bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treating patients in a safe environment: a cross-sectional study of patient safety attitudes among doctors in the Gaza Strip, Palestine
Authors: Alfaqawi Maha , Böttcher Bettina , Abuowda Yousef , Alaloul Enas , Elnajjar Ibrahem , Elhout Somaya , Abu-El-Noor Mysoon , Abu-El-Noor Nasser 
Published: May 2020

Abstract
Background
Patient safety is important, as in increasingly complex medical systems, the potential for unintended harm to patients also increases. This study assessed the attitudes of doctors in the Gaza Strip towards patient safety and medical error. It also explored variables that impacted their attitudes.

Methods
Doctors, working for at least 6 months in one of the four major government hospitals of the Gaza Strip, were invited to complete a 28-item, self-administered Arabic version of the Attitudes to Patient Safety Questionnaire III (APSQ-III); which assessed patient safety attitudes over nine domains, independent of the workplace.

Results
A total of 150 doctors from four government hospitals participated in this study, representing 43.5% of all 345 doctors working in the four study hospitals at the time of the study. The mean age was 36.6 (±9.7) years. The majority (72.7%) were males, 28.7% worked in surgical, 26.7% in pediatric, 23.3% in medical, 16.7% in obstetrics and gynecology, and 4.7% in other departments. Most participants (62.0%) had never received patient safety training. The overall APSQ score was 3.58 ± 0.3 (of a maximum of 5). The highest score was received by the domain “Working hours as a cause of errors” (4.16) and the lowest score by “Importance of Patient Safety in the Curriculum” (3.25). Older doctors with more professional experience had significantly higher scores than younger doctors (p = 0.003), demonstrating more positive attitudes toward patient safety. Furthermore, patient safety attitudes became more positive with increasing years of experience in some domains. However, no significant impact on overall APSQ scores was found by workplace, specialty or whether the participants had received previous training about patient safety.

Conclusion
Doctors in Gaza demonstrated relatively positive patient safety attitudes in areas of “team functioning” and “working hours as a cause for error”, but neutral attitudes in understanding medical error or patient safety training within the curriculum. Patient safety concepts appear to be acquired by doctors via informal learning over time in the job. Inclusion of such concepts into formal postgraduate curricula might improve patient safety attitudes among younger and less experienced doctors, support behaviour change and improve patient outcomes.
Prolonged Scar-in-a-Jar: an in vitro screening tool for anti-fibrotic therapies using biomarkers of extracellular matrix synthesis
Authors: Rønnow Sarah Rank , Dabbagh Rand Qais , Genovese Federica , Nanthakumar Carmel B. , Barrett Vikki J. , Good Robert B. , Brockbank Sarah , Cruwys Simon , Jessen Henrik , Sorensen Grith Lykke , Karsdal Morten Asser , Leeming Diana Julie , Sand Jannie Marie Bülow 
Published: May 2020

Abstract
Background
Idiopathic pulmonary fibrosis (IPF) is a rapidly progressing disease with challenging management. To find novel effective therapies, better preclinical models are needed for the screening of anti-fibrotic compounds. Activated fibroblasts drive fibrogenesis and are the main cells responsible for the accumulation of extracellular matrix (ECM). Here, a prolonged Scar-in-a-Jar assay was combined with clinically validated biochemical markers of ECM synthesis to evaluate ECM synthesis over time. To validate the model as a drug screening tool for novel anti-fibrotic compounds, two approved compounds for IPF, nintedanib and pirfenidone, and a compound in development, omipalisib, were tested.

Methods
Primary human lung fibroblasts from healthy donors were cultured for 12 days in the presence of ficoll and were stimulated with TGF-β1 with or without treatment with an ALK5/TGF-β1 receptor kinase inhibitor (ALK5i), nintedanib, pirfenidone or the mTOR/PI3K inhibitor omipalisib (GSK2126458). Biomarkers of ECM synthesis were evaluated over time in cell supernatants using ELISAs to assess type I, III, IV, V and VI collagen formation (PRO-C1, PRO-C3, PRO-C4, PRO-C5, PRO-C6), fibronectin (FBN-C) deposition and α-smooth muscle actin (α-SMA) expression.

Results
TGF-β1 induced synthesis of PRO-C1, PRO-C6 and FBN-C as compared with unstimulated fibroblasts at all timepoints, while PRO-C3 and α-SMA levels were not elevated until day 8. Elevated biomarkers were reduced by suppressing TGF-β1 signalling with ALK5i. Nintedanib and omipalisib were able to reduce all biomarkers induced by TGF-β1 in a concentration dependent manner, while pirfenidone had no effect on α-SMA.

Conclusions
TGF-β1 stimulated synthesis of type I, III and VI collagen, fibronectin and α-SMA but not type IV or V collagen. Synthesis was increased over time, although temporal profiles differed, and was modulated pharmacologically by ALK5i, nintedanib, pirfenidone and omipalisib. This prolonged 12-day Scar-in-a-Jar assay utilising biochemical markers of ECM synthesis provides a useful screening tool for novel anti-fibrotic compounds.
Lost in the shadows: reflections on the dark side of co-production
Authors: Williams Oli , Sarre Sophie , Papoulias Stan Constantina , Knowles Sarah , Robert Glenn , Beresford Peter , Rose Diana , Carr Sarah , Kaur Meerat , Palmer Victoria J. 
Published: May 2020

AbstractThis article is a response to Oliver et al.’s Commentary ‘The dark side of coproduction: do the costs outweigh the benefits for health research?’ recently published inHealth Research Policy and Systems(2019, 17:33). The original commentary raises some important questions about how and when to co-produce health research, including highlighting various professional costs to those involved. However, we identify four related limitations in their inquiry, as follows: (1) the adoption of a problematically expansive definition of co-production that fails to acknowledge key features that distinguish co-production from broader collaboration; (2) a strong focus on technocratic rationales for co-producing research and a relative neglect of democratic rationales; (3) the transposition of legitimate concerns relating to collaboration between researchers and practitioners onto work with patients, service users and marginalised citizens; and (4) the presentation of badpracticeas an inherent flaw, or indeed ‘dark side’, of co-production without attending to the corrupting influence ofcontextualfactors within academic research that facilitate and even promote such malpractice. The Commentary’s limitations can be seen to reflect the contemporary use of the term ‘co-production’ more broadly. We describe this phenomenon as ‘cobiquity’ – an apparent appetite for participatory research practice and increased emphasis on partnership working, in combination with the related emergence of a plethora of ‘co’ words, promoting a conflation of meanings and practices from different collaborative traditions. This phenomenon commonly leads to a misappropriation of the term ‘co-production’. Our main motivation is to address this imprecision and the detrimental impact it has on efforts to enable co-production with marginalised and disadvantaged groups. We conclude that Oliver et al. stray too close to ‘the problem’ of ‘co-production’ seeing only the dark side rather than what is casting the shadows. We warn against such a restricted view and argue for greater scrutiny of the structural factors that largely explain academia’s failure to accommodate and promote the egalitarian and utilitarian potential of co-produced research.
The prevalence of depression among patients with tuberculosis: a systematic review and meta-analysis
Authors: Duko Bereket , Bedaso Asres , Ayano Getinet 
Published: May 2020

Abstract
Background
Evidence has shown that the prevalence of depression is much higher among patients with tuberculosis (TB) and this, in turn, may adversely impact compliance with anti-TB medications. Therefore, this systematic review and meta-analysis aimed to quantitatively summarize epidemiologic evidence on the prevalence of depression among patients with TB and formulate a recommendation for future clinical practice as well as research.

Methods
We followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines to conduct this review. We searched PubMed, EMBASE, SCOPUS and Psych INFO to identify relevant studies that investigated the prevalence of depression among TB patients. We also supplemented our electronic search with manual searching to include all pertinent studies in the analysis. We used a Comprehensive Meta-Analysis software version 3.0 (CMA 3.0) to conduct a meta-analysis. We conducted a subgroup and sensitivity analysis and Cochran’s Q- and the I2-statistics were used to assess heterogeneity. The evidence for the presence of publication bias was checked by using Egger’s test and visual inspection of the symmetry in funnel plots.

Results
We identified a total of 25 studies that included 4903 participants across seven countries. In our analysis, the pooled estimated prevalence of depression among TB patients was found to be 45.19% (95% CI 38.04–52.55). The prevalence was higher in MDR-TB 52.34% (95% CI 38.09–66.22) than non-MDR-TB 43.47% (95% CI 35.88–51.37) patients. We also found that the pooled prevalence of depression was higher among females 51.54% (95% CI 40.34–62.60) when compared to males 45.25% (95% CI 35.19–55.71). The pooled prevalence of depression was 45.45% as measured by HRDS, and it was 55.62%, 45.52%, and 38.36% as measured by BDI, HADS and PHQ-9, respectively.

Conclusion
Our finding suggested that the pooled estimated prevalence of depression among tuberculosis patients was relatively high. Screening and management of depression among TB patients were warranted to alleviate suffering. Moreover, the integration of tuberculosis program with regular psychiatry services may substantially reduce the burden.
Anti-inflammatory properties of uvaol on DSS-induced colitis and LPS-stimulated macrophages
Authors: Du Shi-yun , Huang Hai-feng , Li Xian-qian , Zhai Li-xiang , Zhu Qin-chang , Zheng Kai , Song Xun , Xu Chen-shu , Li Chen-yang , Li Ying , He Zhen-dan , Xiao Hai-tao 
Published: May 2020

Abstract
Background
Apocynum venetum leaves are used as a kind of phytomedicine and the main ingredient in some traditional Chinese medicine products for the relief of colitis. To understand the bioactive constituents of A. venetum L., we did a phytochemistry study and investigated anti-Inflammatory effects of compounds and explored the underlying mechanisms.

Methods
We isolated compounds from ethanol extract of A. venetum L. leaf and detected the most effective compound by NO inhibition assay. We investigated anti-Inflammatory effects on dextran sulfate sodium (DSS)-induced colitis mice and lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The disease activity index was determined by scores of body weight loss, diarrhea and rectal bleeding; histological damage was analyzed by H&E staining; macrophages change in the colon were analyzed by immunohistochemistry (IHC); myeloperoxidase activity was measured by myeloperoxidase assay kits; levels of proinflammatory cytokines were determined by qPCR and ELISA; protein production such as COX-2, iNOS, STAT3 and ERK1/2 were determined by western blotting.

Results
We isolated uvaol from ethanol extract of A. venetum L. leaf and found uvaol has excellent potential of inhibiting NO production. We further found uvaol could attenuate disease activity index (DAI), colon shortening, colon injury, and colonic myeloperoxidase activity in DSS-induced colitis mice. Moreover, uvaol significantly reduces mRNA expression and production of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, and MCP-1) and infiltration of macrophages in colonic tissues of colitis mice. Studies on LPS challenged murine macrophage RAW246.7 cells also revealed that uvaol reduces mRNA expression and production of pro-inflammatory cytokines and mediators. Mechanically, uvaol inhibits the pro-inflammatory ERK/STAT3 axis in both inflamed colonic tissues and macrophages.

Conclusions
A. venetum leaf contains uvaol and uvaol has potent anti-inflammatory effects on DSS-induced experimental colitis and LPS-stimulated RAW264.7 macrophage cells. These results suggest uvaol is a prospective anti-inflammatory agent for colonic inflammation.
Sur-X, a novel peptide, kills colorectal cancer cells by targeting survivin-XIAP complex
Authors: Fang Wanxia , Che Xiaofang , Li Guohui , Wang Anhui , Wang Yizhe , Shi Xiaonan , Hou Kezuo , Zhang Xiaojie , Qu Xiujuan , Liu Yunpeng 
Published: May 2020

Abstract
Background
Survivin and XIAP are two important members of the inhibitor of apoptosis protein family and have been considered as potential targets for cancer treatment due to their overexpression in large variety of cancers including colorectal cancer. It has been reported that survivin and XIAP can synergistically inhibit apoptosis by forming survivin-XIAP complex. In this study, we aimed to design a peptide that targets the survivin-XIAP complex and elucidate its anticancer mechanisms in colorectal cancer cells.

Methods
We designed and synthetized Sur-X, the peptide targeting survivin-XIAP complex. The anticancer effects of Sur-X were evaluated both in vitro and in vivo. The underlying molecular mechanisms were also investigated.

Results
Sur-X exhibited potent inhibitory effects on four colorectal cancer cell lines HCT116, HCT15, RKO and HT29, but not on human peritoneal mesothelial cell line HMrSV5. Mechanistically, Sur-X induced Caspase 9-dependent intrinsic apoptosis in colorectal cancer cells by disrupting the survivin-XIAP complex and subsequently destabilizing survivin and XIAP. Interestingly, we found that Sur-X can also promote necroptosis. It was demonstrated that Sur-X destroyed the interaction between XIAP and TAB1 in the XIAP-TAB1-TAK1 complex, leading to the instability of TAK1, an endogenous necroptosis inhibitor. Subsequently, the accelerated degradation of TAK1 attenuated its inhibition on necroptosis in colorectal cancer cells. Moreover, knockdown of TAK1 restored the sensitivity of TAB1-overexpressing colorectal cancer cells to Sur-X-induced necroptosis. The in vivo pro-apoptotic effect of Sur-X was confirmed by the enhanced TUNEL staining and the decreased expression of survivin and XIAP in tumor tissues from xenograft mouse models. In addition, extensive necrosis and weaker MLKL expression in xenografts provided evidence for the in vivo pro-necroptotic effect of Sur-X.

Conclusions
Peptide Sur-X exhibits strong pro-apoptotic and pro-necroptotic effects in colorectal cancer cells and has a high clinical translation potential in the treatment of colorectal cancer.
Educational strategy for the development of skills in exchange transfusion: a randomized clinical trial protocol
Authors: Maldonado María José , Agudelo Sergio Iván , Suarez Juan David , Gamboa Oscar 
Published: May 2020

Abstract
Background
Exchange transfusion is a highly complex procedure that requires high levels of expertise. Trainee paediatricians do not have adequate training in exchange transfusion because opportunities to perform this procedure in practice are scarce. This protocol seeks to compare two educational interventions for exchange transfusion that allow students to develop competencies to perform the technique in an appropriate and safe way.

Methods/design
This is a randomized parallel single-blind clinical trial with allocation by simple randomization to the educational intervention (simulation or a digital didactic environment). Students from the paediatric specialization who volunteer to participate will be included. A practical evaluation of the procedure will be performed through a simulated scenario using a standardized clinical case. The main outcome is defined as the result of evaluation using the Objective Structured Clinical Examination; superior performance will be defined when the percentage is greater than or equal to 85%, and non-superior performance will be defined when the result is less than 84%. The chi-square independence test or the Fisher exact test will be used to evaluate the effect of the interventions. Multivariate analysis will be performed using a non-conditional logistic regression model. Stata 15® software will be used.

Discussion
Exchange transfusion is a procedure that requires expertise to achieve adequate outcomes. The inclusion of new educational strategies, such as simulation and digital didactic environments, is seen as a training option that can improve performance in clinical skills, reduce adverse events and increase the level of trust.

Trial registration
ClinicalTrials.gov: NCT04070066. Registered on 28 August 2019. https://clinicaltrials.gov.
Care after pancreatic resection according to an algorithm for early detection and minimally invasive management of pancreatic fistula versus current practice (PORSCH-trial): design and rationale of a nationwide stepped-wedge cluster-randomized trial
Authors:   for the Dutch Pancreatic Cancer Group, Smits F. Jasmijn , Henry Anne Claire , van Eijck Casper H. , Besselink Marc G. , Busch Olivier R. , Arntz Mark , Bollen Thomas L. , van Delden Otto M. , van den Heuvel Daniel , van der Leij Christiaan , van Lienden Krijn P. , Moelker Adriaan , Bonsing Bert A. , Borel Rinkes Inne H. M. , Bosscha Koop , van Dam R. M. , Festen Sebastiaan , Groot Koerkamp B. , van der Harst Erwin , de Hingh Ignace H. , Kazemier Geert , Liem Mike , van der Kolk B. Marion , de Meijer Vincent E. , Patijn Gijs A. , Roos Daphne , Schreinemakers Jennifer M. , Wit Fennie , van Werkhoven C. Henri , Molenaar I. Quintus , van Santvoort Hjalmar C. 
Published: May 2020

Abstract
Background
Pancreatic resection is a major abdominal operation with 50% risk of postoperative complications. A common complication is pancreatic fistula, which may have severe clinical consequences such as postoperative bleeding, organ failure and death. The objective of this study is to investigate whether implementation of an algorithm for early detection and minimally invasive management of pancreatic fistula may improve outcomes after pancreatic resection.

Methods
This is a nationwide stepped-wedge, cluster-randomized, superiority trial, designed in adherence to the Consolidated Standards of Reporting Trials (CONSORT) guidelines. During a period of 22 months, all Dutch centers performing pancreatic surgery will cross over in a randomized order from current practice to best practice according to the algorithm. This evidence-based and consensus-based algorithm will provide daily multilevel advice on the management of patients after pancreatic resection (i.e. indication for abdominal imaging, antibiotic treatment, percutaneous drainage and removal of abdominal drains). The algorithm is designed to aid early detection and minimally invasive step-up management of postoperative pancreatic fistula. Outcomes of current practice will be compared with outcomes after implementation of the algorithm. The primary outcome is a composite of major complications (i.e. post-pancreatectomy bleeding, new-onset organ failure and death) and will be measured in a sample size of at least 1600 patients undergoing pancreatic resection. Secondary endpoints include the individual components of the primary endpoint and other clinical outcomes, healthcare resource utilization and costs analysis. Follow up will be up to 90 days after pancreatic resection.

Discussion
It is hypothesized that a structured nationwide implementation of a dedicated algorithm for early detection and minimally invasive step-up management of postoperative pancreatic fistula will reduce the risk of major complications and death after pancreatic resection, as compared to current practice.

Trial registration
Netherlands Trial Register: NL 6671. Registered on 16 December 2017.
Rats as potential reservoirs for neglected zoonotic Bartonella species in Flanders, Belgium
Authors: Krügel Maria , Pfeffer Martin , Król Nina , Imholt Christian , Baert Kristof , Ulrich Rainer G. , Obiegala Anna 
Published: May 2020

Abstract
Background
Bartonella spp. are vector-borne pathogens transmitted to humans via blood-sucking arthropods. Rodents such as the black rat (Rattus rattus) and Norway rat (R. norvegicus) are thought to be the main reservoirs. An infection with rodent-associated Bartonella spp. may cause severe symptoms in humans such as endocarditis and neuroretinitis. The current knowledge of Bartonella prevalence in rats from western Europe is scarce.

Methods
Rats and a few other rodent by-catches were trapped in the context of a rodenticide resistance study at different sites in Flanders, Belgium. During dissection, biometric data were collected, and spleen tissues were taken. DNA was extracted from spleen samples and tested for Bartonella spp. by conventional generic polymerase chain reaction (PCR). To determine the Bartonella species, a selected number of amplicons were sequenced and compared with GenBank entries.

Results
In total, 1123 rodents were trapped. The predominate species was R. norvegicus (99.64%). Other rodents trapped included: two water voles (Arvicola amphibius, 0.18%); one colour rat (R. norvegicus forma domestica, 0.09%); and one muskrat (Ondatra zibethicus, 0.09%). PCR analysis of 1097 rodents resulted in 410 (37.37%, 95% CI: 34.50–40.31%) Bartonella spp. DNA-positive samples. Bartonella tribocorum (94.68%, 95% CI: 88.02–98.25%) was the most frequently detected Bartonella species, followed by B. grahamii (3.19%, 95% CI: 0.66–9.04%) and B. doshiae (1.06%, 95% CI: 0.03–5.79%). An uncultured Bartonella species occurred in one water vole (1.06%, 95% CI: 0.03–5.79%). There was a significantly higher Bartonella prevalence in older rats compared to juveniles and a significant difference in Bartonella prevalence concerning the localisation of trapping sites. In contrast, there was no statistically significant difference in Bartonella prevalence regarding sex, degree of urbanisation and season.

Conclusions
Based on the high prevalence found, we conclude that the Norway rat seems to be a key reservoir host for zoonotic B. tribocorum in Belgium.