bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of a physiatrist-directed prehabilitation intervention in frail patients with colorectal cancer: a randomised pilot study protocol
Authors: Wong Sherman G , Maida Eugene , Harvey David , Wagner Natalie , Sonnadara Ranil , Amin Nalin 
Published: June 2017

IntroductionPrehabilitation interventions have shown efficacy in the orthopaedic and cardiothoracic surgical populations, but there has been limited evidence for general surgical patients. We present the protocol for a pilot trial of a novel prehabilitation intervention, consisting of a physiatrist-directed preoperative assessment and treatment programme.Methods and analysisThis is a single-centre pilot randomised controlled trial investigating physiatrist-directed prehabilitation for a 4 to 6-week preoperative period. We will block randomise 40–50 participants awaiting surgery for colorectal cancer to prehabilitation versus control. Participants in the prehabilitation arm will undergo assessment by a physiatrist and enrol in a supervised exercise programme. The control group will not undergo any prehabilitation interventions in the preoperative period. Our primary outcome is feasibility, measured by examining recruitment, refusal, retention and adherence rates as well as participant satisfaction and feedback. Secondary outcomes include physical fitness, functional ability, health-related quality of life, postoperative complications, mortality, readmissions, length of stay, prehabilitation interventions performed and exercise complications.Ethics and disseminationThis study has been approved by the Hamilton Integrated Research Ethics Board (HIREB reference number 2015–0090-GRA). The results of this pilot study will be used to design a full-scale study and published in peer-reviewed journals.Trial registration numberNCT02531620; Pre-results.
Systematic review and meta-analysis of prevalence of, and risk factors for, pelvic floor disorders in community-dwelling women in low and middle-income countries: a protocol study
Authors: Islam Rakibul M , Oldroyd John , Karim Md Nazmul , Hossain Sultana Monira , Md Emdadul Hoque Dewan , Romero Lorena , Fisher Jane 
Published: June 2017

IntroductionPelvic floor disorders (PFDs) including urinary incontinence, faecal incontinence and pelvic organ prolapse are common debilitating conditions among women in high-income countries. However, PFDs in women in low/middle-income countries (LMICs) have not been studied extensively. We aim to conduct a systematic review and meta-analysis of the available literature to determine the prevalence of, and/or risk factors for, PFDs in women in LMIC.Methods and analysisWe will search electronic databases including MEDLINE, EMBASE, PsycINFO, CINAHL, Maternity & Infant Care and Google Scholar for eligible studies. Inclusion criteria will be observational studies of healthy women, which have collected data using validated or non-validated tools, are published in English and were conducted in community women in LMICs, defined by the World Bank. A standardised data extraction form will be developed and piloted, based on the template of the Cochrane good practice data extraction form. All included studies will be assessed based on a risk-of-bias tool specifically developed for prevalence studies. Pooled prevalence estimates of PFDs will be generated using RevMan V.5.2.1 software. Forest plots will be generated to display the overall random-effects pooled estimates with CIs. A metaregression will be conducted to identify sources of between-study heterogeneity in the pooled prevalence estimates. We will quantify heterogeneity using the I2measure and its CI. We will use funnel plots to detect potential reporting biases and small-study effects. We will also conduct a sensitivity analysis to verify the robustness of the study conclusions, assessing the impact of methodological quality, study design, sample size and the effect of missing data.Ethics and disseminationOur review is entirely based on published data. Thus, an ethics committee approval or written informed consent will not be required for this study as primary data will not be collected. The results will be disseminated by publication of the manuscript in a peer-reviewed journal and/or will be presented at relevant conferences.PROSPERO registration numberCRD42016043881.
Night work and prostate cancer in men: a Swedish prospective cohort study
Authors: Åkerstedt Torbjrn , Narusyte Jurgita , Svedberg Pia , Kecklund Göran , Alexanderson Kristina 
Published: June 2017

ObjectivesProstate cancer is the most common cancer and the second leading cause of cancer-related deaths among men, but the contributing factors are unclear. One such may be night work because of the day/night alternation of work and the resulting disturbance of the circadian system. The purpose of the present study was to investigate the prospective relation between number of years with night work and prostate cancer in men.DesignCohort study comparing night and day working twins with respect to incident prostate cancer in 12 322 men.SettingIndividuals in the Swedish Twin Registry.Participants12 322 male twins.Outcome measuresProstate cancer diagnoses obtained from the Swedish Cancer Registry with a follow-up time of 12 years, with a total number of cases=454.ResultsMultiple Cox proportional hazard regression analysis, adjusted for a number of covariates, showed no association between ever night work and prostate cancer, nor for duration of night work and prostate cancer. Analysis of twin pairs discordant for prostate cancer (n=332) showed no significant association between night work and prostate cancer.ConclusionsThe results, together with previous studies, suggest that night work does not seem to constitute a risk factor for prostate cancer.
Performance-based functional impairment and readmission and death: a prospective study
Authors: Aubert Carole E , Folly Antoine , Mancinetti Marco , Hayoz Daniel , Donzé Jacques D 
Published: June 2017

ObjectivesReadmission and death are frequent after a hospitalisation and difficult to predict. While many predictors have been identified, few studies have focused on functional status. We assessed whether performance-based functional impairment at discharge is associated with readmission and death after an acute medical hospitalisation.Design, setting and participantsWe prospectively included patients aged ≥50 years admitted to the Department of General Internal Medicine of a large community hospital. Functional status was assessed shortly before discharge using the Timed Up and Go test performed twice in a standard way by trained physiotherapists and was defined as a test duration ≥15 s. Sensitivity analyses using a cut-off at >10 and >20 s were performed.Primary and secondary outcome measuresThe primary and secondary outcome measures were unplanned readmission and death, respectively, within 6 months after discharge.ResultsWithin 6 months after discharge, 107/338 (31.7%) patients had an unplanned readmission and 31/338 (9.2%) died. Functional impairment was associated with higher risk of death (OR 2.44, 95% CI 1.15 to 5.18), but not with unplanned readmission (OR 1.34, 95% CI 0.84 to 2.15). No significant association was found between functional impairment and the total number of unplanned readmissions (adjusted OR 1.59, 95% CI 0.95 to 2.67).ConclusionsFunctional impairment at discharge of an acute medical hospitalisation was associated with higher risk of death, but not of unplanned readmission within 6 months after discharge. Simple performance-based assessment may represent a better prognostic measure for mortality than for readmission.
Association between preoperative anaemia with length of hospital stay among patients undergoing primary total knee arthroplasty in Singapore: a single-centre retrospective study
Authors: Abdullah Hairil Rizal , Sim Yilin Eileen , Hao Ying , Lin Geng Yu , Liew Geoffrey Haw Chieh , Lamoureux Ecosse L , Tan Mann Hong 
Published: June 2017

ObjectivesStudies in western healthcare settings suggest that preoperative anaemia is associated with poor outcomes after elective orthopaedic surgery. We investigated the prevalence of preoperative anaemia among patients with primary unilateral total knee arthroplasty (TKA) in Singapore and its association with length of hospital stay (LOS), perioperative blood transfusion and hospital readmission rates.MethodsRetrospective cohort study performed in a tertiary academic medical centre in Singapore, involving patients who underwent primary unilateral TKA between January 2013 and June 2014. Demographics, comorbidities, preoperative haemoglobin (Hb) level, LOS and 30-day readmission data were collected. Anaemia was classified according to WHO definition. Prolonged LOS was defined as more than 6 days, which corresponds to >75th centile LOS of the data.ResultsWe analysed 2394 patients. The prevalence of anaemia was 23.7%. 403 patients (16.8%) had mild anaemia and 164 patients (6.8%) had moderate to severe anaemia. Overall mean LOS was 5.4±4.8 days. Based on multivariate logistic regression, preoperative anaemia significantly increased LOS (mild anaemia, adjusted OR (aOR) 1.71, p<0.001; moderate/severe anaemia, aOR 2.29, p<0.001). Similar effects were seen when preoperative anaemia was defined by Hb level below 13 g/dL, regardless of gender. Transfusion proportionately increased prolonged LOS (1 unit: aOR 2.12, p=0.006; 2 or more units: aOR 6.71, p<0.001). Repeat operation during hospital stay, previous cerebrovascular accidents, general anaesthesia and age >70 years were associated with prolonged LOS. Our 30-day related readmission rate was 1.7% (42) cases.ConclusionAnaemia is common among patients undergoing elective TKA in Singapore and is independently associated with prolonged LOS and increased perioperative blood transfusion. We suggest measures to correct anaemia prior to surgery, including the use of non-gender-based Hb cut-off for establishing diagnosis.
Practice patterns and outcomes associated with early sedation depth in mechanically ventilated patients: a systematic review protocol
Authors: Stephens Robert J , Dettmer Matthew R , Roberts Brian W , Fowler Susan A , Fuller Brian M 
Published: June 2017

IntroductionMechanical ventilation is a commonly performed intervention in critically ill patients. Frequently, these patients experience deep sedation early in their clinical course. Emerging data suggest that the practice of early deep sedation may negatively impact patient outcomes. The purpose of this review is to assess the world’s literature to describe and determine the impact of early deep sedation on the outcomes of mechanically ventilated patients.Methods and analysisRandomised controlled trials and non-randomised studies will be eligible for inclusion in this systematic review. With the assistance of a medical librarian, we will comprehensively search MEDLINE, Embase, Scopus, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews and Effects, and Cochrane Database of Systematic Reviews for peer-reviewed literature. Grey literature from appropriate professional society conferences, held from 2010 to 2017, will be reviewed manually. Two authors will independently review all search results, and disagreements will be resolved through arbitration by a third author. If appropriate, meta-analysis will be used for quantitative analysis of the data. Heterogeneity between studies will be assessed using the I2statistic.Ethics and disseminationThe proposed systematic review will not collect data that are associated with individual patients and does not require ethical approval. Results of this study will contribute to the understanding of early sedation, identify future research targets and guide early care in mechanically ventilated patients.Trial registration numberThis systematic review has been registered in the international prospective register of systematic reviews (PROSPERO #CRD42017057264).
The somatic mutation landscape of premalignant colorectal adenoma
Authors: Lin Shu-Hong , Raju Gottumukkala S , Huff Chad , Ye Yuanqing , Gu Jian , Chen Jiun-Sheng , Hildebrandt Michelle A T , Liang Han , Menter David G , Morris Jeffery , Hawk Ernest , Stroehlein John R , Futreal Andrew , Kopetz Scott , Mishra Lopa , Wu Xifeng 
Published: June 2017

ObjectiveThere are few studies which characterised the molecular alterations in premalignant colorectal adenomas. Our major goal was to establish colorectal adenoma genome atlas and identify molecular markers of progression from colorectal adenoma to adenocarcinoma.DesignWhole-exome sequencing and targeted sequencing were carried out in 149 adenoma samples and paired blood from patients with conventional adenoma or sessile serrated adenoma to characterise the somatic mutation landscape for premalignant colorectal lesions. The identified somatic mutations were compared with those in colorectal cancer (CRC) samples from The Cancer Genome Atlas. A supervised random forest model was employed to identify gene panels differentiating adenoma from CRC.ResultsSimilar somatic mutation frequencies, but distinctive driver mutations, were observed in sessile serrated adenomas and conventional adenomas. The final model included 20 genes and was able to separate the somatic mutation profile of colorectal adenoma and adenocarcinoma with an area under the curve of 0.941.ConclusionThe findings of this project hold potential to better identify patients with adenoma who may be candidates for targeted surveillance programmes and preventive interventions to reduce the incidence of CRC.
Early proteinuria response: a valid real-life situation predictor of long-term lupus renal outcome in an ethnically diverse group with severe biopsy-proven nephritis?
Authors: Ugolini-Lopes Michelle R , Seguro Luciana Parente C , Castro Maitê Xavier F , Daffre Danielle , Lopes Alex C , Borba Eduardo F , Bonfá Eloisa 
Published: June 2017

ObjectiveTwo recent important lupus nephritis trials reported that proteinuria was a good predictor of renal outcome in Caucasians, but data on real-life situation, other races and severe nephritis are lacking to substantiate this finding as a simple test to guide clinical practice. The aim of this study was to validate proteinuria as a predictor of long-term renal outcome in real-life situation in a racially diverse group of patients with severe nephritis.MethodsProteinuria, serum creatinine (SCr) and urine red blood cells were assessed at baseline and after 3, 6 and 12 months, as early predictors of long-term renal outcome (SCr <1.5 mg/dL at 7 years), in 94 patients with biopsy-proven lupus nephritis. The parameter performance and cut-off values were computed by receiver operating characteristic curves. Kaplan-Meier curves were used to validate the parameter.ResultsA proteinuria <0.8 g/24 hours at 12 months was the best single predictor of long-term renal outcome (sensitivity 90%, specificity 78%, positive predictive value 67%, negative predictive value (NPV) 94% and area under the curve 0.86; p<0.001). Addition of other variables to proteinuria such as SCr and haematuria at 12 months did not improve its performance. The proteinuria cut-off value of 0.8 g/24 hours at 12 months was a good predictor of 7-year renal survival (years free of dialysis) for patients with pure membranous (p=0.005) and proliferative nephritis (p=0.043), as well as black (p=0.002) and white race (p=0.001), anti-dsDNA positive (p=0.001) and anti-dsDNA negative (p=0.04) and male (p=0.028) and female (p=0.003) patients.ConclusionWe provided novel evidence that, in a real-life situation, proteinuria at 12 months of follow-up was the single best predictor of renal outcome at 7 years for an ethnically diverse group of patients with severe nephritis and a valid parameter for distinct histological classes, races, genders and anti-dsDNA profiles. The remarkably high NPV obtained reinforces its recommendation as the ideal predictor for clinical practice, since it is of low cost, easy to interpret, non-invasive and widely available.
A longitudinal and multicentre study of burnout and error in Irish junior doctors
Authors: O’Connor Paul , Lydon Sinéad , O’Dea Angela , Hehir Layla , Offiah Gozie , Vellinga Akke , Byrne Dara 
Published: June 2017

ABSTRACTBackgroundJunior doctors have been found to suffer from high levels of burnout.AimsTo measure burnout in a population of junior doctors in Ireland and identify if: levels of burnout are similar to US medical residents; there is a change in the pattern of burnout during the first year of postgraduate clinical practice; and burnout is associated with self-reported error.MethodsThe Maslach Burnout Inventory—Human Services Survey was distributed to Irish junior doctors from five training networks in the last quarter of 2015 when they were approximately 4 months into their first year of clinical practice (time 1), and again 6 months later (time 2). The survey assessed burnout and whether they had made a medical error that had ‘played on (their) mind’.ResultsA total of 172 respondents out of 601 (28.6%) completed the questionnaire on both occasions. Irish junior doctors at time 2 were more burned out than a sample of US medical residents (72.6% and 60.3% burned out, respectively; p=0.001). There was a significant increase in emotional exhaustion from time 1 to time 2 (p=0.007). The association between burnout and error was significant at time 2 only (p=0.03). At time 2, of those respondents who were burned out, 81/122 (66.4%) reported making an error. A total of 22/46 (47.8%) of the junior doctors who were not burned out at time 2 reported an error.ConclusionCurrent levels of burnout are unsustainable and place the health of both junior doctors and their patients at risk.
Translation surfaces of some new types in 3-dimensional Minkowski space 𝔼13 satisfying Δri = λiri
Authors: Senoussi Bendehiba , Bekkar Mohammed 
Published: June 2017

Following the publication online, it has been brought to the attention of the Editorial Board of Communications in Contemporary Mathematics (CCM) that the result of this paper was known since 1992 and appeared in the article by Luis Alías, Angel Ferrández and Pascual Lucas, Surfaces in the 3-dimensional Lorentz–Minkowski space satisfying [Formula: see text], Pacific J. Math. 156(2) (1992) 201–208. The information has been verified, and therefore the Editors-in-Chief of CCM have decided to retract the acceptance of this paper.
Trabectedin Overrides Osteosarcoma Differentiative Block and Reprograms the Tumor Immune Environment Enabling Effective Combination with Immune Checkpoint Inhibitors
Authors: Ratti Chiara , Botti Laura , Cancila Valeria , Galvan Silvia , Torselli Ilaria , Garofalo Cecilia , Manara Maria Cristina , Bongiovanni Lucia , Valenti Cesare F. , Burocchi Alessia , Parenza Mariella , Cappetti Barbara , Sangaletti Sabina , Tripodo Claudio , Scotlandi Katia , Colombo Mario P. , Chiodoni Claudia 
Published: June 2017

Abstract
Purpose: Osteosarcoma, the most common primary bone tumor, is characterized by an aggressive behavior with high tendency to develop lung metastases as well as by multiple genetic aberrations that have hindered the development of targeted therapies. New therapeutic approaches are urgently needed; however, novel combinations with immunotherapies and checkpoint inhibitors require suitable preclinical models with intact immune systems to be properly tested.
Experimental Design: We have developed immunocompetent osteosarcoma models that grow orthotopically in the bone and spontaneously metastasize to the lungs, mimicking human osteosarcoma. These models have been used to test the efficacy of trabectedin, a chemotherapeutic drug utilized clinically for sarcomas and ovarian cancer.
Results: Trabectedin, as monotherapy, significantly inhibited osteosarcoma primary tumor growth and lung metastases by both targeting neoplastic cells and reprogramming the tumor immune microenvironment. Specifically, trabectedin induced a striking differentiation of tumor cells by favoring the recruitment of Runx2, the master genetic regulator of osteoblastogenesis, on the promoter of genes involved in the physiologic process of terminal osteoblast differentiation. Differentiated neoplastic cells, as expected, showed reduced proliferation rate. Concomitantly, trabectedin enhanced the number of tumor-infiltrating T lymphocytes, with local CD8 T cells, however, likely post-activated or exhausted, as suggested by their high expression of the inhibitory checkpoint molecule PD-1. Accordingly, the combination with a PD-1–blocking antibody significantly increased trabectedin efficacy in controlling osteosarcoma progression.
Conclusions: These results demonstrate the therapeutic efficacy of trabectedin in osteosarcoma treatment, unveiling its multiple activities and providing a solid rationale for its combination with immune checkpoint inhibitors. Clin Cancer Res; 23(17); 5149–61. ©2017 AACR.
miR-193a-3p is a Key Tumor Suppressor in Ulcerative Colitis–Associated Colon Cancer and Promotes Carcinogenesis through Upregulation of IL17RD
Authors: Pekow Joel , Meckel Katherine , Dougherty Urszula , Huang Yong , Chen Xindi , Almoghrabi Anas , Mustafi Reba , Ayaloglu-Butun Fatma , Deng Zifeng , Haider Haider I. , Hart John , Rubin David T. , Kwon John H. , Bissonnette Marc 
Published: June 2017

Abstract
Purpose: Patients with ulcerative colitis are at increased risk for colorectal cancer, although mechanisms underlying neoplastic transformation are poorly understood. We sought to evaluate the role of microRNAs in neoplasia development in this high-risk population.
Experimental Design: Tissue from 12 controls, 9 ulcerative colitis patients without neoplasia, and 11 ulcerative colitis patients with neoplasia was analyzed. miRNA array analysis was performed and select miRNAs assayed by real-time PCR on the discovery cohort and a validation cohort. DNA methylation of miR-193a was assessed. Following transfection of miR-193a-3p, proliferation, IL17RD expression, and luciferase activity of the 3′UTR of IL17RD were measured. Tumor growth in xenografts as well as EGFR signaling were assessed in HCT116 cells expressing IL17RD with either a mutant 3′ untranslated region (UTR) or wild-type (WT) 3′UTR.
Results: miR-31, miR-34a, miR-106b, and miR-193a-3p were significantly dysregulated in ulcerative colitis-neoplasia and adjacent tissue. Significant down-regulation of miR-193a-3p was also seen in an independent cohort of ulcerative colitis cancers. Changes in methylation of miR-193a or expression of pri-miR-193a were not observed in ulcerative colitis cancer. Transfection of miR-193a-3p resulted in decreased proliferation, and identified IL17RD as a direct target of miR-193a-3p. IL17RD expression was increased in ulcerative colitis cancers, and miR-193a-3p treatment decreased growth and EGFR signaling of HCT116 cells in xenografts expressing both IL17RD with WT 3′UTR compared with cells expressing IL17RD with mutant 3′UTR.
Conclusions: miR-193a-3p is downregulated in ulcerative colitis neoplasia, and its loss promotes carcinogenesis through upregulation of IL17RD. These findings provide novel insight into inflammation-driven colorectal cancer and could suggest new therapeutic targets in this high-risk population. Clin Cancer Res; 23(17); 5281–91. ©2017 AACR.