bluuebunny/crossref_metadata_2025_split huggingface dataset:
How an EPA-based curriculum supports professional identity formation
Authors: Bremer Anne E. , van de Pol Marjolein H. J. , Laan Roland F. J. M. , Fluit Cornelia R. M. G. 
Published: January 2022

Abstract
Background
Entrustable professional activities (EPAs) are widely used in medical education, and they might be an important incentive to stimulate professional identity formation (PIF) of medical students, by actively encouraging participation in the workplace. The goal of this study was to explore the effects of an EPA-based curriculum on the PIF of medical students in undergraduate curricula.

Methods
In this study at the Radboud University Medical Center in Nijmegen, the Netherlands, the authors interviewed twenty-one medical students in three focus group interviews (November 2019), and conducted a thematic analysis based on both the synthesizing concepts PIF, communities of practice and EPAs, and newly defined themes.

Results
Four central themes proved crucial for understanding the influence of EPAs on PIF: creating learning opportunities, managing feedback, dealing with supervision in context and developing confidence. EPAs helped students to create learning opportunities and to choose activities purposefully, and the use of EPAs stimulated their feedback-seeking behavior. The context and way of supervision had a great impact on their development, where some contexts offer better learning opportunities than others. EPAs helped them develop trust and self-confidence, but trust from supervisors hardly appears to result from using EPAs.

Conclusions
An EPA-based curriculum does stimulate PIF in the complex context of working and learning by supporting participation in the workplace and by encouraging feedback-seeking behavior. Striking the right balance between participation, feedback-seeking behavior and choosing learning activities is essential.

Trial registration
This study was approved by the ethics committee of the Netherlands Association of Medical Education (NVMO, case number 2019.5.12).
Periostin promotes the proliferation and metastasis of osteosarcoma by increasing cell survival and activates the PI3K/Akt pathway
Authors: Xu Chaojian , Wang Ziyue , Zhang Long , Feng Yi , Lv Jia , Wu Zhuangzhuang , Yang Rong , Wu Taiyong , Li Jian , Zhou Ruhao , Tian Zhi , Bai Junjun , Zhang Huadong , Lan Yanping , Lv Zhi 
Published: January 2022

Abstract
Background
Silencing of the periostin gene (POSTN) can inhibit the biological process of several different cancers, and this inhibition may be related to down-regulation of PI3K/AKT signaling. However, the effect of POSTN on the progression, proliferation, and invasion of osteosarcoma (OS) remain unclear.

Methods
We used the Gene Expression Omnibus (GEO) database to screen datasets on in situ OS and lung metastases to identify core genes and potential pathways. We used additional bioinformatics tools to identify protein–protein interactions (PPIs) and gene networks, and selected the top seven genes whose expression had the strongest correlations with other genes.

Results
The results indicated that POSTN was a major hub gene. Subsequent analysis of gene expression profiles showed that POSTN was highly expressed in 262 cases with sarcoma and expression was closely related to poor prognosis. We also performed enrichment analysis to identify differentially expressed genes and used real-time PCR, western blotting, and immunohistochemistry analyses to measure POSTN expression in cells and tissues. Transfection of a POSTN-shRNA plasmid into cultured OS cells (Saos-2) effectively inhibited the proliferation, invasion, and migration of these cells. Taken together, our results suggest that POSTN may play a role in promoting the proliferation and metastasis of OS by activation of the PI3K/Akt signaling pathway.

Conclusions
Our results provide a preliminary characterization of the mechanism by which POSTN may regulate the migration and invasion of OS cells and also provide a theoretical basis for identifying biomarkers that have potential use for the diagnosis and treatment of OS.
Core policies disparity response to COVID-19 among BRICS countries
Authors: Jiao Jun , Shi Leiyu , Zhang Yuyao , Chen Haiqian , Wang Xiaohan , Yang Manfei , Yang Junyan , Liu Meiheng , Sun Gang 
Published: January 2022

Abstract
Objective
To provide experience for formulating prevention and control policies, this study analyzed the effectiveness of the Coronavirus disease 2019(COVID-19) prevention and control policies, and evaluated health equity and epidemic cooperation among BRICS countries.

Methods
This study summarized the pandemic prevention and control policies in BRICS countries and evaluated the effectiveness of those policies by extracting COVID-19 related data from official websites.

Result
As of May 4, 2021, responding to COVID-19. China adopted containment strategies. China’s total confirmed cases (102,560) were stable, without a second pandemic peak, and the total deaths per million (3.37) were much lower than others. India and South Africa who adopted intermediate strategies have similar pandemic curves, total confirmed cases in India (20,664,979) surpassed South Africa (1,586,148) as the highest in five countries, but total deaths per million (163.90) lower than South Africa (919.11). Brazil and Russia adopted mitigation strategies. Total confirmed cases in Brazil (14,856,888) and Russia (4,784,497) continued to increase, and Brazil’s total deaths per million (1,936.34) is higher than Russia (751.50) and other countries.

Conclusion
This study shows BRICS countries implemented different epidemic interventions. Containment strategy is more effective than intermediate strategy and mitigation strategy in limiting the spread of COVID-19. Especially when a strict containment strategy is implemented in an early stage, but premature relaxation of restrictions may lead to rebounding. It is a good choice to combat COVID-19 by improving the inclusiveness of intervention policies, deepening BRICS epidemic cooperation, and increasing health equities.
High remnant cholesterol level is relevant to diabetic retinopathy in type 2 diabetes mellitus
Authors: Shan Yongyan , Wang Qian , Zhang Yitong , Tong Xuewei , Pu Shengdan , Xu Yuxin , Gao Xinyuan 
Published: January 2022

Abstract
Background
Diabetic retinopathy (DR) is the primary oculopathy causing blindness in diabetic patients. Currently, there is increasing interest in the role of lipids in the development of diabetic retinopathy, but it remains controversial. Remnant cholesterol (RC) is an inexpensive and easily measurable lipid parameter; however, the relationship between RC and DR in type 2 diabetes mellitus (T2DM) has not been elucidated. This research investigates the relevance between RC levels and DR severity while building a risk prediction model about DR.

Methods
In this single-centre retrospective cross-sectional study. Each hospitalised T2DM patient had no oral lipid-lowering drugs in the past three months, and coronary angiography showed epicardial coronary artery stenosis of less than 50% and completed seven-field stereo photographs, fluorescein fundus angiography, and optical coherence tomography detection. The RC value is calculated according to the internationally recognised formula. Binary logistic regression was used to correct confounding factors, and the receiver operating characteristic (ROC) analysis was used to identify risk factors and assess the nomogram’s diagnostic efficiency.

Results
A total of 456 T2DM patients were included in the study. The RC levels in the DR team was higher [0.74 (0.60–1.12) mmo/l vs 0.54 (0.31–0.83) mmol/l P < 0.001] in the non-DR team. After adjusting for confounding elements, RC levels are still associated with DR risk (OR = 5.623 95%CI: 2.996–10.556 P < 0.001). The ratio of DR in every stage (except mild non-proliferative diabetic retinopathy) and DME in the high RC level team were further increased compared to the low-level team (all P < 0.001). After ROC analysis, the overall risk of DR was predicted by a nomogram constructed for RC, diabetes duration, and the neutrophil-lymphocyte ratio as 0.758 (95%CI 0.714–0.802 P < 0.001).

Conclusions
High RC levels may be a potential risk factor for diabetic retinopathy, and the nomogram does better predict DR. Despite these essential findings, the limitation of this study is that it is single-centred and small sample size analysis.
The polymorphism analysis and epitope predicted of Alphapapillomavirus 9 E6 in Sichuan, China
Authors: He Jiaoyu , Li Qiufu , Ma Shiyu , Li Tianjun , Chen Yuning , Liu Yiran , Cui Yanru , Peng Jianying , Shi Yunfan , Wei Xia , Ding Xianping 
Published: January 2022

Abstract
Background
The Alphapapillomavirus 9 (α-9 HPV) is a member of the Alphapapillomavirus genus and Papillomaviridae family. These viruses are almost all carcinogenic HPV, which is closely related to 75% of invasive cervical cancer worldwide, and has a high prevalence in Sichuan. The carcinogenic function is mainly realized by its E6 oncoprotein.

Methods
Cell samples were collected by cervical scraped for HPV detecting and typing.
HPV-16, HPV-31, HPV-33, HPV-52, HPV-58 5 α-9 genus HPV subtype positive samples were selected, their E6 gene was sequenced and analyzed. The positive selection sites of HPV E6 genes were estimated by PAML 4.8 server. The secondary and tertiary structure of E6 protein were predicted by PSIPred and Swiss-model. The T-cell antigen epitopes of E6 protein were predicted by IEDB.

Results
α-9 HPV has a high prevalence in Sichuan, China. From 2012 to 2017, 18,067 cell cervical samples were collected, and 3135 were detected with α-9 HPV infection. Among which, 250 cases HPV-16 E6, 96 cases HPV-31 E6, 216 cases HPV-33 E6, 288 cases HPV-52 E6 and 405 cases HPV-58 E6 were successfully amplified, 17, 6, 6, 13, and 4 non-synonymous nucleotide mutations were respectively detected in HPV-16, 31, 33, 52, and 58 E6, 7 positive selection sites of α-9 HPV E6 were selected out (D32E of HPV-16 E6, K35N, K93N and R145I of HPV-33 E6, K93R of HPV-52 E6, K93N and R145K of HPV-58 E6). The structure and antigen epitopes of E6 protein with amino acid substitution differ from those of wild-type E6 protein, especially for the mutation located in the E6 positive selection site.

Conclusions
HPV E6 nucleotide non-synonymous mutation in the positive selection site influence the protein structure and decrease the antigen epitopes affinity of the E6 protein overall, making it more difficult for the HPV-infected cells to be detected by the immune system, and enhancing the HPV adaptability to the environment. Mutations influence the validity of HPV clinical diagnostic probes, the polymorphism analysis of α-9 HPV E6 enrich the data of HR-risk HPV in Sichuan China, and the detection probes designed with the polymorphism data in mind can improve the efficiency of clinical detection; Mutations influence epitopes affinity, the association of E6 polymorphism and epitope affinity can improve the design of therapeutic vaccine with good immunity and high generality antigen epitope; The above study all provide a good theoretical basis for the prevention and treatment of HPV-related diseases.
Comparison of clinical behavior between mucinous ovarian carcinoma with infiltrative and expansile invasion and high-grade serous ovarian carcinoma: a retrospective analysis
Authors: Hada Taira , Miyamoto Morikazu , Ishibashi Hiroki , Matsuura Hiroko , Kakimoto Soichiro , Iwahashi Hideki , Tsuda Hitoshi , Takano Masashi 
Published: January 2022

Abstract
Background
The aim of this study was to evaluate the clinicopathological factors and prognosis of mucinous carcinoma (MC) with infiltrative invasion, MC with expansile invasion, and high-grade serous carcinoma (HGSC).

Methods
Cases of MC and HGSC between 1984 and 2019 were identified. The clinicopathological factors and prognosis of MC with infiltrative invasion or expansile invasion and HGSC were retrospectively compared. Although our present study included cases in our previous studies, we extended observational period when analysis was performed. Accordingly, our study added increased cases and survival analysis was newly conducted.

Results
After pathological review, 27 cases of MC with infiltrative invasion, 25 cases of MC with expansile invasion, and 219 cases of HGSC were included. MC had a better prognosis in terms of progression-free survival (PFS, p < 0.01) and overall survival (OS, p < 0.01) than HGSC for all International Federation of Gynecology and Obstetrics (FIGO) stages; however, multivariate analysis did not show statistical differences in PFS and OS. There were no statistically significant differences in PFS and OS for all FIGO stages between MC with infiltrative invasion and HGSC. However, in cases with FIGO stages II to IV, MC with infiltrative invasion had worse PFS (p < 0.01) and OS (p < 0.01) than HGSC. In univariate analysis, MC with infiltrative invasion was a worse prognostic factor for PFS (hazard ratio [HR] 2.83, p < 0.01) and OS (HR 3.83, p < 0.01) than HGSC. Compared with HGSC, MC with expansile invasion had better PFS (p < 0.01) and OS (p < 0.01). Multivariate analysis demonstrated that MC with expansile invasion was a better prognostic factor for PFS (HR 0.17, p < 0.01) and OS (HR 0.18, p = 0.03) than HGSC.

Conclusions
Compared to the prognosis of HGSC, that of MC was different according to the invasive pattern and FIGO stage. Therefore, future study may be needed to consider this association.
The boosting effects of melatonin on the expression of related genes to oocyte maturation and antioxidant pathways: a polycystic ovary syndrome- mouse model
Authors: Nikmard Fatemeh , Hosseini Elham , Bakhtiyari Mehrdad , Ashrafi Mahnaz , Amidi Fardin , Aflatoonian Reza 
Published: January 2022

Abstract
Background
Melatonin, as a free radical scavenger exhibiting genomic actions, regulates the antioxidant genes expression and apoptosis mechanisms. In polycystic ovary syndrome (PCOS) patients, an imbalance between free radicals and antioxidants in follicular fluid leads to oxidative stress, aberrant folliculogenesis, and intrinsic defects in PCOS oocytes. In this experimental mouse model study, oocytes of PCOS and the control groups were cultured in different melatonin concentrations (10− 5, 10− 6, and 10− 7 M) to investigate the expression of oocyte maturation-related genes (Gdf9/Bmp15), antioxidant-related genes (Gpx1/Sod1), apoptotic biomarkers (Bcl2/Bax) and total intracellular ROS levels.

Results
Gdf9 and Bmp15, Gpx1 and Sod1 were up-regulated in PCOS and control oocytes cultured in all melatonin concentrations compared to those cultured in IVM basal medium (P < 0.05). A significant decrease in the total ROS level was observed in all groups cultured in the supplemented cultures. Melatonin increased Bcl2 and decreased Bax gene expression in PCOS and control oocytes compared to non-treated oocytes.

Conclusions
Melatonin increased antioxidant gene expression and regulated the apoptosis pathway, effectively reducing the adverse effects of culture conditions on PCOS oocytes. Furthermore, it influenced the expression of oocyte maturation-related genes in PCOS, providing valuable support during the IVM process.
Covid-19 and spirometry in this age
Authors: Klain Angela , Indolfi Cristiana , Dinardo Giulio , Decimo Fabio , Miraglia Del Giudice Michele 
Published: January 2022

AbstractIn the last year, many countries adopted a plan to contain hospital infections by Sars-Cov-2 also limiting pulmonary function tests (PFTs), exclusively to indispensable cases. All the recommendations of the major scientific societies regarding the use of PFTs, in particular spirometry, in the Covid era were formulated in the initial period of the pandemic. Currently, the new scientific knowledge about Sars-Cov-2 and the vaccination among healthcare workers, shown new insight to start doing PFTs again to help the investigation and monitoring of patients with respiratory pathology. In this article, we sum up the recommendations of major International Respiratory Societies, and we shared our experience about PFTs in a Pediatric Respiratory Disease Unit during the pandemic.
The behavioral variant of Alzheimer’s disease does not show a selective loss of Von Economo and phylogenetically related neurons in the anterior cingulate cortex
Authors: Singleton E. H. , Pijnenburg Y. A. L. , Gami-Patel P. , Boon B. D. C. , Bouwman F. , Papma J. M. , Seelaar H. , Scheltens P. , Grinberg L. T. , Spina S. , Nana A. L. , Rabinovici G. D. , Seeley W. W. , Ossenkoppele R. , Dijkstra A. A. 
Published: January 2022

Abstract
Background
The neurobiological origins of the early and predominant behavioral changes seen in the behavioral variant of Alzheimer’s disease (bvAD) remain unclear. A selective loss of Von Economo neurons (VENs) and phylogenetically related neurons have been observed in behavioral variant frontotemporal dementia (bvFTD) and several psychiatric diseases. Here, we assessed whether these specific neuronal populations show a selective loss in bvAD.

Methods
VENs and GABA receptor subunit theta (GABRQ)-immunoreactive pyramidal neurons of the anterior cingulate cortex (ACC) were quantified in post-mortem tissue of patients with bvAD (n = 9) and compared to typical AD (tAD, n = 6), bvFTD due to frontotemporal lobar degeneration based on TDP-43 pathology (FTLD, n = 18) and controls (n = 13) using ANCOVAs adjusted for age and Bonferroni corrected. In addition, ratios of VENs and GABRQ-immunoreactive (GABRQ-ir) pyramidal neurons over all Layer 5 neurons were compared between groups to correct for overall Layer 5 neuronal loss.

Results
The number of VENs or GABRQ-ir neurons did not differ significantly between bvAD (VENs: 26.0 ± 15.3, GABRQ-ir pyramidal: 260.4 ± 87.1) and tAD (VENs: 32.0 ± 18.1, p = 1.00, GABRQ-ir pyramidal: 349.8 ± 109.6, p = 0.38) and controls (VENs: 33.5 ± 20.3, p = 1.00, GABRQ-ir pyramidal: 339.4 ± 95.9, p = 0.37). Compared to bvFTD, patients with bvAD showed significantly more GABRQ-ir pyramidal neurons (bvFTD: 140.5 ± 82.658, p = 0.01) and no significant differences in number of VENs (bvFTD: 10.9 ± 13.8, p = 0.13). Results were similar when assessing the number of VENs and GABRQ-ir relative to all neurons of Layer 5.

Discussion
VENs and phylogenetically related neurons did not show a selective loss in the ACC in patients with bvAD. Our results suggest that, unlike in bvFTD, the clinical presentation in bvAD may not be related to the loss of VENs and related neurons in the ACC.
Clinical characteristics and CT features of hepatic epithelioid haemangioendothelioma and comparison with those of liver metastases
Authors: Wang Xiaopeng , Liang Pan , Lv Peijie , Li Rui , Hou Ping , Gao Jianbo 
Published: January 2022

Abstract
Background
To analyse clinical characteristics and computer tomography (CT) findings of hepatic epithelioid haemangioendothelioma (HEH) and to determine differential features compared with liver metastasis (LM).

Methods
This retrospective study included 80 patients with histopathologically confirmed HEH (n = 20) and LM (n = 60) of different primary tumours who underwent dynamic contrast-enhanced CT scans. CT findings included the location, contour, size, number, margin, and density of lesions, the patterns and degree of contrast enhancement of lesions, vascular invasion and changes in other organs. The enhancement ratio (ER) and tumour-to-normal parenchyma ratio (TNR) were calculated. Receiver operating characteristic curves (ROCs) were used to determine areas under the curve (AUCs).

Results
About 65% of HEH lesions were located in submarginal areas. Significant differences were observed between HEH and LM patients in age, sex, and tumour marker positivity (p < 0.05). HEH showed minimal to slight enhancement, thin ring-like enhancement in arterial phase, and slight, homogeneous, progressive enhancement in the portal phase. HEH presented capsule retraction, and the “target” sign and the “lollipop” sign were significantly more frequent than in LM (p < 0.05). The ER and TNR in the arterial phase of HEH were lower than those of LM (p < 0.05). AUCs of ER and TNR in the arterial phase were 0.74 and 0.73, respectively.

Conclusion
Lesions in subcapsular locations, capsular retraction, slight and thin ring-like enhancement, “target” and “lollipop” signs and lower ER and TNR in the arterial phase may represent important features of HEH compared with LM.
The use of disaggregate data in evaluations of public health interventions: cross-sectional dependence can bias inference
Authors: Halkjelsvik Torleif , Gasparrini Antonio , Hart Rannveig Kaldager 
Published: January 2022

AbstractHigher availability of administrative data and better infrastructure for electronic surveys allow for large sample sizes in evaluations of national and other large scale policies. Although larger datasets have many advantages, the use of big disaggregate data (e.g., on individuals, households, stores, municipalities) can be challenging in terms of statistical inference. Measurements made at the same point in time may be jointly influenced by contemporaneous factors and produce more variation across time than suggested by the model. This excess variation, or co-movement over time, produce observations that are not truly independent (i.e., cross-sectional dependence). If this dependency is not accounted for, statistical uncertainty will be underestimated, and studies may indicate reform effects where there is none. In the context of interrupted time series (segmented regression), we illustrate the potential for bias in inference when using large disaggregate data, and we describe two simple solutions that are available in standard statistical software.
Small-sized type A thymoma with pulmonary metastasis: a case report
Authors: Kawagishi Sachi , Maniwa Tomohiro , Watari Hirokazu , Sakata Ryuhei , Omura Akiisa , Tanaka Ryo , Kimura Toru , Honma Keiichiro , Okami Jiro 
Published: January 2022

Abstract
Background
Type A thymomas comprise a homogenous population of neoplastic epithelial cells that are characterized by a spindle/oval shape without nuclear atypia. They may be accompanied by few non-neoplastic lymphocytes. Most type A thymomas are detected in the earlier Masaoka stages. Compared to other thymoma subtypes, they rarely metastasize or recur. There have been some reports of patients with type A thymomas with pulmonary metastasis; however, these thymomas were 20 mm or more in size. Herein, we report the case of a patient who underwent surgical resection for a small-sized type A thymoma (12 mm) with pulmonary metastasis.

Case presentation
A 62-year-old patient presented with an abnormal shadow in the left lung on plain chest radiography during a medical checkup. Chest computed tomography revealed a 12-mm tumor in the anterior mediastinum and a 13-mm nodule in the left lower lobe. 18F-fluorodeoxyglucose positron emission tomography/computed tomography revealed uptake in the anterior mediastinal tumor, but did not show a significant uptake in the pulmonary nodule. The patient underwent surgical resection on two separate occasions, and was diagnosed with an atypical type A thymoma and pulmonary metastasis. The TNM classification was p-T1aN0M1b stage IVb, and it was stage IVb according to the Masaoka staging system. No recurrence was observed during the follow-up.

Conclusions
We report a case of the smallest type A thymoma with pulmonary metastasis. Pulmonary metastasis secondary to a type A thymoma should be considered even if the thymoma is small in size (< 20 mm).