bluuebunny/crossref_metadata_2025_split huggingface dataset:
Self-management capability in patients with long-term conditions is associated with reduced healthcare utilisation across a whole health economy: cross-sectional analysis of electronic health records
Authors: Barker Isaac , Steventon Adam , Williamson Robert , Deeny Sarah R 
Published: August 2018

ObjectiveTo quantify the association between patient self-management capability measured using the Patient Activation Measure (PAM) and healthcare utilisation across a whole health economy.Results12 270 PAM questionnaires were returned from 9348 patients. In the adjusted analyses, compared with the least activated group, highly activated patients (level 4) had the lowest rate of contact with a general practitioner (rate ratio: 0.82, 95% CI 0.79 to 0.86), emergency department attendances (rate ratio: 0.68, 95% CI 0.60 to 0.78), emergency hospital admissions (rate ratio: 0.62, 95% CI 0.51 to 0.75) and outpatient attendances (rate ratio: 0.81, 95% CI 0.74 to 0.88). These patients also had the lowest relative rate (compared with the least activated) of ‘did not attends’ at the general practitioner (rate ratio: 0.77, 95% CI 0.68 to 0.87), ‘did not attends’ at hospital outpatient appointments (rate ratio: 0.72, 95% CI 0.61 to 0.86) and self-referred attendance at emergency departments for conditions classified as minor severity (rate ratio: 0.67, 95% CI 0.55 to 0.82), a significantly shorter average length of stay for overnight elective admissions (rate ratio 0.59, 95% CI 0.37 to 0.94),and a lower likelihood of 30- day emergency readmission (rate ratio: 0.68 , 95%  CI 0.39 to 1.17), though this did not reach significance.ConclusionsSelf-management capability is associated with lower healthcare utilisation and less wasteful use across primary and secondary care.
Inhibition of endoplasmic reticulum stress by 4-phenylbutyric acid prevents vital organ injury in rat acute pancreatitis
Authors: Hong Yu-pu , Deng Wen-hong , Guo Wen-yi , Shi Qiao , Zhao Liang , You Yun-dong , Mei Fang-chao , Zhou Yu , Wang Chen-yang , Chen Chen , Yu Jia , Wang Wei-xing 
Published: August 2018

This study was conducted to investigate the effect of 4-phenylbutyric acid (4-PBA) on vital organ injury following sodium taurocholate-induced acute pancreatitis (AP) in rats and the pertinent mechanism. The serum biochemical indicators and key inflammatory cytokines, histopathological damage and apoptosis of vital organs in rat AP, were evaluated in the presence or absence of 4-PBA. Moreover, mRNA and protein levels of endoplasmic reticulum stress (ERS) markers were assessed. 4-PBA significantly attenuated the structural and functional damage of vital organs, including serum pancreatic enzymes, hepatic enzymes, creatinine, and urea. The morphological changes and infiltration of neutrophils and macrophages were reduced as well. These effects were accompanied by decreased serum levels of proinflammatory TNF-α and IL-1β. Furthermore, 4-PBA diminished the expression of ERS markers (glucose-regulated protein 78, CCAAT/enhancer-binding protein homologous protein, protein kinase R-like ER kinase, activated transcription factor 6, and type-1 inositol requiring enzyme) in vital organs of AP rats. 4-PBA also reduced AP-induced apoptosis in lung, liver, and kidney tissues as shown by TUNEL assay. The present study demonstrated that 4-PBA protected pancreas, lung, liver, and kidney from injury in rat AP by regulating ERS and mitigating inflammatory response to restrain cell death and further suggested that 4-PBA may have potential therapeutic implications in the disease. NEW & NOTEWORTHY In this study, we suggest that endoplasmic reticulum stress (ERS) is an important player in the development of acute pancreatitis-induced multiorgan injury, providing additional evidence for the proinflammatory role of ERS. Because 4-phenylbutyric acid has been suggested to inhibit ERS in many pathological conditions, it is possible that this effect can be involved in alleviating inflammatory response and cell death to ameliorate vital organ damage following acute pancreatitis induced by sodium taurocholate in rats.
“Z4” Complex Member Fusions in NUT Carcinoma: Implications for a Novel Oncogenic Mechanism
Authors: Shiota Hitoshi , Elya Janine E. , Alekseyenko Artyom A. , Chou Pauline M. , Gorman Shelby A. , Barbash Olena , Becht Kelly , Danga Kristina , Kuroda Mitzi I. , Nardi Valentina , French Christopher A. 
Published: August 2018

Abstract

Nuclear protein in testis (NUT) carcinoma (NC) is a rare, distinctly aggressive subtype of squamous carcinoma defined by the presence of NUT-fusion oncogenes resulting from chromosomal translocation. In most cases, the NUT gene (NUTM1) is fused to bromodomain containing 4 (BRD4) forming the BRD4-NUT oncogene. Here, a novel fusion partner to NUT was discovered using next-generation sequencing and FISH from a young patient with an undifferentiated malignant round cell tumor. Interestingly, the NUT fusion identified involved ZNF592, a zinc finger containing protein, which was previously identified as a component of the BRD4-NUT complex. In BRD4-NUT–expressing NC cells, wild-type ZNF592 and other associated “Z4” complex proteins, including ZNF532 and ZMYND8, colocalize with BRD4-NUT in characteristic nuclear foci. Furthermore, ectopic expression of BRD4-NUT in a non-NC cell line induces sequestration of Z4 factors to BRD4-NUT foci. Finally, the data demonstrate the specific dependency of NC cells on Z4 modules, ZNF532 and ZNF592.

Implications:
This study establishes the oncogenic role of Z4 factors in NC, offering potential new targeted therapeutic strategies in this incurable cancer.
Visual Overview: http://mcr.aacrjournals.org/content/molcanres/16/12/1826/F1.large.jpg.
Pathobiological Pseudohypoxia as a Putative Mechanism Underlying Myelodysplastic Syndromes
Authors: Hayashi Yoshihiro , Zhang Yue , Yokota Asumi , Yan Xiaomei , Liu Jinqin , Choi Kwangmin , Li Bing , Sashida Goro , Peng Yanyan , Xu Zefeng , Huang Rui , Zhang Lulu , Freudiger George M. , Wang Jingya , Dong Yunzhu , Zhou Yile , Wang Jieyu , Wu Lingyun , Bu Jiachen , Chen Aili , Zhao Xinghui , Sun Xiujuan , Chetal Kashish , Olsson Andre , Watanabe Miki , Romick-Rosendale Lindsey E. , Harada Hironori , Shih Lee-Yung , Tse William , Bridges James P. , Caligiuri Michael A. , Huang Taosheng , Zheng Yi , Witte David P. , Wang Qian-fei , Qu Cheng-Kui , Salomonis Nathan , Grimes H. Leighton , Nimer Stephen D. , Xiao Zhijian , Huang Gang 
Published: August 2018

Abstract
Myelodysplastic syndromes (MDS) are heterogeneous hematopoietic disorders that are incurable with conventional therapy. Their incidence is increasing with global population aging. Although many genetic, epigenetic, splicing, and metabolic aberrations have been identified in patients with MDS, their clinical features are quite similar. Here, we show that hypoxia-independent activation of hypoxia-inducible factor 1α (HIF1A) signaling is both necessary and sufficient to induce dysplastic and cytopenic MDS phenotypes. The HIF1A transcriptional signature is generally activated in MDS patient bone marrow stem/progenitors. Major MDS-associated mutations (Dnmt3a, Tet2, Asxl1, Runx1, and Mll1) activate the HIF1A signature. Although inducible activation of HIF1A signaling in hematopoietic cells is sufficient to induce MDS phenotypes, both genetic and chemical inhibition of HIF1A signaling rescues MDS phenotypes in a mouse model of MDS. These findings reveal HIF1A as a central pathobiologic mediator of MDS and as an effective therapeutic target for a broad spectrum of patients with MDS.
Significance: We showed that dysregulation of HIF1A signaling could generate the clinically relevant diversity of MDS phenotypes by functioning as a signaling funnel for MDS driver mutations. This could resolve the disconnection between genotypes and phenotypes and provide a new clue as to how a variety of driver mutations cause common MDS phenotypes. Cancer Discov; 8(11); 1438–57. ©2018 AACR.
See related commentary by Chen and Steidl, p. 1355.
This article is highlighted in the In This Issue feature, p. 1333
Gintonin Attenuates D-Galactose-Induced Hippocampal Senescence by Improving Long-Term Hippocampal Potentiation, Neurogenesis, and Cognitive Functions
Authors: Nam Sung Min , Hwang Hongik , Seo Misun , Chang Byung-Joon , Kim Hyeon-Joong , Choi Sun-Hye , Rhim Hyewhon , Kim Hyoung-Chun , Cho Ik-Hyun , Nah Seung-Yeol 
Published: August 2018

<b><i>Background:</i></b> Ginseng has been used to improve brain function and increase longevity. However, little is known about the ingredients of ginseng and molecular mechanisms of its anti-brain aging effects. Gintonin is a novel exogenous ginseng-derived lysophosphatidic acid (LPA) receptor ligand; LPA and LPA1 receptors are involved in adult hippocampal neurogenesis. D-galactose (D-gal) is used to induce brain ­aging in animal models because long-term treatment with D-gal facilitates hippocampal aging in experimental adult animals by decreasing hippocampal neurogenesis and inducing learning and memory dysfunction. <b><i>Objective:</i></b> To investigate the protective effects of gintonin on D-gal-induced hippocampal senescence, impairment of long-term potentiation (LTP), and memory dysfunction. <b><i>Methods:</i></b> Brain hippocampal aging was induced by D-gal administration (150 mg/kg/day, s.c.; 10 weeks). From the 7th week, gintonin (50 or 100 mg/kg/day, per os) was co-administered with D-gal for 4 weeks. We performed histological analyses, LTP measurements, and object location test. <b><i>Results:</i></b> Co-administration of gintonin ameliorated D-gal-induced reductions in hippocampal Ki67-immunoreactive proliferating cells, doublecortin-immunoreactive neuroblasts, 5-bromo-2’-deoxyuridine-incorporating NeuN-immunoreactive mature neurons, and LPA1 receptor expression. Co-administration of gintonin in D-gal-treated mice increased the expression of phosphorylated cyclic adenosine monophosphate response element binding protein in the hippocampal dentate gyrus. In addition, co-administration of gintonin in D-gal-treated mice enhanced LTP and restored the cognitive functions compared with those in mice treated with D-gal only. <b><i>Conclusion:</i></b> These results show that gintonin administration restores D-gal-induced memory deficits by enhancing hippocampal LPA1 receptor expression, LTP, and neurogenesis. Finally, the present study shows that gintonin exerts anti-brain aging effects that are responsible for alleviating brain aging-related dysfunction.
Effects of omega-3 fatty acid supplementation on cigarette craving and oxidative stress index in heavy-smoker males: A double-blind, randomized, placebo-controlled clinical trial
Authors: Sadeghi-Ardekani Kiana , Haghighi Mahmonir , Zarrin Rasoul 
Published: August 2018

Background: Smoking-induced oxidative stress is thought to contribute to lower levels of omega-3 fatty acids in plasma and brain tissue. This lower level leads to impaired function in a dopaminergic system related to dependence and craving. Aims: The aim of this study was to evaluate the effects of omega-3 fatty acid supplementation on cigarette craving and oxidative stress index in heavy-smoker males. Methods: In this double-blind, randomized clinical trial, 54 heavy-smoker males (smoke ⩾20 cigarettes per day) were randomly selected to receive either five capsules of fish-oil-derived omega-3 fatty acid supplements ( n = 27, each 1 g capsule containing 180 mg of eicosapentaenoic acid and 120 mg of docosahexanoic acid) or a placebo ( n = 27) for 3 months. The psychometric evaluations (nicotine dependence and cigarette craving), biochemical markers (urinary cotinine, serum total antioxidant capacity and total oxidant status) and self-reported smoking status were used to assess the cigarette craving and oxidative stress index (oxidative stress index = total oxidant status/total antioxidant capacity). Results: There was a greater reduction in levels of nicotine dependence, cigarette craving and cigarettes smoked per day in the omega-3 fatty acid group compared to the placebo group, and the difference between the two groups increased from baseline to 3-month follow up. The model estimated that these differences were statistically significant ( p < 0.001, p < 0.001 and p < 0.001, respectively). Also, a significant decrease was observed in levels of total oxidant status ( p = 0.008) and oxidative stress index ( p = 0.011) in the omega-3 fatty acid group after intervention. Conclusions: This study showed that high-dose omega-3 fatty acid supplementation appears to be useful in reducing cigarette craving and oxidative stress index in heavy-smoker males.
Chronic antipsychotic treatment differentially modulates protein kinase A- and glycogen synthase kinase 3 beta-dependent signaling pathways, N-methyl-D-aspartate receptor and γ-aminobutyric acid A receptors in nucleus accumbens of juvenile rats
Authors: Pan Bo , Lian Jiamei , Deng Chao 
Published: August 2018

Background: Antipsychotics are developed to treat mental disorders in adults; however, the prescription (mostly “off-label”) of antipsychotics for children/adolescents has been constantly increasing over years. The influences of antipsychotics on juveniles requires investigation to validate their clinic use. Antipsychotics mainly exert their effects via several receptors and signaling pathways. Aims: This study examined the effects of aripiprazole, olanzapine, and risperidone on selected signaling pathways, N-methyl-D-aspartate, and γ-aminobutyric acid A receptors in juveniles. Methods: Rats were orally administered aripiprazole (1 mg/kg), olanzapine (1 mg/kg), risperidone (0.3 mg/kg), or vehicle three times/day from postnatal day 23 (±1 day) for three weeks. The effects of antipsychotics in the nucleus accumbens and caudate putamen were measured by Western blots. Results: In the nucleus accumbens, all three drugs differentially increased N-methyl-D-aspartate and γ-aminobutyric acid A receptor expression. Additionally, all three antipsychotics differentially elevated the phosphorylation of glycogen synthase kinase 3 beta, β-catenin, and cAMP-responsive element-binding protein 1. In the caudate putamen, olanzapine increased β-catenin phosphorylation; and aripiprazole and olanzapine elevated γ-aminobutyric acid A receptor levels. Correlation analysis indicated that antipsychotics might modulate N-methyl-D-aspartate receptors via glycogen synthase kinase 3 beta-β-catenin signaling and/or cAMP-responsive element-binding protein 1 activation. Conclusions: These findings suggest that antipsychotics can affect protein kinase A- and glycogen synthase kinase 3 beta-dependent signaling pathways in juveniles; and their modulation on N-methyl-D-aspartate and γ-aminobutyric acid A receptors is probably through glycogen synthase kinase 3 beta-β-catenin signaling and/or cAMP-responsive element-binding protein 1 activation.
Downregulation of thioredoxin-1 in the ventral tegmental area delays extinction of methamphetamine-induced conditioned place preference
Authors: Huang Mengbing , Bai Ming , Zhang Zhimin , Ge Lu , Lu Kang , Li Xiang , Li Ye , Zhou Xiaoshuang , Guo Ningning , Yang Lihua , Bai Jie 
Published: August 2018

Background: Drug addiction is characterized by compulsive drug use and relapse. Thioredoxin-1 is emerging as an important modulator involved in the cellular protective response against a variety of toxic stressors. Previous study has reported that thioredoxin-1 overexpression prevents the acquisition of methamphetamine-conditioned place preference. Here, we aimed to investigate the effect of thioredoxin-1 on methamphetamine-conditioned place preference extinction and the possible mechanism. Methods: (a) An extinction procedure in mice was employed to investigate the effect of thioredoxin-1 on the extinction of methamphetamine-conditioned place preference. After the acquisition of methamphetamine-conditioned place preference, mice underwent the following procedures: the injection of thioredoxin-1 small interfering RNA in the ventral tegmental area followed by the post-conditioned place preference test, four days of extinction training followed by four days of recovery after surgery. (b) The levels of thioredoxin-1, dopamine D1 receptor, tyrosine hydroxylase, phosphorylated extracellular regulated kinase, and phosphorylated cyclic adenosine monophosphate response element binding protein were examined by using Western blot analysis. Results: Thioredoxin-1 downregulation in the ventral tegmental area delayed methamphetamine-conditioned place preference extinction. The expression of thioredoxin-1 was decreased in the ventral tegmental area of mice in control and negative groups after methamphetamine-conditioned place preference extinction, but not in the thioredoxin-1 siRNA group. The levels of dopamine D1 receptor, tyrosine hydroxylase, phosphorylated extracellular regulated kinase, and phosphorylated cyclic adenosine monophosphate response element binding protein were decreased in the ventral tegmental area, nucleus accumbens, and prefrontal cortex of mice in the control and negative groups after methamphetamine-conditioned place preference extinction, but were inversely increased in thioredoxin-1 siRNA group. Conclusions: The results suggest that downregulation of thioredoxin-1 in the ventral tegmental area may delay methamphetamine-conditioned place preference extinction by regulating the mesocorticolimbic dopaminergic signaling pathway.
Time to treatment failure of palbociclib and letrozole as second-line therapy or beyond in hormone receptor-positive advanced breast cancer
Authors: Schickli M Alexandra , Berger Michael J , Lustberg Maryam , Palettas Marilly , Vargo Craig A 
Published: August 2018

Purpose The management of endocrine therapy resistance is one of the most challenging facets of advanced breast cancer treatment. Palbociclib is an inhibitor of cyclin-dependent kinases 4 and 6 approved for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced or metastatic breast cancer in combination with fulvestrant in postmenopausal women with disease progression following endocrine therapy. However, treatment responsiveness of tumors to palbociclib after multiple lines of endocrine therapy is not clearly established. The purpose of this study was to determine the efficacy of palbociclib and letrozole in patients pretreated with one or more lines of endocrine therapy. Methods This was a single-center, retrospective cohort study of all postmenopausal hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer patients who received palbociclib and letrozole as a second-line endocrine therapy or beyond (and no prior cyclin-dependent kinases 4 and 6 inhibitor therapy) between February 1, 2015, and July 31, 2016. The primary objective was to evaluate time to treatment failure of palbociclib in combination with letrozole as a second-line of therapy or beyond. Results Fifty-three patients meeting eligibility criteria were included in the analysis. For the primary outcome, the median time to treatment failure of palbociclib and letrozole was 6.3 months (95% CI 3.1–7.4 months). Progression-free survival of palbociclib and letrozole therapy was 6.4 months (95% CI 4.9–8.3 months). Conclusions Palbociclib and letrozole therapy is a viable, effective treatment option for metastatic breast cancer patients who were not exposed to cyclin-dependent kinases 4 and 6 inhibitors as a first-line endocrine therapy. The benefits of palbociclib and letrozole therapy were seen without excessive toxicity, and although neutropenia was common, it may be managed with dose reduction.
The contribution of hand drying in prevention of transmission of microorganisms: Comparison of the efficacy of three hand drying methods in the removal and distribution of microorganisms
Authors: Pitt Sarah J , Crockett Samantha L , Andreou Gregory M 
Published: August 2018

Background: Hand hygiene is a key tool in infection control. While methods of hand washing have been widely researched, there have been fewer studies investigating the effectiveness of available ways to dry hands in public areas. Aims: This study compared the efficacy of using paper towels (PT), warm air dryers (WAD) and jet air dryers (JAD) after hand washing in terms of microbiological effectiveness and potential for dispersal of pathogens. Methods: Microbial flora on palms and fingertips of 30 subjects were sampled on nutrient agar plates before washing hands and after drying with PTs, WADs and JADs. Total colony forming units (cfus) were recorded. Walls in the vicinity of a PT dispenser, WAD and JAD in female and male washrooms were sampled for the presence of viable microorganisms. Results: Mean cfu significantly reduced after drying with PTs (palms t= 2.67, p <0.05; fingertips t=4.44, p<0.01) significantly increased after using WADs (palms t=3.11, p<0.01; fingertips t=2.06, p<0.05), but there was no difference with JAD (palms t= 1.85, p>0.05; fingertips t=0.97, p>0.05). Some dispersal of organisms was detected on the washroom walls, with the least distribution around PT dispensers and unusual opportunistic pathogens isolated from the JAD units. Discussion: PTs are more effective at drying hands than WADs and JADs, they are more likely to be used appropriately and lead to minimal dispersal of microorganisms from wet hands.
Importance of elevated heart rate in the very early phase of ST-segment elevation myocardial infarction: Results from the DANAMI-3 trial
Authors: Nepper-Christensen Lars , Lønborg Jacob , Ahtarovski Kiril A , Høfsten Dan E , Kyhl Kasper , Schoos Mikkel M , Göransson Christoffer , Laursen Peter N , Sadjadieh Golnaz , Ghotbi Adam Ali , Bertelsen Litten , Køber Lars , Helqvist Steffen , Pedersen Frants , Jørgensen Erik , Kelbæk Henning , Vejlstrup Niels , Holmvang Lene , Engstrøm Thomas 
Published: August 2018

Background: Elevated heart rate is associated with poor clinical outcome in patients with acute myocardial infarction. However, in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention the importance of elevated heart rate in the very early phase remains unknown. We evaluated the impact of elevated heart rate in the very early pre-hospital phase of ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention on cardiovascular magnetic resonance markers of reperfusion success and clinical outcome. Methods: In this DANAMI-3 substudy, 1560 ST-segment elevation myocardial infarction patients in sinus rhythm without cardiogenic shock were included in the analyses of clinical outcome and 796 patients underwent cardiovascular magnetic resonance to evaluate area at risk, infarct size and left ventricular ejection fraction. Heart rate was assessed on the first electrocardiogram with ST-elevation (time of diagnosis). Results: Despite equal area at risk (33%±11 versus 36%±16, p=0.174) patients with a pre-hospital heart rate ⩾100 beats per minute developed larger infarcts (19% (interquartile range, 9–17) versus 11% (interquartile range, 10–28), p=0.001) and a lower left ventricular ejection fraction (54%±12 versus 58%±9, p=0.047). Pre-hospital heart rate ⩾100 beats per minute was independently associated with an increased risk of all-cause mortality and heart failure (hazard ratio 2.39 (95% confidence interval 1.58–3.62), p<0.001). Conclusions: Very early heart rate ⩾100 beats per minute in ST-segment elevation myocardial infarction was independently associated with larger infarct size, reduced left ventricular ejection fraction and an increased risk of all-cause mortality and heart failure, and thus serves as an easily obtainable and powerful tool to identify ST-segment elevation myocardial infarction patients at high risk.