bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations between active travel and diet: cross-sectional evidence on healthy, low-carbon behaviours from UK Biobank
Authors: Smith Michaela A , Boehnke Jan Rasmus , Graham Hilary , White Piran C L , Prady Stephanie L 
Published: September 2019

ObjectivesTo examine whether there are associations between active travel and markers of a healthy, low-carbon (HLC) diet (increased consumption of fruit and vegetables (FV), reduced consumption of red and processed meat (RPM)).DesignCross-sectional analysis of a cohort study.SettingsPopulation cohort of over 500 000 people recruited from 22 centres across the UK. Participants aged between 40 and 69 years were recruited between 2006 and 2010.Participants412 299 adults with complete data on travel mode use, consumption of FV and RPM, and sociodemographic covariates were included in the analysis.Exposure measuresMutually exclusive mode or mode combinations of travel (car, public transport, walking, cycling) for non-work and commuting journeys.Outcome measuresConsumption of FV measured as portions per day and RPM measured as frequency per week.ResultsEngaging in all types of active travel was positively associated with higher FV consumption and negatively associated with more frequent RPM consumption. Cycling exclusively or in combination with walking was most strongly associated with increased dietary consumption of FV and reduced consumption of RPM for both non-work and commuting journeys. Overall, the strongest associations were between non-work cycling and FV consumption (males: adjusted OR=2.18, 95% CI 2.06 to 2.30; females: adjusted OR=2.50, 95% CI 2.31 to 2.71) and non-work cycling and RPM consumption (males: adjusted OR=0.57, 95% CI 0.54 to 0.60; females: adjusted OR=0.54, 95% CI 0.50 to 0.59). Associations were generally similar for both commuting and non-work travel, and were robust to adjustment with sociodemographic and behavioural factors.ConclusionsThere are strong associations between engaging in active travel, particularly cycling, and HLC dietary consumption, suggesting that these HLC behaviours are related. Further research is needed to better understand the drivers and dynamics between these behaviours within individuals, and whether they share common underlying causes.
Patient experience of treatment decision making for wet age-related macular degeneration disease: a qualitative study in China
Authors: Bian Wei , Wan Junli , Tan Mingqiong , Wu Xiaoqing , Su Jun , Wang Lihua 
Published: September 2019

ObjectivesThis study aimed to investigate the experience of patients with wet age-related macular degeneration (wAMD) in treatment decision-making process.DesignA descriptive qualitative study was designed by using semistructured interviews, and the data analysis was conducted with the thematic analysis approach.Participants and settingA convenient and purposive sample of 21 participants diagnosed with wAMD was recruited from May 2018 to September 2018. The study was conducted in the Eye Clinic of Southwest Hospital of Army Medical University in Chongqing located in the southwest of China.ResultsThe mean age of the participants was 64.48 years (ranging 50–81 years), and the duration of the disease ranged from 6 months to 48 months. Four major themes were identified from the original data analysis. These themes included facing the darkness (choosing from light and darkness and living in pain), constraints on decision making (doctor-oriented decision making, inadequacy of options and time), weighing alternatives (family influence, financial burden and maintaining social function) and decision-making support (professional decision-making assistance and peer support).ConclusionThis is a qualitative study attempting to explore the patient experience of treatment decision making for wAMD disease in China. Previous literature has focused on treatment effect and symptoms, rather than the individual experience and the wide contexts from a sociocultural perspective. Further studies, such as cross-sectional studies, can be used to describe the status and determine the influencing factors of decision0making process, so as to develop an impact factor model of decision making and to formulate an intervention for patients with wAMD.
Leg ischaemia management collaboration (LIMb): study protocol for a prospective cohort study at a single UK centre
Authors: Houghton John S M , Nduwayo Sarah , Nickinson Andrew T O , Payne Tanya J , Sterland Sue , Nath Mintu , Gray Laura J , McMahon Greg S , Rayt Harjeet S , Singh Sally J , Robinson Thompson G , Conroy Simon P , Haunton Victoria J , McCann Gerry P , Bown Matthew J , Davies Robert S M , Sayers Rob D 
Published: September 2019

IntroductionSevere limb ischaemia (SLI) is the end stage of peripheral arterial occlusive disease where the viability of the limb is threatened. Around 25% of patients with SLI will ultimately require a major lower limb amputation, which has a substantial adverse impact on quality of life. A newly established rapid-access vascular limb salvage clinic and modern revascularisation techniques may reduce amputation rate. The aim of this study was to investigate the 12-month amputation rate in a contemporary cohort of patients and compare this to a historical cohort. Secondary aims are to investigate the use of frailty and cognitive assessments, and cardiac MRI in risk-stratifying patients with SLI undergoing intervention and establish a biobank for future biomarker analyses.Methods and analysisThis single-centre prospective cohort study will recruit patients aged 18–110 years presenting with SLI. Those undergoing intervention will be eligible to undergo additional venepuncture (for biomarker analysis) and/or cardiac MRI. Those aged ≥65 years and undergoing intervention will also be eligible to undergo additional frailty and cognitive assessments. Follow-up will be at 12 and 24 months and subsequently via data linkage with NHS Digital to 10 years postrecruitment. Those undergoing cardiac MRI and/or frailty assessments will receive additional follow-up during the first 12 months to investigate for perioperative myocardial infarction and frailty-related outcomes, respectively. A sample size of 420 patients will be required to detect a 10% reduction in amputation rate in comparison to a similar sized historical cohort, with 90% power and 5% type I error rate. Statistical analysis of this comparison will be by adjusted and unadjusted logistic regression analyses.Ethics and disseminationEthical approval for this study has been granted by the UK National Research Ethics Service (19/LO/0132). Results will be disseminated to participants via scientific meetings, peer-reviewed medical journals and social media.Trial registration numberNCT04027244.
Living strategies for disability in men ageing with HIV in Ontario, Canada: a longitudinal qualitative study
Authors: Solomon Patricia , O'Brien Kelly K , McGuff Rebecca , Sankey Michelle 
Published: September 2019

ObjectivesTo examine the living strategies used by older men living with HIV to deal with the episodic nature of disability and associated uncertainty, over time.DesignQualitative longitudinal study in which men living with HIV were interviewed on four occasions over 20 months.SettingMen were recruited from HIV community organisations in Canada.Participants14 men with a median age of 57.5 years and median time since diagnosis of 21.5 years.ResultsFive themes depict the living strategies used to deal with the episodic nature of disability and uncertainty over time. Actively engaging in problem-solving by prioritising and modifying activities and avoiding stress, advocating for support, being positive and future oriented, engaging in healthy pursuits and providing social support to others helped men to mitigate their disability. By following participants over time, we were able to gather insights into triggers of episodes of disability, and perceptions of the success of implementing their living strategies and avoiding uncertainty.ConclusionsParticipants used living strategies to deal with uncertainty and mitigate episodes of disability over time. This study supports the importance of programmes that promote self-management for older men living with HIV through helping them identify triggers of disability, set realistic goals and problem-solve. These may help build self-efficacy, increase sense of control, and decrease feelings of uncertainty and episodes of disability.
Long-term efficacy and safety of secukinumab 150 mg in ankylosing spondylitis: 5-year results from the phase III MEASURE 1 extension study
Authors: Baraliakos Xenofon , Braun Juergen , Deodhar Atul , Poddubnyy Denis , Kivitz Alan , Tahir Hasan , Van den Bosch Filip , Delicha Evie-Maria , Talloczy Zsolt , Fierlinger Anke 
Published: September 2019

ObjectiveThis study aimed to report end-of-study results on efficacy and safety of secukinumab 150 mg through 5 years in patients with ankylosing spondylitis (AS; MEASURE 1 extension trial (NCT01863732)).MethodsAfter the 2-year core trial, 274 patients receiving subcutaneous secukinumab 150 or 75 mg (following intravenous loading or initial placebo treatment to 16/24 weeks) every 4 weeks were invited to enter the 3-year extension study. Dose escalation from 75 to 150 mg (approved dose) was allowed at or after week 156 based on the judgement of the treating physician. Assessments at week 260 (5 years) included Assessment of SpondyloArthritis international Society (ASAS) 20/40 and other efficacy outcomes. Data are presented as observed. Safety assessment included all patients who received ≥1 dose of study treatment.ResultsOf the 274 patients who entered the extension study, 84% (230/274) completed 5 years of treatment. ASAS20/40 responses were 78.6/65.2%, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 response was 63.4% and mean (±SD) BASDAI total score was 2.6±1.76 with secukinumab 150 mg at 5 years. Improvements in efficacy outcomes were sustained through 5 years. A total of 82 patients on secukinumab 75 mg (56.2%) had their dose escalated to 150 mg after week 168; ASAS40, ASAS-PR, ASAS 5/6 and BASDAI50 responses were improved in patients whose dose was escalated from secukinumab 75 to 150 mg. Secukinumab was well tolerated with a safety profile consistent over the course of the study.ConclusionsSecukinumab 150 mg provided sustained efficacy across multiple domains of AS with a favourable and consistent safety profile through 5-year treatment. Over 50% of patients required dose escalation from 75 to 150 mg and efficacy improved in these patients.
Optimal Sparsification for Some Binary CSPs Using Low-Degree Polynomials
Authors: Jansen Bart M. P. , Pieterse Astrid 
Published: September 2019

This article analyzes to what extent it is possible to efficiently reduce the number of clauses in NP-hard satisfiability problems without changing the answer. Upper and lower bounds are established using the concept of kernelization. Existing results show that if NP ⊈ coNP/poly, no efficient preprocessing algorithm can reduce
n
-variable instances of
cnf-sat
with
d
literals per clause to equivalent instances with
O
(
n

d
−ε

) bits for any ε > 0. For the N
ot
-A
ll
-E
qual sat
problem, a compression to size
Õ
(
n

d
−1

) exists. We put these results in a common framework by analyzing the compressibility of CSPs with a binary domain. We characterize constraint types based on the minimum degree of multivariate polynomials whose roots correspond to the satisfying assignments, obtaining (nearly) matching upper and lower bounds in several settings. Our lower bounds show that not just the number of constraints, but also the encoding size of individual constraints plays an important role. For example, for E
xact
S
atisfiability
with unbounded clause length it is possible to efficiently reduce the number of constraints to
n
+1, yet no polynomial-time algorithm can reduce to an equivalent instance with
O
(
n
2−ε
) bits for any ε > 0, unless NP ⊆ coNP/poly.
Integrated Pan-Cancer Map of EBV-Associated Neoplasms Reveals Functional Host–Virus Interactions
Authors: Chakravorty Srishti , Yan Bingyu , Wang Chong , Wang Luopin , Quaid Joseph Taylor , Lin Chin Fang , Briggs Scott D. , Majumder Joydeb , Canaria D. Alejandro , Chauss Daniel , Chopra Gaurav , Olson Matthew R. , Zhao Bo , Afzali Behdad , Kazemian Majid 
Published: September 2019

Abstract

Epstein–Barr virus (EBV) is a complex oncogenic symbiont. The molecular mechanisms governing EBV carcinogenesis remain elusive and the functional interactions between virus and host cells are incompletely defined. Here we present a comprehensive map of the host cell–pathogen interactome in EBV-associated cancers. We systematically analyzed RNA sequencing from &gt;1,000 patients with 15 different cancer types, comparing virus and host factors of EBV+ to EBV− tissues. EBV preferentially integrated at highly accessible regions of the cancer genome, with significant enrichment in super-enhancer architecture. Twelve EBV transcripts, including LMP1 and LMP2, correlated inversely with EBV reactivation signature. Overexpression of these genes significantly suppressed viral reactivation, consistent with a “virostatic” function. In cancer samples, hundreds of novel frequent missense and nonsense variations in virostatic genes were identified, and variant genes failed to regulate their viral and cellular targets in cancer. For example, one-third of patients with EBV+ NK/T-cell lymphoma carried two novel nonsense variants (Q322X, G342X) of LMP1 and both variant proteins failed to restrict viral reactivation, confirming loss of virostatic function. Host cell transcriptional changes in response to EBV infection classified tumors into two molecular subtypes based on patterns of IFN signature genes and immune checkpoint markers, such as PD-L1 and IDO1. Overall, these findings uncover novel points of interaction between a common oncovirus and the human genome and identify novel regulatory nodes and druggable targets for individualized EBV and cancer-specific therapies.

Significance:
This study provides a comprehensive map of the host cell-pathogen interactome in EBV+ malignancies.
See related commentary by Mbulaiteye and Prokunina-Olsson, p. 5917
TP53 Pathway Alterations Drive Radioresistance in Diffuse Intrinsic Pontine Gliomas (DIPG)
Authors: Werbrouck Coralie , Evangelista Cláudia C.S. , Lobón-Iglesias María-Jesús , Barret Emilie , Le Teuff Gwénaël , Merlevede Jane , Brusini Romain , Kergrohen Thomas , Mondini Michele , Bolle Stéphanie , Varlet Pascale , Beccaria Kevin , Boddaert Nathalie , Puget Stéphanie , Grill Jacques , Debily Marie-Anne , Castel David 
Published: September 2019

Abstract

Purpose:
Diffuse intrinsic pontine gliomas (DIPG) are the most severe pediatric brain tumors. Although accepted as the standard therapeutic, radiotherapy is only efficient transiently and not even in every patient. The goal of the study was to identify the underlying molecular determinants of response to radiotherapy in DIPG.

Experimental Design:
We assessed in vitro response to ionizing radiations in 13 different DIPG cellular models derived from treatment-naïve stereotactic biopsies reflecting the genotype variability encountered in patients at diagnosis and correlated it to their principal molecular alterations. Clinical and radiologic response to radiotherapy of a large cohort of 73 DIPG was analyzed according to their genotype. Using a kinome-wide synthetic lethality RNAi screen, we further identified target genes that can sensitize DIPG cells to ionizing radiations.

Results:
We uncover TP53 mutation as the main driver of increased radioresistance and validated this finding in four isogenic pairs of TP53WT DIPG cells with or without TP53 knockdown. In an integrated clinical, radiological, and molecular study, we show that TP53MUT DIPG patients respond less to irradiation, relapse earlier after radiotherapy, and have a worse prognosis than their TP53WT counterparts. Finally, a kinome-wide synthetic lethality RNAi screen identifies CHK1 as a potential target, whose inhibition increases response to radiation specifically in TP53MUT cells.

Conclusions:
Here, we demonstrate that TP53 mutations are driving DIPG radioresistance both in patients and corresponding cellular models. We suggest alternative treatment strategies to mitigate radioresistance with CHK1 inhibitors. These findings will allow to consequently refine radiotherapy schedules in DIPG.
Phase I Study of a CD45-Targeted Antibody–Radionuclide Conjugate for High-Risk Lymphoma
Authors: Cassaday Ryan D. , Press Oliver W. , Pagel John M. , Rajendran Joseph G. , Gooley Ted A. , Fisher Darrell R. , Holmberg Leona A. , Miyaoka Robert S. , Sandmaier Brenda M. , Green Damian J. , Gopal Ajay K. 
Published: September 2019

Abstract

Purpose:
External-beam radiation is the single most effective therapy for localized lymphoma. However, toxicity limits its use for multifocal disease. We evaluated CD45 as a therapeutic target for an antibody–radionuclide conjugate (ARC) for the treatment of lymphoma based on its ubiquitous expression, infrequent antigen loss or blockade, and the ability to target minimal disease based on panhematopoietic expression.

Patients and Methods:
We performed a phase I trial of escalating doses of single-agent CD45-targeted ARC based on per-patient dosimetry using the BC8 antibody labeled with iodine-131 (131I) followed by autologous stem cell support in adults with relapsed, refractory, or high-risk B-cell non-Hodgkin lymphoma (B-NHL), T-cell NHL (T-NHL), or Hodgkin lymphoma. The primary objective was to estimate the maximum tolerated radiation absorbed dose.

Results:
Sixteen patients were enrolled: 7 patients had B-NHL, 6 had Hodgkin lymphoma, and 3 had T-NHL. Median number of prior therapies was three (range: 2–12). Absorbed doses up to 32 Gy to liver were delivered. No dose-limiting toxicities occurred. Nonhematologic toxicity was infrequent and manageable. Objective responses were seen across histologies. Fourteen patients had measurable disease at enrollment, 57% of whom achieved complete remission (CR), including all 3 with T-NHL. Three patients with B-NHL treated among the highest dose levels (26–32 Gy) remain in CR without subsequent therapy 35–41 months later.

Conclusions:
CD45-targeted ARC therapy is well-tolerated at doses up to at least 32 Gy to the liver. Objective responses and long-term remissions were observed in patients with relapsed/refractory lymphoma. These data validate continued evaluation of anti-CD45 ARCs in lymphoma.
Tobacco Treatment Program Implementation at NCI Cancer Centers: Progress of the NCI Cancer Moonshot-Funded Cancer Center Cessation Initiative
Authors: D'Angelo Heather , Rolland Betsy , Adsit Robert , Baker Timothy B. , Rosenblum Marika , Pauk Danielle , Morgan Glen D. , Fiore Michael C. 
Published: September 2019

Abstract
Quitting smoking leads to improved outcomes for patients with cancer, yet too few patients receive cessation services during their oncology healthcare visits. The National Cancer Institute (NCI) dedicated Cancer Moonshot funding for NCI-Designated Cancer Centers to develop a population-based approach to reach all patients who smoke with tobacco treatment services. As a result, the Cancer Center Cessation Initiative (C3I) offers an unparalleled opportunity to identify effective implementation strategies and barriers to delivering tobacco treatment services across multiple clinical oncology settings. Over one year after receiving funding, the first cohort of C3I funded Centers demonstrated progress in hiring tobacco treatment specialists, adding new tobacco treatment programs, and integrating EHR-based tobacco treatment referrals. However, tobacco treatment program reach remains low in some settings, even using a broad definition of patient engagement. Centers identified implementation challenges related to staff training needs, devising new clinical workflows, and engagement of IT leadership. Understanding implementation challenges may help other clinical oncology settings effectively implement tobacco treatment programs, leading to improved cancer outcomes by helping patients quit smoking.
Association Between Use of Primary-Prevention Implantable Cardioverter-Defibrillators and Mortality in Patients With Heart Failure
Authors: Schrage Benedikt , Uijl Alicia , Benson Lina , Westermann Dirk , Ståhlberg Marcus , Stolfo Davide , Dahlström Ulf , Linde Cecilia , Braunschweig Frieder , Savarese Gianluigi 
Published: September 2019

Background:
Most randomized trials on implantable cardioverter-defibrillator (ICD) use for primary prevention of sudden cardiac death in heart failure with reduced ejection fraction enrolled patients >20 years ago. We investigated the association between ICD use and all-cause mortality in a contemporary heart failure with reduced ejection fraction cohort and examined relevant subgroups.

Methods:
Patients from the Swedish Heart Failure Registry fulfilling the European Society of Cardiology criteria for primary-prevention ICD were included. The association between ICD use and 1-year and 5-year all-cause and cardiovascular (CV) mortality was assessed by Cox regression models in a 1:1 propensity score–matched cohort and in prespecified subgroups.

Results:
Of 16 702 eligible patients, only 1599 (10%) had an ICD. After matching, 1305 ICD recipients were compared with 1305 nonrecipients. ICD use was associated with a reduction in all-cause mortality risk within 1 year (hazard ratio, 0.73 [95% CI, 0.60–0.90]) and 5 years (hazard ratio, 0.88 [95% CI, 0.78–0.99]). Results were consistent in all subgroups including patients with versus without ischemic heart disease, men versus women, those aged <75 versus ≥75 years, those with earlier versus later enrollment in the Swedish heart failure registry, and patients with versus without cardiac resynchronization therapy.

Conclusions:
In a contemporary heart failure with reduced ejection fraction population, ICD for primary prevention was underused, although it was associated with reduced short- and long-term all-cause mortality. This association was consistent across all the investigated subgroups. These results call for better implementation of ICD therapy.
The Respect for Fundamental Human Rights in the Fight against Human Trafficking and Migrant Smuggling across the Central Mediterranean Sea
Authors: Salvadego Laura 
Published: September 2019

AbstractThis study analyzes counter-smuggling and counter-trafficking operations carried out in the Mediterranean, mainly focusing on the EU operations Sophia and Themis. The purpose is to assess a number of issues linked with naval operations from a human rights perspective. These issues include the applicable law, the exercise of criminal jurisdiction over smugglers and traffickers, national strategies of coastal States as regards migration control policy and, finally, international responsibility for human rights violations perpetrated in connection with these operations. Although the study is primarily aimed at both Ph.D students and legal scholars specialized in the field, it also seeks to provide insights that may be of guidance to NGOs, legal practitioners and legislators within the EU and its Member States.
Common method bias in applied settings: The dilemma of researching in organizations
Authors: Jordan Peter J , Troth Ashlea C 
Published: September 2019

Authors are experiencing increasing competition for their articles to be published. One way of ensuring their work is given the best chance of being published is to underpin their research with rigorous methods that are characterized by robustness, accuracy and reliability. A common factor that can stymie research rigour is common method bias. Our aim in this article is to outline the nature of, concerns about and examine reasons why researchers still conduct studies that are susceptible to common method bias. We also provide some solutions for avoiding or managing common method bias concerns. In doing this, we acknowledge the substantial work that has been produced on this topic to date and, therefore, focus our contribution specifically on issues that affect research in applied and managerial settings. JEL Classification: C90, D23