bluuebunny/crossref_metadata_2025_split huggingface dataset:
Specialty career preferences among final year medical students at Makerere University College of health sciences, Uganda: a mixed methods study
Authors: Kuteesa Job , Musiime Victor , Munabi Ian G. , Mubuuke Aloysius G. , Opoka Robert , Mukunya David , Kiguli Sarah 
Published: April 2021

AbstractBackgroundUganda has an imbalanced distribution of the health workforce, which may be influenced by the specialty career preferences of medical students. In spite of this, there is inadequate literature concerning the factors influencing specialty career preferences. We aimed to determine the specialty career preferences and the factors influencing the preferences among fifth year medical students in the School of Medicine, Makerere University College of Health Sciences (MakCHS).MethodsA sequential explanatory mixed methods study design with a descriptive cross-sectional study followed by a qualitative study was used. A total of 135 final year medical students in MakCHS were recruited using consecutive sampling. Self-administered questionnaires and three focus group discussions were conducted. Quantitative data was analysed in STATA version 13 (StataCorp, College Station, Tx, USA) using descriptive statistics, chi-square tests and logistic regression. Qualitative data was analysed in NVIVO version 12 (QRS International, Cambridge, MA) using content analysis.ResultsOf 135 students 91 (67.4%) were male and their median age was 24 years (IQR: 24, 26). As a first choice, the most preferred specialty career was obstetrics and gynecology (34/135, 25.2%), followed by surgery (27/135, 20.0%), pediatrics (18/135, 13.3%) and internal medicine (17/135, 12.6%). Non-established specialties such as anesthesia and Ear Nose and Throat (ENT) were not selected as a first choice by any student. Female students had 63% less odds of selecting surgical related specialties compared to males (aOR = 0.37, 95%CI: 0.17–0.84).The focus group discussions highlighted controlled lifestyle, assurance of a good life through better financial remuneration and inspirational specialists as facilitators for specialty preference. Bad experience during the clinical rotations, lack of career guidance plus perceived poor and miserable specialists were highlighted as barriers to specialty preference.ConclusionObstetrics and Gynecology, Surgery, Pediatrics and Internal Medicine are well-established disciplines, which were dominantly preferred. Females were less likely to select surgical disciplines as a career choice. Therefore, there is a need to implement or establish career guidance and mentorship programs to attract students to the neglected disciplines.
Factors associated with parents’ experiences using a knowledge translation tool for vaccination pain management: a qualitative study
Authors: MacKenzie Nicole E. , Tutelman Perri R. , Chambers Christine T. , Parker Jennifer A. , MacDonald Noni E. , McMurtry C. Meghan , Pluye Pierre , Granikov Vera , Taddio Anna , Barwick Melanie , Birnie Kathryn A. , Boerner Katelynn E. 
Published: April 2021

Abstract
Background
Vaccination is a common painful procedure for children. Parents’ concern regarding vaccination pain is a significant driver of vaccine hesitancy. Despite the wealth of evidence-based practices available for managing vaccination pain, parents lack knowledge of, and access to, these strategies. Knowledge translation (KT) tools can communicate evidence-based information to parents, however little is known about what factors influence parents’ use of these tools. A two-page, electronic KT tool on psychological, physical, and pharmacological vaccination pain management strategies for children, was shared with parents as part of a larger mixed methods study, using explanatory sequential design, exploring factors related to uptake of this KT tool. The aim of this qualitative study was to understand what influenced parents’ perceptions of the relevance of the KT tool, as well as their decision as to whether to use the tool.

Methods
A qualitative descriptive design was used. A total of 20 parents of children aged 0–17 years (n = 19 mothers) reviewed the KT tool ahead of their child’s upcoming vaccination and participated in a semi-structured interview at follow-up. Interviews were recorded, transcribed verbatim, and analyzed with reflexive thematic analysis using an inductive approach.

Results
The analysis generated three interrelated themes which described factors related to parents’ use of the KT tool: (1) Relevance to parents’ needs and circumstances surrounding their child’s vaccination; (2) Alignment with parents’ personal values around, and experiences with, vaccination pain management (e.g., the importance of managing pain); and (3) Support from the clinical environment for implementing evidence-based strategies (e.g., physical clinical environment and quality of interactions with the health care provider).

Conclusions
Several factors were identified as central to parents’ use of the KT tool, including the information itself and the clinical environment. When the tool was perceived as relevant, aligned with parents’ values, and was supported by health care providers, parents were more inclined to use the KT tool to manage their children’s vaccination pain. Future research could explore other factors related to promoting engagement and uptake when creating parent-directed KT tools for a range of health-related contexts.
Engineered sex ratio distortion by X-shredding in the global agricultural pest Ceratitis capitata
Authors: Meccariello Angela , Krsticevic Flavia , Colonna Rita , Del Corsano Giuseppe , Fasulo Barbara , Papathanos Philippos Aris , Windbichler Nikolai 
Published: April 2021

AbstractBackgroundGenetic sex ratio distorters are systems aimed at effecting a bias in the reproductive sex ratio of a population and could be applied for the area-wide control of sexually reproducing insects that vector disease or disrupt agricultural production. One example of such a system leading to male bias is X-shredding, an approach that interferes with the transmission of the X-chromosome by inducing multiple DNA double-strand breaks during male meiosis. Endonucleases targeting the X-chromosome and whose activity is restricted to male gametogenesis have recently been pioneered as a means to engineer such traits.ResultsHere, we enabled endogenous CRISPR/Cas9 and CRISPR/Cas12a activity during spermatogenesis of the Mediterranean fruit flyCeratitis capitata, a worldwide agricultural pest of extensive economic significance. In the absence of a chromosome-level assembly, we analysed long- and short-read genome sequencing data from males and females to identify two clusters of abundant and X-chromosome-specific sequence repeats. When targeted by gRNAs in conjunction with Cas9, cleavage of these repeats yielded a significant and consistent distortion of the sex ratio towards males in independent transgenic strains, while the combination of distinct distorters induced a strong bias (~ 80%).ConclusionWe provide a first demonstration of CRISPR-based sex distortion towards male bias in a non-model organism, the global pest insectCeratitis capitata. Although the sex ratio bias reached in our study would require improvement, possibly through the generation and combination of additional transgenic lines, to result in a system with realistic applicability in the field, our results suggest that strains with characteristics suitable for field application can now be developed for a range of medically or agriculturally relevant insect species.
Chromatin accessibility landscapes of immune cells in rheumatoid arthritis nominate monocytes in disease pathogenesis
Authors: Zong Dandan , Huang Beibei , Li Young , Lu Yichen , Xiang Nan , Guo Chuang , Liu Qian , Sha Qing , Du Pengcheng , Yu Qiaoni , Zhang Wen , Cai Pengfei , Sun Yanping , Tao Jinhui , Li Xiaomei , Cai Shanbao , Qu Kun 
Published: April 2021

Abstract
Background
Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease that involves a variety of cell types. However, how the epigenetic dysregulations of peripheral immune cells contribute to the pathogenesis of RA still remains largely unclear.

Results
Here, we analysed the genome-wide active DNA regulatory elements of four major immune cells, namely monocytes, B cells, CD4+ T cells and CD8+ T cells, in peripheral blood of RA patients, osteoarthritis (OA) patients and healthy donors using Assay of Transposase Accessible Chromatin with sequencing (ATAC-seq). We found a strong RA-associated chromatin dysregulation signature in monocytes, but no other examined cell types. Moreover, we found that serum C-reactive protein (CRP) can induce the RA-associated chromatin dysregulation in monocytes via in vitro experiments. And the extent of this dysregulation was regulated through the transcription factor FRA2.

Conclusions
Together, our study revealed a CRP-induced pathogenic chromatin dysregulation signature in monocytes from RA patients and predicted the responsible signalling pathway as potential therapeutic targets for the disease.
Associations between attainment of incentivised primary care indicators and incident diabetic retinopathy in England: a population-based historical cohort study
Authors: McKay Ailsa J. , Gunn Laura H. , Sathish Thirunavukkarasu , Vamos Eszter , Nugawela Manjula , Majeed Azeem , Molina German , Sivaprasad Sobha 
Published: April 2021

Abstract
Background
The associations between England’s incentivised primary care-based diabetes prevention activities and hard clinical endpoints remain unclear. We aimed to examine the associations between attainment of primary care indicators and incident diabetic retinopathy (DR) among people with type 2 diabetes.

Methods
A historical cohort (n = 60,094) of people aged ≥ 18 years with type 2 diabetes and no DR at baseline was obtained from the UK Clinical Practice Research Datalink (CPRD). Exposures included attainment of the Quality and Outcomes Framework (QOF) HbA1c (≤ 7.5% or 59 mmol/mol), blood pressure (≤ 140/80 mmHg), and cholesterol (≤ 5 mmol/L) indicators, and number of National Diabetes Audit (NDA) care processes completed (categorised as 0–3, 4–6, or 7–9), in 2010–2011. Outcomes were time to development of DR and sight-threatening diabetic retinopathy (STDR). Nearest neighbour propensity score matching was undertaken and Cox proportional hazards models then fitted using the matched samples. Concordance statistics were calculated for each model.

Results
8263 DR and 832 STDR diagnoses were observed over mean follow-up periods of 3.5 (SD 2.1) and 3.8 (SD 2.0) years, respectively. HbA1c and blood pressure (BP) indicator attainment were associated with lower rates of DR (adjusted hazard ratios (aHRs) 0.94 (95% CI 0.89–0.99) and 0.87 (0.83–0.92), respectively), whereas cholesterol indicator attainment was not (aHR 1.03 (0.97–1.10)). All QOF indicators were associated with lower rates of STDR (aHRs 0.74 (0.62–0.87) for HbA1c, 0.78 (0.67–0.91) for BP, and 0.82 (0.67–0.99) for cholesterol). Completion of 7–9 vs. 0–3 NDA processes was associated with fewer STDR diagnoses (aHR 0.72 (0.55–0.94)).

Conclusions
Attainment of key primary care indicators is associated with lower incidence of DR and STDR among patients with type 2 diabetes in England.
Silencing SHMT2 inhibits the progression of tongue squamous cell carcinoma through cell cycle regulation
Authors: Liao Yan , Wang Fang , Zhang Yadong , Cai Hongshi , Song Fan , Hou Jinsong 
Published: April 2021

Abstract
Background
Serine hydroxymethyltransferase 2 (SHMT2) is a vital metabolic enzyme in one carbon metabolism catalyzing the conversion of serine to glycine, which has been reported to play a crucial role in the progression of tumors. However, its function in tongue squamous cell carcinoma (TSCC) remains unclear.

Methods
SHMT2 expression was analyzed using samples in online databases, and was assessed through immunohistochemistry staining of collected clinical specimens. The correlation between SHMT2 expression and the cell cycle was predicted through bioinformatic analysis, including weighted gene co-expression network analysis (WGCNA) and gene set enrichment analysis (GSEA). After transfection with siRNA, CCK8 assay, Edu staining, flow cytometry, trans-well assay, and wound healing experiments were performed to verify the functional role of SHMT2 in vitro. A stable cell line with SHMT2 silencing was established to detect the oncogenic function of SHMT2 in vivo.

Results
The expression of SHMT2 was up-regulated in TSCC tissues and cell lines compared with normal groups, and highly expressed SHMT2 significantly indicated a poorer clinical outcome for TSCC patients. Bioinformatic analysis found that high expression of SHMT2 was closely related with biologic process including cell cycle and cell cycle G1/S transition. Down regulating of SHMT2 significantly suppressed the proliferation, invasive and migrative ability of TSCC cells, and induced the prolongation of the G1 phase of the cell cycle in vitro. Furthermore, western blot showed that cell cycle-related regulators such as cyclin-dependent kinase 4 (CDK4) and cyclinD1 expression levels were decreased, while the expression levels of the cyclin-dependent kinase inhibitors p21Cip1 and p27Kip1 were increased after SHMT2 knockdown. Silencing SHMT2 in the HN6 cell line using short hairpin RNA also impeded tumor growth in vivo.

Conclusions
Overexpression of SHMT2 in TSCC indicated low survival rates, and was associated with aggressive behaviors of TSCC. It was also found to be involved in cell cycle regulation of TSCC cells. SHMT2 may serve as a novel prognostic indicator of TSCC.
Shock and awe or incentive-compatible harm reduction? Graphic health warnings on tobacco packages
Authors: Irvine Ian , Nguyen Hai V. 
Published: April 2021

Abstract
Background
Graphic Health Warnings (GHWs) on cigarette packages were first introduced in Canada in 2001 and will become mandatory in the US as of January 2022. While previous studies have evaluated the impacts of GHWs, the data used in these studies have several shortcomings. The objective of this paper was to investigate the likely impact of such warnings in the US based upon the experience of Canada using hitherto unexplored monthly cigarette sales data, and to explore if alternative approaches involving risk-reduced products might be more successful in reducing smoking.

Methods
We used quasi-experimental segmented regression and difference-in-differences analyses. Data on monthly sales (i.e., shipments) of cigarettes from Canadian manufacturers to Canadian retailers during 1995–2005 were obtained from Statistics Canada.

Results
We found that GHWs did not have a significant impact on the sales of cigarettes in Canada. We propose an alternative type of graphical health messaging that actively combines information on how to quit with the legally required messaging. The novelty of the proposal is that it is incentive compatible for the supply side of the market and if adopted in several states, the measure could be tested by using a suitable treatment–control design.

Conclusions
Our findings imply that we should not expect any notable decline in sales or consumption as a result of implementation of GHWs in the US. The main impact of GHWs will be to add to the anti-smoking culture that has grown steadily over several decades, and this may impact smoking in the longer term.
The differences in health-related quality of life between younger and older adults and its associated factors in patients with type 2 diabetes mellitus in Indonesia
Authors: Sari Yunita , Isworo Atyanti , Upoyo Arif Setyo , Taufik Agis , Setiyani Rahmi , Swasti Keksi Girindra , Haryanto Haryanto , Yusuf Saldy , Nasruddin Nasruddin , Kamaluddin Ridlwan 
Published: April 2021

Abstract
Background
It is well known that diabetes mellitus (DM) affects health-related quality of life (HRQOL) in both younger (aged 18–64 years) and older adults (aged ≥ 65 years). However, to date, no study has compared HRQOL and its predictors between younger and older adults with DM in Indonesia. Such a comparison is important because the results can guide nurses and clinicians to establish evidence-based educational programs that are specific and suitable for patients. Therefore, the aim of this study was to investigate the difference in HRQOL and its predictors in younger and older adults with DM in Indonesia.

Methods
A cross-sectional study was conducted on 641 patients with type 2 diabetes mellitus (T2DM) who were recruited via simple random sampling from 16 primary health centers in Banyumas Regency, Indonesia. A self-administered questionnaire containing the Summary of Diabetes Self-Care Activities, the DDS17 Bahasa Indonesia, the Beck Depression Inventory II, the Self-Efficacy for Diabetes Scale, the Family APGAR, and the 36-item Short-Form Health Survey was used to measure diabetes self-management (DSM), diabetes distress (DD), depression, self-efficacy, family support, and HRQOL, respectively. Independent t-tests were used to compare the physical component summary (PCS) and mental component summary (MCS) scores between younger and older adults with T2DM. Hierarchical multiple regression analyses were used to examine the factors associated with HRQOL in both groups.

Results
PCS scores were significantly different between the two groups. Older adults reported lower PCS scores than younger adults. No differences between the two groups were observed in the MCS scores. The hierarchical multiple regression analysis showed that level of education, employment status, number of diabetes-related complications, DSM, DD, depression, and self-efficacy were significant predictors of HRQOL in younger adults, while income, depression, DD, and self-efficacy were significant predictors of HRQOL in older adults. DD was the strongest predictor of HRQOL in younger adults, and depression was the strongest predictor in older adults.

Conclusion
Older adult patients had lower PCS scores than younger adult patients. This study is the first to show that the predictors of HRQOL differ between younger and older adults with T2DM. It provides insights for nurses and clinicians in Indonesia to establish evidence-based, age-specific educational programs.
Effect of robotic-assisted gait training on objective biomechanical measures of gait in persons post-stroke: a systematic review and meta-analysis
Authors: Nedergård Heidi , Arumugam Ashokan , Sandlund Marlene , Bråndal Anna , Häger Charlotte K. 
Published: April 2021

Abstract
Background
Robotic-Assisted Gait Training (RAGT) may enable high-intensive and task-specific gait training post-stroke. The effect of RAGT on gait movement patterns has however not been comprehensively reviewed. The purpose of this review was to summarize the evidence for potentially superior effects of RAGT on biomechanical measures of gait post-stroke when compared with non-robotic gait training alone.

Methods
Nine databases were searched using database-specific search terms from their inception until January 2021. We included randomized controlled trials investigating the effects of RAGT (e.g., using exoskeletons or end-effectors) on spatiotemporal, kinematic and kinetic parameters among adults suffering from any stage of stroke. Screening, data extraction and judgement of risk of bias (using the Cochrane Risk of bias 2 tool) were performed by 2–3 independent reviewers. The Grading of Recommendations Assessment Development and Evaluation (GRADE) criteria were used to evaluate the certainty of evidence for the biomechanical gait measures of interest.

Results
Thirteen studies including a total of 412 individuals (mean age: 52–69 years; 264 males) met eligibility criteria and were included. RAGT was employed either as monotherapy or in combination with other therapies in a subacute or chronic phase post-stroke. The included studies showed a high risk of bias (n = 6), some concerns (n = 6) or a low risk of bias (n = 1). Meta-analyses using a random-effects model for gait speed, cadence, step length (non-affected side) and spatial asymmetry revealed no significant differences between the RAGT and comparator groups, while stride length (mean difference [MD] 2.86 cm), step length (affected side; MD 2.67 cm) and temporal asymmetry calculated in ratio-values (MD 0.09) improved slightly more in the RAGT groups. There were serious weaknesses with almost all GRADE domains (risk of bias, consistency, directness, or precision of the findings) for the included outcome measures (spatiotemporal and kinematic gait parameters). Kinetic parameters were not reported at all.

Conclusion
There were few relevant studies and the review synthesis revealed a very low certainty in current evidence for employing RAGT to improve gait biomechanics post-stroke. Further high-quality, robust clinical trials on RAGT that complement clinical data with biomechanical data are thus warranted to disentangle the potential effects of such interventions on gait biomechanics post-stroke.
RETRACTED ARTICLE: Calcium-dependent cytosolic phospholipase A2 activation is implicated in neuroinflammation and oxidative stress associated with ApoE4
Authors: Wang Shaowei , Li Boyang , Solomon Victoria , Fonteh Alfred , Rapoport Stanley I. , Bennett David A. , Arvanitakis Zoe , Chui Helena C. , Miller Carol , Sullivan Patrick M. , Wang Hoau-Yan , Yassine Hussein N. 
Published: April 2021

Abstract
Background
Apolipoprotein E4 (APOE4) is associated with a greater response to neuroinflammation and the risk of developing late-onset Alzheimer’s disease (AD), but the mechanisms for this association are not clear. The activation of calcium-dependent cytosolic phospholipase A2 (cPLA2) is involved in inflammatory signaling and is elevated within the plaques of AD brains. The relation between APOE4 genotype and cPLA2 activity is not known.

Methods
Mouse primary astrocytes, mouse and human brain samples differing by APOE genotypes were collected for measuring cPLA2 expression, phosphorylation, and activity in relation to measures of inflammation and oxidative stress.

Results
Greater cPLA2 phosphorylation, cPLA2 activity and leukotriene B4 (LTB4) levels were identified in ApoE4 compared to ApoE3 in primary astrocytes, brains of ApoE-targeted replacement (ApoE-TR) mice, and in human brain homogenates from the inferior frontal cortex of patients with AD carrying APOE3/E4 compared to APOE3/E3. Greater cPLA2 phosphorylation was also observed in human postmortem frontal cortical synaptosomes and primary astrocytes after treatment with recombinant ApoE4 ex vivo. In ApoE4 astrocytes, the greater levels of LTB4, reactive oxygen species (ROS), and inducible nitric oxide synthase (iNOS) were reduced after cPLA2 inhibition.

Conclusions
Our findings implicate greater activation of cPLA2 signaling system with APOE4, which could represent a potential drug target for mitigating the increased neuroinflammation with APOE4 and AD.