bluuebunny/crossref_metadata_2025_split huggingface dataset:
Qualitative investigation into a wearable system for chronic obstructive pulmonary disease: the stakeholders' perspective
Authors: Kayyali Reem , Savickas Vilius , Spruit Martijn A , Kaimakamis Evangelos , Siva Roshan , Costello Richard W , Chang John , Pierscionek Barbara , Davies Nikki , Vaes Anouk W , Paradiso Rita , Philip Nada , Perantoni Eleni , D'Arcy Shona , Raptopoulos Andreas , Nabhani-Gebara Shereen 
Published: September 2016

ObjectivesTo ascertain the stakeholders' views and devise recommendations for further stages of the Wearable Sensing and Smart Cloud Computing for Integrated Care to Chronic Obstructive Pulmonary Disease (COPD) Patients with Co-morbidities (WELCOME) system development. This system aims to create a wearable vest to monitor physiological signals for patients concerned incorporating an inhaler adherence monitoring, weight, temperature, blood pressure and glucose metres, and a mobile health application for communication with healthcare professionals (HCPs).DesignA study of qualitative data derived from focus groups and semistructured interviews.Setting4 participating clinical sites in Greece, the UK, Ireland and the Netherlands.ParticipantsPurposive sampling was used to recruit 32 patients with COPD with heart failure, diabetes, anxiety or depression, 27 informal carers and 23 HCPs from 4 European Union (EU) countries for focus groups and interviews.ResultsMost patients and HCPs described the WELCOME system as ‘brilliant and creative’ and felt it gave a sense of safety. Both users and HCPs agreed that the duration and frequency of vest wear should be individualised as should the mobile application functions. The parameters and frequency of monitoring should be personalised using a multidisciplinary approach. A ‘traffic light’ alert system was proposed by HCPs for abnormal results. Patients were happy to take actions in response.ConclusionsWELCOME stakeholders provided valuable views on the development of the system, which should take into account patient's individual comorbidities, circumstances and concerns. This will enable the development of the individualised system in each member state concerned.
Protocol for a multicentre, parallel-arm, 12-month, randomised, controlled trial of arthroscopic surgery versus conservative care for femoroacetabular impingement syndrome (FASHIoN)
Authors: Griffin D R , Dickenson E J , Wall P D H , Donovan J L , Foster N E , Hutchinson C E , Parsons N , Petrou S , Realpe A , Achten J , Achana F , Adams A , Costa M L , Griffin J , Hobson R , Smith J 
Published: September 2016

IntroductionFemoroacetabular impingement (FAI) syndrome is a recognised cause of young adult hip pain. There has been a large increase in the number of patients undergoing arthroscopic surgery for FAI; however, a recent Cochrane review highlighted that there are no randomised controlled trials (RCTs) evaluating treatment effectiveness. We aim to compare the clinical and cost-effectiveness of arthroscopic surgery versus best conservative care for patients with FAI syndrome.MethodsWe will conduct a multicentre, pragmatic, assessor-blinded, two parallel arm, RCT comparing arthroscopic surgery to physiotherapy-led best conservative care. 24 hospitals treating NHS patients will recruit 344 patients over a 26-month recruitment period. Symptomatic adults with radiographic signs of FAI morphology who are considered suitable for arthroscopic surgery by their surgeon will be eligible. Patients will be excluded if they have radiographic evidence of osteoarthritis, previous significant hip pathology or previous shape changing surgery. Participants will be allocated in a ratio of 1:1 to receive arthroscopic surgery or conservative care. Recruitment will be monitored and supported by qualitative intervention to optimise informed consent and recruitment. The primary outcome will be pain and function assessed by the international hip outcome tool 33 (iHOT-33) measured 1-year following randomisation. Secondary outcomes include general health (short form 12), quality of life (EQ5D-5L) and patient satisfaction. The primary analysis will compare change in pain and function (iHOT-33) at 12 months between the treatment groups, on an intention-to-treat basis, presented as the mean difference between the trial groups with 95% CIs. The study is funded by the Health Technology Assessment Programme (13/103/02).Ethics and disseminationEthical approval is granted by the Edgbaston Research Ethics committee (14/WM/0124). The results will be disseminated through open access peer-reviewed publications, includingHealth Technology Assessment, and presented at relevant conferences.Trial registration numberISRCTN64081839; Pre-results.
Concussion reporting behaviours of community college student-athletes and limits of transferring concussion knowledge during the stress of competition
Authors: Chinn Nancy Resendes , Porter Paul 
Published: September 2016

Concussion education for student-athletes is mandated by several states and is becoming an integral component of concussion management programmes; however, little is known about student-athlete concussion knowledge and self-reporting of suspected concussion. This study explored to what extent collegiate student-athletes are knowledgeable on the topic of concussion, the relationship between having concussion knowledge and reporting behaviours, and factors contributing to not reporting when education has been provided.MethodMixed method explanatory design. The Rosenbaum Concussion Knowledge and Attitudes Survey was administered to 986 community college student-athletes from 6 sports. Follow-up qualitative interviews were conducted using purposive sampling.ResultsConcussion knowledge scores positively correlated with number of times concussion education was received, but were not associated with reporting of concussion. Of respondents with a history of concussion, 64% stated that they reported all of their concussions. The highest ranked reason given for not reporting concussion was, “I was into the game/practice and didn't realize I had a concussion at the time.” Qualitative analysis revealed physiologically related and attitudinal factors particular to competition that precluded participants’ identification and reporting of concussion.ConclusionsDespite receiving concussion education, student-athletes may not be cognizant of a possible concussion particularly during the stress of competition. Results indicate that alternate methods of providing concussion education that can affect knowledge transfer should be explored: providing education in the settings where student-athletes practice and compete, incorporating a kinaesthetic or procedural learning approach to concussion education, and addressing the social and attitudinal aspects of concussion reporting.
Lysophosphatidylcholine acyltransferase 1 is downregulated by hepatitis C virus: impact on production of lipo-viro-particles
Authors: Beilstein Frauke , Lemasson Matthieu , Pène Véronique , Rainteau Dominique , Demignot Sylvie , Rosenberg Arielle R 
Published: September 2016

ObjectiveHCV is intimately linked with the liver lipid metabolism, devoted to the efflux of triacylglycerols stored in lipid droplets (LDs) in the form of triacylglycerol-rich very-low-density lipoproteins (VLDLs): (i) the most infectious HCV particles are those of lowest density due to association with triacylglycerol-rich lipoproteins and (ii) HCV-infected patients frequently develop hepatic steatosis (increased triacylglycerol storage). The recent identification of lysophosphatidylcholine acyltransferase 1 (LPCAT1) as an LD phospholipid-remodelling enzyme prompted us to investigate its role in liver lipid metabolism and HCV infectious cycle.DesignHuh-7.5.1 cells and primary human hepatocytes (PHHs) were infected with JFH1-HCV. LPCAT1 depletion was achieved by RNA interference. Cells were monitored for LPCAT1 expression, lipid metabolism and HCV production and infectivity. The density of viral particles was assessed by isopycnic ultracentrifugation.ResultsUpon HCV infection, both Huh-7.5.1 cells and PHH had decreased levels of LPCAT1 transcript and protein, consistent with transcriptional downregulation. LPCAT1 depletion in either naive or infected Huh-7.5.1 cells resulted in altered lipid metabolism characterised by LD remodelling, increased triacylglycerol storage and increased secretion of VLDL. In infected Huh-7.5.1 cells or PHH, LPCAT1 depletion increased production of the viral particles of lowest density and highest infectivity.ConclusionsWe have identified LPCAT1 as a modulator of liver lipid metabolism downregulated by HCV, which appears as a viral strategy to increase the triacylglycerol content and hence infectivity of viral particles. Targeting this metabolic pathway may represent an attractive therapeutic approach to reduce both the viral titre and hepatic steatosis.
The impact of postexercise essential amino acid ingestion on the ubiquitin proteasome and autophagosomal-lysosomal systems in skeletal muscle of older men
Authors: Dickinson Jared M. , Reidy Paul T. , Gundermann David M. , Borack Michael S. , Walker Dillon K. , D’Lugos Andrew C. , Volpi Elena , Rasmussen Blake B. 
Published: September 2016

Essential amino acid (EAA) ingestion enhances postexercise muscle protein synthesis, and, in particular, the anabolic response of older adults appears sensitive to the quantity of ingested leucine. The effect of leucine ingestion on muscle breakdown following resistance exercise (RE) is less understood. The purpose of this study was to identify the impact of postexercise leucine ingestion on the ubiquitin proteasome and autophagosomal-lysosomal systems following acute RE in older men. Subjects (72 ± 2 yr) performed RE and 1 h postexercise ingested 10 g of EAA containing a leucine quantity similar to quality protein (control, 1.8 g leucine, n = 7) or enriched in leucine (leucine, 3.5 g leucine, n = 8). Stable isotope infusion and muscle biopsies (vastus lateralis) obtained at rest and 2, 5, and 24 h postexercise were used to examine protein content (Western blot), mRNA expression (RT-quantitative PCR), and muscle protein fractional breakdown rate (FBR). Muscle-specific RING finger 1 mRNA increased in both groups at 2 and 5 h ( P < 0.05). LC3 mRNA increased, and the LC3BII-to-LC3BI ratio decreased at all postexercise time points in control ( P < 0.05). Conversely, LC3 mRNA only increased at 2 h, and the LC3BII-to-LC3BI ratio only decreased at 2 and 5 h in leucine ( P < 0.05). Tumor necrosis factor receptor-associated factor-6 mRNA increased ( P < 0.05) in control at 5 h. FBR was not statistically different between groups or from basal 24 h postexercise ( P > 0.05). These data indicate that ingesting a larger quantity of leucine following RE may further reduce postexercise skeletal muscle autophagy in older men; however, it does not appear to influence the acute postexercise elevation in markers of the ubiquitin proteasome system or the breakdown of intact proteins. NEW & NOTEWORTHY The impact of postexercise leucine ingestion on processes of skeletal muscle breakdown in older adults is not well understood. Additional postexercise leucine ingestion appears to further reduce autophagy, but it does not interfere with the increase in ubiquitin proteasome system markers or the breakdown of intact proteins in skeletal muscle of older men. Postexercise leucine ingestion may promote a healthier protein pool and favorable muscle adaptations in older adults through greater accretion of myofibrillar proteins.
Molecular Pathways: Interleukin-35 in Autoimmunity and Cancer
Authors: Pylayeva-Gupta Yuliya 
Published: September 2016

AbstractImmunosuppressive functions conferred by regulatory cytokines are important for maintaining homeostasis in immune responses. IL35 has recently emerged as a novel regulator of immune responses. Once thought to be specifically expressed by T regulatory cells, induction of IL35 expression has now been detected in multiple cell types in a variety of diseases, prompting research into regulation of its expression, signaling specificity, target cell populations, and functional outputs. Recent studies have revealed that by directing de novo generation of regulatory T and B cells and inhibiting T effector responses, IL35 plays an important role in the development of autoimmune diseases and cancer. IL35 is overexpressed in a variety of cancers and may exert its function both on antitumor immune responses as well as directly on tumor cells. As such, IL35 is rapidly emerging as a promising biomarker and an attractive cancer therapy target. Clin Cancer Res; 22(20); 4973–8. ©2016 AACR.
Statistical Considerations in Evaluating a Biosimilar Product in an Oncology Clinical Study
Authors: He Kun , Chen Huanyu , Gwise Thomas , Casak Sandra , Lemery Steven , Keegan Patricia , Pazdur Richard , Sridhara Rajeshwari 
Published: September 2016

Abstract
The Biologics Price Competition and Innovation Act of 2009 (BPCI Act) established an abbreviated approval pathway for biosimilar and interchangeable biological products that was intended to balance innovation and consumer interests. The FDA has published several guidance documents to facilitate implementation of the BPCI Act. Here we discuss the role of comparative clinical studies in the assessment of clinically meaningful differences and illustrate the underlying scientific concepts with a hypothetical example of a clinical study comparing a product to US-licensed bevacizumab. Clin Cancer Res; 22(21); 5167–70. ©2016 AACR.
Autologous T Cells Expressing CD30 Chimeric Antigen Receptors for Relapsed or Refractory Hodgkin Lymphoma: An Open-Label Phase I Trial
Authors: Wang Chun-Meng , Wu Zhi-Qiang , Wang Yao , Guo Ye-Lei , Dai Han-Ren , Wang Xiao-Hui , Li Xiang , Zhang Ya-Jing , Zhang Wen-Ying , Chen Mei-Xia , Zhang Yan , Feng Kai-Chao , Liu Yang , Li Su-Xia , Yang Qing-Ming , Han Wei-Dong 
Published: September 2016

Abstract
Purpose: Relapsed or refractory Hodgkin lymphoma is a challenge for medical oncologists because of poor overall survival. We aimed to assess the feasibility, safety, and efficacy of CD30-targeting CAR T cells in patients with progressive relapsed or refractory Hodgkin lymphoma.
Experimental Design: Patients with relapsed or refractory Hodgkin lymphoma received a conditioning chemotherapy followed by the CART-30 cell infusion. The level of CAR transgenes in peripheral blood and biopsied tumor tissues was measured periodically according to an assigned protocol by quantitative PCR (qPCR).
Results: Eighteen patients were enrolled; most of whom had a heavy treatment history or multiple tumor lesions and received a mean of 1.56 × 107 CAR-positive T cell per kg (SD, 0.25; range, 1.1–2.1) in total during infusion. CART-30 cell infusion was tolerated, with grade ≥3 toxicities occurring only in two of 18 patients. Of 18 patients, seven achieved partial remission and six achieved stable disease. An inconsistent response of lymphoma was observed: lymph nodes presented a better response than extranodal lesions and the response of lung lesions seemed to be relatively poor. Lymphocyte recovery accompanied by an increase of circulating CAR T cells (peaking between 3 and 9 days after infusion) is a probable indictor of clinical response. Analysis of biopsied tissues by qPCR and immunohistochemistry revealed the trafficking of CAR T cells into the targeted sites and reduction of the expression of CD30 in tumors.
Conclusions: CART-30 cell therapy was safe, feasible, and efficient in relapsed or refractory lymphoma and guarantees a large-scale patient recruitment. Clin Cancer Res; 23(5); 1156–66. ©2016 AACR.
Macrophage Susceptibility to Emactuzumab (RG7155) Treatment
Authors: Pradel Leon P. , Ooi Chia-Huey , Romagnoli Solange , Cannarile Michael A. , Sade Hadassah , Rüttinger Dominik , Ries Carola H. 
Published: September 2016

Abstract
Blockade of colony-stimulating factor-1 receptor (CSF-1R) enables the therapeutic targeting of tumor-associated macrophages (TAM) in cancer patients. Various CSF-1R inhibitors, mAbs, and tyrosine kinase inhibitors are currently evaluated in early clinical trials. Presence of an alternative survival signal, such as GM-CSF, rescues human monocyte-derived macrophages from CSF-1R inhibitor–induced apoptosis. In this study, we sought to identify additional factors that mediate resistance to CSF-1R–blocking antibody RG7155 (emactuzumab). We investigated the impact of hypoxia, macrophage-polarizing cytokines IL4 and IL10, and genetic alterations within the CSF1R locus and mitochondrial DNA. Among all investigated factors, only IL4 completely rescued viability of RG7155-treated macrophages in vitro. This RG7155-resistant population was characterized by a substantially increased mannose receptor-1 (CD206) expression. Analysis of CD206 and the hemoglobin scavenger receptor CD163 expression on normal tissue allowed for discrimination of distinct macrophage populations according to localization and frequency. In emactuzumab-treated cancer patients, we found a significant reduction of CSF-1R, CD204, and CD163 mRNA levels in contrast to a less pronounced decrease of CD206 expression by transcriptome analysis of tumor biopsies. However, we detected in normal skin tissue, which shows lower IL4 mRNA expression compared with melanoma tissue, significant reduction of CD206+ dermal macrophages in RG7155-treated skin biopsies. These results suggest that in cancers where the cytokines IL4 and GM-CSF are sufficiently expressed to induce very high CD206 expression on macrophages, CSF-1R inhibition may not deplete CD206hi TAM. This observation can help to identify those patients most likely to benefit from CSF-1R–targeting agents. Mol Cancer Ther; 15(12); 3077–86. ©2016 AACR.
High-Throughput Testing of Novel–Novel Combination Therapies for Cancer: An Idea Whose Time Has Come
Authors: Scarlett Uciane K. , Chang Dennis C. , Murtagh Thomas J. , Flaherty Keith T. 
Published: September 2016

Abstract
Summary: Combination therapies are essential to address the genetic complexity, plasticity, and heterogeneity of tumors and to overcome resistance mechanisms that confound single-agent approaches, and are a paradigm that became well established in the era of conventional cytotoxic chemotherapies. Today, we are well equipped to address many of the scientific, clinical, and collaboration challenges that have existed historically; however, the pace of testing rational combinations is modest. Our analysis shows that the volume of clinical trials testing multiple investigational pipeline agents (“novel–novel” combinations) is dismally low, as out of approximately 1,500 phase I to III investigational combination trials initiated in 2014–2015, only 80 were for novel–novel combinations, and only 9 of those involved more than one company. The Collaborative Novel–Novel Combination Therapies (CoNNCT) initiative aims to alleviate this bottleneck by developing a new, faster paradigm for early investigation of scientifically informed, novel–novel drug combinations. The initiative kicked off on March 7, 2016, when representatives from top academic centers, biopharma, nonprofits, the FDA, and other groups gathered to define an actionable path forward. Cancer Discov; 6(9); 956–62. ©2016 AACR.
Propensity Score–Based Analysis of Percutaneous Closure Versus Medical Therapy in Patients With Cryptogenic Stroke and Patent Foramen Ovale
Authors: Pezzini Alessandro , Grassi Mario , Lodigiani Corrado , Patella Rosalba , Gandolfo Carlo , Zini Andrea , DeLodovici Maria Luisa , Paciaroni Maurizio , Del Sette Massimo , Toriello Antonella , Musolino Rossella , Calabrò Rocco Salvatore , Bovi Paolo , Adami Alessandro , Silvestrelli Giorgio , Sessa Maria , Cavallini Anna , Marcheselli Simona , Marco Bonifati Domenico , Checcarelli Nicoletta , Tancredi Lucia , Chiti Alberto , Del Zotto Elisabetta , Tomelleri Giampaolo , Spalloni Alessandra , Giorli Elisa , Costa Paolo , Giacalone Giacomo , Ferrazzi Paola , Poli Loris , Morotti Andrea , Piras Valeria , Rasura Maurizia , Simone Anna Maria , Gamba Massimo , Cerrato Paolo , Zedde Maria Luisa , Micieli Giuseppe , Melis Maurizio , Massucco Davide , Guido Davide , De Giuli Valeria , Bonaiti Silvia , D’Amore Cataldo , La Starza Sara , Iacoviello Licia , Padovani Alessandro 
Published: September 2016

Background—
We sought to compare the benefit of percutaneous closure to that of medical therapy alone for the secondary prevention of embolism in patients with patent foramen ovale (PFO) and otherwise unexplained ischemic stroke, in a propensity scored study.

Methods and Results—

Between 2000 and 2012, we selected consecutive first-ever ischemic stroke patients aged 18 to 45 years with PFO and no other cause of brain ischemia, as part of the IPSYS registry (Italian Project on Stroke in Young Adults), who underwent either percutaneous PFO closure or medical therapy for comparative analysis. Primary end point was a composite of ischemic stroke, transient ischemic attack, or peripheral embolism. Secondary end point was brain ischemia. Five hundred and twenty-one patients qualified for the analysis. The primary end point occurred in 15 patients treated with percutaneous PFO closure (7.3%) versus 33 patients medically treated (10.5%; hazard ratio, 0.72; 95% confidence interval, 0.39–1.32;
P
=0.285). The rates of the secondary end point brain ischemia were also similar in the 2 treatment groups (6.3% in the PFO closure group versus 10.2% in the medically treated group; hazard ratio, 0.64; 95% confidence interval, 0.33–1.21;
P
=0.168). Closure provided a benefit in patients aged 18 to 36 years (hazard ratio, 0.19; 95% confidence interval, 0.04–0.81;
P
=0.026) and in those with a substantial right-to-left shunt size (hazard ratio, 0.19; 95% confidence interval, 0.05–0.68;
P
=0.011).

Conclusions—
PFO closure seems as effective as medical therapy for secondary prevention of cryptogenic ischemic stroke. Whether device treatment might be more effective in selected cases, such as in patients younger than 37 years and in those with a substantial right-to-left shunt size, deserves further investigation.
Failure Mechanisms and Neoatherosclerosis Patterns in Very Late Drug-Eluting and Bare-Metal Stent Thrombosis
Authors: Nakamura Daisuke , Attizzani Guilherme F. , Toma Catalin , Sheth Tej , Wang Wei , Soud Mohamad , Aoun Reem , Tummala Ramyashree , Leygerman Milana , Fares Anas , Mehanna Emile , Nishino Setsu , Fung Anthony , Costa Marco A. , Bezerra Hiram G. 
Published: September 2016

Background—
There are few clinical studies on the pathophysiological mechanisms of very late stent thrombosis (VLST). We report optical coherence tomography findings in patients with VLST and compare the findings between bare-metal stents (BMS) and drug-eluting stents (DES).

Methods and Results—

We conducted a registry of stent thrombosis at 4 North American centers with optical coherence tomography imaging programs SAFE registry (The Study of Late Stent Failure Evaluated by OCT). Images were acquired in 61 patients (42 DES and 19 BMS) presenting with definite VLST. The median duration from implantation to VLST presentation was 51.4 months in the DES and 69.9 months in the BMS group (
P
=0.011). Uncovered and malapposed struts were observed in 70.5% (43/61) and 62.3% (38/61) of patients, respectively, whereas neoatherosclerosis was revealed in 49.2% (30/61). Stent underexpansion was observed in 42.4% of patients. Malapposed struts and stent underexpansion were more frequently demonstrated in DES than in BMS patients, whereas neoatherosclerosis was frequently observed in BMS (40.5% in DES and 68.4% in BMS;
P
=0.056). The percentage of frames with neoatherosclerosis was lower in DES than in BMS (15.56% [12.24–28.57] versus, 56.41% [40.74–70.00], respectively;
P
<0.001). Maximum consecutive lipid neointima length was shorter in DES than in BMS (2.4 [1.2–3.6] and 5.3 [3.0–7.0] mm;
P
=0.011).

Conclusions—
Optical coherence tomography imaging demonstrated that VLST in DES and BMS had a wide variety of abnormal findings, such as neoatherosclerosis, uncovered strut, and malapposed strut. Neoatherosclerosis and lipid neointima were more frequently observed and had more longitudinal extension in BMS compared with DES.