bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fresh fruit consumption may decrease the long‐term risk of esophageal cancer mortality: A 30‐year follow‐up study in the Linxian Dysplasia Nutrition Intervention trial (NIT)
Authors: Yang Huan , Zhang Su , Yan Huijiao , Wang Jianbing , Fan Jinhu , Qiao Youlin , Taylor Philip R. 
Published: May 2020

BackgroundThe objective of this study was to explore the association between fresh fruit consumption and long‐term risk of upper gastrointestinal cancer (UGI) in the Linxian Dysplasia Nutrition Intervention Trial (NIT) cohort.MethodsA cohort of 3318 subjects with esophageal squamous dysplasia participated in the Linxian Dysplasia NIT in May 1985 and were followed up until 30 September 2015. Demographic characteristics, lifestyle, and history of diseases were collected at the baseline. The primary endpoint was death from esophageal squamous cell carcinoma (ESCC), gastric cardia carcinoma (GCC), and gastric noncardia carcinoma (GNCC). Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated using the Cox proportional hazard model.ResultsIn the 30‐year follow‐up, a total of 541 ESCC, 284 GCC, and 77 GNCC deaths occurred. Relative to those who never or rarely consumed fresh fruit, the risk of ESCC mortality in participants who consumed fresh fruit more than 12 times/year were significantly decreased by 37.3% (HR = 0.63, 95% CI: 0.49–0.81). In the subgroup analyses, significantly protective effects on ESCC mortality were observed especially in females (HR = 0.59, 95% CI: 0.40–0.89), non‐smokers (HR = 0.67, 95% CI: 0.48–0.94), and nondrinkers (HR = 0.69, 95% CI: 0.51–0.93).ConclusionsConsuming fresh fruit more than 12 times/year may reduce the long‐term risk of ESCC mortality in this dysplasia population, particularly in females, non‐smokers, and nondrinkers. Future studies are needed to confirm these findings.
Prognostic role of extracellular vesicles in squamous cell carcinoma of the lung
Authors: An Hyo Jung , Kim Min Hye , Kim Sung Hwan , Lee Gyeong‐Won , Song Dae Hyun 
Published: May 2020

AbstractBackgroundResearch on diagnosing recurrent non‐small cell lung cancer (NSCLC) and applying target gene treatment using exosomes in a less invasive way is very important. Recently, however, it has been argued that exosomes do not contain double‐stranded DNA (dsDNA) or histones. In this study, we describe the expression of extracellular vesicle (EV) markers in specimens from squamous cell carcinoma (SCC) of the lung and analyze their relationship with the prognosis of patients.MethodsClinical and pathological data were obtained from 96 patients who had undergone surgery for SCC of the lung. Tissue microarray blocks were made using representative paraffin blocks of samples from patients with SCC of the lung. Two pathologists graded the intensity of CD63, CD9, LC3A/B, P62, and ANXA1 expression as high or low expression. In addition, the authors designated the combined expression of these five independent markers as “positive EV expression” in this article.ResultsSCCs with low CD63 and SCCs with low EV expression showed unfavorable disease‐free survival (DFS) (P‐value = 0.037 and 0.006, respectively) in the survival analysis. The Kaplan‐Meier survival curve confirmed that the low EV expression showed a statistically significant relationship with unfavorable DFS (P‐value = 0.004). There were no statistically significant differences in DFS and disease‐specific survival in each low and high expression group for CD9, LC3A/B, ANXA1, and P62 in the Cox regression analysis.ConclusionsAs EV expression was related to the prognosis of lung SCC patients, a broader approach using different extracellular vesicles rather than a conventional exosome‐dependent one is needed.
Investigating women with postmenopausal bleeding: The utility of endometrial thickness in transvaginal ultrasound
Authors: Palipana Dinesh , Fomin Igor , Russell Elsa , Chan Brian , Wong Chad , Chan Erick , Ho Debbie , Walker Graeme 
Published: May 2020

BackgroundAustralian clinical guidelines recommend further investigation in females with postmenopausal bleeding (PMB) and endometrial thickness (ET) of ≥4 mm on transvaginal ultrasound (TVUS). However, the literature indicates that an ET of ≥3 mm as an upper limit is a more sensitive predictor of endometrial malignancy (EM) in females with PMB.AimsTo assess whether Australian guidelines for PMB with an upper limit of 4 mm ET on ultrasound investigation, is sensitive enough for malignancy detection.Material and MethodsA retrospective study was performed on tissue results in PMB presentations to the Gold Coast Hospital and Health Service between 2011 and 2015.ResultsTwenty point nine percent of women with PMB had a malignancy. With an upper limit of 4 mm in ET on ultrasound, malignancy was present in 22% of participants. [Correction added on 10 July 2020, after first online publication: percentage of women with PMB that had a malignancy has been amended to twenty point nine percent.]ConclusionsA limit of 3 mm for ET in PMB, along with office endometrial biopsy, should be considered to ensure timely diagnoses.
Minor DNA methylation changes are observed in spermatozoa prepared using different protocols
Authors: Stimpfel Martin , Vrtacnik‐Bokal Eda 
Published: May 2020

AbstractBackgroundDNA methylation patterns can show transgenerational inheritance and are influenced by lifestyle and environmental factors. It is suggested that these patterns can be changed by assisted reproductive technology.ObjectivesTo evaluate the impact of two different sperm preparation methods, conventional density gradient centrifugation (DGC) vs. density gradient centrifugation followed by magnetic‐activated cell sorting (MACS) of non‐apoptotic spermatozoa, on sperm DNA methylation profile.Materials and methodsWe analyzed semen of patients included in our IVF treatment program. Half of the semen from each included patient was prepared for ICSI using the DGC method and the other half with DGC followed by MACS. The remaining samples were processed for DNA methylation analysis with reduced representation bisulfite sequencing (RRBS). In addition to the DNA methylation profile, we assessed the morphology and DNA fragmentation of spermatozoa.ResultsRRBS analysis revealed that the average genome‐wide methylation level was similar between both groups (DGC vs. MACS group) and ranged from 0.53 to 0.56. Furthermore, RRBS analysis identified 99 differentially methylated regions (DMRs) and 800 differentially methylated positions (DMPs). In the DGC group, 43 DMRs and 392 DMPs were hypermethylated whereas 56 DMRs and 408 DMPs were hypomethylated compared with those in the MACS group. When DMRs and DMPs were annotated to genes, 3 genes associated with imprinting were found: IGF2, PRDM16, and CLF4/BRUNOL4. The percentage of morphologically normal spermatozoa (MACS vs. DGC; 14.0 ± 10.8 vs. 13.2 ± 10.0; P = .335) and of spermatozoa with fragmented DNA of patients with RRBS analysis (22.9 ± 21.1% vs. 34.4 ± 21.2; P = .529) were also similar between groups.Discussion and ConclusionAlthough the average genome‐wide level of sperm DNA methylation was similar in both sample groups, a distinctive number of methylation changes were observed in DMR and DMP levels. A larger number of samples should be analyzed and additional sperm preparation methods should be tested to confirm our findings.
Effects of rice feeding and carnitine addition on growth performance and mRNA expression of protein metabolism‐related genes in broiler grower chicks
Authors: Fujimoto Hiroya , Matsumoto Keisuke , Koseki Minori , Yamashiro Hideaki , Yamada Takahisa , Takada Ryozo 
Published: May 2020

AbstractThis study was carried out to evaluate the nutritional effects of rice feeding and carnitine addition to a diet for broiler chicks. Thirty‐six male 10‐day‐old broiler chicks were assigned to one of the following four treatment groups: corn‐based diet (corn group), rice‐based diet (rice group), and each diet with added carnitine (100 ppm). The experimental period was 2 weeks. Rice feeding resulted in significantly higher growth performance (body weight gain and feed efficiency) compared to corn feeding. Carnitine addition also resulted in higher growth performance. Breast muscle and thigh muscle weight (g) were significantly higher in broiler chicks fed rice and those fed diets with added carnitine. Liver mRNA expression of IGF‐I was significantly higher in broiler chicks fed rice compared to those fed corn. There was no significant difference in mRNA expression of muscle atrogin‐1 or liver CPT‐I between broiler chicks fed rice and those fed corn, not between broilers chicks fed diets containing carnitine or not. Overall, these results show that rice feeding and carnitine addition improve the growth performance of broiler chicks by increasing mRNA expression of liver IGF‐I. In addition, carnitine action is not affected by different cereals (corn and rice).
Sacubitril/valsartan (Entresto) utilisation and prescribing patterns in the context of a reimbursement application system
Authors: Kennedy Cormac , Smith Amelia , Doran Stephen , Barry Michael 
Published: May 2020

AimsEntresto (sacubitril/valsartan) is used to treat symptomatic chronic heart failure with reduced ejection fraction. Given its high potential budget impact, the Health Services Executive introduced a reimbursement application system (RAS) to ensure its appropriate use. The aim of this study was to evaluate the utilisation of Entresto in Ireland and compare patient characteristics to those of the pivotal PARADIGM‐HF trial.MethodsWe used dispensed claims data from the Primary Care Reimbursement Services, clinical data obtained from the RAS, and data from published studies of Entresto utilisation. Differences in the baseline characteristics in the study populations vs the Entresto arm of the PARADIGM‐HF trial were analysed. We also investigated cardiovascular medication use in the 6 months pre‐ and post‐Entresto initiation.ResultsIn 2018, there were 1043 individuals receiving Entresto, corresponding to an expenditure of €1.2 million. Patients prescribed Entresto in Ireland were older, had lower left ventricular ejection fraction and were more symptomatic than those in the PARADIGM‐HF trial. Irish patient characteristics were reflective of Entresto‐treated populations in other real‐world studies. More than 63% of patients were commenced on the lowest Entresto dose. Entresto initiation was associated with a reduction in the use of other medications for heart failure.ConclusionThe utilisation of Entresto has been steadily increasing in Ireland since its reimbursement approval. The expenditure in the first year was substantially lower than predicted, and the RAS is an example of how health technology management can facilitate appropriate and cost‐effective use of medicines.
Subunits of BK channels promote breast cancer development and modulate responses to endocrine treatment in preclinical models
Authors: Mohr Corinna J. , Schroth Werner , Mürdter Thomas E. , Gross Dominic , Maier Selina , Stegen Benjamin , Dragoi Alice , Steudel Friederike A. , Stehling Severine , Hoppe Reiner , Madden Stephen , Ruth Peter , Huber Stephan M. , Brauch Hiltrud , Lukowski Robert 
Published: May 2020

Background and PurposePore‐forming α subunits of the voltage‐ and Ca2+‐activated K+ channel with large conductance (BKα) promote malignant phenotypes of breast tumour cells. Auxiliary subunits such as the leucine‐rich repeat containing 26 (LRRC26) protein, also termed BKγ1, may be required to permit activation of BK currents at a depolarized resting membrane potential that frequently occur in non‐excitable tumour cells.Experimental ApproachAnti‐tumour effects of BKα loss were investigated in breast tumour‐bearing MMTV‐PyMT transgenic BKα knockout (KO) mice, primary MMTV‐PyMT cell cultures, and in a syngeneic transplantation model of breast cancer derived from these cells. The therapeutic relevance of BK channels in the context of endocrine treatment was assessed in human breast cancer cell lines expressing either low (MCF‐7) or high (MDA‐MB‐453) levels of BKα and BKγ1, as well as in BKα‐negative MDA‐MB‐157.Key ResultsBKα promoted breast cancer onset and overall survival in preclinical models. Conversely, lack of BKα and/or knockdown of BKγ1 attenuated proliferation of murine and human breast cancer cells in vitro. At low concentrations, tamoxifen and its major active metabolites stimulated proliferation of BKα/γ1‐positive breast cancer cells, independent of the genomic signalling controlled by the oestrogen receptor. Finally, tamoxifen increased the relative survival time of BKα KO but not of wild‐type tumour cell recipient mice.Conclusion and ImplicationsBreast cancer initiation, progression, and tamoxifen sensitivity depend on functional BK channels thereby providing a rationale for the future exploration of the oncogenic actions of BK channels in clinical outcomes with anti‐oestrogen therapy.LINKED ARTICLESThis article is part of a themed issue on New avenues in cancer prevention and treatment (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.12/issuetoc
Improving First Nations water security through governance
Authors: Alcantara Christopher , Longboat Sheri , Vanhooren Shanaya 
Published: May 2020

AbstractMany First Nations communities lack access to safe drinking water. In this article, we examine an under‐appreciated tool for improving First Nations water security – governance – and develop a framework for guiding the design and analysis of First Nations water governance models. In particular, we argue that three key ideas from the public administration literature – financial resources, regulation, and formalization – should be integrated with Indigenous insights and philosophies that are specific to each First Nations community. We illustrate how this might work by focusing on the insights, traditions, and philosophies of an Anishinaabek community in southern Ontario.
Eating disorders and needs of disabled children at primary school
Authors: Kabasakal Esma , Özcebe Hilal , Arslan Umut Ece 
Published: May 2020

AbstractAimThe aim of this study was to provide current information on the eating disorders, needs and confronted problems of children with disabilities during their school hours at primary schools.BackgroundEating disorders and needs of disabled children are important in their participation in school life, cognition, and academic achievement.ResultsIn this study, It was aimed to reach all children with disabilities attending at 72 primary schools located in low, medium and high socio‐economic districts in Ankara, capital of Turkey; 404 parents voluntarly accepted to participate in the study. This study has revealed that students with disabilities experienced eating disorders such as forget to eat foods at feeding time, cannot go to canteen to buy food, have sucking and/or chewing problems, lack of self‐care skills and need support while eating at schools. The percentage of children who had breakfast at school was 18.1%. The percentage of those who indicated that their child had lunch at school was 59.0%. The children from low socio‐economic district had the highest percentage of adequate nutrition at schools in the last week. Families whose children having lack of self‐care skills (50.0%), were picky eaters (38.5%), having lack of appetite (42.1%), experienced from constipation frequently (50.0%), have reflux problem (29.0%) considered that their children needed feeding supports at school.ConclusionFamilies whose children having eating disorders at schools considered that their children needed feeding supports. Fulfilling the needs of children with disability and providing them support as positive discrimination would ensure healthy development and participation in school life and generate positive effects on their academic achievement. The school health policies have to encompass nutritional needs of vulnerable children to benefit from right to education in an adequate and effective manner.
Participation‐focused practices in paediatric rehabilitation for children with neurodisability in New Zealand: An observational study using MAPi audit tool
Authors: Graham Fiona , Timothy Emily , Williman Jonathan , Levack William 
Published: May 2020

AbstractBackgroundParticipation outcomes and family‐centred services are now widely agreed standards of care in paediatric rehabilitation. Evidence suggests that adoption of these practices into usual care has been slow internationally, and no studies of participation‐focused or family‐centred practices in New Zealand have been undertaken to date. The aims of this study were to identify the extent that goal setting in paediatric rehabilitation services is participation focused and family centred and to profile clinicians' beliefs about these foci.MethodsObservational study including a retrospective case note audit and questionnaire. Case notes (‘charts’) were audited for participation‐focused goal‐related practice. Subgroup analysis of audit data by service, profession and child ethnicity were completed using weighted mean differences. Clinicians whose case notes were audited completed a 42‐item questionnaire on factors related to practice behaviour including text responses with each item. Numerical and text data were analysed descriptively.ResultsFive services were recruited (N = 46 clinicians) with case notes for 220 children audited. Auditors extracted 368 potentially participation‐related goals (Mdn = 2 goals per child) with no goals extracted for 43 (20%) of case notes. Subsequent coding of extracted goals identified 61% reflected participation (225/368). Subgroup analysis revealed significant differences between services (p = 0.006) and professions (p < 0.001). Clinicians' reported valuing participation outcomes and family involvement and largely felt they did target participation. Skill gaps, absence of self‐monitoring strategies and unsupportive professional and work cultures were cited as key challenges.ConclusionsAlthough valued by clinicians, participation‐focused practice is unusual care in paediatric rehabilitation in New Zealand. Substantial gains in the quality of care for children with disabilities could be afforded through training in collaborative goal setting to target participation outcomes.
Effectiveness and safety of dupilumab for the treatment of severe asthma in a real‐life French multi‐centre adult cohort
Authors: Dupin Clairelyne , Belhadi Drifa , Guilleminault Laurent , Gamez Anne‐Sophie , Berger Patrick , De Blay Frédéric , Bonniaud Philippe , Leroyer Christophe , Mahay Guillaume , Girodet Pierre‐Olivier , Raherison Chantal , Fry Stéphanie , Le Bourdellès Geneviève , Proust Alain , Rosencher Lise , Garcia Gilles , Bourdin Arnaud , Chenivesse Cécile , Didier Alain , Couffignal Camille , Taillé Camille 
Published: May 2020

AbstractBackgroundDupilumab is a monoclonal anti‐IL‐4Rα antibody developed for the treatment of severe asthma (SA). An early access programme for dupilumab was opened in France in SA patients experiencing unacceptable steroids side‐effects and/or life‐threatening exacerbations.ObjectiveTo assess changes in asthma control between baseline and 12 months of treatment.MethodsMulti‐centre (n = 13) retrospective real‐life cohort study. This study is registered on ClinicalTrials.gov (NCT04022447).ResultsOverall, 64 patients with SA (median age 51, interquartile range [44‐61]; 53% females) received dupilumab as add‐on therapy to maximal standard of care; and 76% were on oral daily steroids at baseline. After 12 months, median asthma control test score improved from 14 [7‐16] to 22 [17‐24] (P < .001); median forced expiratory volume in 1 seconds increased from 58% [47‐75] to 68% [58‐88] (P = .001); and daily prednisone dose was reduced from 20 [10‐30] to 5 [0‐7] mg/d (P < .001). Annual exacerbations decreased from 4 [2‐7] to 1 [0‐2] (P < .001). Hypereosinophilia ≥1500/mm3 was observed at least once during follow‐up in 16 patients (25%), persisting after 6 months in 8 (14%) of them. Increase in blood eosinophil count did not modify the clinical response during the study period. Injection‐site reaction was the most common side effect (14%). Three deaths were observed, none related to treatment by investigators.Conclusion & clinical relevanceIn this first real‐life cohort study of predominantly steroid‐dependent SA, dupilumab significantly improved asthma control and lung function and reduced oral steroids use and exacerbations rate. Despite limitations due to the retrospective study, these results are consistent with controlled trials efficacy data. Further studies are required to assess the clinical significance and long‐term prognosis of sustained dupilumab‐induced hypereosinophilia.
Advanced glycation end products inhibit the osteogenic differentiation potential of adipose‐derived stem cells by modulating Wnt/β‐catenin signalling pathway via DNA methylation
Authors: Li Yong , Wang Lang , zhang Maorui , Huang Kui , Yao Zhihao , Rao Pengcheng , Cai Xiaoxiao , Xiao Jingang 
Published: May 2020

AbstractObjectivesAdvanced glycation end products (AGEs) are considered a cause of diabetic osteoporosis. Although adipose‐derived stem cells (ASCs) are widely used in the research of bone regeneration, the mechanisms of the osteogenic differentiation of ASCs from diabetic osteoporosis model remain unclear. This work aimed to investigate the influence and the molecular mechanisms of AGEs on the osteogenic potential of ASCs.Materials and methodsEnzyme‐linked immunosorbent assay was used to measure the change of AGEs in diabetic osteoporotic and control C57BL/6 mice. ASCs were obtained from the inguinal fat of C57BL/6 mice. AGEs, 5‐aza2′‐deoxycytidine (5‐aza‐dC) and DKK‐1 were used to treat ASCs. Real‐time cell analysis and cell counting kit‐8 were used to monitor the proliferation of ASCs within and without AGEs. Real‐time PCR, Western blot and Immunofluorescence were used to analyse the genes and proteins expression of osteogenic factors, DNA methylation factors and Wnt/β‐catenin signalling pathway among the different groups.ResultsThe AGEs and DNA methylation were increased in the adipose and bone tissue of the diabetic osteoporosis group. Untreated ASCs had higher cell proliferation activity than AGEs‐treatment group. The expression levels of osteogenic genes, Opn and Runx2, were lower, and mineralized nodules were less in AGEs‐treatment group. Meanwhile, DNA methylation was increased, and the Wnt signalling pathway markers, including β‐Catenin, Lef1 and P‐GSK‐3β, were inhibited. After treatment with 5‐aza‐dC, the osteogenic differentiation capacity of ASCs in the AGEs environment was restored and the Wnt signalling pathway was activated during this process.ConclusionsAdvanced glycation end products inhibit the osteogenic differentiation ability of ASCs by activating DNA methylation and inhibiting Wnt/β‐catenin pathway in vitro. Therefore, DNA methylation may be promising targets for the bone regeneration of ASCs with diabetic osteoporosis.