bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global differences in the prevalence of the CpG island methylator phenotype of colorectal cancer
Authors: Advani Shailesh Mahesh , Advani Pragati Shailesh , Brown Derek W. , DeSantis Stacia M. , Korphaisarn Krittiya , VonVille Helena M. , Bressler Jan , Lopez David S. , Davis Jennifer S. , Daniel Carrie R. , Sarshekeh Amir Mehrvarz , Braithwaite Dejana , Swartz Michael D. , Kopetz Scott 
Published: October 2019

AbstractBackgroundCpG Island Methylator Phenotype (CIMP) is an epigenetic phenotype in CRC characterized by hypermethylation of CpG islands in promoter regions of tumor suppressor genes, leading to their transcriptional silencing and loss of function. While the prevalence of CRC differs across geographical regions, no studies have compared prevalence of CIMP-High phenotype across regions. The purpose of this project was to compare the prevalence of CIMP across geographical regions after adjusting for variations in methodologies to measure CIMP in a meta-analysis.MethodsWe searched PubMed, Medline, and Embase for articles focusing on CIMP published from 2000 to 2018. Two reviewers independently identified 111 articles to be included in final meta-analysis. We classified methods used to quantify CIMP into 4 categories: a) Classical (MINT marker) Panel group b) Weisenberg-Ogino (W-O) group c) Human Methylation Arrays group and d) Miscellaneous group. We compared the prevalence of CIMP across geographical regions after correcting for methodological variations using meta-regression techniques.ResultsThe pooled prevalence of CIMP-High across all studies was 22% (95% confidence interval:21–24%; I2 = 94.75%). Pooled prevalence of CIMP-H across Asia, Australia, Europe, North America and South America was 22, 21, 21, 27 and 25%, respectively. Meta-regression analysis identified no significant differences in the prevalence of CIMP-H across geographical regions after correction for methodological variations. In exploratory analysis, we observed variations in CIMP-H prevalence across countries.ConclusionAlthough no differences were found for CIMP-H prevalence across countries, further studies are needed to compare the influence of demographic, lifestyle and environmental factors in relation to the prevalence of CIMP across geographical regions.
Synchronous colonic adenoma and intestinal marginal zone B-cell lymphoma associated with Crohn’s disease: a case report and literature review
Authors: Bennani Amal , Kharrasse Ghizlane , Achraf Miry , Wafa Khanoussi , Zahi Ismaili , Imane Kamaoui , Mohamed Bouziane 
Published: October 2019

Abstract

Background
Lymphoma and dysplasia are rare complications of long-standing Crohn’s disease. We report an exceptional case of a synchronous intestinal marginal zone B-cell lymphoma (MALT lymphoma) and colonic adenoma in a Crohn’s disease patient.

Case presentation
A 50-year-old male patient presented with right lower quadrant for the last 9 months. He also had associated weight loss and diarrhea alternating with constipation. Ileo-colonoscopy revealed a pseudopolypoid appearance of the colonic and ileal mucosa with many discontinuous ulcerations with a 3 cm sessile polypoid mass at 17 cm from the anal verge. Histological examination of the polypoid lesion revealed an adenoma with high grade dysplasia, while the biopsies of colonic mucosa showed histologic features of Crohn’s disease. Abdominal computed tomography scan (CT scan) and magnetic resonance imaging (MRI) showed circumferential wall thickening of the colon and ileum, enlarged mesenteric lymph nodes and a sessile polypoid mass of the rectosigmoid junction. The patient was scheduled for an ileocoletectomy with resection of the upper rectum and ileorectostomy.
The histological examination of the resected segment showed histologic features of Crohn’s disease, a recto-sigmoid polyp with high grade.
dysplasia and extensive small lymphocytic infiltrate in both colonic and ileal wall which is strongly stained by CD20 and BCL2. The diagnosis of MALT lymphoma with adenoma on a background of Crohn’s disease was made.
The patient successfully completed 8 cycles of Rituximab+ chlorambucil chemotherapy.
Nowadays the patient is asymptomatic without evidence of lymphoproliferative recurrence 10 months after surgery.

Conclusion
We report the first case in the literature of Malt lymphoma with colonic adenoma associated with Crohn’s disease, and discuss his unique macroscopic and histological features in a patient.
Without immunosuppressive therapy.
Cost-effectiveness of a mindfulness-based mental health promotion program: economic evaluation of a nonrandomized controlled trial with propensity score matching
Authors: Müller Gerhard , Pfinder Manuela , Schmahl Christian , Bohus Martin , Lyssenko Lisa 
Published: October 2019

Abstract

Background
Mental health promotion programs have been shown to reduce the burden associated with mental distress and prevent the onset of mental disorders, but evidence of cost-effectiveness is scarce.

Objective
To evaluate the cost-effectiveness of a mindfulness-based mental health prevention program provided by health coaches in a multi-site field setting in Germany.

Methods
The single-study based economic evaluation was conducted as part of a nonrandomized controlled trial, comparing the effects of a group-based prevention program to usual care based on propensity score matching. Participants (N = 1166) were recruited via a large statutory health insurance fund. Health outcome was assessed with the Hospital Anxiety and Depression Scale (HADS). Cost outcomes were actually incurred costs compiled from the health insurance’ records. Incremental cost-effectiveness ratios (ICER) were analyzed from a societal and a health care perspective for a 12-month time horizon with sampling uncertainty being handled using nonparametric bootstrapping. A cost-effectiveness acceptability curve was graphed to determine the probability of cost-effectiveness at different willingness-to-pay ceiling ratios.

Results
From a societal perspective, prevention was cost-effective compared to usual-care by providing larger effects of 1.97 units on the HADS (95% CI [1.14, 2.81], p < 0.001) at lower mean incremental total costs of €-57 (95% CI [− 634, 480], p = 0.84), yielding an ICER of €-29 (savings) per unit improvement. From a health care perspective, the incremental health benefits were achieved at additional direct costs of €181 for prevention participants (95% CI [40, 318], p = 0.01) with an ICER of €91 per unit improvement on the HADS. Willingness-to-pay for the prevention program to achieve a 95% probability of being cost-effective compared to usual-care, was estimated at €225 per unit improvement on the HADS score from a societal, and €191 from a health care perspective respectively. Sensitivity analyses suggested differential cost-effect-ratios depending on the initial distress of participants.

Limitations
Due to the complexity of the field trial, it was not feasible to randomize participants and offer an active control condition. This limitation was met by applying a rigorous matching procedure.

Conclusions
Our results indicate that universal mental health promotion programs in community settings might be a cost-effective strategy to enhance well-being. Differences between the societal and health care perspective underline the call for joint funding in the dissemination of preventive services.

Trial registration
German Clinical Trials Registration ID: DRKS00006216 (2014/06/11, retrospective registration).
Prevalence of chronic obstructive pulmonary disease (COPD) and its associated factors among adults in Abeshge District, Ethiopia: a cross sectional study
Authors: Woldeamanuel Gashaw Garedew , Mingude Alemu Basazin , Geta Teshome Gensa 
Published: October 2019

Abstract

Background
Chronic obstructive pulmonary disease (COPD) is one of the major public health problems worldwide. Despite an increasing burden of COPD in the world, it is often a neglected disease in low income countries and COPD prevalence studies are rare in Sub-Saharan Africa. The objective of this study was to determine the prevalence of COPD and its associated factors among adults in Ethiopia.

Methods
A community based cross sectional study was conducted from February 5 to May 20, 2019 in Abeshge district, Southern Ethiopia. A total of 734 adults aged at least 30 years were selected using multistage cluster sampling technique and included in the study. All participants were interviewed about socio-demographic characteristics, respiratory symptoms, smoking status and clinical characteristics. Moreover, all participants underwent spirometry. We defined COPD as a post-bronchodilator FEV1/FVC of less than 70%. Data were entered into Epi-data manager 4.4 and analyzed using SPSS version 23. Descriptive statistics and binary logistic regression analysis were used and p-value < 0.05 was considered as significant.

Results
Of the 779 adults invited to participate, 734 adults (421 men and 313 women) were participated in this study. The mean (SD) age of the participants was 39.15 (± 9.36) years, within the age range of 30–75 years. The prevalence of COPD was 17.8% (95% confidence interval [CI], 15.1–20.6). Factors significantly associated with COPD were age above 50 years (adjusted odds ratio [AOR] = 1.91, 95% CI [1.10, 3.30]), being smoker (AOR = 4.54, 95% CI [2.69, 7.66]), Exposed to biomass smoke (AOR = 2.05, 95% CI [1.06, 3.95]) and poor ventilated kitchen (AOR = 4.12, 95% CI [2.67, 6.34]).

Conclusion
It is evident from this study that the prevalence of COPD in Ethiopia is high. Factors such as old age, cigarette smoking, exposure to biomass smoke and poor kitchen ventilation plays a role in the development of COPD.
Supernumerary kidneys: a clinical and radiological analysis of nine cases
Authors: Rehder Peter , Rehwald Rafael , Böhm Julia M. , Grams Astrid E. , Loizides Alexander , Pedrini Marco , Stühmeier Jannik , Glodny Bernhard 
Published: October 2019

AbstractBackgroundA supernumerary kidney (SK) is an additional kidney with its own capsule and blood supply that is not fused with the ipsilateral kidney (IK). Because individual case reports indicate a high morbidity rate, the aim of this retrospective study was a detailed analysis of this rare anatomical variant.MethodsOur systematic imaging-based search for SKs, conducted in the period from 2000 and to 2017, yielded 9 cases in total (5 men, 4 women; mean age: 51.8 ± 22.8 years).ResultsThe SKs were observed on the right in six and on the left side in three cases. In six subjects (66%) they were located caudal and in three cases (33%) cranial to the ipsilateral kidney. Calculi were found in three (33%) of the renal collecting systems. Five (56%) of the SKs had hydronephrosis grade IV and one SK had recurrent pyelonephritis (11%). Two of the ureters opened into the ipsilateral seminal vesicle (22%). Two (22%) SKs were functional but atrophic. Clinically relevant findings were made in 33% of the IKs: atrophy (n = 2), calculi (n = 1), and reflux with recurrent pyelonephritis (n = 1); another 33% had anatomical anomalies without functional impairment. The correct diagnosis of a SK is possible using CT imaging in all subjects. The prevalence of SK based on CT imaging can be estimated to be 1:26750.ConclusionsCT is the method of choice for visualizing SKs. The correct diagnosis is crucial in preventing dispensable surgical procedures and for providing optimal patient treatment and outcome.
Development of a novel human phage display-derived anti-LAG3 scFv antibody targeting CD8+ T lymphocyte exhaustion
Authors: Ascione Alessandro , Arenaccio Claudia , Mallano Alessandra , Flego Michela , Gellini Mara , Andreotti Mauro , Fenwick Craig , Pantaleo Giuseppe , Vella Stefano , Federico Maurizio 
Published: October 2019

AbstractBackgroundLymphocyte-activation gene (LAG)3 is a 498 aa transmembrane type I protein acting as an immune inhibitory receptor. It is expressed on activated lymphocytes, natural killer cells and plasmacytoid dendritic cells. In activated lymphocytes, LAG3 expression is involved in negative control of cell activation/proliferation to ensure modulation and control of immune responses. In view of its deregulated expression in tumor-infiltrating lymphocytes, LAG3, together with the additional immune checkpoint inhibitors CTLA4 and PD1, is considered a major target in order to reverse the immunosuppression typically mounting in oncologic diseases. Since many patients still fail to respond to current immune checkpoints-based therapies, the identification of new effective immune inhibitors is a priority in the ongoing fight against cancer.ResultsWe identified a novel human single-chain variable fragment (scFv) Ab against a conformational epitope of LAG3 by in vitro phage display technology using the recombinant antigen as a bait. This scFv (referred to as F7) was characterized in terms of binding specificity to both recombinant antigen and human LAG3-expressing cells. It was then rebuilt into an IgG format pre-optimized for clinical usage, and the resulting bivalent construct was shown to preserve its ability to bind LAG3 on human cells.Next, we analyzed the activity of the anti-LAG3 scFvF7 using two different antigen-specific CD8+T lymphocyte clones as target cells. We proved that the reconstituted anti-LAG3 F7 Ab efficiently binds the cell membrane of both cell clones after peptide-activation. Still more significantly, we observed a striking increase in the peptide-dependent cell activation upon Ab treatment as measured in terms of IFN-γ release by both ELISA and ELISPOT assays.ConclusionsOverall, the biotechnological strategy described herein represents a guiding development model for the search of novel useful immune checkpoint inhibitors. In addition, our functional data propose a novel candidate reagent for consideration as a cancer treatment.
Fit for fight – self-reported health in military women: a cross-sectional study
Authors: Fadum Elin Anita , Strand Leif Åge , Martinussen Monica , Breidvik Laila , Isaksen Nina , Borud Einar 
Published: October 2019

Abstract

Background
Substantial research has found that women assess their health as poor relative to men, but the reasons for this are not fully understood. Military women are characterised by good health and the ability to work in an archetypically male culture. Thus, studies on the gender pattern of self-reported health in military personnel could generate hypotheses for future research on the possible associations between gender and health. However, such studies are rare and limited to a few countries. The aim of this study was to examine self-reported physical and mental health in Norwegian military women.

Methods
We compared responses on self-reported health of 1068 active duty military women in Norway to those of active duty military men (n = 8100). Further, we compared the military women to civilian women working in the Norwegian Armed Forces (n = 1081). Participants were stratified into three age groups: 20–29; 30–39; and 40–60 years. We used Pearson Chi-square tests, Students t-tests and regression models to assess differences between the groups.

Results
The military women in our study reported physical illness and injuries equal to those of military men, but more military women used pain relieving and psychotropic drugs. More military women aged 20–29 and 30–39 years reported mental health issues than military men of the same age. In the age group 30–39 years, twice as many military women assessed their health as poor compared to military men. In the age group 40–60 years, more military women than men reported musculoskeletal pain. Military women used less smokeless tobacco than military men, but there were few differences in alcohol consumption and smoking. Military women appeared to be more physically healthy than civilian women, but we found few differences in mental health between these two groups.

Conclusion
Most military women reported physical symptoms equal to those of military men, but there were differences between the genders in mental health and drug use. More favourable health compared to civilian women was most evident in the youngest age group and did not apply to mental health.
Physiotherapy students’ DiSC behaviour styles can be used to predict the likelihood of success in clinical placements
Authors: Milne Nikki , Louwen Chanelle , Reidlinger Dianne , Bishop Jo , Dalton Megan , Crane Linda 
Published: October 2019

Abstract

Background
Behaviour can be defined as the internally coordinated responses (actions or inactions) of whole living organisms (individuals or groups) to internal and/or external stimuli, excluding responses more easily understood as developmental changes. Unlike personality traits, that are thought to be biologically consistent, behaviour, through the application of cognition and reasoning is open to change across time and circumstance, although most humans will display preferred ways of behaving. The objective of this study was to: i) identify the behaviour styles of physiotherapy students and investigate if there is a relationship (predictive or otherwise) between students’ unique behaviour patterns and their clinical placement grades and; ii) examine if this relationship differs when student’s in a Master’s level program as well as student’s in a Bachelor’s level program are explored separately.

Methods
This cross-sectional study with 132 (F = 78, M = 54) physiotherapy students was conducted across two Australian university settings. Measures included Everything DiSC Workplace profile, Assessment of Physiotherapy Practice (APP).

Results
Physiotherapy students (n = 133) profiled the following ways: Dominance (D) style n = 20 (15%), Influence (i) style n = 33 (25%), Steadiness (S) style n = 36 (27%) and Conscientiousness (C) n = 44 (33%). Students with the individual DiSC styles of i and Conscientiousness / Steadiness (CS) were in the lowest APP quartile for clinical grades and the D style was in the highest quartile. Binary logistic regressions revealed students with an i DiSC style had 3.96 times higher odds, and students with a CS DiSC style had 4.34 times higher odds, of failing a clinical placement. When explored independently, the same trend remained for Master’s level students. Bachelor’s level students with DiSC styles of S and C had failed placements, however these styles were not significantly associated with failure (DiSC S Style: Exp(B) 1.667, p = 0.713 (CI: 0.109 to 25.433), DiSC C Style: Exp(B) 11.00, p = 0.097 (CI: 0.646 to 187.166)).

Conclusion
Physiotherapy students with DiSC styles i and CS appear to be more likely to fail physiotherapy clinical placements. Further research with larger undergraduate samples is required to establish if relations differ for undergraduate versus postgraduate students.
Circular RNA FOXP1 promotes tumor progression and Warburg effect in gallbladder cancer by regulating PKLR expression
Authors: Wang Shouhua , Zhang Yongjie , Cai Qiang , Ma Mingzhe , Jin Long Yang , Weng Mingzhe , Zhou Di , Tang Zhaohui , Wang Jian Dong , Quan Zhiwei 
Published: October 2019

Abstract

Background
Circular RNAs (circRNAs) have recently been identified as potential functional modulators of the cellular physiology processes. The study aims to uncover the potential clinical value and driving molecular mechanisms of circRNAs in gallbladder cancer (GBC).

Patients and methods
We performed RNA sequencing from four GBC and paired adjacent normal tissues to analyze the circRNA candidates. Quantitative real-time polymerase chain reaction (QRT-PCR) was used to measure the circFOXP1 expression from 40 patient tissue samples. Short hairpin RNA mediated knockdown or exogenous expression of circFOXP1 combined with in vitro and in vivo assays were performed to prove the functional significance of circFOXP1. Double luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays were also performed.

Results
By performing RNA sequencing from GBC and paired adjacent normal tissues to analyze the circRNA candidates, we identified that circFOXP1 (hsa_circ_0008234) expression was significantly upregulated in GBC tissues and positively associated with lymph node metastasis, advanced TNM stage and poor prognosis in patients. Short hairpin RNA mediated knockdown or exogenous expression of circFOXP1 combined with in vitro assays demonstrated that circFOXP1 has pleiotropic effects, including promotion of cell proliferation, migration, invasion, and inhibition of cell apoptosis in GBC. In vivo, circFOXP1 promoted tumor growth. Mechanistically, double luciferase reporter, RNA immunoprecipitation (RIP) and biotin-labeled RNA pull-down assays clarified that circFOXP1 interacted with PTBP1 that could bind to the 3’UTR region and coding region (CDS) of enzyme pyruvate kinase, liver and RBC (PKLR) mRNA (UCUU binding bites) to protect PKLR mRNA from decay. Additionally, circFOXP1 acted as the sponge of miR-370 to regulate PKLR, resulting in promoting Warburg effect in GBC progression.

Conclusions
These results demonstrated that circFOXP1 serve as a prognostic biomarker and critical regulator in GBC progression and Warburg effect, suggesting a potential target for GBC treatment.
Early prognostication of neurological outcome by heart rate variability in adult patients with out-of-hospital sudden cardiac arrest
Authors: Endoh Hiroshi , Kamimura Natuo , Honda Hiroyuki , Nitta Masakazu 
Published: October 2019

Abstract

Background
Most deaths of comatose survivors of out-of-hospital sudden cardiac arrest result from withdrawal of life-sustaining treatment (WLST) decisions based on poor neurological prognostication and the family’s intention. Thus, accurate prognostication is crucial to avoid premature WLST decisions. However, targeted temperature management (TTM) with sedation or neuromuscular blockade against shivering significantly affects early prognostication. In this study, we investigated whether heart rate variability (HRV) analysis could prognosticate poor neurological outcome in comatose patients undergoing hypothermic TTM.

Methods
Between January 2015 and December 2017, adult patients with out-of-hospital sudden cardiac arrest, successfully resuscitated in the emergency department and admitted to the intensive care unit of the Niigata University in Japan, were prospectively included. All patients had an initial Glasgow Coma Scale motor score of 1 and received hypothermic TTM (at 34 °C). Twenty HRV-related variables (deceleration capacity; 4 time-, 3 geometric-, and 7 frequency-domain; and 5 complexity variables) were computed based on RR intervals between 0:00 and 8:00 am within 24 h after return of spontaneous circulation (ROSC). Based on Glasgow Outcome Scale (GOS) at 2 weeks after ROSC, patients were divided into good outcome (GOS 1–2) and poor outcome (GOS 3–5) groups.

Results
Seventy-six patients were recruited and allocated to the good (n = 22) or poor (n = 54) outcome groups. Of the 20 HRV-related variables, ln very-low frequency (ln VLF) power, detrended fluctuation analysis (DFA) (α1), and multiscale entropy (MSE) index significantly differed between the groups (p = 0.001), with a statistically significant odds ratio (OR) by univariate logistic regression analysis (p = 0.001). Multivariate logistic regression analysis of the 3 variables identified ln VLF power and DFA (α1) as significant predictors for poor outcome (OR = 0.436, p = 0.006 and OR = 0.709, p = 0.024, respectively). The area under the receiver operating characteristic curve for ln VLF power and DFA (α1) in predicting poor outcome was 0.84 and 0.82, respectively. In addition, the minimum value of ln VLF power or DFA (α1) for the good outcome group predicted poor outcome with sensitivity = 61% and specificity = 100%.

Conclusions
The present data indicate that HRV analysis could be useful for prognostication for comatose patients during hypothermic TTM.