bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Examination of Repeated Self-Mobilizations With Movement and Joint Mobilizations on Individuals With Chronic Ankle Instability
Authors: Burton Connor A. , Arthur Robert J. , Rivera Matthew J. , Powden Cameron J. 
Published: October 2020

Context: Chronic ankle instability (CAI) is one of the most common chronic conditions in the world, resulting in millions of dollars contributed to the health care system. Joint mobilizations have been shown to effectively improve patient and disease-specific impairments secondary to CAI. The ability for patients to complete an effective manual therapy intervention without the need for continuous visits to a health care provider can alleviate burdens on the health care system and improve patient satisfaction. Objective: To examine the effect of clinician-applied Maitland talocrural joint mobilization and self-mobilization (Self-Mob) on dorsiflexion range of motion (DFROM), dynamic balance, strength, and perceived function in those with CAI. Design: Single-blind randomized trial. Setting: Research laboratory. Participants: A total of 18 participants (7 males and 11 females; age = 20.78 [2.02] y, height = 67.66 [3.83] cm, limb length = 87.74 [5.05] cm) with self-reported CAI participated. Interventions: The participants received 6 interventions over a 2-week period. The participants received either Maitland grade III anterior-to-posterior talocrural joint mobilizations or weight-bearing lunge Self-Mob. Each intervention consisted of four 2-minute sets, with a 1-minute rest between sets. Main Outcome Measures: The DFROM (weight-bearing lunge), dynamic balance (Y-Balance Test), isometric strength, Foot and Ankle Ability Measure Quick, Disablement of the Physically Active modified, Fear Avoidance Beliefs Questionnaire, and Tampa Scale of Kinesiophobia-11 were measured preintervention and postintervention. Results: Dynamic balance, isometric strength, and perceived function significantly improved in both groups at postintervention. The DFROM significantly improved in the Self-Mob group. Higher individual responder rates were demonstrated within the Self-Mob group compared with clinician-applied mobilizations. Conclusions: Clinician-applied mobilizations and Self-Mobs are effective interventions for improving dynamic balance, isometric strength, and perceived function. Application of Self-Mobs can effectively improve DFROM compared with joint mobilization. Self-Mobs may be an effective intervention to incorporate into a home care plan.
Challenges in clinical trials for children and young people
Authors: Lagler Florian B , Hirschfeld Steven , Kindblom Jenny M 
Published: October 2020

There is a well-known knowledge gap regarding the efficacy and safety of medicines in children of all ages and children are often treated with medicines off-label. Children are thus deprived of treatment based on the same quality of information that guides treatment in adults. The knowledge gap regarding efficacy and safety of medicines in children has been acknowledged by authorities and is reflected in legislation both in North America and in the European Union. Recent reports on the effects of legislation indicates that paediatric clinical trials remain a challenge.
Paediatric clinical trials are needed in the entire developmental age spectrum and are especially needed in certain therapy areas. Paediatric clinical trials have special features compared with trials in adults, and these need to be taken into account. These special features include scientific issues related to small samples and heterogeneity, the consent/assent procedure, the need for age-appropriate study information, specific outcomes and safety issues related to development and maturation. Competence in paediatric clinical trials is required in both designing, planning, co-ordinating and organising paediatric clinical trials, as well as research infrastructure and networks to increase power and disseminate information and expert advice. Strengthening of paediatric clinical research is essential to facilitate generating the data that will let children enjoy new medical advances in a similar manner as adults.
Efficacy of intravitreal AFlibercept injection For Improvement of retinal Nonperfusion In diabeTic retinopathY (AFFINITY study)
Authors: Kim Yoon Jeon , Yeo Joon Hyung , Son Gisung , Kang Hyojoo , Sung Yu Sub , Lee Joo Yong , Kim June-Gone , Yoon Young Hee 
Published: October 2020

IntroductionTo evaluate the effects of intravitreal aflibercept injection on retinal nonperfusion in patients with diabetic retinopathy (DR) using ultrawide field (UWF) fluorescein angiography (FA).Research design and methodsThirty-eight eyes of 38 consecutive patients with DR and substantial retinal nonperfusion (nonperfusion index (NPI): nonperfused/total gradable area >0.2) without macular edema were included in this prospective case series. Monthly injections of 2 mg aflibercept were given for 6 months. UWF-fundus photography and UWF-FA images were acquired at baseline, 6 months, and 12 months and evaluated by 2 masked, independent graders for the extent of retinal nonperfusion and vascular leakage. Twenty untreated fellow eyes were analyzed as controls.ResultsInter-grader agreement was strong (r=0.875) for NPI measurements. NPI was 0.46±0.10 at baseline; NPI was decreased to 0.43±0.08 (p=0.015) after 6 monthly injections of aflibercept and then slightly increased to 0.44±0.09 (p=0.123) after 6 months of observation. Vascular leakage also significantly decreased by 21.0% at 6 months (p=0.010). Untreated fellow eyes did not show significant changes in NPI and vascular leakage during follow-up. Reduction in retinal nonperfusion was associated with severe nonproliferative diabetic retinopathy (NPDR) (vs PDR, OR 19.119, p=0.025) and higher leakage index (per 0.1, OR 15.152, p=0.020).ConclusionsIntensive aflibercept treatment was effective in reducing retinal capillary nonperfusion in patients with DR without macular edema. Severe NPDR and profound vascular leakage were significantly associated with retinal reperfusion after aflibercept treatment.Trial registration numberNCT03006081.
Exposure to traffic-related particle matter and effects on lung function and potential interactions in a cross-sectional analysis of a cohort study in west Sweden
Authors: Carlsen Hanne Krage , Nyberg Fredrik , Torén Kjell , Segersson David , Olin Anna-Carin 
Published: October 2020

ObjectivesTo investigate the long-term effects of source-specific particle matter (PM) on lung function, effects of Surfactant Protein A (SP-A) and glutathione S-transferase (GST) genes GSTP1 and GSTT1 gene variants and effect modification by single-nucleotide polymorphism (SNP) genotype.DesignCohort study with address-based annual PM exposure assigned from annual estimates of size (PM10, PM2.5 and PMBC) and source-specific (traffic, industry, marine traffic and wood burning) dispersion modelling.SettingGothenburg, Sweden.ParticipantsThe ADult-Onset asthma and NItric oXide Study had 6685 participants recruited from the general population, of which 5216 (78%) were included in the current study with information on all variables of interest. Mean age at the time of enrolment was 51.4 years (range 24–76) and 2427 (46.5%) were men.Primary and secondary outcome measuresThe primary outcome was forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). Secondary outcome measures were effects and gene–environment interactions of SP-A and GSTT1 and GSTP1 genotypes.ResultsExposure to traffic-related PM10 and PM2.5 was associated with decreases in percent-predicted (% predicted) FEV1 by −0.48% (95% CI −0.89% to −0.07%) and −0.47% (95% CI −0.88% to −0.07%) per IQR 3.05 and 2.47 µg/m3, respectively, and with decreases in % predicted FVC by −0.46% (95% CI −0.83% to −0.08%) and −0.47% (95% CI −0.83% to −0.10%). Total and traffic-related PMBC was strongly associated with both FEV1 and FVC by −0.53 (95% CI −0.94 to −0.13%) and −0.43% (95% CI −0.77 to −0.09%) per IQR, respectively, for FVC, and similarly for FEV1. Minor allele carrier status for two GSTP1 SNPs and the GSTT1 null genotype were associated with decreases in % predicted lung function. Three SP-A SNPs showed effect modification with exposure to PM2.5 from industry and marine traffic.ConclusionsPM exposure, specifically traffic related, was associated with FVC and FEV1 reductions and not modified by genotype. Genetic effect modification was suggested for industry and marine traffic PM2.5.
Group-based intervention to improve developmental status among children age 6–18 months in rural Shanxi province, China: a study protocol for a cluster randomised controlled trial
Authors: Xu Mengxue , Liu Aihua , Zhao Chunxia , Fang Hai , Huang Xiaona , Berman Stephen , Guan Hongyan 
Published: October 2020

IntroductionEarly childhood development (ECD) is a critical component for building the foundation of future physical and emotional health and subsequent academic success. The quality of the home environment to promote development is an important factor in ECD. Since large rural–urban disparities in the home environment exist in China, there is a critical need to develop and evaluate interventions to promote ECD in rural areas. Individual center-based or home-based interventions dominate the current ECD programmes in rural China. However, group-based interventions offer potential advantages in terms of both effectiveness and cost. Thus, we aim to: (1) evaluate the effectiveness of an integrated group-based intervention, the Care Group Intervention, in enhancing ECD among children age 6–18 months and (2) conduct a cost-effectiveness analysis.Methods and analysisThe Care Group Intervention uses a cluster (by township) randomised controlled trial conducted in Fenxi county, Shanxi province, China, from July 2019, for 1 year. The intervention focuses on five key components of nurturing care including good health, adequate nutrition, responsive caregiving, security and safety, and opportunities for early learning. The intervention comprises small groups of 3–10 children within a certain age range and their primary caregivers that are led by well-trained local facilitators. Outcomes includes infants’ developmental quotient (Bayley Scales of Infant Development III, Ages & Stages Questionnaire: Social–Emotional, second edition); anaemia (HemoCue Hb 301+); nurturing environment (Infant/Toddler Home Observation for Measurement of the Environment), parent-child interaction (Teaching Scale) and caregiver depression (Center for Epidemiological Studies Depression). Cost data are collected throughout the entire study to carry out a cost-effectiveness analysis.Ethics and disseminationThis study was approved by the Ethical Committee of Capital Institute of Pediatrics, Beijing, China on 10 July 2018 (SHERLL2018014). Findings and results from this project will be disseminated via publications and presentations.Trial registration numberChinese Clinical Trials Registry: ChiCTR1900022894. Registered on 30 April 2019.
Impact of expanding smoke-free policies beyond enclosed public places and workplaces on children’s tobacco smoke exposure and respiratory health: protocol for a systematic review and meta-analysis
Authors: Radó Márta K , Mölenberg Famke JM , Sheikh Aziz , Millett Christopher , Bramer Wichor M , Burdorf Alex , van Lenthe Frank J , Been Jasper V 
Published: October 2020

IntroductionTobacco smoke exposure (TSE) has considerable adverse respiratory health impact among children. Smoke-free policies covering enclosed public places are known to reduce child TSE and benefit child health. An increasing number of jurisdictions are now expanding smoke-free policies to also cover outdoor areas and/or (semi)private spaces (indoor and/or outdoor). We aim to systematically review the evidence on the impact of these ‘novel smoke-free policies’ on children’s TSE and respiratory health.Methods and analysis13 electronic databases will be searched by two independent reviewers for eligible studies. We will consult experts from the field and hand-search references and citations to identify additional published and unpublished studies. Study designs recommended by the Cochrane Effective Practice and Organisation of Care (EPOC) group are eligible, without restrictions on the observational period, publication date or language. Our primary outcomes are: self-reported or parental-reported TSE in places covered by the policy; unplanned hospital attendance for wheezing/asthma and unplanned hospital attendance for respiratory infections. We will assess risk of bias of individual studies following the EPOC or Risk Of Bias In Non-randomised Studies of Interventions tool, as appropriate. We will conduct separate random effects meta-analyses for smoke-free policies covering (1) indoor private places, (2) indoor semiprivate places, (3) outdoor (semi)private places and (4) outdoor public places. We will assess whether the policies were associated with changes in TSE in other locations (eg, displacement). Subgroup analyses will be conducted based on country income classification (ie, high, middle or low income) and by socioeconomic status. Sensitivity analyses will be undertaken via broadening our study design eligibility criteria (ie, including non-EPOC designs) or via excluding studies with a high risk of bias. This review will inform policymakers regarding the implementation of extended smoke-free policies to safeguard children’s health.Ethics and disseminationEthical approval is not required. Findings will be disseminated to academics and the general public.PROSPERO registration numberCRD42020190563.
Baseline BMI and BMI variation during first line pembrolizumab in NSCLC patients with a PD-L1 expression ≥ 50%: a multicenter study with external validation
Authors: Cortellini Alessio , Ricciuti Biagio , Tiseo Marcello , Bria Emilio , Banna Giuseppe L , Aerts Joachim GJV , Barbieri Fausto , Giusti Raffaele , Cortinovis Diego L , Migliorino Maria R , Catino Annamaria , Passiglia Francesco , Torniai Mariangela , Morabito Alessandro , Genova Carlo , Mazzoni Francesca , Di Noia Vincenzo , Signorelli Diego , Gelibter Alain , Occhipinti Mario Alberto , Rastelli Francesca , Chiari Rita , Rocco Danilo , Inno Alessandro , De Tursi Michele , Di Marino Pietro , Mansueto Giovanni , Zoratto Federica , Grossi Francesco , Filetti Marco , Pizzutilo Pamela , Russano Marco , Citarella Fabrizio , Cantini Luca , Targato Giada , Nigro Olga , Ferrara Miriam G , Buti Sebastiano , Scodes Simona , Landi Lorenza , Guaitoli Giorgia , Della Gravara Luigi , Tabbò Fabrizio , Ricciardi Serena , De Toma Alessandro , Friedlaender Alex , Petrelli Fausto , Addeo Alfredo , Porzio Giampiero , Ficorella Corrado 
Published: October 2020

BackgroundThe association between obesity and outcomes in patients receiving programmed death-1/programmed death ligand-1 (PD-L1) checkpoint inhibitors has already been confirmed in pre-treated non-small cell lung cancer (NSCLC) patients, regardless of PD-L1 tumor expression.MethodsWe present the outcomes analysis according to baseline body mass index (BMI) and BMI variation in a large cohort of metastatic NSCLC patients with a PD-L1 expression ≥50%, receiving first line pembrolizumab. We also evaluated a control cohort of metastatic NSCLC patients treated with first line platinum-based chemotherapy. Normal weight was set as control group.Results962 patients and 426 patients were included in the pembrolizumab and chemotherapy cohorts, respectively. Obese patients had a significantly higher objective response rate (ORR) (OR=1.61 (95% CI: 1.04–2.50)) in the pembrolizumab cohort, while overweight patients had a significantly lower ORR (OR=0.59 (95% CI: 0.37–0.92)) within the chemotherapy cohort. Obese patients had a significantly longer progression-free survival (PFS) (HR=0.61 (95% CI: 0.45–0.82)) in the pembrolizumab cohort. Conversely, they had a significantly shorter PFS in the chemotherapy cohort (HR=1.27 (95% CI: 1.01–1.60)). Obese patients had a significantly longer overall survival (OS) within the pembrolizumab cohort (HR=0.70 (95% CI: 0.49–0.99)), while no significant differences according to baseline BMI were found in the chemotherapy cohort. BMI variation significantly affected ORR, PFS and OS in both the pembrolizumab and the chemotherapy cohorts.ConclusionsBaseline obesity is associated to significantly improved ORR, PFS and OS in metastatic NSCLC patients with a PD-L1 expression of ≥50%, receiving first line pembrolizumab, but not among patients treated with chemotherapy. BMI variation is also significantly related to clinical outcomes.
Why boundary conditions do not generally determine the universality class for boundary critical behavior
Authors: Diehl Hans Werner 
Published: October 2020

Abstract
Interacting field theories for systems with a free surface frequently exhibit distinct universality classes of boundary critical behaviors depending on gross surface properties. The boundary condition satisfied by the continuum field theory on some scale may or may not be decisive for the universality class that applies. In many recent papers on boundary field theories, it is taken for granted that Dirichlet or Neumann boundary conditions decide whether the ordinary or special boundary universality class is observed. While true in a certain sense for the Dirichlet boundary condition, this is not the case for the Neumann boundary condition. Building on results that have been worked out in the 1980s, but have not always been appropriately appreciated in the literature, the subtle role of boundary conditions and their scale dependence is elucidated and the question of whether or not they determine the observed boundary universality class is discussed.

Graphical abstract
One-loop corrections to the two-body decays of the neutral Higgs bosons in the complex NMSSM
Authors: Baglio Julien , Dao Thi Nhung , Mühlleitner Margarete 
Published: October 2020

AbstractSince no direct signs of new physics have been observed so far indirect searches in the Higgs sector have become increasingly important. With the discovered Higgs boson behaving very standard model (SM)-like, however, indirect new physics manifestations are in general expected to be small. On the theory side, this makes precision predictions for the Higgs parameters and observables indispensable. In this paper, we provide in the framework of the CP-violating next-to-minimal supersymmetric extension of the SM (NMSSM) the complete next-to-leading order (SUSY-)electroweak corrections to the neutral Higgs boson decays that are on-shell and non-loop induced. We also investigate possible gauge-dependence issues in the decays of light Higgs bosons into fermion pairs. Together with the also provided SUSY-QCD corrections to colored final states, the newly calculated SUSY-electroweak corrections are implemented in the Fortran code which already includes the state-of-the art QCD corrections. The new code is called . This way we provide the NMSSM Higgs boson decays and branching ratios at presently highest possible precision and thereby contribute to the endeavor of searching for New Physics at present and future colliders.
NRF2 Activation Promotes Aggressive Lung Cancer and Associates with Poor Clinical Outcomes
Authors: Singh Anju , Daemen Anneleen , Nickles Dorothee , Jeon Sang-Min , Foreman Oded , Sudini Kuladeep , Gnad Florian , Lajoie Stephane , Gour Naina , Mitzner Wayne , Chatterjee Samit , Choi Eun-Ji , Ravishankar Buvana , Rappaport Amy , Patil Namrata , McCleland Mark , Johnson Leisa , Acquaah-Mensah George , Gabrielson Edward , Biswal Shyam , Hatzivassiliou Georgia 
Published: October 2020

Abstract

Purpose:
Stabilization of the transcription factor NRF2 through genomic alterations in KEAP1 and NFE2L2 occurs in a quarter of patients with lung adenocarcinoma and a third of patients with lung squamous cell carcinoma. In lung adenocarcinoma, KEAP1 loss often co-occurs with STK11 loss and KRAS-activating alterations. Despite its prevalence, the impact of NRF2 activation on tumor progression and patient outcomes is not fully defined.

Experimental Design:
We model NRF2 activation, STK11 loss, and KRAS activation in vivo using novel genetically engineered mouse models. Furthermore, we derive a NRF2 activation signature from human non–small cell lung tumors that we use to dissect how these genomic events impact outcomes and immune contexture of participants in the OAK and IMpower131 immunotherapy trials.

Results:
Our in vivo data reveal roles for NRF2 activation in (i) promoting rapid-onset, multifocal intrabronchiolar carcinomas, leading to lethal pulmonary dysfunction, and (ii) decreasing elevated redox stress in KRAS-mutant, STK11-null tumors. In patients with nonsquamous tumors, the NRF2 signature is negatively prognostic independently of STK11 loss. Patients with lung squamous cell carcinoma with low NRF2 signature survive longer when receiving anti–PD-L1 treatment.

Conclusions:
Our in vivo modeling establishes NRF2 activation as a critical oncogenic driver, cooperating with STK11 loss and KRAS activation to promote aggressive lung adenocarcinoma. In patients, oncogenic events alter the tumor immune contexture, possibly having an impact on treatment responses. Importantly, patients with NRF2-activated nonsquamous or squamous tumors have poor prognosis and show limited response to anti–PD-L1 treatment.
Dual Screen for Efficacy and Toxicity Identifies HDAC Inhibitor with Distinctive Activity Spectrum for BAP1-Mutant Uveal Melanoma
Authors: Kuznetsoff Jeffim N. , Owens Dawn A. , Lopez Andy , Rodriguez Daniel A. , Chee Nancy T. , Kurtenbach Stefan , Bilbao Daniel , Roberts Evan R. , Volmar Claude-Henry , Wahlestedt Claes , Brothers Shaun P. , Harbour J. William 
Published: October 2020

Abstract

Drug screens leading to successful targeted therapies in cancer have been mainly based on cell viability assays identifying inhibitors of dominantly acting oncogenes. In contrast, there has been little success in discovering targeted therapies that reverse the effects of inactivating mutations in tumor-suppressor genes. BAP1 is one such tumor suppressor that is frequently inactivated in a variety of cancers, including uveal melanoma, renal cell carcinoma, and mesothelioma. Because BAP1 is an epigenetic transcriptional regulator of developmental genes, we designed a two-phase drug screen involving a cell-based rescue screen of transcriptional repression caused by BAP1 loss, followed by an in vivo screen of lead compounds for rescue of a BAP1-deficient phenotype with minimal toxicity in Xenopus embryos. The first screen identified 9 compounds, 8 of which were HDAC inhibitors. The second screen eliminated all except one compound due to inefficacy or toxicity. The resulting lead compound, quisinostat, has a distinctive activity spectrum, including high potency against HDAC4, which was recently shown to be a key target of BAP1. Quisinostat was further validated in a mouse model and found to prevent the growth of BAP1-mutant uveal melanomas. This innovative strategy demonstrates the potential for identifying therapeutic compounds that target tumor-suppressor mutations in cancer.

Implications:
Few drugs have been identified that target mutations in tumor suppressors. Using a novel 2-step screening approach, strategy, we identified quisinostat as a candidate for therapy in BAP1-mutant uveal melanoma. HDAC4 is implicated as a key target in uveal melanoma and perhaps other BAP1-mutant cancers.