bluuebunny/crossref_metadata_2025_split huggingface dataset:
Morphologic and biochemical changes in the retina and sclera induced by form deprivation high myopia in guinea pigs
Authors: zi yingxin , Deng Yu , Zhao Jingru , Ji Meiqi , Qin Yali , Deng Tingting , Jin Ming 
Published: March 2020

Abstract
Background: To study the morphologic and biochemical changes in the retina and sclera induced by form deprivation high myopia (FDHM) in guinea pigs and explore the possible mechanisms of FDHM formation. Methods: Forty 3-week-old guinea pigs were randomized into the blank control (Group I, 20 cases) and model groups (20 cases). In the model group, the right eyes of the guinea pigs were sutured for 8 weeks to induce FDHM (Group II) and the left eyes were considered a self-control group (Group III). The refractive errors were measured with retinoscopy. The anterior chamber depth (AC), lens thickness (L), vitreous chamber depth (V) and axial length (AL) were measured using ultrasonometry A. Retinal and scleral morphology and ultrastructural features were observed with light and electron microscopy. The malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in the retina and sclera were detected with a chemical colorimetric assay. Results: After eight weeks of stitching, the refractive errors of Group II changed from (+3.59±0.33) D to (-7.96±0.55) D, and these values were significantly higher than those of Group I (+0.89±0.32) D and Group III (-0.55±0.49) D (P < 0.05). The vitreous chamber depth (4.12±0.13) mm and axial length (8.93±0.22) mm of Group II were significantly longer than those of Group I [(3.71±0.23) mm and (7.95±0.37) mm, respectively] and Group III [(3.93±0.04) mm and (8.01±0.15) mm, respectively] (P < 0.05). With the prolongation of form deprivation (FD), the retina and scleral tissues showed thinning, the ganglion cell and inner and outer nuclear layers of the retina became decreased, and the arrangement was disordered. In Group II, the SOD activity was significantly lower than that in Group I and Group III; the MDA content was significantly higher than that in Group I and Group III. The differences were statistically significant (P < 0.05). Conclusions: These findings suggested that in the FDHM guinea pigs model, the refractive errors, the vitreous chamber depth, and axial length increased significantly with prolongation of monocular FD time, and morphological structural changes in the retina and sclera were observed. Oxygen free radicals might participate in the formation of FDHM.
Feasibility cluster randomised controlled trial evaluating a theory-driven group-based complex intervention versus usual physiotherapy to support self-management of osteoarthritis and low back pain (SOLAS)
Authors: Hurley Deirdre , Jeffares Isabelle , Hall Amanda M , Keogh Alison , Toomey Elaine , McArdle Danielle , McDonough Suzanne M , Guerin Suzanne , Segurado Ricardo , Matthews James 
Published: March 2020

Abstract
Background The Self-management of Osteoarthritis (OA) and Low back pain (LBP) through Activity and Skills (SOLAS) theory-driven group-based complex intervention was developed primarily for the evaluation of its acceptability to patients and physiotherapists and the feasibility of trial procedures, to inform the potential for a definitive trial. Methods This assessor-blinded multicentre two-arm parallel cluster randomised controlled feasibility trial compared the SOLAS intervention to usual individual physiotherapy (UP; pragmatic control group). Patients with OA of the hip, knee, lumbar spine and/or chronic LBP were recruited in primary care physiotherapy clinics (i.e. clusters) in Dublin, Ireland between September 2014 and November 2015. The primary feasibility objectives were evaluated using quantitative methods and individual telephone interviews with purposive samples of participants and physiotherapists. A range of secondary outcomes were collected at baseline, 6 weeks (behaviour change only), 2 months and 6 months to explore the preliminary effects of the intervention. Analysis was by intention-to-treat according to participants’ cluster allocation and involved descriptive analysis of the quantitative data and inductive thematic analysis of the qualitative interviews. A linear mixed model was used to contrast change over time in participant secondary outcomes between treatment arms, while adjusting for study waves and clusters. Results 14 clusters were recruited (7 per trial arm), each cluster participated in two waves of recruitment, with the average cluster size below the target of six participants (Intervention: mean (SD) =4.92 (1.31), range 2-7; UP: mean (SD) =5.08 (2.43), range 1-9). 120 participants (83.3% of n=144 expected) were recruited (Intervention n=59; UP n=61), with follow up data obtained from 80.8% (n=97) at 6 weeks, 84.2% (n=101) at 2 months and 71.7% (n=86) at 6 months. Most participants received treatment as allocated (Intervention n=49; UP n=54). The qualitative interviews (12 participants; 10 PTs) found the Intervention and trial procedures acceptable and appropriate, with minimal feasible adaptations required. Linear mixed methods showed improvements in most secondary outcomes at 2 and 6 months with small between group effects. Conclusions While the SOLAS intervention and trial procedures were acceptable to participants and PTs, the recruitment of enough participants is the biggest obstacle to a definitive trial. Trial Registration: ISRCTN Registry, ISRCTN49875385, Registered 26 March 2014. https://doi.org/10.1186/ISRCTN49875385
Inter-rater Reliability in Clinical Assessments: Do Examiner Pairings Influence Candidate Ratings?
Authors: Faherty Aileen , Counihan Tim , Kropmans Thomas , Finn Yvonne 
Published: March 2020

Abstract
Background: The reliability of clinical assessments is known to vary considerably with inter-rater reliability a key contributor. Many of the mechanisms that contribute to inter-rater reliability however remain largely unexplained and unclear. While research in other fields suggests personality of raters can impact ratings, studies looking at personality factors in clinical assessments are few. Many schools use the approach of pairing examiners in clinical assessments and asking them to come to an agreed score. Little is known however, about what occurs when these paired examiners interact to generate a score. Could personality factors have an impact? Methods: A fully-crossed design was employed with each participant examiner observing and scoring. A quasi-experimental research design used candidate’s observed scores in a mock clinical assessment as the dependent variable. The independent variables were examiner numbers, demographics and personality with data collected by questionnaire. A purposeful sample of doctors who examine in the Final Medical examination at our institution was recruited. Results: Variability between scores given by examiner pairs (N=6) was less than the variability with individual examiners (N=12). 75% of examiners (N=9) scored below average for neuroticism and 75% also scored high or very high for extroversion. Two-thirds scored high or very high for conscientiousness. The higher an examiner’s personality score for extroversion, the lower the amount of change in his/her score when paired up with a co-examiner; reflecting possibly a more dominant role in the process of reaching a consensus score. Conclusions: The reliability of clinical assessments using paired examiners is comparable to assessments with single examiners. Personality factors, such as extroversion, may influence the magnitude of change in score an individual examiner agrees to when paired up with another examiner. Further studies on personality factors and examiner behaviour are needed to test associations and determine if personality testing has a role in reducing examiner variability.
Characterization of the Interleukin-17 Effect on Articular Cartilage in a Translational Model. An Explorative Study
Authors: Sinkeviciute Dovile , Aspberg Anders , He Yi , Bay-Jensen Anne-Christine , Önnerfjord Patrik 
Published: March 2020

Abstract
Background
Osteoarthritis (OA) is a progressive, chronic disease characterized by articular cartilage destruction. The pro-inflammatory cytokine IL-17 levels have been reported elevated in serum and synovial fluid of OA patients and correlated with increased cartilage defects and bone remodeling. The aim of this study was to characterize an IL-17-mediated articular cartilage degradation ex-vivo model and to investigate IL-17 effect on cartilage extracellular matrix protein turnover.
Methods
Full-depth bovine femoral condyle articular cartilage explants were cultured in serum-free medium for three weeks in the absence, or presence of cytokines: IL-17A (100 ng/ml or 25 ng/ml), or 10 ng OSM combined with 20 ng/ml TNFα (O+T). RNA isolation and PCR analysis were performed on tissue lysates to confirm IL-17 receptor expression. GAG and ECM-turnover biomarker release into conditioned media was assessed with dimethyl methylene blue and ELISA assays, respectively. Gelatin zymography was used for matrix metalloproteinase (MMP) 2 and MMP9 activity assessment in conditioned media, and shotgun LC-MS/MS for identification and label-free quantification of proteins and protein fragments in conditioned media. Western blotting was used to validate MS results.
Results
IL-17RA mRNA was expressed in bovine articular cartilage and the treatment with IL-17A did not interfere with metabolic activity of the model. IL-17A induced cartilage breakdown; conditioned media GAG levels were 3.6-fold-elevated compared to untreated. IL-17A [100 ng/ml] induced ADAMTS-mediated aggrecan degradation fragment release (14-fold increase compared to untreated) and MMP-mediated type II collagen fragment release (6-fold-change compared to untreated). MS data analysis revealed 16 differentially expressed proteins in IL-17A conditioned media compared to untreated. CHI3L1 upregulation in conditioned media in response to IL-17A was confirmed by Western blotting.
Conclusions
We showed that IL-17A has cartilage modulating potential. It induces collagen and aggrecan degradation indicating an upregulation of MMPs. This was confirmed by zymography and mass spectrometry data. We also showed that the expression of other cytokines is induced by IL-17A, which provide further insight to the pathways that are active in response to IL-17A. This exploratory study confirms that IL-17A may play a role in cartilage pathology and that the applied model may be a good tool to further investigate it.
Use of Student-generated Multiple Choice Questions to Enhance Team-based Learning of Anatomy at the University of Rwanda
Authors: SIBOMANA ISAIE , Karenzi Irenee David , Niyongombwa Irenee , Byiringiro Jean Claude , Gashegu Julien , Ntirenganya Faustin 
Published: March 2020

AbstractBackground: Teaching of human anatomy has undergone significant changes in last 3 decades. At the University of Rwanda, anatomy is being taught using team-based learning. While student generated multiple choice questions (MCQs) stimulate deeper thinking of a given topic, their impact on anatomy learning is not known. This study aimed to improve anatomy teaching and student satisfaction by combining both models. Methods: It was a comparative interventional study where two similar chapters of anatomy were selected and one taught using team based learning (TBL) while the other one, in addition to TBL, student were encouraged to set MCQs while studying. Pre- and post-test scores were analysed using SPSS 23 and student t-test was used to compare the mean score obtained. Results: 31 medical students were recruited. Pre-test mean scores in both chapters were 25.10 and 25.19 over 50 for chapter 1 and chapter 2 respectively. Although the students’ post-test scores improved after teaching for each chapter, it was much more for chapter 2 than chapter one with mean score of 39.97 and 32.45 over 50 respectively (P<0.05). Despite such improvement, setting MCQs was not easy in almost a half of students. Conclusion: This study has found that student generated MCQs can be used as a simple and cost effective tool to enhance TBL learning of anatomy.
Associations of Mitochondrial DNA 3777-4679 region mutations with maternally inherited essential hypertensive subjects in China.
Authors: Zhu Ye , You Jia , Xu Chao , Gu Xiang 
Published: March 2020

AbstractBackground: Nuclear genome or family mitochondrial screening system has become the hot focus of studies into essential hypertension. The role of mitochondrial DNA (mtDNA) in sporadic Chinese patients with hypertension has not been fully understood. The study was to evaluate the associations of mtDNA mutations with maternally inherited essential hypertensive subjects in China. Methods: From June 2009 to June 2016, a total of 800 gender-matched Chinese patients with maternally inherited essential hypertension (MIEH) and control group were 1:1 enrolled in this case-control study. Genomic DNA was extracted from each person's peripheral blood cells. The main mtDNA locations for MIEH were screened with oligodeoxynucleotides 3777-4679bp, analyzed and compared with the updated consensus Cambridge Sequence. Pathogenic mtDNA mutations were identified from the mitochondrial map. Results: MIEH subjects presented significantly higher values than those of control group in abdominal circumference(AC), waist circumference(WC), body mass index(BMI), fasting blood glucose(FBG), triglyceride(TG), low-density lipoprotein cholesterol (LDL) and renal function ( P <0.05). MIEH subjects carried more amino acid changes and coding sequence variants ( P <0.01) than control group. The allele frequencies of the eight single nucleotide polymorphisms(SNPs) were significantly different between the two groups, including m.3970 C>T, m.4048G>A, m.4071C>T, m.4086C>T, m. 4164A>G and m.4248T>C in ND1 gene, and m.4386T>C and m.4394C>T in tRNA Gln gene( P <0.001). Fifty-five homoplasmic or heteroplasmic mutations were detected in 5 genes: ND1, tRNA Ile , tRNA Met , tRNA Gln and ND2 gene. The ND1 gene was the main mutation site, where the most mtDNA mutation was m.3970 C>T. Conclusions: The mtDNA mutations were involved in the process of MIEH. We identified mitochondrial genetic characteristics in MIEH patients in China. The present research serves as a solid foundation for further detailed research on the association between MIEH and mitochondrial dysfunction, and their causal relationship in Chinese and other populations with a similar lifestyle.
SIP SMART: A parallel group randomised feasibility trial of a tailored pre-treatment Swallowing Intervention Package compared with usual care for patients with head and neck cancer
Authors: Govender Roganie , Smith Christina H , Barratt Helen , Gardner Benjamin , Taylor Stuart 
Published: March 2020

Abstract
Background: Dysphagia or difficulty in swallowing affects quality of life for most patients with head and neck cancer. SIP SMART – [Swallowing Intervention Package: Self-Monitoring, Assessment, Rehabilitation Training] aims to improve post-treatment swallowing outcomes through a targeted and tailored pre-treatment intervention. This feasibility study assessed 1) recruitment and retention, 2) patient acceptability of randomisation and participation, 3) patient adherence, and 4) sought to identify a suitable primary outcome for a definitive trial, including sample size estimation.
Methods: This two-arm parallel group non-blinded randomised feasibility trial took place within a head and neck centre at a teaching hospital in London, UK. Patients newly diagnosed with stage III/IV head and neck cancer were recruited and underwent 6-month follow-up. Patients were randomised to SIP-SMART or usual care via an online web-based system. SIP SMART comprised two 45-minute consultations including a baseline clinical and instrumental swallowing assessment, relevant educational information, targeted swallowing exercises, and specific behaviour change strategies to increase exercise adherence. Usual care comprised a single session including a baseline clinical assessment and generic information about the likely impact of treatment on swallowing.
Results: A total of 106 patients were identified at pre-screening, 70 were assessed for eligibility. Twenty-six patients did not meet eligibility criteria [0.37, 95% CI 0.27 to 0.49]. Five of 44 [0.11, 95% CI 0.05 to 0.24] eligible patients were not approached by researchers during clinic. Seven [0.18, 95% CI 0.08 to 0.33] of the 39 approached declined participation. Target recruitment (32 consented patients) was achieved within the timeframe. At 6-months 29/32 [0.91, 95% CI 0.76 to 0.97] patients remained in the trial. Acceptability of randomisation and participation in the intervention was favourable, and adherence to the exercises exceeded the pre-defined 35% minimum criterion. The MD Anderson Dysphagia Inventory swallow related quality of life measure was selected as the most suitable primary outcome for sample size estimation. No adverse effects arose from the intervention, or study participation.
Conclusions: A definitive trial of the SIP SMART intervention compared to usual care is feasible and can be undertaken with patients with head and neck cancer treated within the NHS.
Trial Registration: ISRCTN40215425
Intention to quit water pipe smoking among Iranian women: A qualitative directed content analysis
Authors: Sabzmakan Leila , Eslami Fatemeh , Sighaldeh Shirin Shahbazi , Izuka Nkeonye Judith 
Published: March 2020

Abstract
Background Water-pipe smoking is the most common type of tobacco used among Iranian women. The aim of this study was to explain women’s perceptions of their intention for quitting water-pipe smoking based on the theory of planned behavior. Methods The study was a qualitative content analysis which was carried out over four months in 2016 in Tehran-Iran. The participants were 26 women ages 18 to 45-years-old who smoked water-pipe and were selected through snowball sampling. The study was performed in hookah cafes, parks, and homes. The data were collected through individual interviews. The interviews were open-ended questions based on the theory of planned behavior. Directed content analysis was used to analyze the data. Results Findings showed that women did not intend to quit water-pipe in that time. Main contributing factors influencing not having intention of cessation were positive attitude and false beliefs toward hookah smoking, as well as having peers and family members who smoked water-pipe or approved its use. Although most females realized the obstacles associated with hookah cessation, they believed that quitting water-pipe smoking was up to them and could control more barriers. Conclusion Social pressure, positive attitude and false beliefs towards hookah smoking, as well as external and internal obstacles diminished women ‘s intention for cessation. Therefore, it is recommended to apply the theory of planned behavior into behavior change interventions in order to increase the intention to quit water-pipe smoking.
Durvalumab in frail and elder patients with stage four NSCLC: Study protocol of the randomized phase II DURATION trial
Authors: Kuon Jonas , Hommertgen Adriane , Krisam Johannes , Lasitschka Felix , Stenzinger Albrecht , Blasi Miriam , Bozorgmehr Farastuk , Maenz Martin , Kieser Meinhard , Schneider Marc , Thomas Michael 
Published: March 2020

Abstract
Background: Elderly patients represent a major fraction of non-small cell lung cancer (NSCLC) patients in routine clinical practice, but they are still underrepresented in clinical trials. In particular, data regarding efficacy and safety in frail or elderly patients with respect to immunotherapy are lacking. Importantly, immunosenescence in elderly patients might interfere with activities of immune-modulating drugs such as PD-1/PD-L1 inhibitors. Thus, there is an urgent need to assess safety and efficacy of such inhibitors in this group. Methods/design: In this prospective, open label, treatment stratified, and randomized phase II study, 200 patients with stage IV NSCLC amenable at least to single-agent chemotherapy (CT). Eligible patients must be 70 years or older and/or “frail” (Charlson Comorbidity Index >1) or have a restricted performance status (Eastern Cooperative Oncology Group, ECOG >1). Patients are stratified according to modified Cancer and Age Research Group (CARG) score:”fit” patients are allocated to combination CT (carboplatin/ nab -paclitaxel), “less fit” patients receive single-agent CT (gemcitabine or vinorelbine). After allocation to strata, patients are randomized 1:1 to receive either 4 cycles of CT or 2 cycles of CT followed by 2 cycles of durvalumab and subsequent maintenance treatment with durvalumab every 4 weeks. The primary endpoint is the rate of treatment related grade III/IV adverse events (Common Terminology Criteria for Adverse Events, CTCAE V4.03). As secondary endpoints, progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1, response rate (RR), overall survival (OS), descriptive subgroup analyses according to PD-L1 expression, and quality of life are addressed. Geriatric screening assessments and functional tests will be performed to complete the phenotyping of a potential “frail” and “elderly” patient cohort. The trial is accompanied by a biomaterial repository to explore potential biomarkers. Discussion: The DURATION trial will prospectively investigate the safety and tolerability of anti-PD-L1 treatment with durvalumab after chemotherapy in elderly and frail patients and thereby provide new insights into the effect of PD-L1 blockade and the impact of immunosenescence in this cohort of patients.