bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protocol of a cluster randomised controlled trial evaluating the effectiveness of an online parenting intervention for promoting oral health of 2–6 years old Australian children
Authors: Tadakamadla Santosh Kumar , Rathore Vatsna , Mitchell Amy E , Johnson Newell , Morawska Alina 
Published: October 2022

IntroductionDental decay is a major problem among Australian children. It can be prevented through good self-care and limiting sugar intake, but many parents/caregivers lack the skills and confidence to help their children adopt these practices. This trial will evaluate the efficacy ofHealthy Habits Triple P - Oral health,a web-based online programme, in improving children’s oral health-related behaviours (toothbrushing, snacking practices and dental visits) and related parenting practices, thereby preventing dental caries.Methods and analysisThis is a cluster, parallel-group, single-blinded, randomised controlled trial of an online intervention for parents/caregivers of children aged 2–6 years. From the City of Gold Coast (Australia), 18 childcare centres will be randomly selected, with equal numbers randomised into intervention and control arms. Intervention arm parents/caregivers will receive access to a web-based parenting intervention while those in the control arm will be directed to oral health-related information published by Australian oral health agencies. After the completion of the study, theHealthy Habits Triple P - Oral healthintervention will be offered to parents/caregivers in the control arm. The primary outcome of this trial is toothbrushing frequency, which will be assessed via Bluetooth supported smart toothbrushes and parent/caregiver report. Data on other outcomes: parenting practices and child behaviour during toothbrushing, consumption of sugar rich foods and parents’ confidence in dealing with children’s demands for sugar rich food, and dental visiting practices, will be collected through a self-administered questionnaire at baseline (before randomisation), and 6 weeks (primary endpoint), 6 months and 12 months after randomisation. Data on dental caries will be collected at baseline, 12 and 18 months post-randomisation.Ethics and disseminationEthical approval has been obtained from Human Research Ethics Committees of Griffith University (2020/700) and the University of Queensland (2020002839). Findings will be submitted for publication in leading international peer-reviewed journals.Trial registration numberACTRN12621000566831.
Real-time automatic quantification of left ventricular function by hand-held ultrasound devices in patients with suspected heart failure: a feasibility study of a diagnostic test with data from general practitioners, nurses and cardiologists
Authors: Hjorth-Hansen Anna Katarina , Magelssen Malgorzata Izabela , Andersen Garrett Newton , Graven Torbjørn , Kleinau Jens Olaf , Landstad Bodil , Løvstakken Lasse , Skjetne Kyrre , Mjølstad Ole Christian , Dalen Havard 
Published: October 2022

ObjectivesTo evaluate the feasibility and reliability of hand-held ultrasound (HUD) examinations with real-time automatic decision-making software for ejection fraction (autoEF) and mitral annular plane systolic excursion (autoMAPSE) by novices (general practitioners), intermediate users (registered cardiac nurses) and expert users (cardiologists), respectively, compared to reference echocardiography by cardiologists in an outpatient cohort with suspected heart failure (HF).DesignFeasibility study of a diagnostic test.Setting and participants166 patients with suspected HF underwent HUD examinations with autoEF and autoMAPSE measurements by five novices, three intermediate-skilled users and five experts. HUD results were compared with a reference echocardiography by experts. A blinded cardiologist scored all HUD recordings with automatic measurements as (1) discard, (2) accept, but adjust the measurement or (3) accept the measurement as it is.Primary outcome measureThe feasibility of automatic decision-making software for quantification of left ventricular function.ResultsThe users were able to run autoEF and autoMAPSE in most patients. The feasibility for obtaining accepted images (score of ≥2) with automatic measurements ranged from 50% to 91%. The feasibility was lowest for novices and highest for experts for both autoEF and autoMAPSE (p≤0.001). Large coefficients of variation and wide coefficients of repeatability indicate moderate agreement. The corresponding intraclass correlations (ICC) were moderate to good (ICC 0.51–0.85) for intra-rater and poor (ICC 0.35–0.51) for inter-rater analyses. The findings of modest to poor agreement and reliability were not explained by the experience of the users alone.ConclusionNovices, intermediate and expert users were able to record four-chamber views for automatic assessment of autoEF and autoMAPSE using HUD devices. The modest feasibility, agreement and reliability suggest this should not be implemented into clinical practice without further refinement and clinical evaluation.Trial registration numberNCT03547076.
HIV testing uptake and determinants among adolescents and young people in Burundi: a cross-sectional analysis of the Demographic and Health Survey 2016–2017
Authors: Nshimirimana Clement , Vuylsteke Bea , Smekens Tom , Benova Lenka 
Published: October 2022

ObjectivesTo assess HIV testing uptake and its determinants among adolescents and young adults.DesignCross-sectional design involving analysis of 2016 Demographic and Health Survey data.SettingNationally representative survey of Burundi.ParticipantsA total of 7218 young women and 2860 young men were included.Primary and secondary outcomeWe estimated the proportion of adolescent (15–19 years) and young adult (20–24 years) women and men who had tested for HIV and received results in the 12 months preceding the survey. Multivariable logistic models for determining predictors of HIV testing uptake were fitted among respondents aged 15–24 regardless of sexual activity in the 12 months before the survey and separately among a subset that reporting having had sex in the 12 months preceding the survey.ResultsAn estimated 27.1% (95% CI 25.8% to 28.4%) women and 16.6% (95% CI 15.1% to 18.1%) men had tested for HIV and received results in the 12 months preceding the survey. The proportion was more than twice as high among those aged 20–24 years compared with 15–19 years, among both sexes. In multivariable analysis, older age (20–24 years) was associated with HIV testing (adjusted OR (aOR): 1.62, 95% CI 1.38 to 1.91) among women; (aOR: 1.78, 95% CI 1.32 to 2.40) among men. Higher educational level (aOR: 1.40, 95% CI 1.11 to 1.76) was significantly associated with HIV testing uptake among women. Male circumcision status, condom use, number of sex partners, history of STIs were not associated with HIV testing among the subset that reported having had sex in the 12 months preceding the survey.ConclusionDespite the interventions implemented to reach the 90-90-90 UNAIDS goals, HIV testing among youth in Burundi was low. Youth-friendly health centres should be part of strategies to stimulate young people to increase uptake of HIV preventive services in Burundi.
Prevalence of polypharmacy and associated adverse outcomes and risk factors among children with asthma in the USA: a cross-sectional study
Authors: Xie Luyu , Gelfand Andrew , Murphy Caitlin C , Mathew M Sunil , Atem Folefac , Delclos George L , Messiah Sarah 
Published: October 2022

ObjectiveTo estimate the prevalence of polypharmacy, identify risk factors and examine related adverse outcomes in the US children with asthma.Design, setting and participantsThis population-based, cross-sectional study included 1776 children with asthma from the 2011–2020 National Health and Nutrition Examination Surveys.ExposuresPolypharmacy is defined as taking ≥2 medications concurrently for ≥1 day over the past 30 days.Main outcomes and measures(1) Weighted prevalence estimates of polypharmacy in children with asthma; (2) asthma attacks and emergency department (ED) visits.ResultsThe estimated prevalence of polypharmacy in the US children with asthma was 33.49% (95% CI 31.81% to 35.17%). 15.53% (95% CI 14.31% to 16.75%), 12.63% (95% CI 11.37% to 13.88%) and 5.33% (95% CI) of participants were taking 2, 3–4, and 5 prescription medications, respectively. In addition to asthma medications, the most common sources of polypharmacy included antihistamines (20.17%, 95% CI 16.07% to 24.28%), glucocorticoids (16.67%, 95% 12.57% to 20.78%), and anti-infectives (14.28%, 95% CI 10.29 to 18.28). Risk factors for the increased number of medications included age 5–11 years old (vs 1–4 years: adjusted incidence rate ratio (aIRR) 1.38, 95% CI 1.10 to 1.72), fair-to-poor health (vs excellent or very good: aIRR 1.42, 95% CI 1.05 to 1.92), or ≥6 healthcare utilisation encounters over the last year (vs 0–5 encounters: aIRR 1.45, 95% CI 1.26 to 1.66). Polypharmacy increased the odds of an asthma attack (adjusted OR (aOR) 2.80, 95% CI 1.99 to 3.93) and ED visit (aOR 2.41, 95%1.59–3.63) after adjusting for demographics, insurance and health status.ConclusionsEvery one in three US children with asthma experienced polypharmacy. Although it may reflect the treatment guidelines that various asthma medications are needed for maintenance therapy, our results suggested that polypharmacy increased the odds of asthma attacks or ED visits. This may be due to the concurrent use with other non-asthma medications indicating that there is an opportunity to improve medication management in children with asthma.
Monoaminergic network abnormalities: a marker for multiple sclerosis-related fatigue and depression
Authors: Carotenuto Antonio , Valsasina Paola , Preziosa Paolo , Mistri Damiano , Filippi Massimo , Rocca Maria A 
Published: October 2022

ObjectiveTo investigate monoaminergic network abnormalities in patients with multiple sclerosis (MS) according to their fatigue and depressive status through a positron emission tomography (PET)-based constrained independent component analysis (ICA) on resting state (RS) functional MRI (fMRI).MethodsIn this prospective study, 213 patients with MS (mean age=40.6±12.5 years; 94/119 men/women; 153 relapsing-remitting; 60 progressive) and 62 healthy controls (HCs, mean age=39.0±10.4 years; 30/32 men/women) underwent neurological, fatigue, depression and RS fMRI assessment. Patterns of dopamine, norepinephrine-related and serotonin-related RS functional connectivity (FC) were derived by ICA, constrained to PET atlases for dopamine, norepinephrine and serotonin transporters, obtained in HCs’ brain.ResultsCompared with HCs, patients with MS showed abnormalities in all three explored monoaminergic networks, mostly with decreased RS FC within PET-guided monoaminergic networks in frontal regions and subcortical areas including the cerebellum and thalamus, and increased RS FC in temporo-parieto-occipital cortical areas, including bilateral precunei.MS-related fatigue was associated with decreased RS FC within the PET-guided dopamine network in the left thalamus and left cerebellum, and with increased RS FC within the PET-guided serotonin network in the left middle occipital gyrus. MS-related depression was associated with more distributed abnormalities involving the three explored monoaminergic networks, resulting in overall reduced RS FC in the frontal lobe, limbic areas and the precuneus.ConclusionsPatients with MS present diffuse dysregulation in the monoaminergic networks. Specific alterations in these networks were associated with fatigue and depression, providing a pathological marker for these bothersome symptoms and putative targets for their treatment.
Effect of Liraglutide on Serum TSH Levels in Patients with NAFLD and its Underlying Mechanisms
Authors: Ye JiaoJiao , Xu Jing , Wen WenJie , Huang Bin 
Published: October 2022

This study aimed to evaluate the effect of liraglutide on serum thyroid-stimulating hormone (TSH) levels in patients with type 2 diabetes mellitus (T2DM) and explore the underlying mechanisms via bioinformatics analysis. A total of 49 obese/overweight patients with T2DM received liraglutide during outpatient visits or hospitalization in the Department of Endocrinology. Meanwhile, the control group included 49 patients with T2DM but without nonalcoholic fatty liver disease (NAFLD) who were matched for age and sex (baseline from July 2016 to June 2021). Follow-up data on the last use of liraglutide were also retrieved. Age, sex, body mass index (BMI), and duration of diabetes were obtained from the participants’ records. All patients were tested for biochemical markers hemoglobin A1c (HbA1c), alanine transaminase, aspartate transaminase, free triiodothyronine, free thyroxine (FT4), and TSH at baseline and follow-up. After adjusting for all factors with a

p

-value < 0.05, BMI, HbA1c, LDL, FT4, and TSH were identified as significant independent risk factors for NAFLD in the univariate analysis. Following liraglutide therapy (average time 16 months), these patients had significantly lower BMI, HbA1c, and TSH but higher high-density lipoprotein (HDL) levels than those in the baseline data (all

p

< 0.05), and further subgroup analysis stratified by duration of liraglutide use showed that the test for time trends had statistical differences in BMI and TSH but not in HbA1c and HDL. After the therapy, the NAFLD and NASH groups showed significantly decreased TSH levels after liraglutide therapy compared with the corresponding baseline data. Furthermore, the expression of THRB, which encodes TRβ, was significantly decreased in the NAFLD group, which may explain the thyroid hormone resistance-like manifestation in the clinical findings. In conclusion, liraglutide improves hepatic thyroid hormone resistance in T2DM with NAFLD, and restoration of impaired TRβ expression in NAFLD is a potential mechanism involved in the process of liraglutide therapy.
Waterloo Handedness Questionnaire: Cross-Cultural Adaptation and Psychometric Properties of the Arabic Version
Authors: Aloraini Saleh M. 
Published: October 2022

Handedness is one of the most studied behavioural predictors of cerebral lateralization. Assessing handedness is often essential in neuropsychology and motor behaviour research. Thus, it is important that self-reported assessment tools for determining handedness are available in multiple languages for different cultures. The purpose of the present study was to conduct a translation and cross-cultural adaptation of the Waterloo Handedness Questionnaire into the Arabic language and to assess its psychometric properties. Two independent forward translations were performed by two native Arabic speakers and then synthesized into one version. The synthesized version was backtranslated into English by two independent bilingual translators. An expert committee was formed to review the translation and adaptation process. A final Arabic version of the WHQ was obtained, the WHQ-Ar. Two hundred and ninety adult Arabic speakers were recruited to participate in the study and investigate the properties of the WHQ-Ar. Results showed that the WHQ-Ar had no floor or ceiling effect. For construct validity, results of factor analysis revealed that the WHQ-Ar had two dimensions. Further, the WHQ-Ar had excellent internal consistency with

Cronbac

h

’

s

alpha
=
0.93

. For test-retest reliability, intraclass correlation coefficient score was 0.94. The Bland-Altman plot showed acceptable agreement between test and retest scores. Therefore, the WHQ-Ar is a valid, reliable tool and ready for use among the Arabic-speaking population for determining handedness.
A Sequential Targeting Strategy Interrupts AKT-Driven Subclone-Mediated Progression in Glioblastoma
Authors: Kebir Sied , Ullrich Vivien , Berger Pia , Dobersalske Celia , Langer Sarah , Rauschenbach Laurèl , Trageser Daniel , Till Andreas , Lorbeer Franziska K. , Wieland Anja , Wilhelm-Buchstab Timo , Ahmad Ashar , Fröhlich Holger , Cima Igor , Prasad Shruthi , Matschke Johann , Jendrossek Verena , Remke Marc , Grüner Barbara M. , Roesch Alexander , Siveke Jens T. , Herold-Mende Christel , Blau Tobias , Keyvani Kathy , van Landeghem Frank K.H. , Pietsch Torsten , Felsberg Jörg , Reifenberger Guido , Weller Michael , Sure Ulrich , Brüstle Oliver , Simon Matthias , Glas Martin , Scheffler Björn 
Published: October 2022

AbstractPurpose:Therapy resistance and fatal disease progression in glioblastoma are thought to result from the dynamics of intra-tumor heterogeneity. This study aimed at identifying and molecularly targeting tumor cells that can survive, adapt, and subclonally expand under primary therapy.Experimental Design:To identify candidate markers and to experimentally access dynamics of subclonal progression in glioblastoma, we established a discovery cohort of paired vital cell samples obtained before and after primary therapy. We further used two independent validation cohorts of paired clinical tissues to test our findings. Follow-up preclinical treatment strategies were evaluated in patient-derived xenografts.Results:We describe, in clinical samples, an archetype of rare ALDH1A1+ tumor cells that enrich and acquire AKT-mediated drug resistance in response to standard-of-care temozolomide (TMZ). Importantly, we observe that drug resistance of ALDH1A1+ cells is not intrinsic, but rather an adaptive mechanism emerging exclusively after TMZ treatment. In patient cells and xenograft models of disease, we recapitulate the enrichment of ALDH1A1+ cells under the influence of TMZ. We demonstrate that their subclonal progression is AKT-driven and can be interfered with by well-timed sequential rather than simultaneous antitumor combination strategy.Conclusions:Drug-resistant ALDH1A1+/pAKT+ subclones accumulate in patient tissues upon adaptation to TMZ therapy. These subclones may therefore represent a dynamic target in glioblastoma. Our study proposes the combination of TMZ and AKT inhibitors in a sequential treatment schedule as a rationale for future clinical investigation.
Anlotinib plus Epirubicin Followed by Anlotinib Maintenance as First-line Treatment for Advanced Soft-tissue Sarcoma: An Open-label, Single-arm, Phase II Trial
Authors: Wang Zhi-ming , Zhuang Rong-yuan , Guo Xi , Zhang Chen-lu , You Yang , Chen Li-sha , Liu Wen-shuai , Zhang Yong , Luo Rong-kui , Hou Ying-yong , Lu Wei-qi , Zhou Yu-hong 
Published: October 2022

Abstract

Purpose:
The treatment outcome for locally advanced or metastatic soft-tissue sarcoma (STS) remains unsatisfactory. Anlotinib had demonstrated impressive activity in the subsequent-line treatment of STS. This study investigated the combination of anlotinib and epirubicin followed by anlotinib maintenance as first-line treatment for patients with advanced STS.

Patients and Methods:
This prospective, open-label, single-arm, phase II trial was conducted in Zhongshan Hospital, Fudan University. Eligible patients were ages 18 years or older and had previously untreated, pathologically confirmed, unresectable locally advanced or metastatic STS. All patients received up to six cycles of anlotinib plus epirubicin followed by anlotinib maintenance until disease progression, unacceptable toxicity, or death. The primary endpoint was the progression-free survival (PFS) rate at 6 months. The study was registered on chictr.org (identifier ChiCTR1900024928).

Results:
From June 2019 to August 2020, 30 patients were enrolled. By December 2021, the median PFS was 11.5 months [95% confidence interval (CI): 8.6–14.4 months], while the median overall survival was not reached (95% CI: NE–NE). The objective response rate was 13.33% and the disease control rate was 80.0%. The most common adverse events (AE) included anemia (43.3%), nausea/vomiting (40.0%), fatigue (36.7%), leukopenia (30.0%), and proteinuria (10.0%), which were mainly of grade 1 or 2. The most frequent grade 3 or 4 AEs were anemia (10.0%), febrile neutropenia (33.3%), hypothyroidism (3.3%), and leukopenia (3.3%). No treatment-related death occurred.

Conclusions:
The combination of anlotinib and epirubicin followed by anlotinib maintenance demonstrated promising efficacy with a favorable safety profile.
Targeted Therapy on the Screen: Do We Hit the Target?
Authors: Lyng Heidi , Skipar Kjersti , Hompland Tord 
Published: October 2022

SummaryA phase II trial, investigating whether the antidiabetic drug metformin could reduce hypoxia in cervical cancer, used imaging to preselect patients and test the biological hypothesis behind the drug effect. This trial design would be of importance for the implementation of targeted treatment in the clinic.See related article by Han et al., p. 5263
Arginase-1 Deletion in Erythrocytes Promotes Vascular Calcification via Enhanced GSNOR (S-Nitrosoglutathione Reductase) Expression and NO Signaling in Smooth Muscle Cells
Authors: Gogiraju Rajinikanth , Renner Luisa , Bochenek Magdalena L. , Zifkos Konstantinos , Molitor Michael , Danckwardt Sven , Wenzel Philip , Münzel Thomas , Konstantinides Stavros , Schäfer Katrin 
Published: October 2022

Background:
Erythrocytes (red blood cells) participate in the control of vascular NO bioavailability. The purpose of this study was to determine whether and how genetic deletion of ARG1 (arginase-1) affects vascular smooth muscle cell NO signaling, osteoblastic differentiation, and atherosclerotic lesion calcification.

Methods:

Atherosclerosis-prone mice with conditional, erythrocyte-restricted deletion of ARG1 (apoE
−/−
red blood cell.ARG1 knockout) were generated and vascular calcification studied using molecular imaging of the osteogenic activity agent OsteoSense, Alizarin staining or immunohistochemistry, qPCR of osteogenic markers and ex vivo assays.

Results:

Atherosclerotic lesion size at the aortic root did not differ, but calcification was significantly more pronounced in apoE
−/−
mice lacking erythrocyte ARG1. Incubation of murine and human VSMCs with lysed erythrocyte membranes from apoE
−/−
red blood cell. ARG1-knockout mice accelerated their osteogenic differentiation, and mRNA transcripts of osteogenic markers decreased following NO scavenging. In addition to NO signaling via sGC (soluble guanylyl cyclase), overexpression of GSNOR (S-nitrosoglutathione reductase) enhanced degradation of S-nitrosoglutathione to glutathione and reduced protein S-nitrosation of HSP (heat shock protein)-70 were identified as potential mechanisms of vascular smooth muscle cell calcification in mice lacking ARG1 in erythrocytes, and calcium phosphate deposition was enhanced by heat shock and prevented by GSNOR inhibition. Messenger RNA levels of enzymes metabolizing the arginase products L-ornithine and L-proline also were elevated in VSMCs, paralleled by increased proliferation, myofibroblast marker and collagen type 1 expression.

Conclusions:
Our findings support an important role of erythrocyte ARG1 for NO bioavailability and L-arginine metabolism in VSMCs, which controls atherosclerotic lesion composition and calcification.