bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of an isoenergetic low Glycaemic Index (GI) diet on liver fat accumulation and gut microbiota composition in patients with non-alcoholic fatty liver disease (NAFLD): a study protocol of an efficacy mechanism evaluation
Authors: Al-Awadi Amina , Grove Jane , Taylor Moira , Valdes Ana , Vijay Amrita , Bawden Stephen , Gowland Penny , Aithal Guruprasad 
Published: October 2021

IntroductionA Low Glycaemic Index (LGI) diet is a proposed lifestyle intervention in non-alcoholic fatty liver diseases (NAFLD) which is designed to reduce circulating blood glucose levels, hepatic glucose influx, insulin resistance and de novo lipogenesis. A significant reduction in liver fat content through following a 1-week LGI diet has been reported in healthy volunteers. Changes in dietary fat and carbohydrates have also been shown to alter gut microbiota composition and lead to hepatic steatosis through the gut-liver axis. There are no available trials examining the effects of an LGI diet on liver fat accumulation in patients with NAFLD; nor has the impact of consuming an LGI diet on gut microbiota composition been studied in this population. The aim of this trial is to investigate the effects of LGI diet consumption on liver fat content and its effects on gut microbiota composition in participants with NAFLD compared with a High Glycaemic Index (HGI) control diet.Methods and analysisA 2×2 cross-over randomised mechanistic dietary trial will allocate 16 participants with NAFLD to a 2-week either HGI or LGI diet followed by a 4-week wash-out period and then the LGI or HGI diet, alternative to that followed in the first 2 weeks. Baseline and postintervention (four visits) outcome measures will be collected to assess liver fat content (using MRI/S and controlled attenuation parameter-FibroScan), gut microbiota composition (using 16S RNA analysis) and blood biomarkers including glycaemic, insulinaemic, liver, lipid and haematological profiles, gut hormones levels and short-chain fatty acids.Ethics and disseminationStudy protocol has been approved by the ethics committees of The University of Nottingham and East Midlands Nottingham-2 Research Ethics Committee (REC reference 19/EM/0291). Data from this trial will be used as part of a Philosophy Doctorate thesis. Publications will be in peer-reviewed journals.Trial registration numberNCT04415632.
Shingles, Zostavax vaccination and risk of developing dementia: a nested case–control study—results from the UK Biobank cohort
Authors: Lophatananon Artitaya , Mekli Krisztina , Cant Rachel , Burns Alistair , Dobson Curtis , Itzhaki Ruth , Muir Kenneth 
Published: October 2021

ObjectivesTo investigate the association between shingles and dementia, and between Zostavax vaccination and dementia.DesignNested case–control study.SettingsData were drawn from the UK Biobank cohort study with a total of 228 223 participants with Hospital Episodes Statistics and primary care linkage health records.ParticipantsThe analyses included 2378 incident dementia cases and 225 845 controls. Inclusion criteria for incident cases were a dementia diagnosis 3 years or more after the first assessment date derived from all sources including International Classification of Diseases (ICD)-10, ICD-9, self-report and primary care linkage records. Subjects with no dementia code from all sources were coded as controls. Both shingles and Zostavax vaccination were investigated for their association with dementia risk.ResultsThere was a small but non-significant increase in the risk of dementia in subjects with shingles diagnosed 3 years or more prior to dementia diagnosis (OR: 1.088 with 95% CI: 0.978 to 1.211). In those subjects who had had Zostavax vaccination, the risk of dementia significantly decreased (OR: 0.808 with 95% CI: 0.657 to 0.993).ConclusionA history of shingles was not associated with an increased risk of dementia. In subjects who were eligible for the immunisation and vaccinated with Zostavax, we saw reduced risk of developing dementia.
Detection by fluorescence of pituitary neuroendocrine tumour (PitNET) tissue during endoscopic transsphenoidal surgery using bevacizumab-800CW (DEPARTURE trial): study protocol for a non-randomised, non-blinded, single centre, feasibility and dose-finding trial
Authors: Vergeer Rob A , Postma Mark R , Schmidt Iris , Korsten-Meijer Astrid GW , Feijen Robert A , Kruijff Schelto , Nagengast Wouter B , van Dijk J Marc C , den Dunnen Wilfred F A , van Beek André P , Kuijlen Jos M A , van den Berg Gerrit 
Published: October 2021

IntroductionAchieving gross total resection and endocrine remission in pituitary neuroendocrine tumours (PitNET) can be challenging, especially in PitNETs with cavernous sinus (CS) invasion, defined as a Knosp grade of 3 or 4. A potential target to identify PitNET tissue is vascular endothelial growth factor A (VEGF-A), which expression is known to be significantly higher in PitNETs with CS invasion.Methods and analysisThe aim of this non-randomised, non-blinded, single centre, feasibility and dose-finding phase 1 trial is to determine the feasibility of intraoperative fluorescence imaging detection of PitNET tissue during endoscopic transsphenoidal surgery using the VEGF-A targeting optical agent bevacizumab-800CW (4, 5, 10 or 25 mg). Nine to fifteen patients with a PitNET with a Knosp grade of 3 or 4 will be included. Secondary objectives are: (1) To identify the optimal tracer dose for imaging of PitNET tissue during transsphenoidal surgery for further development in a phase 2 fluorescence molecular endoscopy trial. (2) To quantify fluorescence intensity in vivo and ex vivo with multidiameter single-fibre reflectance, single-fibre fluorescence (MDSFR/SFF) spectroscopy. (3) To correlate and validate both the in vivo and ex vivo measured fluorescence signals with histopathological analysis and immunohistochemical staining. (4) To assess the (sub)cellular location of bevacizumab-800CW by ex vivo fluorescence microscopy. Intraoperative, three imaging moments are defined to detect the fluorescent signal. The tumour-to-background ratios are defined by intraoperative fluorescence in vivo measurements including MDSFR/SFF spectroscopy data and by ex vivo back-table fluorescence imaging. After inclusion of three patients in each dose group, an interim analysis will be performed to define the optimal dose.Ethics and disseminationApproval was obtained from the Medical Ethics Review Board of the University Medical Centre Groningen. Results will be disseminated through national and international journals. The participants and relevant patient support groups will be informed about the results.Trial registration numberNCT04212793
Relationship between medical students’ negative perceptions of colleagues’ work–life and burn-out during clerkships: a longitudinal observational cohort study
Authors: Lin Yung Kai , Lin Blossom Yen-Ju , Lin Chia-Der , Chen Der-Yuan 
Published: October 2021

ObjectiveBecause work and educational environments are closely related and can affect each other, this study examined whether medical students’ negative perceptions of their colleagues’ work–life balance (NWLB) during their clinical rotations would be related to burn-out in clerkships and investigated the effect of students’ gender on this relationship.DesignA longitudinal, prospective 2-year cohort study conducted between September 2013 and April 2015.SettingMedical students from a university school of medicine in Taiwan.ParticipantsOne voluntary cohort of undergraduate medical students in clerkships was invited to participate. Among 190 medical students recruited in September 2013, a total of 124 students provided written informed consent. Participants were free to decide whether to complete each survey; therefore, varying numbers of responses were obtained during the study period. Those who responded to our survey for more than 6 months were included in our analyses. Overall, 2128 responses from 94 medical students were analysed, with each student providing an average of 23 responses for 2 years.Primary outcome measureBurn-out was measured using the Professional Quality of Life Scale.ResultsOur study found that a strong NWLB was related to high burn-out levels among medical students during their clerkships (p<0.001). However, the gender of the student had no effect on this relationship (p>0.05). In addition, our study indicated that medical students living with a companion had decreased burn-out levels than did those living alone during their clerkships.ConclusionsThe significance of policies promoting employee work–life balance should be emphasised because of the potential for social contagion effects on medical students. Clerkship trainees might be vulnerable to such negative contagion effects during the transition to their early clinical workplace training and may, therefore, require advanced socialisation and mentoring.
Impacts of clinical academic activity: qualitative interviews with healthcare managers and research-active nurses, midwives, allied health professionals and pharmacists
Authors: Newington Lisa , Alexander Caroline M , Wells Mary 
Published: October 2021

ObjectivesTo explore the perceived impacts of clinical academic activity among the professions outside medicine.DesignQualitative semistructured interviews.Setting and participantsThere were two groups of interviewees: Research-active nurses, midwives, allied health professionals, healthcare scientists, psychologists and pharmacists (NMAHPPs) and managers of these professions. All participants were employed in a single, multisite healthcare organisation in the UK.AnalysisInterview transcripts were analysed using the framework method to identify key themes, subthemes and areas of divergence.ResultsFour themes were identified. The first, cultural shifts, described the perceived improvements in the approach to patient care and research culture that were associated with clinical academic activity. The second theme explored visibility and included the positive reputation that clinical academics were identified as bringing to the organisation in contrast with perceived levels of invisibility and inaccessibility of these roles. The third theme identified the impacts of the clinical academic pathways, including the precarity of these roles. The final theme explored making impact tangible, and described interviewees’ suggestions of possible methods to record and demonstrate impact.ConclusionsPerceived positive impacts of NMAHPP clinical academic activity focused on interlinked positive changes for patients and clinical teams. This included delivery of evidence-based healthcare, patient involvement in clinical decision making and improved staff recruitment and retention. However, the positive impacts of clinical academic activity often centred around individual clinicians and did not necessarily translate throughout the organisation. The current clinical academic pathway was identified as causing tension between the perceived value of clinical academic activity and the need to find sufficient staffing to cover clinical services.
Factors related to the adoption and adherence of physical activity mobile applications by older people: a scoping review protocol
Authors: Lorenzi Lorena Jorge , Belo Letícia Fernanda , Frohlich David Mark , Dourado Victor Zuniga , Castro Paula Costa , Gomes Grace Angélica de Oliveira 
Published: October 2021

IntroductionAgeing is a natural process marked by physiological changes and declines in functional capacity. One strategy to encourage healthy habits in older people is the use of applications on mobile devices to promote physical activity (PA). An immediate challenge is for these applications to be accessible to older people themselves, while a second challenge is to retain their interest and engagement in connection with PA itself. Therefore, the purpose of this review is to map the factors related to the adoption and adherence of PA mobile applications by older people.Methods and analysisFive databases will be searched where articles and reviews, available between 2010 and present, in English, Portuguese or Spanish, at full text, will be included. In addition, two additional strategies will be performed, including grey literature. The search terms adoption, adherence, factors, mobile application, PA, older people and other terms related to them will be used in the search strategy. This review will include studies that identify factors related to the adoption and adherence to PA mobile applications by people over 60 years. The selection of studies will be carried out by two reviewers in five stages: identification of studies and duplicate removal; pilot test; selection by reading abstracts; inclusion by reading the full text and search in additional sources. Disagreements will be resolved by a third reviewer. Data will be extracted using a data extraction tool. Quantitative data will be described in a narrative manner and qualitative data will be categorised through inductive thematic analysis.Ethics and disseminationEthical approval is not required for this scoping review. Plans for the dissemination of the review include the presentation of the results at relevant scientific conferences and the submission and publication in significant journals.
Development and field testing of primary care screening tools for harms of long-term opioid therapy continuation and tapering to discontinuation: a study protocol
Authors: Timko Christine , Kroenke Kurt , Nevedal Andrea , Lor Mai Chee , Oliva Elizabeth , Drexler Karen , Sandbrink Friedhelm , Hoggatt Katherine 
Published: October 2021

IntroductionDespite calls for screening tools to help providers monitor long-term opioid therapy (LTOT) harms, and identify patients likely to experience harms of discontinuation, such screening tools do not yet exist. Current assessment tools are infeasible to use routinely in primary care and focus mainly on behaviours suggestive of opioid use disorder to the exclusion of other potential harms. This paper describes a study protocol to develop two screening tools that comprise one integrated instrument,Screen toEvaluate andTreat (SET). SET1 will indicate if LTOT may be harmful to continue (yes or no), and SET2 will indicate if tapering to discontinue opioids may be harmful to initiate (yes or no). Patients receiving LTOT who screen positive on the SET tools should receive subsequent additional assessment. SET will give providers methods that are feasible to implement routinely to facilitate more intensive and comprehensive monitoring of patients on LTOT and decision-making about discontinuation.Methods and analysisWe will develop the screening tools, SET1 and SET2, concurrently. Tool development will be done in stages: (1) comprehensive literature searches to yield an initial item pool for domains covered by each screening tool; (2) qualitative item analyses using interviews, expert review and cognitive interviewing, with subsequent item revision, to yield draft versions of each tool; and (3) field testing of the draft screening tools to assess internal consistency, test–retest reliability and convergent and discriminant validity.Ethics and disseminationEthical approval was obtained from the Institutional Review Boards of Stanford University and the University of California, San Francisco for the VA Palo Alto Health Care System, and the VA San Francisco Healthcare System, respectively. Findings will be disseminated through peer-reviewed manuscripts and presentations at research conferences.
Acceptance of COVID-19 vaccines in Palestine: a cross-sectional online study
Authors: Zawahrah Hassan J , Saca-Hazboun Hanan , Melhem Shatha S , Adwan Rabee , Sabateen Ali , Abu-Rmeileh Niveen M E 
Published: October 2021

IntroductionIn Palestine (West Bank and Gaza), there have been more than 320 890 known cases of COVID-19, resulting in 3452 deaths. The detrimental effects of the virus can be seen in the nation’s health, economy and government operations, leading to radical uncertainty that is exacerbated by the absence of any definitive treatment or vaccines. The level of knowledge about and trust in treatment and vaccination varies worldwide. This study aims to assess the willingness of Palestinians to receive a COVID-19 vaccine and their knowledge about such vaccines.MethodsAn online survey of adults over 18 years old (n=1080) was conducted in Palestine in October 2020. Using multivariate logistic regression, we identified correlates of participants’ willingness to get a COVID-19 vaccine.ResultsWe found that about 63% of participants were willing to get a COVID-19 vaccine. However, acceptance varied with the specific demographic variables that were investigated. Women, married participants and those aged 18–24 years are more likely to take the vaccine. Further, participants with good knowledge about the vaccine and its side effects are more willing to get the vaccine.ConclusionThe availability of a safe and effective COVID-19 vaccine in Palestine is crucial to decrease the burden of COVID-19 morbidity and mortality. In addition, to ensure a high vaccination rate, health awareness campaigns should target those who are not willing to get the vaccine, especially those who are more vulnerable and the elderly.
Risk of pneumothorax in pneumoconiosis patients in Taiwan: a retrospective cohort study
Authors: Pan Jo-Hui , Cheng Chih-Hung , Wang Chao-Ling , Dai Chia-Yen , Sheu Chau-Chyun , Tsai Ming-Ju , Hung Jen-Yu , Chong Inn-Wen 
Published: October 2021

ObjectivesThis study was conducted to explore the association between pneumoconiosis and pneumothorax.DesignRetrospective cohort study.SettingNationwide population-based study using the Taiwan National Health Insurance Database.ParticipantsA total of 2333 pneumoconiosis patients were identified (1935 patients for propensity score (PS)-matched cohort) and matched to 23 330 control subjects by age and sex (7740 subjects for PS-matched cohort).Primary and secondary outcome measuresThe incidence and the cumulative incidence of pneumothorax.ResultsBoth incidence and the cumulative incidence of pneumothorax were significantly higher in the pneumoconiosis patients as compared with the control subjects (p<0.0001). For multivariable Cox regression analysis adjusted for age, sex, residency, income level and other comorbidities, patients with pneumoconiosis exhibited a significantly higher risk of pneumothorax than those without pneumoconiosis (HR 3.05, 95% CI 2.18 to 4.28, p<0.0001). The male sex, heart disease, peripheral vascular disease, chronic pulmonary disease and connective tissue disease were risk factors for developing pneumothorax in pneumoconiosis patients.ConclusionsOur study revealed a higher risk of pneumothorax in pneumoconiosis patients and suggested potential risk factors in these patients. Clinicians should be aware about the risk of pneumothorax in pneumoconiosis patients.
How does implementation of an electronic medical record system impact nurses’ work motivation, engagement, satisfaction and well-being? A realist review protocol
Authors: Jedwab Rebecca M , Redley Bernice , Manias Elizabeth , Dobroff Naomi , Hutchinson Alison M 
Published: October 2021

IntroductionElectronic medical record (EMR) systems are used worldwide as repositories for patients’ clinical information, providing clinical decision support and increasing visibility of and access to clinical information. While EMR systems facilitate improved healthcare delivery, emerging reports suggest potential detrimental effects on clinician well-being. EMR system implementation influences on nurses’ work motivation, engagement, satisfaction and well-being (including burnout) are not well understood, nor have they been examined in relation to contextual factors and mechanisms of action. This paper presents a realist review protocol to examine causal explanations to address the question: How, why and under what circumstances does the implementation of a new hospital EMR system or similar technology impact nurses’ work motivation, engagement, satisfaction or well-being?Methods and analysisThe five-step method for realist review will be used to identify causal relationships, how the relationships work, for whom and under what circumstances: (1) defining the review scope; (2) developing initial program theories; (3) searching the evidence; (4) selecting and appraising the evidence; (5) extracting and synthesising the data. Initial program theories were developed using scoping review findings and qualitative data collected from nurses pre-EMR and post-EMR. Five databases will be systematically searched from 1 January 2000 to 31 October 2021 (APA PsycInfo, CINAHL, Embase, IEEE Xplore and MEDLINE Complete), and forward and backward citation searching, grey literature searching and literature recommended by the research team. Search results will be screened by two research team members. Data extracted will assist in refining program theories to develop a conceptual model that synthesises how work motivation, engagement, satisfaction and well-being may influence, or be influenced by, an EMR implementation.Ethics and disseminationThe larger project has previously obtained low-risk ethics approval. The review will be published in a peer-reviewed journal and reported as per RAMESES guidelines.PROSPERO registration numberCRD42020131875.
Increased coexpression of PD-L1 and TIM3/TIGIT is associated with poor overall survival of patients with esophageal squamous cell carcinoma
Authors: Wang Peipei , Chen Yueyun , Long Qingqin , Li Qing , Tian Jiangfang , Liu Ting , Wu Yong , Ding Zhenyu 
Published: October 2021

BackgroundImmune checkpoint (IC) blockades (ICBs) significantly improve patients’ clinical outcomes with solid tumors. Because the objective response rate of single-agent ICB is limited, it is meaningful to explore the combination of ICs for immunotherapy.MethodsRNA sequencing data of 95 newly diagnosed patients with esophageal squamous cell carcinoma (ESCC) from The Cancer Genome Atlas (TCGA) database were used to explore the prognostic significance of ICs. The results were validated by immunohistochemistry of 58 ESCC tissue samples from our clinical center.ResultsThe results of both TCGA and validation data suggested that high expression of programmed cell death 1 ligand 1 (PD-L1), T-cell immunoglobulin and mucin-domain-containing-3 (TIM3), and T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) was associated with poor overall survival (OS) of patients with ESCC. Importantly, PD-L1/TIM3 or PD-L1/TIGIT was the optimal combination for predicting poor OS and short restricted mean survival time of patients with ESCC and was an independent prognostic factor. Moreover, a nomogram model constructed by PD-L1, TIM3, and TIGIT together with the primary tumor, regional lymph node, distant metastasis stage could provide a concise and precise prediction of 1-year and 2-year OS rates and median survival time. PD-L1/TIM3 or PD-L1/TIGIT had a positive correlation with CD8+ T cells. Notably, PD-1 and TIM3/TIGIT were primarily coexpressed on CD8+ tumor-infiltrating lymphocyte in patients with ESCC by multiplexed immunofluorescence.ConclusionHigh expression of ICs was associated with poor OS of patients with ESCC. PD-L1/TIM3 and PD-L1/TIGIT were the optimal combinations for predicting OS, which might be potential targets for future ICBs therapy of ESCC.