bluuebunny/crossref_metadata_2025_split huggingface dataset:
Qualitative study of physicians' varied uses of biomedical research in the USA
Authors: Maggio Lauren A , Moorhead Laura L , Willinsky John M 
Published: November 2016

ObjectiveTo investigate the nature of physicians' use of research evidence in experimental conditions of open access to inform training and policy.DesignThis qualitative study was a component of a larger mixed-methods initiative that provided 336 physicians with relatively complete access to research literature via PubMed and UpToDate, for 1 year via an online portal, with their usage recorded in web logs. Using a semistructured interview protocol, a subset of 38 physician participants were interviewed about their use of research articles in general and were probed about their reasons for accessing specific articles as identified through their web logs. Transcripts were analysed using a general inductive approach.SettingPhysician participants were recruited from and registered in the USA.Participants38 physicians from 16 US states, engaged in 22 medical specialties, possessing more than 1 year of experience postresidency training participated.Results26 participants attested to the value of consulting research literature within the context of the study by making reference to their roles as clinicians, educators, researchers, learners, administrators and advocates. The physicians reported previously encountering what they experienced as a prohibitive paywall barrier to the research literature and other frustrations with the nature of information systems, such as the need for passwords.ConclusionsThe findings, against the backdrop of growing open access to biomedical research, indicate that a minority of physicians, at least initially, is likely to seek out and use research and do so in a variety of common roles. Physicians' use of research in these roles has not traditionally been part of their training or part of the considerations for open access policies. The findings have implications for educational and policy initiatives directed towards increasing the effectiveness of this access to and use of research in improving the quality of healthcare.
Primary cilia are increased in number and demonstrate structural abnormalities in human cancer
Authors: Yasar Binnaz , Linton Kim , Slater Christian , Byers Richard 
Published: November 2016

AimsPrimary cilia play an important role in the regulation of cell signalling pathways and are thought to have a role in cancer but have seldom been studied in human cancer samples.MethodsPrimary cilia were visualised by dual immunofluorescence for anti-CROCC (ciliary rootlet coiled-coil) and anti-tubulin in a range of human cancers (including carcinomas of stomach, pancreas, prostate, lung and colon, lobular and ductal breast cancers and follicular lymphoma) and in matched normal tissue (stomach, pancreas, lung, large and small intestines, breast and reactive lymph nodes) samples using a tissue microarray; their frequency, association with proliferation, was measured by Ki-67 staining and their structure was analysed.ResultsCompared with normal tissues, primary cilia frequency was significantly elevated in adenocarcinoma of the lung (2.75% vs 1.85%, p=0.016), adenocarcinoma of the colon (3.80% vs 2.43%, respectively, p=0.017), follicular lymphoma (1.18% vs 0.83%, p=0.003) and pancreatic adenocarcinoma (7.00% vs 5.26%, p=0.002); there was no statistically significant difference compared with normal control tissue for gastric and prostatic adenocarcinomas or for lobular and ductal breast cancers. Additionally, structural abnormalities of primary cilia were identified in cancer tissues, including elongation of the axoneme, multiple basal bodies and branching of the axoneme. Ki-67 scores ranged from 0.7% to 78.4% and showed no statistically significant correlation with primary cilia frequency across all tissues (p=0.1501).ConclusionsThe results show upregulation of primary cilia and the presence of structural defects in a wide range of human cancer tissue samples demonstrating association of dysregulation of primary cilia with human cancer.
No association between elevated homocysteine levels and carotid atherosclerosis in a rural population in China
Authors: Li Yang , Wang Li , Zhang Wei , Fang Yalan , Niu Xiaoyuan 
Published: November 2016

ObjectivesWe wish to determine if homocysteine (Hcy) is an independent risk factor for carotid atherosclerosis in a rural Chinese population.Methods2291 individuals (1016 men and 1275 women), aged 64.6±7.4 years, from Lvliang, China participated in this study. Tests performed included carotid artery ultrasound scan and blood analysis, to measure Hcy levels and other blood components.ResultsThe mean serum Hcy level was 24.7±18.0 µmol/L. The overall detection rate of carotid atherosclerotic lesions was 76.3% and the detection rate of plaque was 48.6%. Participants were divided into 4 groups based on their Hcy levels, <14.49, 14.49–19.43, 19.44–28.30, and ≥28.30 µmol/L. The relative risk of carotid atherosclerosis for each quartile as compared with the risk for the lowest quartile was estimated as the OR derived from the logistic regression coefficients. After adjusting for age and gender, the OR of carotid atherosclerosis in the third and fourth quartiles of Hcy were 1.219 (95% CI 0.922 to 1.612) and 1.156 (95% CI 0.859 to 1.555; p>0.05), respectively. After controlling for demographic variables (age, gender, current smoker, fasting blood glucose, low-density lipoprotein and systolic blood pressure) the OR of carotid plaque(s) in the third and fourth quartiles were 1.246 (95% CI 0.967 to 1.606) and 1.259 (95% CI 0.963 to 1.646; p>0.05).ConclusionsThe mean value of Hcy among participants in this study was much higher than that previously reported. However, no significant correlation between elevated Hcy and carotid atherosclerosis was found.
T Cells Redirected to a Minor Histocompatibility Antigen Instruct Intratumoral TNFα Expression and Empower Adoptive Cell Therapy for Solid Tumors
Authors: Manzo Teresa , Sturmheit Tabea , Basso Veronica , Petrozziello Elisabetta , Hess Michelini Rodrigo , Riba Michela , Freschi Massimo , Elia Angela R. , Grioni Matteo , Curnis Flavio , Protti Maria Pia , Schumacher Ton N. , Debets Reno , Swartz Melody A. , Corti Angelo , Bellone Matteo , Mondino Anna 
Published: November 2016

Abstract
Donor-derived allogeneic T cells evoke potent graft versus tumor (GVT) effects likely due to the simultaneous recognition of tumor-specific and host-restricted minor histocompatibility (H) antigens. Here we investigated whether such effects could be reproduced in autologous settings by TCR gene–engineered lymphocytes. We report that T cells redirected either to a broadly expressed Y-encoded minor H antigen or to a tumor-associated antigen, although poorly effective if individually transferred, when simultaneously administered enabled acute autochthonous tumor debulking and resulted in durable clinical remission. Y-redirected T cells proved hyporesponsive in peripheral lymphoid organs, whereas they retained effector function at the tumor site, where in synergy with tumor-redirected lymphocytes, they instructed TNFα expression, endothelial cell activation, and intratumoral T-cell infiltration. While neutralizing TNFα hindered GVT effects by the combined T-cell infusion, a single injection of picogram amounts of NGR-TNF, a tumor vessel–targeted TNFα derivative currently in phase III clinical trials, substituted for Y-redirected cells and enabled tumor debulking by tumor-redirected lymphocytes. Together, our results provide new mechanistic insights into allogeneic GVT, validate the importance of targeting the tumor and its associated stroma, and prove the potency of a novel combined approach suitable for immediate clinical implementation. Cancer Res; 77(3); 658–71. ©2016 AACR.
MIF-Induced Stromal PKCβ/IL8 Is Essential in Human Acute Myeloid Leukemia
Authors: Abdul-Aziz Amina M. , Shafat Manar S. , Mehta Tarang K. , Di Palma Federica , Lawes Matthew J. , Rushworth Stuart A. , Bowles Kristian M. 
Published: November 2016

Abstract
Acute myeloid leukemia (AML) cells exhibit a high level of spontaneous apoptosis when cultured in vitro but have a prolonged survival time in vivo, indicating that tissue microenvironment plays a critical role in promoting AML cell survival. In vitro studies have shown that bone marrow mesenchymal stromal cells (BM-MSC) protect AML blasts from spontaneous and chemotherapy-induced apoptosis. Here, we report a novel interaction between AML blasts and BM-MSCs, which benefits AML proliferation and survival. We initially examined the cytokine profile in cultured human AML compared with AML cultured with BM-MSCs and found that macrophage migration inhibitory factor (MIF) was highly expressed by primary AML, and that IL8 was increased in AML/BM-MSC cocultures. Recombinant MIF increased IL8 expression in BM-MSCs via its receptor CD74. Moreover, the MIF inhibitor ISO-1 inhibited AML-induced IL8 expression by BM-MSCs as well as BM-MSC–induced AML survival. Protein kinase C β (PKCβ) regulated MIF-induced IL8 in BM-MSCs. Finally, targeted IL8 shRNA inhibited BM-MSC–induced AML survival. These results describe a novel, bidirectional, prosurvival mechanism between AML blasts and BM-MSCs. Furthermore, they provide biologic rationale for therapeutic strategies in AML targeting the microenvironment, specifically MIF and IL8. Cancer Res; 77(2); 303–11. ©2016 AACR.
Regeneration of CD8αβ T Cells from T-cell–Derived iPSC Imparts Potent Tumor Antigen-Specific Cytotoxicity
Authors: Maeda Takuya , Nagano Seiji , Ichise Hiroshi , Kataoka Keisuke , Yamada Daisuke , Ogawa Seishi , Koseki Haruhiko , Kitawaki Toshio , Kadowaki Norimitsu , Takaori-Kondo Akifumi , Masuda Kyoko , Kawamoto Hiroshi 
Published: November 2016

AbstractAlthough adoptive transfer of cytotoxic T lymphocytes (CTL) offer a promising cancer therapeutic direction, the generation of antigen-specific CTL from patients has faced difficulty in efficient expansion in ex vivo culture. To resolve this issue, several groups have proposed that induced pluripotent stem cell technology be applied for the expansion of antigen-specific CTL, which retain expression of the same T-cell receptor as original CTL. However, in these previous studies, the regenerated CTL are mostly of the CD8αα+ innate type and have less antigen-specific cytotoxic activity than primary CTL. Here we report that, by stimulating purified iPSC-derived CD4/CD8 double-positive cells with anti-CD3 antibody, T cells expressing CD8αβ were generated and exhibited improved antigen-specific cytotoxicity compared with CD8αα+ CTL. Failure of CD8αβ T-cell production using the previous method was found to be due to killing of double-positive cells by the double-negative cells in the mixed cultures. We found that WT1 tumor antigen-specific CTL regenerated by this method prolonged the survival of mice bearing WT1-expressing leukemic cells. Implementation of our methods may offer a useful clinical tool. Cancer Res; 76(23); 6839–50. ©2016 AACR.
A Novel Platinum(II)–Based Bifunctional ADC Linker Benchmarked Using 89Zr-Desferal and Auristatin F–Conjugated Trastuzumab
Authors: Sijbrandi Niels J. , Merkul Eugen , Muns Joey A. , Waalboer Dennis C.J. , Adamzek Kevin , Bolijn Marije , Montserrat Veronica , Somsen Govert W. , Haselberg Rob , Steverink Paul J.G.M. , Houthoff Hendrik-Jan , van Dongen Guus A.M.S. 
Published: November 2016

Abstract
Greater control is desirable in the stochastic conjugation technology used to synthesize antibody–drug conjugates (ADC). We have shown recently that a fluorescent dye can be stably conjugated to a mAb using a bifunctional platinum(II) linker. Here, we describe the general applicability of this novel linker technology for the preparation of stable and efficacious ADCs. The ethylenediamine platinum(II) moiety, herein called Lx, was coordinated to Desferal (DFO) or auristatin F (AF) to provide storable “semifinal” products, which were directly conjugated to unmodified mAbs. Conjugation resulted in ADCs with unimpaired mAb-binding characteristics, DAR in the range of 2.5 to 2.7 and approximately 85% payload bound to the Fc region, presumably to histidine residues. To evaluate the in vivo stability of Lx and its effect on pharmacokinetics and tumor targeting of an ADC, Lx-DFO was conjugated to the HER2 mAb trastuzumab, followed by radiolabeling with 89Zr. Trastuzumab-Lx-DFO-89Zr was stable in vivo and exhibited pharmacokinetic and tumor-targeting properties similar to parental trastuzumab. In a xenograft mouse model of gastric cancer (NCI-N87) or an ado-trastuzumab emtansine-resistant breast cancer (JIMT-1), a single dose of trastuzumab-Lx-AF outperformed its maleimide benchmark trastuzumab-Mal-AF and FDA-approved ado-trastuzumab emtansine. Overall, our findings show the potential of the Lx technology as a robust conjugation platform for the preparation of anticancer ADCs. Cancer Res; 77(2); 257–67. ©2016 AACR.
Natural Killer Cells to the Attack: Combination Therapy against Neuroblastoma
Authors: Zenarruzabeitia Olatz , Vitallé Joana , Astigarraga Itziar , Borrego Francisco 
Published: November 2016

Abstract
TGFβ in the tumor microenvironment diminishes natural killer (NK) cell–mediated anti-disialoganglioside (anti-GD2) mAb elimination of neuroblastoma cells. Consequently, blockade of TGFβ signaling with galunisertib in combination with the anti-GD2 mAb dinutuximab plus adoptively transferred NK cells is a promising tool for the treatment of neuroblastoma. Clin Cancer Res; 23(3); 615–7. ©2016 AACR.
See related article by Tran et al., p. 804
ОПИС КОРИСНОЇ МОДЕЛІ НА КЛІНІЧНИХ КАФЕДРАХ (ДЛЯ ОТРИМАННЯ ПАТЕНТУ УКРАЇНИ): АВТОРСЬКІ ПОГЛЯДИ)
Authors: Chopyak V. V. , Verhun A. R. , Yavorska O. Ya. , Verhun O. M. 
Published: November 2016

Формулювання структурної схеми опису для отримання Патенту України на корисну модель на клінічних кафедрах здійснене згідно з вимогами Державної служби інтелектуальної власності на основі стилістичного аналізу описів 12 патентів України, отриманих працівниками кафедр Львівського національного медичного університету імені Данила Галицького. Запропонований нами опис корисної моделі на клінічних кафедрах (для отримання Патенту України) сприятиме подоланню об’єктивних труднощів щодо адекватного послідовного описання клінічних спостережень, способів діагностики та лікування окремих захворювань згідно з вимогами, задекларованими для патентування.
ПРОБЛЕМА АКАДЕМІЧНОЇ ЧЕСНОСТІ В НАВЧАЛЬНОМУ ПРОЦЕСІ ТА НАУЦІ: ДОСВІД НАЦІОНАЛЬНОГО МЕДИЧНОГО УНІВЕРСИТЕТУ ІМЕНІ О. О. БОГОМОЛЬЦЯ
Authors: Stechenko O. V. 
Published: November 2016

У статті проаналізовано досвід Національного медичного університету імені О. О. Богомольця з розробки та впровадження Положення про академічну чесність як важливого документа в рамках функціонування внутрішньовузівської системи управління якістю освіти. Наведено результати аналізу анонімного анкетування 412 респондентів щодо рівня академічної культури та розповсюдження академічного шахрайства в різних формах. Виявлено, що 55 % студентів Університету самостійно складають підсумковий контроль з дисциплін навчального плану, в той час як визнали несамостійність у складанні сесії 16 % респондентів. Визначено важливість трансформації академічної культури науково-педагогічних працівників та студентів для забезпечення успішності євроінтеграційних змін освітнього процесу в країні.
Heart Rate Turbulence Is a Powerful Predictor of Cardiac Death and Ventricular Arrhythmias in Postmyocardial Infarction and Heart Failure Patients
Authors: Disertori Marcello , Masè Michela , Rigoni Marta , Nollo Giandomenico , Ravelli Flavia 
Published: November 2016

Background—
Heart rate turbulence (HRT) has been proposed as a candidate marker of altered autonomic tone, and some studies showed its prognostic value for both cardiac death (CD) and sudden death. Nevertheless, HRT is not currently used in the clinical practice.

Methods and Results—
We performed a systematic review and meta-analysis of the predictive value of HRT for the end points of total mortality, CD, and fatal and nonfatal ventricular arrhythmias in postacute myocardial infarction and heart failure patients. MEDLINE and The Cochrane Library databases were systematically searched to identify studies, which analyzed the predictive value of abnormal HRT for the defined end points. Twenty studies (25 cohorts: 12 832 patients) were identified by the systematic review, and 15 studies (20 cohorts: 11 499 patients) were included in the meta-analyses. Abnormal HRT was a predictive marker for all the end points in heart failure patients and more markedly in postacute myocardial infarction patients, where 9 out of the 10 cohorts had an ejection fraction >30%. In postacute myocardial infarction patients, HRT had pooled risk ratios of 3.53 (95% confidence interval [CI], 2.54–4.90), 4.82 (95% CI, 3.12–7.45), and 4.48 (95% CI, 3.04–6.60), and positive likelihood ratios of 3.5 (95% CI, 2.6–4.8), 4.1 (95% CI, 3.0–5.7), and 2.7 (95% CI, 2.2–3.3) for total mortality, CD, and arrhythmic events, respectively. The combination of abnormal HRT and T-wave alternans (5 cohorts: 1516 patients) increased the predictive power for CD and arrhythmic events.

Conclusions—
HRT is a powerful predictor of both CD and arrhythmic events, particularly in postacute myocardial infarction patients with ejection fraction >30%. HRT power increases in combination with T-wave alternans analysis.
Myrmeleon almohadarum sp. nov., from Spain and North Africa, with description of the larva (Neuroptera Myrmeleontidae)
Authors: BADANO DAVIDE , ACEVEDO FERNANDO , PANTALEONI ROBERTO A. , MONSERRAT VÍCTOR J. 
Published: November 2016

A new antlion (Neuroptera Myrmeleontidae Myrmeleontini), Myrmeleon almohadarum sp. nov., is described from southern Spain and Tunisia. The new taxon is closely related to the mostly sympatric M. inconspicuus Rambur and M. mariaemathildae Pantaleoni, Cesaroni & Nicoli Aldini but differing in body pattern, wing venation and larval chaetotaxy. The validity of the new species is also supported by a phylogenetic analysis based on COI sequences. The larva of this new species is described and compared with congeners. M. almohadarum appears to be associated with sandy environments.
The Effects of Arrest, Reporting to the Police, and Victim Services on Intimate Partner Violence
Authors: Xie Min , Lynch James P. 
Published: November 2016

Objectives: To estimate the effects of three types of responses to intimate partner violence: (1) reporting of crime to the police, (2) arresting the suspect, and (3) receiving services from agencies other than the police that assist victims of crime. Methods: We obtained a nationally representative sample of 2,221 victims, using longitudinal records from the area-identified National Crime Victimization Survey from 1996 through 2012. To reduce the threat of nonrandom selection into treatment, we estimated effects using propensity score matched and weighted survival analysis. Results: Victims’ probability of repeat victimization is not related to arrest (hazard ratio, 0.87; 95 percent confidence interval [CI], 0.55 to 1.40; p = .57). In contrast, the reporting of crime to the police is associated with a 34 percent reduction in the risk of repeat victimization (hazard ratio, 0.66; 95 percent CI, 0.53 to 0.82; p < .001), and the use of victim services is associated with a 40 percent reduction in the risk of repeat victimization (hazard ratio, 0.60; 95 percent CI, 0.44 to 0.83; p < .01). Conclusions: The results support a model in which the deterrent effect of arrest is not substantively important, but police notification and victim-centered services produce important reductions in repeat victimization.
Comparison of airf low environmental effects on thermal fabrics
Authors: Tong Jiahui , Zhao Yuanfang , Yang Chenxiao , Li Li 
Published: November 2016

Smart thermal textiles are becoming increasingly popular and temperature precision is one of the important targets in their industrialization and commercialization. Some thermal products do not rely on temperature sensors but rather the input electric current pulse to achieve thermal control. In this situation, the surrounding environment, especially ventilation, can greatly affect the thermal control process. Therefore, in this paper, a case study of an apparel system will be provided to study the effect of airflow on the heating process of thermal fabric. The relationship between temperature precision and ventilation is determined when the air flows at any angle to the surface of the thermal fabric. The results show that the thermal conductivity is proportional to the wind speed when the wind speed is high; in contrast, when the wind speed is near to zero, the thermal conductivity of the thermal fabric will not proportionally tend to zero as the result of self-generated heat transfer. This research also shows that the air inflow angle and the wind direction has little effect on the heat dissipation of thermal fabric. This research may generate the data archive and become a valuable reference for future soft thermal studies. It is expected that the developed system will span multidisciplinary gaps and contribute to a new form in a precise and controllable way within the textile industry.
Estimates of Intraclass Correlation Coefficients and Other Design Parameters for Studies of School-Based Nutritional Interventions
Authors: Juras Randall 
Published: November 2016

Introduction: When cluster randomized trials are used to evaluate school-based nutritional interventions such as school lunch programs, design-stage estimates of the required sample size must take into account the correlation in outcomes among individuals within each cluster (e.g., classrooms, schools, or districts). Estimates of the necessary parameters have been carefully developed for educational interventions, but for nutritional interventions the literature is thin. Methods: Using data from two large multi-school, multi-district impact evaluations conducted in the United States, this article calculates estimates of the design parameters required for sizing school-based nutritional studies. The large size of the trials (252 and 1,327 schools) yields precise estimates of the parameters of interest. Variance components are estimated by fitting random-intercept multilevel models in Stata. Results: School-level intraclass correlations are similar to those typically found for educational outcomes. In particular, school-level estimates range from less than .01 to .26 across the two studies, and district-level estimates ranged from less than .01 to .19. This suggests that cluster randomized trials of nutritional interventions may require samples with numbers of schools similar to the education studies to detect similar effect sizes.