bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole‐exome sequencing and RNA sequencing analyses of acinic cell carcinomas of the breast
Authors: Beca Francisco , Lee Simon S K , Pareja Fresia , Da Cruz Paula Arnaud , Selenica Pier , Ferrando Lorenzo , Gularte‐Mérida Rodrigo , Wen Hannah Y , Zhang Hong , Guerini‐Rocco Elena , Rakha Emad A , Weigelt Britta , Reis‐Filho Jorge S 
Published: July 2019

AimsAcinic cell carcinoma (ACC) of the breast is a rare histological form of triple‐negative breast cancer (TNBC). Despite its unique histology, targeted sequencing analysis has failed to identify recurrent genetic alterations other than those found in common forms of TNBC. Here we subjected three breast ACCs to whole‐exome and RNA sequencing to determine whether they would harbour a pathognomonic genetic alteration.Methods and resultsDNA and RNA samples from three breast ACCs were subjected to whole‐exome sequencing and RNA‐sequencing, respectively. Somatic mutations, copy number alterations, mutational signatures and fusion genes were determined with state‐of‐the‐art bioinformatics methods. Our analyses revealed TP53 hotspot mutations associated with loss of heterozygosity of the wild‐type allele in two cases. Mutations affecting homologous recombination DNA repair‐related genes were found in two cases, and an MLH1 pathogenic germline variant was found in one case. In addition, copy number analysis revealed the presence of a somatic BRCA1 homozygous deletion and focal amplification of 12q14.3–12q21.1, encompassing MDM2, HMGA2, FRS2, and PTPRB. No oncogenic in‐frame fusion transcript was identified in the three breast ACCs analysed.ConclusionsNo pathognomonic genetic alterations were detected in the breast ACCs analysed. These tumours have somatic genetic alterations similar to those of common forms of TNBC, and may show homologous recombination deficiency or microsatellite instability. These findings provide further insights into why breast ACCs, which are usually clinically indolent, may evolve into or in parallel with high‐grade TNBC.
Immune‐related adverse events in the gastrointestinal tract: diagnostic utility of upper gastrointestinal biopsies
Authors: Zhang M. Lisa , Neyaz Azfar , Patil Deepa , Chen Jonathan , Dougan Michael , Deshpande Vikram 
Published: July 2019

AimsImmune checkpoint inhibitors (ICIs) improve survival across a range of malignancies but are also associated with a spectrum of gastrointestinal (GI) immune‐related adverse events (GI‐irAEs). The aims of this study were to explore the diagnostic value of gastric and duodenal biopsies and to address considerations in the differential diagnosis.Methods and resultsWe identified 39 patients who were treated with ICIs and had a subsequent upper GI biopsy. We recorded clinical data and endoscopic findings, and reviewed their gastric, duodenal and colonic biopsies. Twenty‐one (54%) patients were treated with an anti‐programmed cell death protein 1 (PD‐1)/anti‐programmed cell death ligand 1 antibody alone, and 17 (44%) patients were treated with a combination of anti‐cytotoxic T‐lymphocyte‐associated protein‐4 and anti‐PD‐1 antibodies. Thirty‐two (82%) patients presented with diarrhoea. Gastric alterations included periglandular inflammation and granulomas, and duodenal changes included villous blunting, intraepithelial lymphocytosis, granulomas, and neutrophilic activity. We recognised four patterns of colonic injury: (i) acute self‐limiting colitis; (ii) lymphocytic colitis; (iii) collagenous colitis; and (iv) apoptosis‐only. Twenty‐nine (74%) and 10 (26%) patients were diagnosed clinically as positive and negative for GI‐irAEs, respectively. Gastric periglandular inflammation (P = 0.004) and an increased number of colonic lamina propria mononuclear cells (P = 0.04) correlated with the clinical diagnosis of a GI‐irAE. Histological alterations associated with ICI injury were more often identified in upper GI biopsies (71%) than in colonic biopsies (65%).ConclusionsThe morphological spectrum of ICI‐related GI disease is broad, and mimics a range of infectious and inflammatory diseases. Gastric periglandular inflammation represents one of the more characteristic histological features of GI‐irAEs. The study underscores the importance of a comprehensive review of upper and lower GI biopsies for the diagnosis of GI‐irAEs.
Exploring the fluid boundary between ‘legitimate performance management’ and ‘downward bullying’: an experimental approach
Authors: Timming Andrew R. , French Michael T. , Fan Di 
Published: July 2019

AbstractUsing an experimental design, this research examines the extent to which managers and employees perceive management behaviours differently. Eight simulated employment scenarios were presented to an aggregated sample of managers and non‐managerial employees (n = 435), and the respondents were asked to evaluate the extent to which the behaviours depicted are seen as bullying. It was found that employees are more likely than managers to perceive ‘legitimate performance management’ as bullying but also that managers are more likely than employees to perceive more overt bullying as bullying per se. This divergence in perceptions suggests that what constitutes bullying, ontologically speaking, depends on one's point of view and implies that reality is socially constructed. The research has important implications for organisations and trade unions in the development of bullying policies and procedures.
Role of light‐intensity‐dependent changes in thiol and amino acid metabolism in the adaptation of wheat to drought
Authors: Gyugos Mónika , Ahres Mohamed , Gulyás Zsolt , Szalai Gabriella , Darkó Éva , Végh Balázs , Boldizsár Ákos , Mednyánszky Zsuzsa , Kar Rup Kumar , Dey Narottam , Simon‐Sarkadi Livia , Galiba Gábor , Kocsy Gábor 
Published: July 2019

AbstractLight‐intensity‐dependent (low, normal and high) differences in thiol and amino acid metabolism during drought were compared in wheat seedlings. The drought‐tolerant genotype (Plainsman) recovered better than the sensitive one (Cappelle Desprez) after the stress as shown by growth and photosynthetic parameters, the levels of which were greater in low and high light, respectively. Glutathione as an antioxidant contributed to this difference, since its level was twofold greater in Plainsman throughout the experiment. In addition, the accumulation of most amino acids even increased in normal light during drought in Plainsman, while such change occurred in Cappelle Desprez only in high light. The higher contents of proline, glutamate and γ‐aminobutyrate are especially important because of their involvement in the protection against drought. The transcription of certain genes related to amino acid and glutathione metabolism and various antioxidants was even induced by higher light intensities before drought, which can contribute to the subsequent increase in the amount of the corresponding metabolites during stress. Increase in light intensity activated various protective mechanisms including greater accumulation of glutathione, proline and other amino acids during drought, which contributed to the efficient recovery of wheat after stress.
Forest community assembly is driven by different strata‐dependent mechanisms along an elevational gradient
Authors: Luo Ya‐Huang , Cadotte Marc W. , Burgess Kevin S. , Liu Jie , Tan Shao‐Lin , Xu Kun , Li De‐Zhu , Gao Lian‐Ming 
Published: July 2019

AbstractAimThe mechanisms driving forest community assembly along elevational gradients remain elusive. The distinct strata in heterogeneous forest are subject to differing assembly mechanisms. This study aims to evaluate how different ecological mechanisms driving forest community assembly across strata and spatial scales, and to identify how these assemblages respond to different abiotic or biotic variables along an elevational gradient.LocationYulong Mountain within Hengduan Mountains, Southwest China.TaxonSeed plants.MethodsWe sampled plant species along a 1,200 m elevational gradient across forest strata (trees, shrubs and herbs) at different spatial scales (neighbourhood and community). We integrated phylogenetic and functional diversity to disentangle the roles of ecological mechanisms in structuring community assembly. We also determined the relative effects of climatic, soil and biotic variables and their interactions on these community assemblages.ResultsThe phylogenetic and functional diversity of trees were lower at the extremes of the elevational gradient, where they were constrained by water availability or temperature. While communities with higher species diversity exhibited an overdispersed structure at mid‐elevations. For shrubs, overdispersion was exhibited at high elevations despite low species richness, which could be consistent with facilitative interactions or competition exclusion. However, most communities of herbs appear to have a markedly random structure, despite some incongruence between phylogenetic divergence and functional convergence, as well as influences from overstorey trees and local light conditions. The relative effects of abiotic variables on community structure were larger at the community scale than at the neighbourhood scale.Main conclusionsOur study emphasises the importance of considering phylogenies and traits in understanding the strata‐ and scale‐dependent mechanisms of forest community assembly. Collectively, results indicate that contrasting assembly mechanisms interact across different strata along elevational gradients to shape diverse forest communities.
Functional study of a KCNH2 mutant: Novel insights on the pathogenesis of the LQT2 syndrome
Authors: De Zio Roberta , Gerbino Andrea , Forleo Cinzia , Pepe Martino , Milano Serena , Favale Stefano , Procino Giuseppe , Svelto Maria , Carmosino Monica 
Published: July 2019

AbstractThe K+ voltage‐gated channel subfamily H member 2 (KCNH2) transports the rapid component of the cardiac delayed rectifying K+ current. The aim of this study was to characterize the biophysical properties of a C‐terminus‐truncated KCNH2 channel, G1006fs/49 causing long QT syndrome type II in heterozygous members of an Italian family. Mutant carriers underwent clinical workup, including 12‐lead electrocardiogram, transthoracic echocardiography and 24‐hour ECG recording. Electrophysiological experiments compared the biophysical properties of G1006fs/49 with those of KCNH2 both expressed either as homotetramers or as heterotetramers in HEK293 cells. Major findings of this work are as follows: (a) G1006fs/49 is functional at the plasma membrane even when co‐expressed with KCNH2, (b) G1006fs/49 exerts a dominant‐negative effect on KCNH2 conferring specific biophysical properties to the heterotetrameric channel such as a significant delay in the voltage‐sensitive transition to the open state, faster kinetics of both inactivation and recovery from the inactivation and (c) the activation kinetics of the G1006fs/49 heterotetrameric channels is partially restored by a specific KCNH2 activator. The functional characterization of G1006fs/49 homo/heterotetramers provided crucial findings about the pathogenesis of LQTS type II in the mutant carriers, thus providing a new and potential pharmacological strategy.
Effect of tofogliflozin on cardiac and vascular endothelial function in patients with type 2 diabetes and heart diseases: A pilot study
Authors: Tochiya Mayu , Makino Hisashi , Tamanaha Tamiko , Matsuo Miki , Hishida Ai , Koezuka Ryo , Ohata Yoko , Tomita Tsutomu , Son Choel , Miyamoto Yoshihiro , Yasuda Satoshi , Hosoda Kiminori 
Published: July 2019

AbstractRecent studies have shown that sodium–glucose cotransporter 2 inhibitors decrease the risk of heart failure in patients with type 2 diabetes. However, the precise mechanisms of action of these drugs are not well understood. In the present study, we evaluated the effect of treatment with tofogliflozin for 6 months on cardiac and vascular endothelial function in 26 patients with type 2 diabetes and heart diseases. Tofogliflozin treatment significantly decreased left ventricular end‐diastolic dimensions and significantly increased flow‐mediated vasodilation. Although E/e′ did not significantly change after treatment, the decrease observed in the E/e′ ratio was significantly correlated with the increase in acetoacetic acid and 3‐hydroxybutyrate levels. These results suggest that sodium–glucose cotransporter 2 inhibitor might improve left ventricular dilatation and vascular endothelial function in patients with type 2 diabetes. Furthermore, it is suggested that the elevation of ketone bodies induced by sodium–glucose cotransporter 2 inhibitors might contribute to a protective effect in left ventricular diastolic dysfunction.
Dietary emulsifier polysorbate‐80‐induced small‐intestinal vulnerability to indomethacin‐induced lesions via dysbiosis
Authors: Furuhashi Hirotaka , Higashiyama Masaaki , Okada Yoshikiyo , Kurihara Chie , Wada Akinori , Horiuchi Kazuki , Hanawa Yoshinori , Mizoguchi Akinori , Nishii Shin , Inaba Kenichi , Sugihara Nao , Watanabe Chikako , Komoto Shunsuke , Tomita Kengo , Miura Soichiro , Hokari Ryota 
Published: July 2019

AbstractBackground and AimDietary emulsifiers are widely used in processed foods and officially approved as safe for intake. However, recent studies have demonstrated that some emulsifiers alter the colonic microbiota, leading to colonic low‐grade inflammation, in mice. The effect of dietary emulsifiers on small‐intestinal microbiota, which is important for gut immunity, has not been studied. We aimed to investigate the effect of a representative dietary emulsifier, polysorbate‐80 (P80), on the small‐intestinal microbiota in normal mice.MethodsSome mice were pretreated with P80 for 8 weeks with or without indomethacin administration on the last 2 days, and intestinal damage was evaluated histologically. The ileal and colonic microbiota composition was assessed using 16S rRNA polymerase chain reaction.ResultsPolysorbate‐80 increased the Gammaproteobacteria abundance and decreased the α‐diversity in the small intestine. No decrease in α‐diversity was observed in the colon. P80 pretreatment exacerbated the indomethacin‐induced small‐intestinal lesions and significantly increased the interleukin‐1β expression. Culture of ileal content on deoxycholate hydrogen sulfide lactose agar showed that P80 significantly increased the colonies of the sulfide‐producing bacteria Proteus spp. (genetically identified as Proteus mirabilis). Antibiotic pretreatment abolished the P80‐induced aggravation of indomethacin‐induced ileitis. Motility assay in semisolid agar showed that adding 0.02% P80 to the agar significantly increased the diameter of P. mirabilis colonies but not that of Escherichia coli colonies.ConclusionsPolysorbate‐80 enhances the vulnerability of the small intestine to indomethacin‐induced injury by inducing ileal dysbiosis. Direct enhancement of the motility of specific flagellated microbiota by P80 might be related to dysbiosis and intestinal injury.
Increasing burden of biliary tract infection caused by extended‐spectrum beta‐lactamase‐producing organisms in Korea: A nationwide population‐based study
Authors: Jang Dong Kee , Kim Jungmee , Park Wan Beom , Yi Sun Young , Lee Jun Kyu , Yoon Won Jae 
Published: July 2019

AbstractBackground and AimBiliary tract infections (BTIs) are a major cause of bacteremia. The prevalence of antibiotic‐resistant pathogens in BTI patients is reported to be increasing. We used a nationwide database to evaluate the prevalence of, and risk factors for, BTIs caused by extended‐spectrum beta‐lactamase‐producing organisms (ESBL‐PO) in Korea.MethodsPatients with a BTI diagnosis, an admission history, a history of a BTI‐related procedure, and antibiotic use for ≥ 4 days between 2007 and 2016 were identified from the Health Insurance Review and Assessment Service database. A BTI treated with carbapenems (BTI‐TC) was used as the surrogate for a BTI caused by ESBL‐PO. We conducted a multivariate logistic regression analysis to determine the risk factors for BTI‐TC.ResultsIn total, 341 002 patients were enrolled. The overall percentage of BTI‐TC among BTIs was 2.4%, with an increasing annual trend (P < 0.0001). The risk of acute cholangitis caused by ESBL‐PO increased significantly in men, older patients, patients with comorbidities, patients with a history of a biliary procedure within the previous year, and patients with a history of antibiotic use within the previous 90 days. Regarding antibiotic use, the patients at highest risk were those previously prescribed carbapenems (adjusted odds ratio, 4.77; P < 0.0001).ConclusionsThe prevalence of BTIs caused by ESBL‐PO has increased during the last 10 years. Initial carbapenem therapy should be considered for elderly patients with acute cholangitis if they have had a previous biliary procedure and/or a history of carbapenem administration within the previous 90 days.
The role of adenosine receptors in mood and anxiety disorders
Authors: van Calker Dietrich , Biber Knut , Domschke Katharina , Serchov Tsvetan 
Published: July 2019

AbstractAdenosine receptor subtypes, first described 40 years ago, are known to regulate diverse biological functions and have a role in various conditions, such as cerebral and cardiac ischemia, immune and inflammatory disorders and cancer. In the brain, they limit potentially dangerous over excitation, but also regulate mechanisms essential in sleep and psychiatric disorders. In this review, we discuss the role of adenosine receptors in mood and anxiety disorders. Activation of A2A receptors is associated with increased depression‐like symptoms, while increased A1 receptors signaling elicits rapid antidepressant effects. Indeed, several lines of evidence demonstrate that the therapeutic effects of different non‐pharmacological treatments of depression, like sleep deprivation and electroconvulsive therapy are mediated by A1 receptor up‐regulation or activation. In addition, A1 receptors may also play a role in the antidepressant effects of transcranial direct current stimulation and deep brain stimulation. As a potential downstream mechanism, which facilitates the antidepressant effects of A1 receptors, we propose a crosstalk between adenosinergic and glutamatergic systems mediated via synaptic plasticity protein Homer1a and α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptors. Moreover, adenosine receptors are also involved in the control of circadian rhythms, sleep homeostasis and some neuro‐immunological mechanisms, all of them implicated in mood regulation. Antagonists of adenosine receptors such as caffeine have general anxiogenic effects. In particular, A2A receptors appear to have an important role in the pathophysiology of anxiety disorders. Taken together, the results discussed here indicate that the adenosinergic system is involved in both the etiology and the treatment of mood and anxiety disorders.
image
Women's experience of shiftwork in nursing whilst caring for children: A juggling act
Authors: Matheson Annabel , O’Brien Louise , Reid Jo‐Anne 
Published: July 2019

AbstractAims and ObjectivesTo explore women's experiences of working shiftwork in nursing whilst caring for children.BackgroundIn nursing, almost 90% of Australia's practising nurses and midwives are women. Much of the research undertaken in the shiftwork area uses men as their sample and uses a quantitative methodology to achieve results. Little work has been undertaken that explores the experience of women working shiftwork whilst raising children.DesignHeideggerian Hermeneutic Phenomenological Design.MethodsSemistructured interviews were conducted with ten women who cared for children about their experience of shiftwork. Each interview was digitally audio‐recorded. The interviews were transcribed verbatim and thematically analysed. The interpretation used first Heideggerian phenomenology as a lens and then second research on women's work and gender roles to resituate the experience in context. Reporting rigour has been demonstrated using the COREQ checklist.ResultsTwo major themes were derived from the data, Being Guilty and Being Juggler. Each is discussed in this paper.ConclusionsThis study adds a qualitative voice to the substantial quantitative shiftwork body of literature. The themes uncovered in this study have thrown light on the nature of work done by women who are nurses, particularly the work related to their home and children.Relevance to Clinical PracticeThere are opportunities to increase education around the importance of sleep and shiftwork self‐care in both preservice and new graduate education to assist nurses to ensure that sleep is a priority whilst working shiftwork.
Nonalcoholic fatty liver disease increases risk of incident advanced chronic kidney disease: a propensity‐matched cohort study
Authors: Park Haesuk , Dawwas Ghadeer K. , Liu Xinyue , Nguyen Mindie H. 
Published: July 2019

AbstractBackgroundAs the prevalence of nonalcoholic fatty liver disease (NAFLD) escalates, understanding its potential impact on the development of chronic kidney disease (CKD) is needed.ObjectiveTo determine the longitudinal association of NAFLD with the development of advanced CKD in the United States.MethodsA retrospective cohort analysis of the Truven Health MarketScan Database (2006–2015) was conducted. We used Cox proportional hazards models to compare the risk of developing CKD stages 3–5 in patients with NAFLD versus non‐NAFLD, identified by ICD‐9 codes, after 1:3 propensity score (PS) matching.ResultsIn a cohort of 262 619 newly diagnosed patients with NAFLD and 769 878 PS (1:3)‐matched non‐NAFLD patients, we identified 5766 and 8655 new advanced (stage 3–5) CKD cases, respectively. The crude CKD incidence rate was 8.2 and 5.5 per 1000 person‐years in NAFLD and non‐NAFLD groups, respectively. In multivariable Cox model, patients with NAFLD had a 41% increased risk of developing advanced CKD compared with non‐NAFLD patients [adjusted hazard ratio (aHR), 1.41; 95% confidence interval (CI), 1.36–1.46]. In the sensitivity analysis adjusting for time‐varying covariates after NAFLD diagnosis, NAFLD persisted as a significant CKD risk factor (aHR, 1.58; 95% CI, 1.52–1.66) and the association remained significant when stratified by age, gender and pre‐existing comorbidities. The risk of CKD increased in NAFLD with compensated cirrhosis (aHR, 1.47; 95% CI, 1.36–1.59) and decompensated cirrhosis (aHR, 2.28; 95% CI, 2.12–2.46).ConclusionNonalcoholic fatty liver disease was independently associated with an increased risk of advanced CKD development suggesting renal function screening and regular monitoring are needed in this population.