bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insurance status, inhospital mortality and length of stay in hospitalised patients in Shanxi, China: a cross-sectional study
Authors: Lin Xiaojun , Cai Miao , Tao Hongbing , Liu Echu , Cheng Zhaohui , Xu Chang , Wang Manli , Xia Shuxu , Jiang Tianyu 
Published: August 2017

ObjectivesTo determine insurance-related disparities in hospital care for patients with acute myocardial infarction (AMI), heart failure (HF) and pneumonia.Setting and participantsA total of 22 392 patients with AMI, 8056 patients with HF and 17 161 patients with pneumonia were selected from 31 tertiary hospitals in Shanxi, China, from 2014 to 2015 using the International Classification of Diseases, Tenth Revision codes. Patients were stratified by health insurance status, namely, urban employee-based basic medical insurance (UEBMI), urban resident-based basic medical insurance (URBMI), new cooperative medical scheme (NCMS) and self-payment.Outcome measuresInhospital mortality and length of stay (LOS).ResultsThe highest unadjusted inhospital mortality rate was detected in NCMS patients independent of medical conditions (4.7%, 4.4% and 11.1% for AMI, HF and pneumonia, respectively). The lowest unadjusted inhospital mortality rate and the longest LOS were observed in UEBMI patients. After controlling patient-level and hospital-level covariates, the adjusted inhospital mortality was significantly higher for NCMS and self-payment among patients with AMI, for NCMS among patients with HF and for URBMI, NCMS and self-payment among patients with pneumonia compared with UEBMI. The LOS of the URBMI, NCMS and self-payment groups was significantly shorter than that of the UEBMI group.ConclusionInsurance-related disparities in hospital care for patients with three common medical conditions were observed in this study. NCMS patients had significantly higher adjusted inhospital mortality and shorter LOS compared with UEBMI patients. Policies on minimising the disparities among different insurance schemes should be established by the government.
Medical school selection criteria as predictors of medical student empathy: a cross-sectional study of medical students, Ireland
Authors: O’Sullivan Donnchadh M , Moran Joseph , Corcoran Paul , O’Flynn Siun , O’Tuathaigh Colm , O’Sullivan Aoife M 
Published: August 2017

ObjectivesTo determine whether performance in any of the Health Professions Admissions Test (HPAT) sections, most specifically the interpersonal understanding section, correlates with self-reported empathy levels in medical students.SettingThe study was conducted in University College Cork, Ireland.Participants290 students participated in the study. Matching HPAT scores were available for 263 students. All male and female undergraduate students were invited to participate. Postgraduate and international students were excluded.Primary and secondary outcome measuresPrimary measures: HPAT-Ireland and Jefferson Scale of Physician Empathy (JSE) scores were compared including subsection analysis. Secondary measures: comparisons were made between groups such as gender and year of programme.ResultsA total of 290 students participated. Males scored significantly higher than females for total HPAT-Ireland (U=7329, z=−2.04, p<0.05), HPAT-Ireland section 1 (U=5382, z=−5.21, p<0.001) and section 3 scores (U=6833, z=−2.85, p<0.01). In contrast, females scored significantly higher than males on HPAT-Ireland section 2 (U=5844, z=−4.46, p<0.001). Females demonstrated significantly higher total JSE scores relative to males (mean score ± SEM: 113.33±1.05vs109.21±0.95; U=8450, z=−2.83, p<0.01). No significant association was observed between JSE scores and any of the HPAT-Ireland measures (all p>0.05). There was no effect of programme year on JSE scores (all p>0.05).ConclusionThe introduction of the HPAT-Ireland test was partly designed to identify students with strong interpersonal skills. A significant finding of this study is that JSE values did not correlate with HPAT-Ireland scores. This study suggests no clear link between scores on a selection test, the HPAT-Ireland, which is designed to assess several skill domains including interpersonal skills, and scores on a psychometric measure of empathy, at any point during medical education.
A systematic review to identify and assess the effectiveness of alternatives for people over the age of 65 who are at risk of potentially avoidable hospital admission
Authors: Huntley Alyson L , Chalder Melanie , Shaw Ali R G , Hollingworth William , Metcalfe Chris , Benger Jonathan Richard , Purdy Sarah 
Published: August 2017

Background/objectivesThere are some older patients who are ‘at the decision margin’ of admission. This systematic review sought to explore this issue with the following objective: what admission alternatives are there for older patients and are they safe, effective and cost-effective? A secondary objective was to identify the characteristics of those older patients for whom the decision to admit to hospital may be unclear.DesignSystematic review of controlled studies (April 2005–December 2016) with searches in Medline, Embase, Cinahl and CENTRAL databases. The protocol is registered at PROSPERO (CRD42015020371). Studies were assessed using Cochrane risk of bias criteria, and relevant reviews were assessed with the AMSTAR tool. The results are presented narratively and discussed.SettingPrimary and secondary healthcare interface.ParticipantsPeople aged over 65 years at risk of an unplanned admission.InterventionsAny community-based intervention offered as an alternative to admission to an acute hospital.Primary and secondary outcomes measuresReduction in secondary care use, patient-related outcomes, safety and costs.ResultsNineteen studies and seven systematic reviews were identified. These recruited patients with both specific conditions and mixed chronic and acute conditions. The interventions involved paramedic/emergency care practitioners (n=3), emergency department-based interventions (n=3), community hospitals (n=2) and hospital-at-home services (n=11). Data suggest that alternatives to admission appear safe with potential to reduce secondary care use and length of time receiving care. There is a lack of patient-related outcomes and cost data. The important features of older patients for whom the decision to admit is uncertain are: age over 75 years, comorbidities/multi-morbidities, dementia, home situation, social support and individual coping abilities.ConclusionsThis systematic review describes and assesses evidence on alternatives to acute care for older patients and shows that many of the options available are safe and appear to reduce resource use. However, cost analyses and patient preference data are lacking.
The use of feasibility studies for stepped-wedge cluster randomised trials: protocol for a review of impact and scope
Authors: Kristunas Caroline A , Hemming Karla , Eborall Helen C , Gray Laura J 
Published: August 2017

IntroductionThe stepped-wedge cluster randomised trial (SW-CRT) is a complex design, for which many decisions about key design parameters must be made during the planning. These include the number of steps and the duration of time needed to embed the intervention. Feasibility studies are likely to be useful for informing these decisions and increasing the likelihood of the main trial's success. However, the number of feasibility studies being conducted for SW-CRTs is currently unknown. This review aims to establish the number of feasibility studies being conducted for SW-CRTs and determine which feasibility issues are commonly investigated.Methods and analysisFully published feasibility studies for SW-CRTs will be identified, according to predefined inclusion criteria, from searches conducted in Ovid MEDLINE, Scopus, Embase and PsycINFO. To also identify and gain information on unpublished feasibility studies the following will be contacted: authors of published SW-CRTs (identified from the most recent systematic reviews); contacts for registered SW-CRTs (identified from clinical trials registries); lead statisticians of UK registered clinical trials units and researchers known to work in the area of SW-CRTs.Data extraction will be conducted independently by two reviewers. For the fully published feasibility studies, data will be extracted on the study characteristics, the rationale for the study, the process for determining progression to a main trial, how the study informed the main trial and whether the main trial went ahead. The researchers involved in the unpublished feasibility studies will be contacted to elicit the same information.A narrative synthesis will be conducted and provided alongside a descriptive analysis of the study characteristics.Ethics and disseminationThis review does not require ethical approval, as no individual patient data will be used. The results of this review will be published in an open-access peer-reviewed journal.
Gemcitabine-Induced TIMP1 Attenuates Therapy Response and Promotes Tumor Growth and Liver Metastasis in Pancreatic Cancer
Authors: D'Costa Zenobia , Jones Keaton , Azad Abul , van Stiphout Ruud , Lim Su Y. , Gomes Ana L. , Kinchesh Paul , Smart Sean C. , Gillies McKenna W. , Buffa Francesca M. , Sansom Owen J. , Muschel Ruth J. , O'Neill Eric , Fokas Emmanouil 
Published: August 2017

Abstract
Gemcitabine constitutes one of the backbones for chemotherapy treatment in pancreatic ductal adenocarcinoma (PDAC), but patients often respond poorly to this agent. Molecular markers downstream of gemcitabine treatment in preclinical models may provide an insight into resistance mechanisms. Using cytokine arrays, we identified potential secretory biomarkers of gemcitabine resistance (response) in the transgenic KRasG12D; Trp53R172H; Pdx-1 Cre (KPC) mouse model of PDAC. We verified the oncogenic role of the cytokine tissue inhibitor of matrix metalloproteinases 1 (TIMP1) in primary pancreatic tumors and metastases using both in vitro techniques and animal models. We identified potential pathways affected downstream of TIMP1 using the Illumina Human H12 array. Our findings were validated in both primary and metastatic models of pancreatic cancer. Gemcitabine increased inflammatory cytokines including TIMP1 in the KPC mouse model. TIMP1 was upregulated in patients with pancreatic intraepithelial neoplasias grade 3 and PDAC lesions relative to matched normal pancreatic tissue. In addition, TIMP1 played a role in tumor clonogenic survival and vascular density, while TIMP1 inhibition resensitized tumors to gemcitabine and radiotherapy. We observed a linear relationship between TIMP-1 expression, liver metastatic burden, and infiltration by CD11b+Gr1+ myeloid cells and CD4+CD25+FOXP3+ Tregs, whereas the presence of tumor cells was required for immune cell infiltration. Overall, our results identify TIMP1 upregulation as a resistance mechanism to gemcitabine and provide a rationale for combining chemo/radiotherapy with TIMP1 inhibitors in PDAC. Cancer Res; 77(21); 5952–62. ©2017 AACR.
Phase I Dose-Escalation Study of the Anti-CD70 Antibody ARGX-110 in Advanced Malignancies
Authors: Aftimos Philippe , Rolfo Christian , Rottey Sylvie , Offner Fritz , Bron Dominique , Maerevoet Marie , Soria Jean-Charles , Moshir Mahan , Dreier Torsten , Van Rompaey Luc , Michot Jean-Marie , Silence Karen , Hultberg Anna , Gandini Domenica , de Haard Hans , Ribrag Vincent , Peeters Marc , Thibault Alain , Leupin Nicolas , Awada Ahmad 
Published: August 2017

AbstractPurpose: The purpose of this study was to evaluate safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor efficacy of ARGX-110, a glyco-engineered monoclonal antibody, targeting CD70, in patients with CD70 expressing advanced malignancies.Experimental Design: Dose escalation with a sequential 3+3 design was performed in five steps at the 0.1, 1, 2, 5, and 10 mg/kg dose levels (N = 26). ARGX-110 was administered intravenously every 3 weeks until progression or intolerable toxicity. Dose-limiting toxicity was evaluated in the 21 days following the first ARGX-110 administration (Cycle 1). Samples for pharmacokinetics and pharmacodynamics were collected.Results: Dose-limiting toxicity was not observed and the maximum tolerated dose was not reached. ARGX-110 was generally well tolerated, with no dose-related increase in treatment-emergent adverse events (TEAE). The most common TEAE were fatigue and drug related infusion-related reactions (IRR). Of the 20 SAEs reported, five events, all IRRs, were considered related to ARGX-110. ARGX-110 demonstrates dose proportionality over the dose range 1 to 10 mg/kg, but not at 0.1 mg/kg and a terminal half-life of 10 to 13 days. The best overall response was stable disease (14/26) in all 26 evaluable patients with various malignancies and the mean duration of treatment was 15 weeks. No dose–response related antitumor activity was observed, but biomarker readouts provided signs of biological activity, particularly in patients with hematologic malignancies.Conclusions: This dose-escalation phase I trial provides evidence of good tolerability of ARGX-110, pharmacokinetics, and preliminary antitumor activity at all dose levels in generally heavily pretreated patients with advanced CD70-positive malignancies. Clin Cancer Res; 23(21); 6411–20. ©2017 AACR.
The KMT1A-GATA3-STAT3 Circuit Is a Novel Self-Renewal Signaling of Human Bladder Cancer Stem Cells
Authors: Yang Zhao , He Luyun , Lin Kaisu , Zhang Yun , Deng Aihua , Liang Yong , Li Chong , Wen Tingyi 
Published: August 2017

Abstract
Purpose: Bladder cancer is one of the most common urinary malignancies worldwide characterized by a high rate of recurrence and no targeted therapy method. Bladder cancer stem cells (BCSCs) play a crucial role in tumor initiation, metastasis, and drug resistance. However, the regulatory signaling and self-renewal mechanisms of BCSCs remain largely unknown. Here, we identified a novel signal, the KMT1A-GATA3-STAT3 circuit, which promoted the self-renewal and tumorigenicity of human BCSCs.
Experimental Design: In a discovery step, human BCSCs and bladder cancer non-stem cells (BCNSCs) isolated from primary bladder cancer samples #1 and #2, and the bladder cancer cell line EJ were analyzed by transcriptome microarray. In a validation step, 10 paired bladder cancer and normal tissues, different tumor cell lines, the public microarray datasets of human bladder cancer, and The Cancer Genome Atlas database were applied for the verification of gene expression.
Results: KMT1A was highly expressed and responsible for the increase of tri-methylating lysine 9 of histone H3 (H3K9me3) modification in BCSCs compared with either BCNSCs or normal bladder tissue. GATA3 bound to the -1710∼-1530 region of STAT3 promoter and repressed its transcription. H3K9me3 modification on the -1351∼-1172bp region of the GATA3 promoter mediated by KMT1A repressed the transcription of GATA3 and upregulated the expression of STAT3. In addition, the activated STAT3 triggered self-renewal of BCSCs. Furthermore, depletion of KMT1A or STAT3 abrogated the formation of BCSC tumorspheres and xenograft tumors.
Conclusions: KMT1A positively regulated the self-renewal and tumorigenicity of human BCSCs via KMT1A-GATA3-STAT3 circuit, in which KMT1A could be a promising target for bladder cancer therapy. Clin Cancer Res; 23(21); 6673–85. ©2017 AACR.
СУЧАСНІ РЕАЛІЇ ГЕПАТИТУ А У ЖИТЕЛІВ ЗАКАРПАТСЬКОЇ ОБЛАСТІ
Authors: Kohutych A. I. , Halamba A. A. 
Published: August 2017

Мета роботи – встановити реальну поширеність серопозитивності ГА методом виявлення anti-HAV IgG та співвідношення жовтяничних форм захворювання до стертих, атипових, безжовтяничних у жителів Закарпатської області.Пацієнти і методи. Дослідження наявності anti-HAV ІgG проводилось у 262 дорослих осіб, пацієнтів обласних лікувальних закладів. Цілеспрямоване опитування на наявність в анамнезі захворювання з ознаками жовтяниці проведено у 203 хворих Обласної клінічної інфекційної лікарні.Результати. Антитіла IgG до вірусу гепатиту А виявлено у 77,48 % обстежених. Частота знаходження їх залежала від віку та місця проживання і не залежала від статі: найменшою була у віці від 18 до 29 років і найбільшою у віці 60 років і більше (р<0,001); у жителів м. Ужгорода вірогідно меншою за жителів інших міст, сільських населених пунктів і жителів Закарпатської області в цілому (р<0,01-0,001). Висновки. Отримані результати свідчать про значну серопозитивність гепатиту А серед жителів Закарпатській області. Офіційно реєструється менше десятої частини хворих, які перенесли дане захворювання. Серед дорослого населення переважають безжовтяничні форми гепатиту А. Частота виявлення анамнестичних антитіл до гепатиту А залежить від віку та місця проживання обстежених.
Loss of Y Chromosome in Blood Is Associated With Major Cardiovascular Events During Follow-Up in Men After Carotid Endarterectomy
Authors: Haitjema Saskia , Kofink Daniel , van Setten Jessica , van der Laan Sander W. , Schoneveld Arjan H. , Eales James , Tomaszewski Maciej , de Jager Saskia C.A. , Pasterkamp Gerard , Asselbergs Folkert W. , den Ruijter Hester M. 
Published: August 2017

Background—
Recent studies found an immune regulatory role for Y chromosome and a relationship between loss of Y chromosome (LOY) in blood cells and a higher risk of cancer and mortality. Given involvement of immune cells in atherosclerosis, we hypothesized that LOY is associated with the severity of atherosclerotic plaque characteristics and outcome in men undergoing carotid endarterectomy.

Methods and Results—

LOY was quantified in blood and plaque from raw intensity genotyping data in men within the Athero-Express biobank study. Plaques were dissected, and the culprit lesions used for histology and the measurement of inflammatory proteins. We tested LOY for association with (inflammatory) atherosclerotic plaque phenotypes and cytokines and assessed the association of LOY with secondary events during 3-year follow-up. Of 366 patients with carotid endarterectomy, 61 exhibited some degree of LOY in blood. LOY was also present in atherosclerotic plaque lesions (n=8/242, 3%). LOY in blood was negatively associated with age (β=−0.03/10 y;
r
2
=0.07;
P
=1.6×10
–7
) but not with cardiovascular disease severity at baseline. LOY in blood was associated with a larger atheroma size (odds ratio, 2.15; 95% confidence interval, 1.06–4.76;
P
=0.04); however, this association was not significant after correction for multiple testing. LOY was independently associated with secondary major cardiovascular events (hazard ratio=2.28; 95% confidence interval, 1.11–4.67;
P
=0.02) in blood when corrected for confounders.

Conclusions—
In this hypothesis-generating study, LOY in blood is independently associated with secondary major cardiovascular events in a severely atherosclerotic population. Our data could indicate that LOY affects secondary outcome via other mechanisms than inflammation in the atherosclerotic plaque.
Activation of Transient Receptor Potential Melastatin Subtype 8 Attenuates Cold‐Induced Hypertension Through Ameliorating Vascular Mitochondrial Dysfunction
Authors: Xiong Shiqiang , Wang Bin , Lin Shaoyang , Zhang Hexuan , Li Yingsha , Wei Xing , Cui Yuanting , Wei Xiao , Lu Zongshi , Gao Peng , Li Li , Zhao Zhigang , Liu Daoyan , Zhu Zhiming 
Published: August 2017

Background

Environmental cold‐induced hypertension is common, but how to treat cold‐induced hypertension remains an obstacle. Transient receptor potential melastatin subtype 8 (TRPM8) is a mild cold‐sensing nonselective cation channel that is activated by menthol. Little is known about the effect of TRPM8 activation by menthol on mitochondrial Ca
2+
homeostasis and the vascular function in cold‐induced hypertension.

Methods and Results

Primary vascular smooth muscle cells from wild‐type or Trpm8
−/−
mice were cultured. In vitro, we confirmed that sarcoplasmic reticulum–resident TRPM8 participated in the regulation of cellular and mitochondrial Ca
2+
homeostasis in the vascular smooth muscle cells. TRPM8 activation by menthol antagonized angiotensin
II
induced mitochondrial respiratory dysfunction and excess reactive oxygen species generation by preserving pyruvate dehydrogenase activity, which hindered reactive oxygen species–triggered Ca
2+
influx and the activation of RhoA/Rho kinase pathway. In vivo, long‐term noxious cold stimulation dramatically increased vasoconstriction and blood pressure. The activation of TRPM8 by dietary menthol inhibited vascular reactive oxygen species generation, vasoconstriction, and lowered blood pressure through attenuating excessive mitochondrial reactive oxygen species mediated the activation of RhoA/Rho kinase in a TRPM8‐dependent manner. These effects of menthol were further validated in angiotensin II–induced hypertensive mice.

Conclusions
Long‐term dietary menthol treatment targeting and preserving mitochondrial function may represent a nonpharmaceutical measure for environmental noxious cold–induced hypertension.
Persistent Hyperglycemia Is Associated With Increased Mortality After Intracerebral Hemorrhage
Authors: Wu Teddy Y. , Putaala Jukka , Sharma Gagan , Strbian Daniel , Tatlisumak Turgut , Davis Stephen M. , Meretoja Atte 
Published: August 2017

Background

Hyperglycemia may be associated with worse outcome after intracerebral hemorrhage (
ICH
). We assessed the association of early glycemic trajectory on
ICH
mortality and edema growth.

Methods and Results

We included patients from the Helsinki
ICH
study with glucose measurements at least once between both 0 to 24 and 24 to 72 hours from onset. Hyperglycemia was defined as blood glucose ≥8 mmol/L (144 mg/dL) based on the local threshold for treatment. Glycemic trajectory was defined on maximum values 0 to 24 and 24 to 72 hours after
ICH
: (1) persistent normoglycemia in both epochs; (2) late hyperglycemia (only between 24 and 72 hours); (3) early hyperglycemia (only before 24 hours); and (4) persistent hyperglycemia in both epochs. Logistic regression with known predictors of outcome estimated the association of glycemic trajectory and 6‐month mortality. A generalized linear model assessed the association of glycemic trajectory and interpolated 72‐hour edema extension distance. A total of 576 patients met eligibility criteria, of whom 214 (37.2%) had persistent normoglycemia, 44 (7.6%) late hyperglycemia, 151 (26.2%) early hyperglycemia, and 167 (29.0%) persistent hyperglycemia. Six‐month mortality was higher in the persistent (51.1%) and early (26.3%) hyperglycemia groups than the normoglycemia (19.0%) and late hyperglycemia (3.6%) groups. Persistent hyperglycemia was associated with 6‐month mortality (odds ratio 3.675, 95%
CI
1.989–6.792;
P
<0.001). Both univariate (
P
=0.426) and multivariable (
P
=0.493) generalized linear model analyses showed no association between glycemic trajectory and 72‐hour edema extension distance.

Conclusion

Early hyperglycemia after
ICH
is harmful if it is persistent. Strategies to achieve glycemic control after
ICH
may influence patient outcome and need to be assessed in clinical trials.