountability (SA) is an effective strategy for building equitable health systems and providing quality healthcare services to all, yet SA in mental health is an under-researched area in Nepal.

Objective
This study explores changes in mental health service delivery in the re-configured federal health system and discusses the functioning and effectiveness of SA in the federalized context of Nepal.

Method
This case study research used a qualitative approach to data collection. We conducted Key Informant Interviews (KIIs), and Focus Group Discussions (FGDs) with local stakeholders including people with experience of mental health problems. The audio-recorded interviews and discussions were transcribed and analyzed using a thematic content method.

Results
A total of 49 participants were recruited, and 17 participated in interviews and 32 participated in six focus group discussions. From the data, eight themes emerged: Policy challenges in mental health, Governance and service delivery, Tokenism in the application of social accountability processes, Weak role of key actors in promoting accountability, Complaints and response, Discriminatory health and welfare system, Public attitudes and commitment towards mental health, and No differences experienced by the change to a federal system. It was found that existing health policies in Nepal inadequately cover mental health issues and needs. The prevailing laws and policies related to mental health were poorly implemented. There is a lack of clarity at different levels of government about the roles and responsibilities in the delivery of mental health services. Poor intra- and inter-governmental coordination, and delays in law-making processes negatively impacted on mental health service delivery. SA mechanisms such as social audits and public hearings exist within government health systems, however, application of these in mental health services was found poor. Rights-holders with mental health problems had not experienced any change in the provision of healthcare services for them even after the federalization.

Conclusion
Mental health is insufficiently addressed by the health policies in Nepal, and SA mechanisms appeared to be rarely institutionalized to promote good governance and provide effective healthcare services to vulnerable populations. The provision of more equitable services and honest implementation of SA tools may foster greater accountability and thereby better service delivery for people with mental health problems.
A functional mechanism for a non-coding variant near AGTR2 associated with risk for preterm birth
Authors: Wang Li , Rossi Robert M. , Chen Xiaoting , Chen Jing , Runyon Jilian , Chawla Mehak , Miller Daniel , Forney Carmy , Lynch Arthur , Zhang Xuzhe , Kong Fansheng , Jacobsson Bo , Kottyan Leah C. , Weirauch Matthew T. , Zhang Ge , Muglia Louis J. 
Published: July 2023

Abstract
Background
Preterm birth (PTB), defined as delivery before 37 gestational weeks, imposes significant public health burdens. A recent maternal genome-wide association study of spontaneous PTB identified a noncoding locus near the angiotensin II receptor type 2 (AGTR2) gene. Genotype-Tissue Expression data revealed that alleles associated with decreased AGTR2 expression in the uterus were linked to an increased risk of PTB and shortened gestational duration. We hypothesized that a causative variant in this locus modifies AGTR2 expression by altering transcription factor (TF) binding.

Methods
To investigate this hypothesis, we performed bioinformatics analyses and functional characterizations at the implicated locus. Potential causal single nucleotide polymorphisms (SNPs) were prioritized, and allele-dependent binding of TFs was predicted. Reporter assays were employed to assess the enhancer activity of the top PTB-associated non-coding variant, rs7889204, and its impact on TF binding.

Results
Our analyses revealed that rs7889204, a top PTB-associated non-coding genetic variant is one of the strongest eQTLs for the AGTR2 gene in uterine tissue samples. We observed differential binding of CEBPB (CCAAT enhancer binding protein beta) and HOXA10 (homeobox A10) to the alleles of rs7889204. Reporter assays demonstrated decreased enhancer activity for the rs7889204 risk “C” allele.

Conclusion
Collectively, these results demonstrate that decreased AGTR2 expression caused by reduced transcription factor binding increases the risk for PTB and suggest that enhancing AGTR2 activity may be a preventative measure in reducing PTB risk.
Elevated plasma factor XI predicts cardiovascular events in patients with type 2 diabetes: a long-term observational study
Authors: Paszek Elżbieta , Polak Maciej , Bryk-Wiązania Agata Hanna , Konieczyńska Małgorzata , Undas Anetta 
Published: July 2023

Abstract
Background
Type 2 diabetes mellitus (T2DM) patients are at high risk of cardiovascular (CV) events. Factor XI (FXI) is associated with arterial thromboembolism, including myocardial infarction (MI), stroke, and CV mortality. The role of FXI in T2DM is unknown. We investigated whether plasma FXI is associated with CV events in T2DM patients in long-term observation.

Methods
In 133 T2DM patients (aged 66 ± 8 years, 40.6% women, median T2DM duration 5 [2–10] years) we assessed plasma FXI levels, along with fibrin clot properties, thrombin generation, and fibrinolysis proteins. A composite endpoint of MI, stroke, or CV death, as well as CV mortality alone were assessed during a median follow-up of 72 months.

Results
Plasma FXI above the 120% upper normal limit was detected in 25 (18.8%) patients and showed positive association with LDL cholesterol and thrombin activatable fibrinolysis inhibitor, but not glycated hemoglobin, inflammatory markers or thrombin generation. The composite endpoint (n = 21, 15.8%) and CV death alone (n = 16, 12%) were more common in patients with elevated FXI (hazard ratio [HR] 10.94, 95% confidence interval [CI] 4.46–26.87, p < 0.001 and HR 7.11, 95% CI 2.61–19.31, p < 0.001, respectively). On multivariable analysis, FXI remained an independent predictor of the composite endpoint and CV death, regardless of concomitant coronary artery disease.

Conclusions
To our knowledge, this study is the first to show that in T2DM patients, elevated FXI could predict major CV events, including mortality, which suggest that anti-FXI agents might be a potential novel antithrombotic option in this disease.
Exosome-mediated miR-144-3p promotes ferroptosis to inhibit osteosarcoma proliferation, migration, and invasion through regulating ZEB1
Authors: Jiang Mingyang , Jike Yiji , Liu Kaicheng , Gan Fu , Zhang Ke , Xie Mingjing , Zhang Junlei , Chen Chuanliang , Zou Xiaochong , Jiang Xiaohong , Dai Yongheng , Chen Weikui , Qiu Yue , Bo Zhandong 
Published: July 2023

Abstract
Background
Osteosarcoma (OS) is the most prevalent orthopedic malignancy with a dismal prognosis. The high iron absorption rate in OS cells of patients suggests that ferroptosis may be related to the progression of OS, but its potential molecular regulatory role is still unclear. Based on the ability to couple with exosomes for targeted delivery of signals, exosome-derived micro ribonucleic acids (miRNAs) can potentially serve as diagnostic biomarkers for OS.

Methods
We identified ferroptosis-related miRNAs and messenger ribonucleic acids(mRNAs) in OS using bioinformatics analysis and performed survival analysis. Then we measured miRNA expression levels through exosome microarray sequencing, and used RT-qPCR and IHC to verify the expression level of miR-144-3p and ZEB1. Stable gene expression cell lines were fabricated for in vitro experiments. Cell viability, migration and invasion were determined by CCK-8 and transwell experiment. Use the corresponding reagent kit to detect GSH/GSSG ratio, Fe2+ level, MDA level and ROS level, and measure the expression levels of GPX4, ACSL4 and xCT through RT-qPCR and WB. We also constructed nude mice model for in vivo experiments. Finally, the stability of the miRNA/mRNA axis was verified through functional rescue experiments.

Results
Low expression of miR-144-3p and high expression of ZEB1 in OS cell lines and tissues was observed. Overexpression of miR-144-3p can promote ferroptosis, reduce the survival ability of OS cells, and prevent the progression of OS. In addition, overexpression of miR-144-3p can downregulate the expression of ZEB1 in cell lines and nude mice. Knockdown of miR-144-3p has the opposite effect. The functional rescue experiment validated that miR-144-3p can regulate downstream ZEB1, and participates in the occurrence and development of OS by interfering with redox homeostasis and iron metabolism.

Conclusions
MiR-144-3p can induce the occurrence of ferroptosis by negatively regulating the expression of ZEB1, thereby inhibiting the proliferation, migration, and invasion of OS cells.

Graphical Abstract
Pancreaticoduodenectomy combined gastroduodenal collateral reconstruction and preservation due to median arcuate ligament syndrome: technical notes with two surgical cases report (with video)
Authors: Nguyen Thanh Khiem , Nguyen Ham Hoi , Luong Tuan Hiep , Chantha Pisey , Ngo Gia Khanh , Le Van Duy , Dang Kim Khue , Tran Duc Huy , Nguyen Cuong Thinh 
Published: July 2023

Abstract
Introduction
Pancreaticoduodenectomy in patients with CA stenosis due to median arcuate ligament often required carefully collateral pathways management to avoid hepatic ischemic complications.

Cases presentation
Case 1: A 63-year-old man was referred to our department because of jaundice with distal common bile duct tumor. Pancreaticoduodenectomy with left posterior SMA first approach and circumferential lymphadenectomy was performed. Case 2: A 48-year-old man was referred to our department because of right-upper-quadrant abdominal pain with Vater tumor. Laparoscopic pancreaticoduodenectomy with left posterior SMA first approach and circumferential lymphadenectomy was performed. Postoperatively, in all two cases, three-dimensional reconstruction images showed developed collateral pathways around the pancreatic head, and the CA was stenosis in 75% and 70% due to MAL, respectively. Intraoperatively, in all two cases, we confirmed poor blood flow in the common hepatic artery (CHA) by palpation and observation. So that in the first case, we have decided to proceed a no-touch technique of GDA segmental resection en bloc with the tumor and reconstructed with an end-to-end GDA anastomosis; in the second cases, we have decided to proceed gastroduodenal collateral preservation. When preserving these collateral pathways, we confirmed that the PHA flow remained pulsatile as an indicator that the blood flow was adequate.

Conclusion
Celiac axis stenosis was a rare but difficult-to-managed condition associated with pancreaticoduodenectomy. Collateral pathways management depends on variety of collateral pathways.
Trends in insufficient physical activity among adults in China 2010–18: a population-based study
Authors: Zhang Mei , Ma Yanan , Xie Xili , Sun Ming , Huang Zhengjing , Zhao Zhenping , Zhang Xiao , Li Chun , Gao Xingxing , Wu Jing , Wang Limin , Zhou Maigeng , Wen Deliang 
Published: July 2023

Abstract
Background
The global prevalence of insufficient physical activity (PA) was reported to be 27.5% in 2016, and there were stable levels of insufficient PA worldwide between 2001 and 2016. The global target of a 10% reduction in insufficient PA by 2025 will not be met if the trends remain. The relevant data for trends in China were still scarce. This study aimed to determine nationwide temporal trends in insufficient PA among adults in China from 2010 to 2018.

Methods
645 903 adults aged 18 years or older were randomly selected from four nationally representative cross-sectional surveys of the China Chronic Disease and Risk Factor Surveillance conducted in 2010, 2013, 2015, and 2018. PA was measured using the Global Physical Activity Questionnaire. Temporal changes in insufficient PA prevalence and participation of domain-specific moderate- to vigorous-intensity PA (MVPA) were analyzed using logistic regression.

Results
From 2010 to 2018, the age-adjusted prevalence of insufficient PA in China increased from 17.9% (95% confidence interval 16.3% to 19.5%) in 2010 to 22.3% (20.9% to 23.8%) in 2018 (P for trend < 0.001). By age group, with a significant increase in insufficient PA in adults aged 18–34 years (P for trend < 0.001), which rose more rapidly than in adults aged ≥ 35 years (P for interaction < 0.001). Insufficient PA has increased significantly among adults engaged in agriculture-related work, non-manual work, and other manual work (all P for trend < 0.05). And among the occupational groups, those engaged in agriculture-related work had the fastest increase (P for interaction = 0.01). The percentage of adults participating in work-related MVPA decreased from 79.6% (77.8% to 81.5%) to 66.8% (64.9% to 68.7%) along with a decrease in time spent on work-related MVPA, while percentages of adults participating in recreation-related MVPA increased from 14.2% (12.5% to 15.9%) to 17.2% (16.0% to 18.4%) (all P for trend < 0.05).

Conclusions
Among Chinese adults, an increasing trend was found in insufficient PA from 2010 to 2018, with more than one-fifth of adults failing to achieve the recommendation of adequate PA. More targeted PA promotion strategies should be developed to improve population health.
Genetic characterization of dilated cardiomyopathy patients undergoing heart transplantation in the Chinese population by whole-exome sequencing
Authors: Lian Hong , Song Shen , Chen Wenzheng , Shi Anteng , Jiang Haobin , Hu Shengshou 
Published: July 2023

Abstract
Background
Dilated cardiomyopathy (DCM) is one of the most frequent causes of heart failure and heart transplantation (HTx). The genetic basis of DCM among patients undergoing HTx remains to be further studied. This study aimed to characterize the genetic basis of DCM HTx in the Chinese population.

Methods
In total, 208 unrelated DCM patients who underwent HTx at Fuwai Hospital between June 2004 and June 2017 were included in this study. Whole-exome sequencing (WES) was performed for all patients. Gene burden analysis, variant classification, and genotype–phenotype correlation analysis were subsequently performed.

Results
After completing the bioinformatics analysis, gene burden analysis suggested that titin (TTN), filamin C (FLNC) and lamin A/C (LMNA) were significantly enriched with rare protein-altering variants. The frequencies of TTN and FLNC truncating variants in our cohort were 18.8% and 8.7%, respectively. Among the 165 rare variants in high evidence DCM-related genes, 27 (16.4%) and 59 (35.8%) were interpreted as pathogenic (P) and likely pathogenic (LP), respectively. In addition, 41 (47.7%) and 16 (18.6%) of these 86 P/LP variants are located in TTN and FLNC, respectively. The FLNC group contained more patients with NYHA class IV than the P/LP-negative group (FLNC, 16/18 vs. P/LP-negative, 81/123, P = 0.049).

Conclusions
Based on WES, we provided a primary genetic spectrum of DCM patients undergoing HTx in the Chinese population. TTN and FLNC harbour the most P/LP variants. FLNC truncation may lead to severe clinical symptoms in DCM patients.
Unraveling the epigenetic landscape of pulmonary arterial hypertension: implications for personalized medicine development
Authors: Dave Jaydev , Jagana Vineeta , Janostiak Radoslav , Bisserier Malik 
Published: July 2023

AbstractPulmonary arterial hypertension (PAH) is a multifactorial disease associated with the remodeling of pulmonary blood vessels. If left unaddressed, PAH can lead to right heart failure and even death. Multiple biological processes, such as smooth muscle proliferation, endothelial dysfunction, inflammation, and resistance to apoptosis, are associated with PAH. Increasing evidence suggests that epigenetic factors play an important role in PAH by regulating the chromatin structure and altering the expression of critical genes. For example, aberrant DNA methylation and histone modifications such as histone acetylation and methylation have been observed in patients with PAH and are linked to vascular remodeling and pulmonary vascular dysfunction. In this review article, we provide a comprehensive overview of the role of key epigenetic targets in PAH pathogenesis, including DNA methyltransferase (DNMT), ten-eleven translocation enzymes (TET), switch-independent 3A (SIN3A), enhancer of zeste homolog 2 (EZH2), histone deacetylase (HDAC), and bromodomain-containing protein 4 (BRD4). Finally, we discuss the potential of multi-omics integration to better understand the molecular signature and profile of PAH patients and how this approach can help identify personalized treatment approaches.