bluuebunny/crossref_metadata_2025_split huggingface dataset:
Entrustable professional activities for Junior Brazilian Medical Students in community medicine
Authors: Francischetti Ieda , Holzhausen Ylva , Peters Harm 
Published: October 2022

AbstractBackgroundEntrustable professional activities (EPAs) have been defined to promote the workplace participation of undergraduate medical students, generally in the context of high-income countries with a focus on the secondary and tertiary health care sectors. These EPAs have limited applicability to training and health care contexts in low- to middle-income countries that have a focus on primary health care, for instance, the context of community medicine. The purpose of this article is to report the process and results of defining EPAs for undergraduate medical training in a community health care setting.MethodsA modified Delphi study was performed to develop EPAs for the training of medical students in community medicine during their first and second years of education at the Marília Medical School (FAMEMA), Brazil. The supervision level was operationalized in terms of a student’s ability to perform the EPA autonomously in an effective and safe manner with supervision readily available on request. Panellists (9 physicians and 6 nurses) rated the completeness of the proposed list of EPAs and EPA categories on four-point Likert scales. The threshold for consensus among panellists was a mean content validity index of at least 80%.ResultsConsensus was reached after two Delphi rounds, resulting in 11 EPAs for undergraduate medical education and training in community medicine. These EPAs were organized into three overarching EPA domains: integrality of care for individual health needs in all phases of the life cycle (5 EPAs), integrality of care for family health needs (3 EPAs), and integrality of care for community health needs (3 EPAs). For each EPA, descriptions of the following categories were created: title; specifications and limitations; conditions and implications of the entrustment decision; knowledge, skills, and attitudes; links to competencies; and assessment sources.ConclusionThe resulting 11 EPAs for training medical students in community medicine expand the application of the EPA framework to both early undergraduate medical education and the context of primary health care. This report can support and guide other medical schools in their attempts to train students in primary health care contexts and to incorporate EPAs into their curricula.
Developing a competence framework for gerontological nursing in China: a two-phase research design including a needs analysis and verification study
Authors: Dijkman Bea L. , Hirjaba Marina , Wang Wenwen , Palovaara Marjo , Annen Marjolein , Varik Merle , Cui Ying’ai , Li Jing , van Slochteren Cornelia , Jihong Wang , Feiteng Chen , Luo Yu , Chen Yudong , Paans Wolter 
Published: October 2022

AbstractBackgroundChina faces a serious shortage of competent nurses who can address the healthcare needs of older people in an ageing society. Chinese higher education institutes face serious challenges when it comes to developing new curricula that are capable of educating sufficient numbers of competent gerontological nurses. Therefore, the aim of this research study was to identify and verify competencies for gerontological nurses in China that are needed to provide nursing care for the growing number of older people in all care settings. This study takes into account the possible opportunities that trends and developments may offer in the near future.MethodsIn this study, a two-phase research design was used. The first phase concerned needs analysis, including a situational analysis, a trend analysis and a competence analysis. This process resulted in a draft competence framework. The second phase addressed the verification of the competence framework through a two-round Delphi study with a panel of Chinese and European experts. This process led to the final competence framework.ResultsThe final competence framework for gerontological nursing in China included six competencies divided into 13 essential and five relevant learning outcomes. The competencies are: ‘providing gerontological care’, ‘communication and collaboration’, ‘organization of gerontological nursing care’, ‘health promotion’, ‘evidence-based nursing and lifelong learning’ and ‘professional behaviour’.ConclusionThe framework comprehensively covers the six core competencies that nurses who care for older people should possess. These competencies are well-embedded in a Chinese context. The framework therefore offers concrete, practical suggestions for the competencies and skills that nursing graduates will need to work in current and future professions related to gerontological nursing education and practice.
(Dis)advantaged positions in accessing gender-affirming healthcare in Finland: an intersectional qualitative study of foreign-origin transgender people
Authors: Czimbalmos Mercédesz , Rask Shadia 
Published: October 2022

Abstract
Background
An increasing body of scholarship focuses on transgender individuals’ experiences when accessing gender-affirming healthcare. However, the experiences of transgender individuals who identify as being of foreign-origin in Finland have rarely been studied. This study aims to fill the gap in research and contribute to the understanding of the experiences of transgender individuals who also identify as belonging to the foreign-origin populations in Finland.

Methods
Fourteen semi-structured qualitative interviews were conducted and analyzed with reflexive thematic analysis (RTA), through the framework of intersectionality. The interviews were part of a broader sample of qualitative data, collected about the experiences of sexual and gender minorities among the foreign-origin populations in Finland.

Results
The analysis showed two main interconnected themes. Firstly, perceived barriers when accessing gender-affirming care. In this theme, the intersections of transgender identity, foreign background, class, and age affected the experiences of the individuals. Secondly, the necessity of “performing identities:” the intersections of class, transgender identity, nativity, and race affected those.

Conclusion
The findings of the current study suggest that the intersectional aspects of individual identities create structural inequalities in the Finnish gender-affirming healthcare system. To tackle these inequalities, further research is needed on the healthcare experiences of gender minorities in Finland both within and outside the scope of transgender-specific healthcare.
Why do older people not use the public health services of the integrated aging program? A multidimensional approach in a qualitative study
Authors: Moghadasi Amir Mohamad , Sum Shima , Matlabi Hossein 
Published: October 2022

Abstract
Objectives
The world’s population is aging rapidly and a huge amount of services are being provided to meet the needs of the older people. Identifying the factors affecting the non-attendance of the older people to health care centres is of particular importance. We focused on the reasons why older people do not use the services of the integrated aging program in Iran from the perspective of the older people, general practitioners, and primary health providers.

Methods
A qualitative study in Ghaemshahr (IRAN) carried out during 2021. Data were collected through semi-structured interviews in two groups with the participation of 29 older adults and 18 employees of the health centres Purposeful sampling and sample size were determined based on data saturation. Data were analyzed manually using conventional content analysis.

Results
Potential barriers to and challenges of older adults were generally categorized into four main themes including individual, systemic-structural, environmental, and social factors.

Conclusions
Both groups agreed on many aspects, including lack of education of the patients and lack of proper medical services. Existing problems in health care relate to both medical and non-medical factors. Improvement in health care delivery requires a deliberate focus on the patients’ specific needs.
Metabolomic profile of prostate cancer-specific survival among 1812 Finnish men
Authors: Huang Jiaqi , Zhao Bin , Weinstein Stephanie J. , Albanes Demetrius , Mondul Alison M. 
Published: October 2022

Abstract
Background
Abnormal metabolism and perturbations in metabolic pathways play significant roles in the development and progression of prostate cancer; however, comprehensive metabolomic analyses of human data are lacking and needed to elucidate the interrelationships.

Methods
We examined the serum metabolome in relation to prostate cancer survival in a cohort of 1812 cases in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Using an ultrahigh-performance LC-MS/MS platform, we identified 961 known metabolites in prospectively collected serum. Median survival time from diagnosis to prostate cancer-specific death (N=472) was 6.6 years (interquartile range=2.9–11.1 years). Cox proportional hazards regression models estimated hazard ratios and 95% confidence intervals of the associations between the serum metabolites (in quartiles) and prostate cancer death, adjusted for age at baseline and diagnosis, disease stage, and Gleason sum. In order to calculate risk scores, we first randomly divided the metabolomic data into a discovery set (70%) and validated in a replication set (30%).

Results
Overall, 49 metabolites were associated with prostate cancer survival after Bonferroni correction. Notably, higher levels of the phospholipid choline, amino acid glutamate, long-chain polyunsaturated fatty acid (n6) arachidonate (20:4n6), and glutamyl amino acids gamma-glutamylglutamate, gamma-glutamylglycine, and gamma-glutamylleucine were associated with increased risk of prostate cancer-specific mortality (fourth versus first quartile HRs=2.07–2.14; P-values <5.2×10−5). By contrast, the ascorbate/aldarate metabolite oxalate, xenobiotics S-carboxymethyl-L-cysteine, fibrinogen cleavage peptides ADpSGEGDFXAEGGGVR and fibrinopeptide B (1-12) were related to reduced disease-specific mortality (fourth versus first quartile HRs=0.82–0.84; P-value <5.2×10−5). Further adjustment for years from blood collection to cancer diagnosis, body mass index, smoking intensity and duration, and serum total and high-density lipoprotein cholesterol did not alter the results. Participants with a higher metabolic score based on the discovery set had an elevated risk of prostate cancer-specific mortality in the replication set (fourth versus first quartile, HR=3.9, P-value for trend<0.0001).

Conclusions
The metabolic traits identified in this study, including for choline, glutamate, arachidonate, gamma-glutamyl amino acids, fibrinopeptides, and endocannabinoid and redox pathways and their composite risk score, corroborate our previous analysis of fatal prostate cancer and provide novel insights and potential leads regarding the molecular basis of prostate cancer progression and mortality.
Bifunctional anti-PD-L1/TGF-βRII agent SHR-1701 in advanced solid tumors: a dose-escalation, dose-expansion, and clinical-expansion phase 1 trial
Authors: Liu Dan , Zhou Jun , Wang Yongsheng , Li Mingjun , Jiang Haiping , Liu Yunpeng , Yin Xianli , Ge Minghua , Xiang Xiaojun , Ying Jieer , Huang Jian , Zhang Yan-qiao , Cheng Ying , Huang Zhigang , Yuan Xianglin , Han Weiqing , Yan Dong , Wang Xinshuai , Liu Pan , Wang Linna , Zhang Xiaojing , Luo Suxia , Liu Tianshu , Shen Lin 
Published: October 2022

Abstract
Background
Dual inhibition of PD-1/PD-L1 and TGF-β pathways is a rational therapeutic strategy for malignancies. SHR-1701 is a new bifunctional fusion protein composed of a monoclonal antibody against PD-L1 fused with the extracellular domain of TGF-β receptor II. This first-in-human trial aimed to assess SHR-1701 in pretreated advanced solid tumors and find the population who could benefit from SHR-1701.

Methods
This was a dose-escalation, dose-expansion, and clinical-expansion phase 1 study. Dose escalation was initiated by accelerated titration (1 mg/kg q3w; intravenous infusion) and then switched to a 3+3 scheme (3, 10, 20, and 30 mg/kg q3w and 30 mg/kg q2w), followed by dose expansion at 10, 20, and 30 mg/kg q3w and 30 mg/kg q2w. The primary endpoints of the dose-escalation and dose-expansion parts were the maximum tolerated dose and recommended phase 2 dose. In the clinical-expansion part, selected tumors were enrolled to receive SHR-1701 at the recommended dose, with a primary endpoint of confirmed objective response rate (ORR).

Results
In total, 171 patients were enrolled (dose-escalation: n=17; dose-expansion, n=33; clinical-expansion, n=121). In the dose-escalation part, no dose-limiting toxicity was observed, and the maximum tolerated dose was not reached. SHR-1701 showed a linear dose-exposure relationship and the highest ORR at 30 mg/kg every 3 weeks, without obviously aggravated toxicities across doses in the dose-escalation and dose-expansion parts. Combined, 30 mg/kg every 3 weeks was determined as the recommended phase 2 dose. In the clinical-expansion part, SHR-1701 showed the most favorable efficacy in the gastric cancer cohort, with an ORR of 20.0% (7/35; 95% CI, 8.4–36.9) and a 12-month overall survival rate of 54.5% (95% CI, 29.5–73.9). Grade ≥3 treatment-related adverse events occurred in 37 of 171 patients (22%), mainly including increased gamma-glutamyltransferase (4%), increased aspartate aminotransferase (3%), anemia (3%), hyponatremia (3%), and rash (2%). Generally, patients with PD-L1 CPS ≥1 or pSMAD2 histochemical score ≥235 had numerically higher ORR.

Conclusions
SHR-1701 showed an acceptable safety profile and encouraging antitumor activity in pretreated advanced solid tumors, especially in gastric cancer, establishing the foundation for further exploration.

Trial registration
ClinicalTrials.gov, NCT03710265
Biomarkers beyond BRCA: promising combinatorial treatment strategies in overcoming resistance to PARP inhibitors
Authors: Chu Yu-Yi , Yam Clinton , Yamaguchi Hirohito , Hung Mien-Chie 
Published: October 2022

AbstractPoly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) exploit the concept of synthetic lethality and offer great promise in the treatment of tumors with deficiencies in homologous recombination (HR) repair. PARPi exert antitumor activity by blocking Poly(ADP-ribosyl)ation (PARylation) and trapping PARP1 on damaged DNA. To date, the U.S. Food and Drug Administration (FDA) has approved four PARPi for the treatment of several cancer types including ovarian, breast, pancreatic and prostate cancer. Although patients with HR-deficient tumors benefit from PARPi, majority of tumors ultimately develop acquired resistance to PARPi. Furthermore, even though BRCA1/2 mutations are commonly used as markers of PARPi sensitivity in current clinical practice, not all patients with BRCA1/2 mutations have PARPi-sensitive disease. Thus, there is an urgent need to elucidate the molecular mechanisms of PARPi resistance to support the development of rational effective treatment strategies aimed at overcoming resistance to PARPi, as well as reliable biomarkers to accurately identify patients who will most likely benefit from treatment with PARPi, either as monotherapy or in combination with other agents, so called marker-guided effective therapy (Mget). In this review, we summarize the molecular mechanisms driving the efficacy of and resistance to PARPi as well as emerging therapeutic strategies to overcome PARPi resistance. We also highlight the identification of potential markers to predict PARPi resistance and guide promising PARPi-based combination strategies.
Role of triglycerides as a predictor of autoimmune hepatitis with cirrhosis
Authors: Wang Peng , Wang Yuqi , Liu Hui , Han Xiaoxu , Yi Yunyun , Wang Xin , Li Xin 
Published: October 2022

AbstractBackgroundMetabolism-related indicators have been suggested as possible prognostic indicators of liver disease in recent relevant studies, but their value in predicting autoimmune hepatitis (AIH) cirrhosis is unclear. This study evaluated the role of lipid levels in determining the prognosis of AIH-related cirrhosis.MethodsWe retrospectively included 345 patients with AIH who were initially diagnosed at Beijing Ditan Hospital from 2010-2019, and ultimately screened 196 patients who met the criteria. A logistic regression analysis was performed to screen factors associated with cirrhosis. Kaplan–Meier (KM) curves were constructed to analyze the effects of different triglyceride (TG) levels on the survival of patients with cirrhosis. A restricted cubic spline fitted Cox regression model was used to analyze the nonlinear relationship between serum TG levels and patient prognosis.ResultsPatients with AIH cirrhosis have lower TG levels than those without cirrhosis. Lower serum TG levels correlated with the severity of cirrhosis. The survival analysis showed that TG levels were associated with the overall survival of patients with AIH, as a lower 5-year survival rate (log-rankP<0.05) was observed for patients in the TG≤0.95 mmol/L group (hazard ratio (HR)=3.79, 95% CI: 1.528-9.423). In addition, lower TG levels were associated with a higher incidence of death in patients with AIH cirrhosis. The risk of death gradually increased for the interval of TG levels of 0.5-0.8 mmol/L (Pfor nonlinearity<0.001), and the hazard ratio per standard deviation increase in the TG level was 0.97 (95% CI: 0.94-0.99). The plot showed a U-shaped relationship between TG levels and the survival of patients with decompensated cirrhosis. The risk ratio progressively decreased with lower TG levels (Pfor nonlinearity=0.002). Below 0.6 mmol/L, the probability of TG risk per standard deviation prediction was 1.49 (95% CI: 1.00-2.24).ConclusionSerum TG levels are closely related to the disease severity and overall survival of patients with AIH cirrhosis and may be used as a new indicator of advanced liver disease and long-term prognosis.
Extracellular vesicles derived from endometrial epithelial cells deliver exogenous miR-92b-3p to affect the function of embryonic trophoblast cells via targeting TSC1 and DKK3
Authors: Hua Renwu , Liu Qiaorui , Lian Weisi , Kang Ting ting , Gao Dengying , Huang Cheng , Wang Yueying , Lei Minggang 
Published: October 2022

AbstractBackgroundExtracellular vesicles (EVs) could mediate embryo-maternal communication to affect embryo implantation by delivering biology information, including microRNA (miRNA), protein, lipid. Our previous research shows that miR-92b-3p was differentially expressed in EVs of uterine flushing fluids during the embryo implantation period. However, the role of miR-92b-3p from EVs in embryo implantation remains elusive.Materials and methodsEVs were isolated from porcine endometrial epithelial cells (EECs) by ultracentrifugation. MiR-92b-3p mimics and EVs were used to regulate the expression of miR-92b-3p in porcine trophoblast cells (PTr2 cells). Cell proliferation, migration and adhesion analyses were used to observe the phenotype. RT-qPCR, western blot and dual-luciferase reporter assay were used to assess the targets of miR-92b-3p.ResultsIn this study, EVs derived from porcine EECs were identified and could be taken up by PTr2 cells. We found that the EVs derived from EECs transfected with miR-92b-3p mimic (EVs-miR-92b-3p) significantly promoted the proliferation, migration and adhesion of PTr2 cells. We verified thatTuberous sclerosis complex subunit(TSC1) andDickkopf 3(DKK3) were the target genes of miR-92b-3p. Moreover, our study showed that miR-92b-3p plays a vital role in PTr2 cells via targetingTSC1andDKK3.Furthermore, the 3'UTR vectors of TSC1 and DKK3 can rescue the effect of miR-92b-3p on PTr2 cells.ConclusionsTaken together, this study reveals a novel mechanism that EVs derived from porcine EECs treated with miR-92b-3p crosstalk with trophoblasts by targetingTSC1andDKK3, leading to an enhanced ability for implantation.
Metformin alleviates bone loss in ovariectomized mice through inhibition of autophagy of osteoclast precursors mediated by E2F1
Authors: Xie Xudong , Hu Liangcong , Mi Bobin , Xue Hang , Hu Yiqiang , Panayi Adriana C. , Endo Yori , Chen Lang , Yan Chenchen , Lin Ze , Li Hui , Zhou Wu , Liu Guohui 
Published: October 2022

Abstract
Background
Postmenopausal bone loss, mainly caused by excessive bone resorption mediated by osteoclasts, has become a global public health burden. Metformin, a hypoglycemic drug, has been reported to have beneficial effects on maintaining bone health. However, the role and underlying mechanism of metformin in ovariectomized (OVX)-induced bone loss is still vague.

Results
In this study, we demonstrated for the first time that metformin administration alleviated bone loss in postmenopausal women and ovariectomized mice, based on reduced bone resorption markers, increased bone mineral density (BMD) and improvement of bone microstructure. Then, osteoclast precursors administered metformin in vitro and in vivo were collected to examine the differentiation potential and autophagical level. The mechanism was investigated by infection with lentivirus-mediated BNIP3 or E2F1 overexpression. We observed a dramatical inhibition of autophagosome synthesis and osteoclast formation and activity. Treatment with RAPA, an autophagy activator, abrogated the metformin-mediated autophagy downregulation and inhibition of osteoclastogenesis. Additionally, overexpression of E2F1 demonstrated that reduction of OVX-upregulated autophagy mediated by metformin was E2F1 dependent. Mechanistically, metformin-mediated downregulation of E2F1 in ovariectomized mice could downregulate BECN1 and BNIP3 levels, which subsequently perturbed the binding of BECN1 to BCL2. Furthermore, the disconnect between BECN1 and BCL2 was shown by BNIP3 overexpression.

Conclusion
In summary, we demonstrated the effect and underlying mechanism of metformin on OVX-induced bone loss, which could be, at least in part, ascribed to its role in downregulating autophagy during osteoclastogenesis via E2F1-dependent BECN1 and BCL2 downregulation, suggesting that metformin or E2F1 inhibitor is a potential agent against postmenopausal bone loss.
Immune checkpoint of B7-H3 in cancer: from immunology to clinical immunotherapy
Authors: Zhao Binghao , Li Huanzhang , Xia Yu , Wang Yaning , Wang Yuekun , Shi Yixin , Xing Hao , Qu Tian , Wang Yu , Ma Wenbin 
Published: October 2022

AbstractImmunotherapy for cancer is a rapidly developing treatment that modifies the immune system and enhances the antitumor immune response. B7-H3 (CD276), a member of the B7 family that plays an immunoregulatory role in the T cell response, has been highlighted as a novel potential target for cancer immunotherapy. B7-H3 has been shown to play an inhibitory role in T cell activation and proliferation, participate in tumor immune evasion and influence both the immune response and tumor behavior through different signaling pathways. B7-H3 expression has been found to be aberrantly upregulated in many different cancer types, and an association between B7-H3 expression and poor prognosis has been established. Immunotherapy targeting B7-H3 through different approaches has been developing rapidly, and many ongoing clinical trials are exploring the safety and efficacy profiles of these therapies in cancer. In this review, we summarize the emerging research on the function and underlying pathways of B7-H3, the expression and roles of B7-H3 in different cancer types, and the advances in B7-H3-targeted therapy. Considering different tumor microenvironment characteristics and results from preclinical models to clinical practice, the research indicates that B7-H3 is a promising target for future immunotherapy, which might eventually contribute to an improvement in cancer immunotherapy that will benefit patients.