bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of Problem-Based Learning implementation in a College of Medicine, Kingdom of Saudi Arabia: a cross sectional comparative study
Authors: Almulhem Manahel A. , Almulhem Jwaher A. 
Published: April 2022

Abstract
Background
Problem-Based Learning (PBL) is an innovative student-centered learning method that has been implemented in numerous medical colleges worldwide. However, the newly adopting PBL institutes may face challenges during its implementation. This study aims to evaluate PBL implementation in the medical college of Imam Abdulrahman bin Faisal University (IAU) from the facilitators’ and students’ perspectives.

Methods
This is a cross-sectional study using a quantitative self-administered online questionnaire. The questionnaire evaluated PBL implementation using the three scales: small group learning, problem case scenario, and facilitator role. A total of 52 facilitators and 1289 students (from second to sixth years) were invited to participate in the study at the end of the 2019–2020 academic year.

Results
Forty-six facilitators (88.46%) and 324 students (25.13%) responded to the questionnaire. There was an overall positive evaluation of PBL implementation. However, the facilitators’ rating was significantly higher than the students’ rating across the three scales. Regarding the small group learning, a significant difference was found between types of facilitation status (p = 0.017) and between trained and not trained facilitators (p = 0.029). In respect to the problem case scenario, there was a significant difference based on the types of facilitation status (p = 0.017) and facilitating tutorials related to the facilitator’s specialty (p = 0.004). Regarding the facilitator role, a significant difference was found between the academic year they had facilitated (p = 0.032). Female students rated the three scales significantly higher than male students (p < 0.001). Students aged between 24 and 25 years old and sixth years students also rated the three scales significantly higher than other students (P < 0.05).

Conclusions
The participants rated PBL implementation positively as measured by the three scales rating. However, specific concerns have been highlighted that are related to group dynamics, training before starting PBL, relevancy of the case scenarios, and the facilitator’s role in nominating group members and providing feedback.
Effect of distance learning on the quality of life, anxiety and stress levels of dental students during the COVID-19 pandemic
Authors: Başağaoğlu Demirekin Zeynep , Buyukcavus Muhammed Hilmi 
Published: April 2022

Abstract
Background
The long-term psychological effects of COVID-19 on dental students are unclear. The aim of this cross-sectional online study was to investigate the psychological effects of the COVID-19 pandemic on dental students.

Method
The Quality of Life Scale (WHOQOL-BREF) was sent to all dental students through Google Forms to evaluate their quality of life (QoL), and the DASS-21 scale was used to evaluate their psychosocial status due to distance learning during the COVID-19 pandemic. The answers were analyzed both on the basis of year of education and type of education (online versus classroom learning). One-way ANOVA was used for comparison of students in the different years of education; post hoc LSD test was used for pairwise comparisons. Sample t-test was used to compare the two groups separated as classroom/face-to-face learning and distance/online learning.

Result
The questionnaire was completed by 580 students with a response rate of 87.74%. According to the QoL scale results, there was no significant difference between the groups regarding general health, physical health, and psychology, both between different years and learning methods (p > 0.05). According to the results of the DASS-21 scale, anxiety and depression in the 3rd year students were significantly higher than the other years. The stress level of the 2nd year students was statistically significantly different from the other years (p < 0.05). Evaluation of anxiety, stress and the QoL showed an overall detrimental effect of distance learning on the dental students, although the evaluation did not reach statistical significance.

Conclusion
Anxiety, stress and factors affecting the quality of life negatively affected dental students who received online/distance learning, although the difference did not reach statistical significance when compared to students who received in-classroom learning.
Using video reflexive ethnography to explore the use of variable rate intravenous insulin infusions
Authors: Iflaifel Mais , Lim Rosemary , Crowley Clare , Greco Francesca , Iedema Rick 
Published: April 2022

Abstract
Background
The use of variable rate intravenous insulin infusion (VRIII) is a complex process that has consistently been implicated in reports of error and consequent harm. Investment in patient safety has focused mainly on learning from errors, though this has yet to be proved to reduce error rates. The Resilient Health Care approach advocates learning from everyday practices. Video reflexive ethnography (VRE) is an innovative methodology used to capture everyday practices, reflect on and thereby improve these. This study set out to explore the use of VRIIIs by utilising the VRE methodology.

Methods
This study was conducted in a Vascular Surgery Unit. VRE methodology was used to collect qualitative data that involved videoing healthcare practitioners caring for patients treated with VRIII and discussing the resulting clips with participants in reflexive meetings. Transcripts of these were subjected to thematic analysis. Quantitative data (e.g. blood glucose measurements) were collected from electronic patient records in order to contextualise the outcomes of the video-observed tasks.

Results
The use of VRE in conjunction with quantitative data revealed that context-dependent adaptations (seeking verbal orders to treat hypoglycaemia) and standardised practices (using VRIII guidelines) were strategies used in everyday work. Reflexive meetings highlighted the challenges faced while using VRIII, which were mainly related to lack of clinical knowledge, e.g. prescribing/continuing long-acting insulin analogues alongside the VRIII, and problems with organisational infrastructure, i.e. the wireless blood glucose meter results sometimes not updating on the electronic system. Reflexive meetings also enabled participants to share the meanings of the reality surrounding them and encouraged them to suggest solutions tailored to their work, for example face-to-face, VRIII-focused training.

Conclusions
VRE deepened understanding of VRIII by shedding light on its essential tasks and the challenges and adaptations entailed by its use. Future research might focus on collecting data across various units and hospitals to develop a full picture of the use of VRIIIs.
Mycobacterium bovis and M. caprae in Bulgaria: insight into transmission and phylogeography gained through whole-genome sequencing
Authors: Valcheva Violeta , Perea Claudia , Savova-Lalkovska Tanya , Dimitrova Albena , Radulski Lukasz , Mokrousov Igor , Marinov Krustyu , Najdenski Hristo , Bonovska Magdalena 
Published: April 2022

Abstract
Background
This study aimed to characterize recent Mycobacterium bovis/M. caprae isolates from Bulgaria by whole-genome sequencing (WGS) to gain a first insight into their molecular diversity, transmission, and position within the global phylogeography of this important zoonotic species.

Results
The isolates were obtained from cattle in diverse locations of Bulgaria in 2015-2020 and were identified by microbiological and PCR assays. WGS data were used for phylogenetic analysis that also included M. bovis global dataset. Thirty-seven M. bovis/caprae isolates from Bulgaria were studied and 34 of them were SNP genotyped. The isolates were subdivided into 3 major phylogenetic groups. Type Mbovis-13 (Eu2 complex [western Europe and northern Africa]) included one isolate. Mbovis-37 type included 5 isolates outside of known clonal complexes. The Bulgarian M. caprae isolates formed a sub-group within the Mcaprae-27B cluster which also included 22 M. caprae isolates from Poland, Spain, Germany, and the Republic of Congo. The Bulgarian M. caprae isolates share their latest common ancestors with Spanish isolates. The Mbovis-37 group shares a distant common ancestor (pairwise distance 22-29 SNPs) with an isolate from Poland but was very distant (> 200 SNPs) from the rest of the tree. The Mbovis-13 group shares a common ancestor with two human isolates from Germany. Phylogeographically, both M. bovis clades had limited circulation in northeastern Bulgaria while the majority of the studied isolates (M. caprae) were from central and western provinces. A phylogenetic network-based analysis demonstrated that 11 Bulgarian isolates were separated by 1 to 6 SNPs within four clusters, mostly forming pairs of isolates.

Conclusion
The obtained WGS analysis positioned the Bulgarian isolates within the global phylogeography of M. bovis/M. caprae. Hypothetically, the observed phylogenetic diversity may not have resulted from livestock trade routes, but instead may reflect the deeply rooted M. bovis/M. caprae phylogeography of Europe. A high level of genetic divergence between the majority of the studied isolates suggests limited active transmission of bTB in Bulgaria during the survey period. At the same time, a possibility of the endemic presence of circulating bTB strains in the form of the latent persistent disease cannot be ruled out.
Piezo1 promoted hepatocellular carcinoma progression and EMT through activating TGF-β signaling by recruiting Rab5c
Authors: Li Yi-ming , Xu Cong , Sun Bo , Zhong Fang-jing , Cao Momo , Yang Lian-yue 
Published: April 2022

Abstract
Background
Piezo1 has been revealed to play a regulatory role in vascular development and progression of variety tumors. However, whether and how the progression of hepatocellular carcinoma (HCC) regulated by Piezo1 remains elusive. This study aimed to elucidate the effect and mechanisms of Piezo1 in HCC.

Methods
The mRNA and protein expression level of Piezo1 in HCC samples and cell lines was determined by qRT-PCR, western blot and immunohistochemistry analyses. Two independent study cohorts containing 280 patients were analyzed to reveal the association between Piezo1 expression and clinicopathological characteristics. Series of in vitro and in vivo experiments were used to validate the function of Piezo1 in HCC. Gene set enrichment analysis (GSEA) was performed to explore the signaling pathway of Piezo1. Immunoprecipitation, immunofluorescence and in vitro and in vivo experiments were used to explore the molecular mechanism of Piezo1 in HCC progression.

Results
Our results demonstrated the Piezo1 expression was significantly upregulated in HCC tissues and cell lines, and upregulation of Piezo1 closely correlated with aggressive clinicopathological features and poor prognosis. Knockdown of Piezo1 in HCCLM3 and Hep3B cells significantly restrained proliferation, migration, invasion and epithelial–mesenchymal transition (EMT) of HCC cells in vitro, and tumor growth, metastasis, EMT in vivo. TGF-β signaling pathway was most significant enriched pathway in GSEA. Finally, tumor promotion effect of Piezo1 was found to exerted through recruiting and combining Rab5c to activating TGF-β signaling pathway.

Conclusions
Piezo1 significantly related to poor prognosis and promotes progression of hepatocellular carcinoma via activating TGF-β signaling, which suggesting that Piezo1 may serve as a novel prognostic predictor and the potential therapeutic target for HCC patients.
Exploring the potential for a new measure of socioeconomic deprivation status to monitor health inequality
Authors: Dirksen Jakob , Pinilla-Roncancio Monica , Wehrmeister Fernando C. , Ferreira Leonardo Z. , Vidaletti Luis Paulo , Kirkby Katherine , Koller Theadora Swift , Schlotheuber Anne , Tapia Heriberto , Vidal Fuertes Cecilia , Alkire Sabina , Barros Aluisio J. D. , Hosseinpoor Ahmad Reza 
Published: April 2022

Abstract
Background
Monitoring health inequalities is an important task for health research and policy, to uncover who is being left behind – and where – and to inform effective and equitable policies and programmes to tackle existing inequities. The choice of which measure to use to monitor and analyse health inequalities is thereby not trivial. This article explores a new measure of socioeconomic deprivation status (SDS) to monitor health inequalities.

Methods
The SDS measure was constructed using the Alkire-Foster method. It includes eight indicators across two equally weighted dimensions (education and living standards) and specifies a four-level gradient of socioeconomic deprivation at the household-level. We conducted four exercises to examine the value-added of the proposed SDS measure, using Demographic and Health Surveys data. First, we examined the discriminatory power of the new measure when applied to outcomes in four select reproductive, maternal, neonatal, and child health (RMNCH) indicators across six countries: skilled birth attendance, stunting, U5MR, and DTP3 immunisation. Then, we analysed the behaviour and association of the new SDS measure vis-à-vis the DHS Wealth Index, including chi-squared test and Pearson correlation coefficient. Third, we analysed the robustness of the SDS measure results to changes in its structure, using pairwise comparisons and Kendal Tau-b rank correlation. Finally, we illustrated some of the advantageous properties of the new measure, disaggregation and decomposition, on Haitian data.

Results
1) Higher levels of socioeconomic deprivation are generally consistently associated with lower levels of achievements in the RMNCH indicators across countries. 2) 87% of all pairwise rank comparisons across a range of SDS measure structures were robust. 3) SDS and DHS Wealth Index are associated, but with considerable cross-country variation, highlighting their complementarity. 4) Haitian households in rural areas experienced, on average, more severe socioeconomic deprivation as well as lower levels of RMNCH achievement than urban households.

Conclusions
The proposed SDS measure adds analytical possibilities to the health inequality monitoring literature, in line with ethically and conceptually well-founded notions of absolute, multidimensional disadvantage. In addition, it allows for breakdown by its dimensions and components, which may facilitate nuanced analyses of health inequality, its correlates, and determinants.
Targeting TGF-β signal transduction for fibrosis and cancer therapy
Authors: Peng Dandan , Fu Minyang , Wang Manni , Wei Yuquan , Wei Xiawei 
Published: April 2022

AbstractTransforming growth factor β (TGF-β) has long been identified with its intensive involvement in early embryonic development and organogenesis, immune supervision, tissue repair, and adult homeostasis. The role of TGF-β in fibrosis and cancer is complex and sometimes even contradictory, exhibiting either inhibitory or promoting effects depending on the stage of the disease. Under pathological conditions, overexpressed TGF-β causes epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) deposition, cancer-associated fibroblast (CAF) formation, which leads to fibrotic disease, and cancer. Given the critical role of TGF-β and its downstream molecules in the progression of fibrosis and cancers, therapeutics targeting TGF-β signaling appears to be a promising strategy. However, due to potential systemic cytotoxicity, the development of TGF-β therapeutics has lagged. In this review, we summarized the biological process of TGF-β, with its dual role in fibrosis and tumorigenesis, and the clinical application of TGF-β-targeting therapies.
RNA-based therapy in the management of lipid disorders: a review
Authors: Blom Dirk Jacobus , Marais Adrian David , Moodley Rajen , van der Merwe Nico , van Tonder Alet , Raal Frederick Johan 
Published: April 2022

AbstractThis review focuses on antisense oligonucleotides and small interfering ribonucleic acid therapies approved or under development for the management of lipid disorders. Recent advances in RNA-based therapeutics allow tissue-specific targeting improving safety. Multiple potential target proteins have been identified and RNA-based therapeutics have the potential to significantly improve outcomes for patients with or at risk for atherosclerotic cardiovascular disease. The advantages of RNA-based lipid modifying therapies include the ability to reduce the concentration of almost any target protein highly selectively, allowing for more precise control of metabolic pathways than can often be achieved with small molecule-based drugs. RNA-based lipid modifying therapies also make it possible to reduce the expression of target proteins for which there are no small molecule inhibitors. RNA-based therapies can also reduce pill burden as their administration schedule typically varies from weekly to twice yearly injections. The safety profile of most current RNA-based lipid therapies is acceptable but adverse events associated with various therapies targeting lipid pathways have included injection site reactions, inflammatory reactions, hepatic steatosis and thrombocytopenia. While the body of evidence for these therapies is expanding, clinical experience with these therapies is currently limited in duration and the results of long-term studies are eagerly awaited.
Extraperitoneal laparoscopic radical cystectomy with intracorporeal neobladder: a comparison with transperitoneal approach
Authors: Zhang Ying , Zhou Huan , Tuo Zhou Ting , Wang Jinyou , Sun Chenyu , Bi Liangkuan 
Published: April 2022

Abstract
Background
Bladder cancer is one of the most common genitourinary cancers. Traditional transperitoneal radical cystectomy is the gold standard treatment for muscle-invasive bladder cancer. Our study was to compare the perioperative and oncological outcomes of extraperitoneal laparoscopic radical cystectomy (ELRC) with intracorporeal neobladder versus transperitoneal urinary diversion for bladder cancer.

Method
A total of 113 patients who underwent laparoscopic radical cystectomy performed at our center were included in this retrospective study. The perioperative data of the extraperitoneal laparoscopic radical cystectomy (ELRC) with intracorporeal urinary diversion (ICUD) and transperitoneal laparoscopic radical cystectomy (TLRC) with ICUD groups were compared. The demographic, perioperative, oncological, and complication data were collected and analyzed.

Results
In total, 113 patients were enrolled for the final analysis. The median follow-up period was 22 months. The ELRC group had shorter interval to flatus (p < 0.001), solid food (p < 0.001), shorter length of hospital stay (p < 0.01), and fewer early gastrointestinal complications (p < 0.05). Furthermore, urinary continence, recurrence-free, cancer-specific, and overall survival rates and recurrence patterns did not significantly differ.

Conclusions
Surgical technique of ELRC with ICUD can achieve the established oncologic criteria of TLRC, and such technique can improve perioperative and early postoperative outcomes.
Prognostic factors of BRAF V600E colorectal cancer with liver metastases: a retrospective multicentric study
Authors: Javed Sahir , Benoist Stéphane , Devos Patrick , Truant Stéphanie , Guimbaud Rosine , Lièvre Astrid , Sefrioui David , Cohen Romain , Artru Pascal , Dupré Aurélien , Bachet Jean-Baptiste , de la Fouchardière Christelle , Ploquin Anne , Turpin Anthony 
Published: April 2022

Abstract
Background
BRAF V600E-mutant colorectal cancers (CRCs) are associated with shorter survival than BRAF wild-type tumors. Therapeutic decision-making for colorectal liver metastases (CRLM) harboring this mutation remains difficult due to the scarce literature. The aim was to study a large cohort of BRAF V600E-mutant CRLM patients in order to see if surgery extend overall survival among others prognostic factors.

Methods
BRAF V600E-mutant CRCs diagnosed with liver-only metastases, resected or not, were retrospectively identified between April 2008 and December 2017, in 25 French centers. Clinical, molecular, pathological characteristics and treatment features were collected. Overall survival (OS) was defined as the time from CRLM diagnosis to death from any cause. Cox proportional hazard models were used for statistical analysis.

Results
Among the 105 patients included, 79 (75%) received chemotherapy, 18 (17%) underwent upfront CRLM surgery, and 8 (8%) received exclusive best supportive care. CRLM surgery was performed in 49 (46.7%) patients. CRLM were mainly synchronous (90%) with bilobar presentation (61%). The median OS was 34 months (range, 28.9–67.3 months) for resected patients and 10.6 (6.7–12.5) months for unresected patients (P < 0.0001). In multivariate analysis, primary tumor surgery (hazard ratio (HR) = 0.349; 95% confidence interval (CI) 0.164–0.744, P = 0.0064) and CRLM resection (HR = 0.169; 95% CI 0.082–0.348, P < 0.0001) were associated with significantly better OS.

Conclusions
In the era of systemic cytotoxic chemotherapies, liver surgery seems to extend OS in BRAF V600E-mutant CRCs with liver only metastases historical cohort.
ACT001 attenuates microglia-mediated neuroinflammation after traumatic brain injury via inhibiting AKT/NFκB/NLRP3 pathway
Authors: Cai Lin , Gong Qiuyuan , Qi Lin , Xu Tongtong , Suo Qian , Li Xiang , Wang Wei , Jing Yao , Yang Dianxu , Xu Zhiming , Yuan Fang , Tang Yaohui , Yang Guoyuan , Ding Jun , Chen Hao , Tian Hengli 
Published: April 2022

Abstract
Background
Microglia-mediated neuroinflammatory response following traumatic brain injury (TBI) is considered as a vital secondary injury factor, which drives trauma-induced neurodegeneration and is lack of efficient treatment. ACT001, a sesquiterpene lactone derivative, is reportedly involved in alleviation of inflammatory response. However, little is known regarding its function in regulating innate immune response of central nervous system (CNS) after TBI. This study aimed to investigate the role and underlying mechanism of ACT001 in TBI.

Methods
Controlled cortical impact (CCI) models were used to establish model of TBI. Cresyl violet staining, evans blue extravasation, neurobehavioral function assessments, immunofluorescence and transmission electron microscopy were used to evaluate therapeutic effects of ACT001 in vivo. Microglial depletion was induced by administering mice with colony stimulating factor 1 receptor (CSF1R) inhibitor, PLX5622. Cell-cell interaction models were established as co-culture system to simulate TBI conditions in vitro. Cytotoxic effect of ACT001 on cell viability was assessed by cell counting kit-8 and activation of microglia cells were induced by Lipopolysaccharides (LPS). Pro-inflammatory cytokines expression was determined by Real-time PCR and nitric oxide production. Apoptotic cells were detected by TUNEL and flow cytometry assays. Tube formation was performed to evaluate cellular angiogenic ability. ELISA and western blot experiments were used to determine proteins expression. Pull-down assay was used to analyze proteins that bound ACT001.

Results
ACT001 relieved the extent of blood-brain barrier integrity damage and alleviated motor function deficits after TBI via reducing trauma-induced activation of microglia cells. Delayed depletion of microglia with PLX5622 hindered therapeutic effect of ACT001. Furthermore, ACT001 alleviated LPS-induced activation in mouse and rat primary microglia cells. Besides, ACT001 was effective in suppressing LPS-induced pro-inflammatory cytokines production in BV2 cells, resulting in reduction of neuronal apoptosis in HT22 cells and improvement of tube formation in bEnd.3 cells. Mechanism by which ACT001 functioned was related to AKT/NFκB/NLRP3 pathway. ACT001 restrained NFκB nuclear translocation in microglia cells through inhibiting AKT phosphorylation, resulting in decrease of NLRP3 inflammasome activation, and finally down-regulated microglial neuroinflammatory response.

Conclusions
Our study indicated that ACT001 played critical role in microglia-mediated neuroinflammatory response and might be a novel potential chemotherapeutic drug for TBI.