bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developing Social Skills of Children With Autism Spectrum Disorder for Physical Activity Using a Movement-Based Program
Authors: Lee Jihyun , Chang Seung Ho , Jolin Jerred 
Published: November 2020

The motor and social skill difficulties experienced by many children with autism spectrum disorder (ASD) can create challenges when participating in age appropriate physical activity contexts. Although behavioral interventions can increase the general social communicative skills of children with ASD, often the skills targeted are not relevant to physical activity contexts. Thus, this pilot study utilized a movement-based intervention program to support children with ASD in learning both social and movement skills that are relevant to physical activity contexts. Nineteen children with ASD with a mean age of 9.3 (±3.0) years participated in this program for 8 weeks, twice a week, at a recreation center as an afterschool activity. Six object control skills were selected and tested before and after the intervention because these gross motor skills were considered to elicit human interactions and place demands on social skills. Ten social skills were selected, aligned to each program context, taught, and evaluated. This intervention resulted in significant improvements in object-control skills for the participants. Additionally, there were significantly more participants who demonstrated improvements in their performance of the target social skills than who did not demonstrate improvements. These preliminary findings provide support for the feasibility of developing interventions that address social skill deficits in the context of physically active settings for children with ASD.
Rituximab in childhood steroid-sensitive nephrotic syndrome: are multiple subsequent courses safe and effective?
Authors: Subun Chantida , Suwannahitatorn Picha , Webb Hazel , Tullus Kjell 
Published: November 2020

IntroductionIdiopathic nephrotic syndrome is the most common glomerular disease in children. The majority of patients respond well to steroids. However, the relapse rate is high and many develop steroid dependency. Although other immunosuppressive medicines are successfully used as steroid-sparing agents, some children still have frequent relapsing episodes. Rituximab (RTX), a chimeric anti-CD20 monoclonal antibody, has shown to be effective in treating difficult frequently relapsing/steroid-dependent nephrotic syndrome (FR/SDNS). Data on the effectiveness and long-term treatment outcomes of repeated courses of RTX are, however, scarce.Material and methodsChildren and young people with FR/SDNS, aged 1–18 years, who received RTX at Great Ormond Street Hospital (GOSH) from 2006 to 2018 were reviewed.ResultsDuring these 12 years, 103 children with FR/SDNS received RTX infusions at GOSH. Among these, 58 cases needed repeated courses of RTX: 2, 3, 4, 5, 6 and 7 repeated courses were given to 21, 21, 7, 5, 1 and 3 patients, respectively. The overall median time to relapse post-RTX was 11 months (range 1–53 months). There was no change in relapse-free interval with subsequent courses of RTX. No difference was found between age groups, genders and ethnicities. No severe side effects were noted.ConclusionsRTX seems to be safe even after several repeated courses. However, long-term follow-up and further studies are needed, with a focus on side-effects in particular.
Protocol for a systematic review on the methodological and reporting quality of prediction model studies using machine learning techniques
Authors: Andaur Navarro Constanza L , Damen Johanna A A G , Takada Toshihiko , Nijman Steven W J , Dhiman Paula , Ma Jie , Collins Gary S , Bajpai Ram , Riley Richard D , Moons Karel GM , Hooft Lotty 
Published: November 2020

IntroductionStudies addressing the development and/or validation of diagnostic and prognostic prediction models are abundant in most clinical domains. Systematic reviews have shown that the methodological and reporting quality of prediction model studies is suboptimal. Due to the increasing availability of larger, routinely collected and complex medical data, and the rising application of Artificial Intelligence (AI) or machine learning (ML) techniques, the number of prediction model studies is expected to increase even further. Prediction models developed using AI or ML techniques are often labelled as a ‘black box’ and little is known about their methodological and reporting quality. Therefore, this comprehensive systematic review aims to evaluate the reporting quality, the methodological conduct, and the risk of bias of prediction model studies that applied ML techniques for model development and/or validation.Methods and analysisA search will be performed in PubMed to identify studies developing and/or validating prediction models using any ML methodology and across all medical fields. Studies will be included if they were published between January 2018 and December 2019, predict patient-related outcomes, use any study design or data source, and available in English. Screening of search results and data extraction from included articles will be performed by two independent reviewers. The primary outcomes of this systematic review are: (1) the adherence of ML-based prediction model studies to the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD), and (2) the risk of bias in such studies as assessed using the Prediction model Risk Of Bias ASsessment Tool (PROBAST). A narrative synthesis will be conducted for all included studies. Findings will be stratified by study type, medical field and prevalent ML methods, and will inform necessary extensions or updates of TRIPOD and PROBAST to better address prediction model studies that used AI or ML techniques.Ethics and disseminationEthical approval is not required for this study because only available published data will be analysed. Findings will be disseminated through peer-reviewed publications and scientific conferences.Systematic review registrationPROSPERO, CRD42019161764.
Technology and implementation science to forge the future of evidence-based psychotherapies: the PRIDE scale-up study
Authors: Wainberg Milton L , Gouveia Maria Lídia , Stockton Melissa Ann , Feliciano Paulino , Suleman Antonio , Mootz Jennifer J. , Mello Milena , Fiks Salem Andre , Greene M. Claire , Bezuidenhout Charl , Ngwepe Phuti , Lovero Kathryn L , Fortunato dos Santos Palmira , Schriger Simone H. , Mandell David S. , Mulumba Rogerio , Neves Anube Anibal , Mabunda Dirceu , Mandlate Flavio , Cournos Francine , Alves-Bradford Jean-Marie , Nicholson Terriann , Kann Bianca , Fumo Wilza , Duarte Cristiane S , de Jesus Mari Jair , Mello Marcelo F. , Mocumbi Ana O , Oquendo Maria A , Weissman Myrna M 
Published: November 2020

ObjectiveTo report the interim results from the training of providers inevidence-based psychotherapies (EBPs) and use of mobile applications.Design and SettingThe Partnerships in Research to Implement and Disseminate Sustainable and Scalable Evidence (PRIDE) study is a cluster-randomised hybrid effectiveness-implementation trial comparing three delivery pathways for integrating comprehensive mental healthcare into primary care in Mozambique. Innovations include the use of EBPs and scaling-up of task-shifted mental health services using mobile applications.Main outcome measuresWe examined EBP training attendance, certification, knowledge and intentions to deliver each component. We collected qualitative data through rapid ethnography and focus groups. We tracked the use of the mobile applications to investigate early reach of a valid screening tool (Electronic Mental Wellness Tool) and the roll out of the EBPsParticipantsPsychiatric technicians and primary care providers trained in the EBPs.ResultsPRIDE has trained 110 EBP providers, supervisors and trainers and will train 279 community health workers in upcoming months. The trainings improved knowledge about the EBPs and trainees indicated strong intentions to deliver the EBP core components. Trained providers began using the mobile applications and appear to identify cases and provide appropriate treatment.ConclusionsThe future of EBPs requires implementation within existing systems of care with fidelity to their core evidence-based components. To sustainably address the vast mental health treatment gap globally, EBP implementation demands: expanding the mental health workforce by training existing human resources; sequential use of EBPs to comprehensively treat mental disorders and their comorbid presentations and leveraging digital screening and treatment applications.
Are we addressing the top 10 research priorities in IBD?
Authors: Geldof Jeroen , LeBlanc Jean-Frédéric , Lucaciu Laura , Segal Jonathan , Lees Charlie W , Hart Ailsa 
Published: November 2020

BackgroundSince publication of the top 10 research priorities in inflammatory bowel disease (IBD) based on the James Lind Alliance Priority Setting Partnership, the question remains whether this has influenced the IBD-research landscape. This study aimed to create an overview of the current distribution of research interests of trials in the UK.MethodsThe ClinicalTrials.gov database and European Union Clinical Trials Register were screened for clinical trials set up from 9 August 2016 to 16 November 2019 in the UK involving adult patients with IBD.ResultsOf 20 non-industry-sponsored studies, a quarter investigated treatment strategies considering efficacy, safety and cost-effectiveness (priority 1). Four evaluated the role of diet (priorities 3 and 7). Development/assessment of biomarkers for patient stratification (priority 2) and fatigue (priority 8) were subject of three studies. IBD-related pain and control of diarrhoea/incontinence were each subject of 2 studies (priorities 4 and 6). The effect of gut microbiota (priority 10) and optimal strategy for perianal Crohn’s disease (priority 5) was the focus of 2 studies each. One study evaluated surgery for terminal ileal Crohn’s disease (priority 9). Of 63 industry-sponsored studies, 59 focused on priority 1.ConclusionsThis study presents an impression of the breadth of the IBD-research landscape in the UK, in light of the top 10 research priorities published in 2016. Optimal treatment strategy has been the most studied research priority by academic and industry-sponsored trials. Fewer studies focused on patient-reported outcomes. It remains debatable to what extent the current research landscape adequately represents all stakeholders’ viewpoints on needs for expanded knowledge in IBD, particularly the patients’ perspective.
Menthol cigarette use in substance use disorder treatment before and after implementation of a county-wide flavoured tobacco ban
Authors: Guydish Joseph R , Straus Elana R , Le Thao , Gubner Noah , Delucchi Kevin L 
Published: November 2020

IntroductionThis study examined the impact of a San Francisco City and County ban on all flavoured tobacco products, including menthol cigarettes, among clients in residential substance use disorder (SUD) treatment.MethodsWe conducted cross-sectional surveys of clients at two residential SUD programmes before the County began enforcing the ban (n=160) and twice after enforcement began (n=102, n=120). The samples were compared on demographic characteristics, smoking status, smoking behaviours and the proportion reporting menthol as their usual cigarette. Menthol smokers were asked whether they smoked only menthol cigarettes, mostly menthol, both menthol and non-menthol or mostly non-menthol. Post-ban samples were asked about awareness of the ban and access to menthol cigarettes.ResultsIn multivariate analyses, we found no evidence that the ban was associated with decreased number of cigarettes per day or increased readiness to quit among current smokers. However, odds were lower post-ban for reporting menthol as the usual cigarette (OR=0.80, 95% CI 0.72 to 0.90), and for smoking only menthol cigarettes (OR=0.19, 95% CI 0.18 to 0.19). Perhaps most importantly, and with the ability to influence all other findings, 50% of self-identified menthol smokers reported purchasing menthol cigarettes in San Francisco nearly 1 year after the ban was implemented.ConclusionIn subgroups where smoking has remained elevated, like those receiving SUD treatment, local menthol bans may have only modest impacts on smoking behaviour. Broader regional, state or national bans, that effectively restrict access to menthol products, may be needed to show stronger effects on smoking behaviour.
Ethanol and cyclophosphamide induce similar nephrotoxic effects: possible role for Nox4 and superoxide
Authors: Sousa Arthur H. , do Vale Gabriel T. , da Silva Carla B.P. , Awata Wanessa M.C. , Pinheiro Lucas C. , Tirapelli Carlos R. 
Published: November 2020

We tested the hypothesis that ethanol consumption would aggravate the renal damage induced by cyclophosphamide (CYP). Male C57BL/6 J mice from control (n = 8) and CYP (n = 12) groups had free access to filtered water and standard rodent chow for 12 weeks. Then, 24 h before euthanasia mice received an intraperitoneal injection of saline or CYP (300 mg/kg). Mice from ethanol (n = 8) and CYP + ethanol (n = 12) groups had free access to increasing doses of ethanol for 12 weeks. Twenty-four hours before euthanasia, mice from ethanol and CYP + ethanol groups received an intraperitoneal injection of saline or CYP, respectively. Ethanol, CYP, or the association of both drugs augmented serum levels of creatinine and increased the levels of superoxide ([Formula: see text]) generation and thiobarbituric acid reactive substances in the renal cortex. Upregulation of Nox4 and increased activity of superoxide dismutase were detected in the renal cortex of mice treated with ethanol, CYP, or the combination of these drugs; however, these molecular alterations induced by CYP were not potentiated by ethanol consumption. Our findings revealed that chronic ethanol consumption had no potentiating effect on the nephrotoxic effects displayed by CYP. It is possible that the combination of these drugs showed no synergistic effect because they share the same molecular mechanisms of renal toxicity.
Lepton dark matter portal in the inert Zee model
Authors: Gaviria Alexandra , Longas Robinson , Rivera Andrés 
Published: November 2020

The inert Zee model is an extension of the Zee model for neutrino masses. This new model explains the dark matter relic abundance, generates a one-loop neutrino masses and forbids tree-level Higgs-mediated flavor changing neutral currents. Although the dark matter phenomenology of the model is similar to that of the inert doublet model, the presence of new vector-like fermions opens the lepton portal as a new dark matter annihilation channel. We study the impact of this new portal in the low-mass regime and show the parameter space allowed by direct and indirect searches of dark matter. Remarkably, the region for [Formula: see text] GeV is recovered for [Formula: see text]. We also show that future experiments like LZ and DARWIN could probe a large region of the parameter space of the model.
In well-differentiated primary human bronchial epithelial cells, TGF-β1 and TGF-β2 induce expression of furin
Authors: O’Sullivan Michael J. , Mitchel Jennifer A. , Mwase Chimwemwe , McGill Maureen , Kanki Phyllis , Park Jin-Ah 
Published: November 2020

The COVID-19 pandemic is an ongoing threat to public health. Since the identification of COVID-19, the disease caused by SARS-CoV-2, no drugs have been developed to specifically target SARS-CoV-2. To develop effective and safe treatment options, a better understanding of cellular mechanisms underlying SARS-CoV-2 infection is required. To fill this knowledge gap, researchers require reliable experimental systems that express the host factor proteins necessary for the cellular entry of SARS-CoV-2. These proteins include the viral receptor, angiotensin-converting enzyme 2 (ACE2), and the proteases, transmembrane serine protease 2 (TMPRSS2) and furin. A number of studies have reported cell-type-specific expression of the genes encoding these molecules. However, less is known about the protein expression of these molecules. We assessed the suitability of primary human bronchial epithelial (HBE) cells maintained in an air-liquid interface (ALI) as an experimental system for studying SARS-CoV-2 infection in vitro. During cellular differentiation, we measured the expression of ACE2, TMPRSS2, and furin over progressive ALI days by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blot, and immunofluorescence staining. We also explored the effect of the fibrotic cytokine TGF-β on the expression of these proteins in well-differentiated HBE cells. Like ACE2, TMPRSS2 and furin proteins are localized in differentiated ciliated cells, as confirmed by immunofluorescence staining. These data suggest that well-differentiated HBE cells maintained in ALI are a reliable in vitro system for investigating cellular mechanisms of SARS-CoV-2 infection. We further identified that the profibrotic mediators, TGF-β1 and TGF-β2, increase the expression of furin, which is a protease required for the cellular entry of SARS-CoV-2.
Circulating Tumor Cells and Biomarker Modulation with Olaratumab Monotherapy Followed by Olaratumab plus Doxorubicin: Phase Ib Study in Patients with Soft-Tissue Sarcoma
Authors: Martín-Broto Javier , Pousa Antonio López , Brohl Andrew S. , Van Tine Brian A. , Powers Benjamin , Stacchiotti Silvia , Blay Jean-Yves , Hu James S. , Oakley Gerard J. , Wang Hong , Szpurka Anna M. , Levy Donna E. , Mo Gary , Ceccarelli Matteo , Jones Robin L. 
Published: November 2020

Abstract
This phase Ib study enumerated whole blood circulating tumor cells (CTC) and evaluated biomarkers in patients with potentially resectable soft-tissue sarcoma (STS) treated with olaratumab monotherapy (20 mg/kg) for one cycle followed by up to six cycles of olaratumab (20 mg/kg, cycles 1–2; 15 mg/kg, cycles 3–7) plus doxorubicin (75 mg/m2 on day 1). CTCs, platelet-derived growth factor receptors (PDGFR), and PDGF ligand expression in tumor tissue pre- and post-olaratumab monotherapy were evaluated. Antitumor activity, safety, pharmacokinetics, and PET/biomarker association with clinical outcome were assessed. Of 51 treated patients, 35, 43, and 37 were evaluable for CTC enumeration, PDGFRs, and PDGF ligand expression, respectively. An increase in CTCs at cycle 1 day 8 was observed, followed by a significant reduction by cycle 3 day 1 or 30-day follow-up. Decrease in CTC counts after olaratumab monotherapy was higher in patients with disease control than without disease control (57.9% vs. 31.2%). Baseline IHC expression was positive in most patients for PDGFRα [n = 31 (72.1%)] and PDGFRβ [n = 36 (83.7%)]. Similar rates were observed post-olaratumab monotherapy [PDGFRα, n = 30 (69.8%); PDGFRβ, n = 33 (76.7%)]. Eleven patients (29.7%) showed a 30% reduction by RT-PCR in PDGFRα at cycle 2. PDGFR expression and PET response showed no correlation with clinical outcome. Safety and pharmacokinetic profiles were consistent with previous reports. This study, the first to use a validated method for CTC detection, confirms that CTC enumeration in STS is feasible. However, no correlation was observed between PDGFRα expression and clinical outcome.
Antibody Co-Administration Can Improve Systemic and Local Distribution of Antibody–Drug Conjugates to IncreaseIn VivoEfficacy
Authors: Ponte Jose F. , Lanieri Leanne , Khera Eshita , Laleau Rassol , Ab Olga , Espelin Christopher , Kohli Neeraj , Matin Bahar , Setiady Yulius , Miller Michael L. , Keating Thomas A. , Chari Ravi , Pinkas Jan , Gregory Richard , Thurber Greg M. 
Published: November 2020

AbstractSeveral antibody–drug conjugates (ADC) showing strong clinical responses in solid tumors target high expression antigens (HER2, TROP2, Nectin-4, and folate receptor alpha/FRα). Highly expressed tumor antigens often have significant low-level expression in normal tissues, resulting in the potential for target-mediated drug disposition (TMDD) and increased clearance. However, ADCs often do not cross-react with normal tissue in animal models used to test efficacy (typically mice), and the impact of ADC binding to normal tissue antigens on tumor response remains unclear. An antibody that cross-reacts with human and murine FRα was generated and tested in an animal model where the antibody/ADC bind both human tumor FRα and mouse FRα in normal tissue. Previous work has demonstrated that a “carrier” dose of unconjugated antibody can improve the tumor penetration of ADCs with high expression target-antigens. A carrier dose was employed to study the impact on cross-reactive ADC clearance, distribution, and efficacy. Co-administration of unconjugated anti-FRα antibody with the ADC-improved efficacy, even in low expression models where co-administration normally lowers efficacy. By reducing target-antigen–mediated clearance in normal tissue, the co-administered antibody increased systemic exposure, improved tumor tissue penetration, reduced target-antigen–mediated uptake in normal tissue, and increased ADC efficacy. However, payload potency and tumor antigen saturation are also critical to efficacy, as shown with reduced efficacy using too high of a carrier dose. The judicious use of higher antibody doses, either through lower DAR or carrier doses, can improve the therapeutic window by increasing efficacy while lowering target-mediated toxicity in normal tissue.
Development of New‐Onset or Progressive Atrial Fibrillation in Patients With Permanent HIS Bundle Pacing Versus Right Ventricular Pacing: Results From the RUSH HBP Registry
Authors: Ravi Venkatesh , Beer Dominik , Pietrasik Grzegorz M. , Hanifin Jillian L. , Ooms Sara , Ayub Muhammad Talha , Larsen Timothy , Huang Henry D. , Krishnan Kousik , Trohman Richard G. , Vijayaraman Pugazhendhi , Sharma Parikshit S. 
Published: November 2020

Background
Conventional right ventricular pacing (RVP) has been associated with an increased incidence of atrial fibrillation (AF). We sought to compare the occurrence of new‐onset AF and assessed AF disease progression during long‐term follow‐up between His bundle pacing (HBP) and RVP.

Methods and Results

We included patients undergoing initial dual‐chamber pacemaker implants at Rush University Medical Center between January 1, 2016, and June 30, 2019. A total of 360 patients were evaluated, and 225 patients (HBP, n=105; RVP, n=120) were included in the study. Among the 148 patients (HBP, n=72; RVP, n=76) with no history of AF, HBP demonstrated a lower risk of new‐onset AF (adjusted hazard ratio [HR], 0.53; 95% CI, 0.28–0.99;
P
=0.046) compared with traditional RVP. This benefit was observed with His or RVP burden exceeding 20% (HR, 0.29; 95% CI, 0.13–0.64;
P
=0.002), ≥40% (HR, 0.31;
P
=0.007), ≥60% (HR, 0.35;
P
=0.015), and ≥80% (HR, 0.40;
P
=0.038). There was no difference with His or RV pacing burden <20% (HR, 0.613; 95% CI, 0.213–1.864;
P
=0.404). In patients with a prior history of AF, there was no difference in AF progression (
P
=0.715); however, in a subgroup of patients with a pacing burden ≥40%, HBP demonstrated a trend toward a lower risk of AF progression (HR, 0.19; 95% CI, 0.03–1.16;
P
=0.072).

Conclusions
HBP demonstrated a lower risk of new‐onset AF compared with RVP, which was primarily observed at a higher pacing burden.