bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intense versus standard regimens of intermittent occlusion therapy for unilateral moderate amblyopia in children: study protocol for a randomized controlled trial
Authors: Wang Jingyun , Malik Ayesha , Jin Jing , Pang Yi , Yin Kelly , Allen Megan , Grigorian Adriana , Scombordi Brandy , Bailey Joann , Aljohani Saeed , Funari Katharine , Shoge Ruth , Meiyeppen Siva , Myung Jenny , Soni Ajay , Neely Daniel E. 
Published: April 2020

Abstract
Background
We reported that in our previous study that wearing intermittent occlusion therapy glasses (IO-therapy) for 4 hours (h) was non-inferior to patching for 2 h in 3 to 8-year-old children with amblyopia. We hypothesize that an intense regimen of 12-h IO-therapy per day for 4 weeks could be as effective as the standard regimen of 4-h IO-therapy per day for 12 weeks in treating moderate amblyopia in 3 to 8-year-old children.

Methods/Design
A total of 56 children between 3 and 8 years of age with amblyopia in association with anisometropia and/or strabismus will be enrolled. All participants will be prescribed IO-therapy glasses (Amblyz™), set at 30-s opaque/transparent intervals (i.e., occluded 50% of wear time). They will be randomized to receive the standard regimen for 12 weeks or the intense regimen for 4 weeks. Adherence to using the IO-therapy glasses will be objectively monitored in each participant by means of a microsensor dose monitor. The primary study objective is to compare the effectiveness of an intense regimen to a standard regimen of IO-therapy in 3 to 8-year-old children with moderate amblyopia. The secondary study objectives are to determine whether adherence differs between an intense regimen and a standard regimen of IO-therapy, and to determine the dose-response relationship of IO-therapy.

Discussion
In addition to testing the effectiveness, this study will test for the first time the association between treatment adherence and the visual outcome of IO-therapy, which will enhance our understanding of the dose-response relationship of IO-therapy. If an intense regimen is shown to be effective, it would alter amblyopia treatment strategies and improve visual outcomes.

Trial registration
ClinicalTrials.gov: NCT02767856. Registered on 10 May 2016.
Protocol for a randomized multicenter study for isolated skin vasculitis (ARAMIS) comparing the efficacy of three drugs: azathioprine, colchicine, and dapsone
Authors:   for the Vasculitis Clinical Research Consortium, Micheletti Robert G. , Pagnoux Christian , Tamura Roy N. , Grayson Peter C. , McAlear Carol A. , Borchin Renee , Krischer Jeffrey P. , Merkel Peter A. 
Published: April 2020

Abstract
Background
Skin-limited forms of vasculitis, while lacking systemic manifestations, can persist or recur indefinitely, cause pain, itch, or ulceration, and be complicated by infection or scarring. High-quality evidence on how to treat these conditions is lacking. The aim of this comparative effectiveness study is to determine the optimal management of patients with chronic skin-limited vasculitis.

Methods
ARAMIS is a multicenter, sequential, multiple assignment randomized trial with an enrichment design (SMARTER) aimed at comparing the efficacy of three drugs—azathioprine, colchicine, and dapsone—commonly used to treat various forms of isolated skin vasculitis. ARAMIS will enroll patients with isolated cutaneous small or medium vessel vasculitis, including cutaneous small vessel vasculitis, immunoglobulin A (IgA) vasculitis (skin-limited Henoch-Schönlein purpura), and cutaneous polyarteritis nodosa. Patients not responding to the initial assigned therapy will be re-randomized to one of the remaining two study drugs (Stage 2). Those with intolerance or contraindication to a study drug can be randomized directly into Stage 2. Target enrollment is 90 participants, recruited from international centers affiliated with the Vasculitis Clinical Research Consortium. The number of patients enrolled directly into Stage 2 of the study will be capped at 10% of the total recruitment target. The primary study endpoint is the proportion of participants from the pooled study stages with a response to therapy at month 6, according to the study definition.

Discussion
ARAMIS will help identify effective agents for skin-limited forms of vasculitis, an understudied group of diseases. The SMARTER design may serve as an example for future trials in rare diseases.

Trial registration
ClinicalTrials.gov: NCT02939573. Registered on 18 October 2016.
Lay-therapist-delivered, low-intensity, psychosocial intervention for refugees and asylum seekers (PROSPER): protocol for a pilot randomised controlled trial
Authors: Rawlinson Rebecca , Aslam Rabeea’h W. , Burnside Girvan , Chiumento Anna , Eriksson-Lee Malena , Humphreys Amy , Khan Naila , Lawrence Daniel , McCluskey Rachel , Mackinnon Annette , Orton Lois , Rahman Atif , Roberts Ewan , Rosala-Hallas Anna , Edwards Rhiannon Tudor , Uwamaliya Philomene , White Ross G. , Winrow Eira , Dowrick Christopher 
Published: April 2020

Abstract
Background
Asylum seekers and refugees (AS&Rs) experience impaired mental health and wellbeing, related to stresses in their country of origin, experiences in transit and reception on arrival, including significant barriers to accessing mainstream services. Their contact with health care is often crisis-driven and mediated through non-governmental organisations (NGOs).
Problem Management Plus (PM+) is a psychosocial intervention recommended by the World Health Organisation to address distress experienced by adults affected by humanitarian crises. We are investigating its application for the first time in a high-income country.

Methods
In a pilot randomised controlled trial (RCT), PM+ will be delivered to AS&Rs in contact with NGOs in Liverpool City Region, UK by lay therapists who have lived experience of forced migration. Following systematic review and stakeholder engagement, PM+ has been adapted to the local context, and lay therapists have been trained in its delivery.
We will assess the feasibility of conducting a three-arm RCT of five 90-min sessions of PM+, delivered individually or in groups by lay therapists to AS&Rs experiencing emotional distress and functional impairment, compared with each other and with usual support offered by local NGOs. Distress and impairment at baseline will be measured by the Hospital Anxiety and Depression Scale (HADS) and the WHO Disability Assessment Schedule (WHO-DAS). We aim to recruit 105 participants, 35 per arm.
Primary health outcomes are anxiety and depressive symptoms at 3 months, measured by HADS. Secondary outcomes include subjective wellbeing, functional status, progress on identified problems, presence of post-traumatic stress disorder and depressive disorder and service usage. Longer-term impact will be assessed at 6 months post baseline, on the same parameters.
We will assess the feasibility of conducting a full RCT in relation to the following elements: recruitment and retention of lay therapists and study participants; fidelity of delivery of PM+; and suitability of the study measures, including any linguistic or cultural barriers.

Discussion
We will use these findings to specify the parameters for a full RCT to test the effectiveness and cost-effectiveness of PM+ in reducing emotional distress and health inequalities, and improving functional ability and wellbeing, amongst asylum seekers and refugees.

Trial registration
ISRCTN, ID: ISRCTN15214107. Registered on 10 September 2019.
Nonexistence and existence of positive radial solutions to a class of quasilinear Schrödinger equations in $\mathbb{R}^{N}$
Authors: Li Jing , Wang Ying 
Published: April 2020

AbstractThis paper aims to investigate the class of quasilinear Schrödinger equations $$\begin{aligned} \begin{aligned}[b] &-\Delta u-\bigl[\Delta \bigl(1+u^{2}\bigr)^{\frac{\gamma }{2}}\bigr] \frac{\gamma u}{2(1+u^{2})^{\frac{2-\gamma }{2}}}\\ &\quad =\alpha h\bigl( \vert x \vert \bigr) \vert u \vert ^{p-1}u+ \beta H\bigl( \vert x \vert \bigr) \vert u \vert ^{q-1}u, \quad x\in \mathbb{R}^{N}, \end{aligned} \end{aligned}$$ −Δu−[Δ(1+u2)γ2]γu2(1+u2)2−γ2=αh(|x|)|u|p−1u+βH(|x|)|u|q−1u,x∈RN, where $N >2$N>2, $1 \le \gamma \le 2$1≤γ≤2, $\alpha ,\beta \in \mathbb{R}$α,β∈R and either $0< p<1<q$0<p<1<q or $1< p< q$1<p<q. Functions $h(|x|)$h(|x|), $H(|x|)$H(|x|) are continuous and positive in $\mathbb{R}^{N} $RN. Relying on some special arguments and the Schauder–Tychonoff fixed point theorem, nonexistence criteria, existence of positive ground state solutions and blow-up solutions to Eq. (0.1) with $0< p<1<q$0<p<1<q or $1< p< q$1<p<q will be obtained.
The controllability of nonlinear fractional differential system with pure delay
Authors: Nawaz Musarrat , Jiang Wei , Sheng Jiale 
Published: April 2020

AbstractIn this study, we are currently investigating the controllability of nonlinear fractional differential control systems with delays in the state function. The solution representations of fractional delay differential equations have been established by using the delayed Mittag-Leffler function. Firstly we obtain the result of the controllability of a linear fractional control system with delay. Then, for the controllability criteria of nonlinear fractional delay system, we establish the set of sufficient conditions of nonlinear fractional differential systems with delay in their state function by using Schauder’s fixed point theorem. In the end, a numerical example is constructed to support the results.
Local fractional Newton’s inequalities involving generalized harmonic convex functions
Authors: Iftikhar Sabah , Erden Samet , Kumam Poom , Awan Muhammad Uzair 
Published: April 2020

AbstractA new auxiliary result based on a three step quadratic kernel utilizing the concepts of local fractional calculus is obtained. Using this new auxiliary result we have several new Newton type inequalities whose power q of local fractional derivative in modulus is a generalized harmonic convex function.
Enhanced accumulation of N-terminally truncated Aβ with and without pyroglutamate-11 modification in parvalbumin-expressing GABAergic neurons in idiopathic and dup15q11.2-q13 autism
Authors: Frackowiak Janusz , Mazur-Kolecka Bozena , Mehta Pankaj , Wegiel Jerzy 
Published: April 2020

AbstractAutism, the most frequent neurodevelopmental disorder of a very complex etiopathology, is associated with dysregulation of cellular homeostatic mechanisms, including processing of amyloid-β precursor protein (APP). Products of APP processing — N-terminally truncated amyloid-β peptide (N-tr-Aβ) species — are accumulated in autism in neurons and glia in the cortex, cerebellum, and subcortical structures of the brain. This process in neurons is correlated with increased oxidative stress. Because abnormally high levels of N-tr-Aβ are detected in only a fraction of neurons in the prefrontal cortex, we applied immunohistochemical staining and confocal microscopy in autopsy brain material from idiopathic and chromosome 15q11.2-q13 duplication (dup-15) autism to measure the load of N-tr-Aβ in the cells and synapses and to identify the subpopulation of neurons affected by these pathophysiological processes. The peptides accumulated in autism are N-terminally truncated; therefore, we produced a new antibody against Aβ truncated at N-terminal amino acid 11 modified to pyroglutamate to evaluate the presence and distribution of this peptide species in autism. We also quantified and characterized the oligomerization patterns of the Aβ-immunoreactive peptides in autism and control frozen brain samples. We provide morphological evidence, that in idiopathic and dup-15 autism, accumulation of N-tr-Aβ with and without pyroglutamate-11 modified N-terminus affects mainly the parvalbumin-expressing subpopulation of GABAergic neurons. N-tr-Aβ peptides are accumulated in neurons’ cytoplasm and nucleus as well as in GABAergic synapses. Aβ peptides with both C-terminus 40 and 42 were detected by immunoblotting in frozen cortex samples, in the form of dimers and complexes of the molecular sizes of 18–24kD and 32–34kD. We propose that deposition of N-tr-Aβ specifically affects the functions of the parvalbumin-expressing GABAergic neurons and results in a dysregulation of brain excitatory–inhibitory homeostasis in autism. This process may be the target of new therapies.
Validation of machine learning models to detect amyloid pathologies across institutions
Authors: Vizcarra Juan C. , Gearing Marla , Keiser Michael J. , Glass Jonathan D. , Dugger Brittany N. , Gutman David A. 
Published: April 2020

AbstractSemi-quantitative scoring schemes like the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) are the most commonly used method in Alzheimer’s disease (AD) neuropathology practice. Computational approaches based on machine learning have recently generated quantitative scores for whole slide images (WSIs) that are highly correlated with human derived semi-quantitative scores, such as those of CERAD, for Alzheimer’s disease pathology. However, the robustness of such models have yet to be tested in different cohorts. To validate previously published machine learning algorithms using convolutional neural networks (CNNs) and determine if pathological heterogeneity may alter algorithm derived measures, 40 cases from the Goizueta Emory Alzheimer’s Disease Center brain bank displaying an array of pathological diagnoses (including AD with and without Lewy body disease (LBD), and / or TDP-43-positive inclusions) and levels of Aβ pathologies were evaluated. Furthermore, to provide deeper phenotyping, amyloid burden in gray matter vs whole tissue were compared, and quantitative CNN scores for both correlated significantly to CERAD-like scores. Quantitative scores also show clear stratification based on AD pathologies with or without additional diagnoses (including LBD and TDP-43 inclusions) vs cases with no significant neurodegeneration (control cases) as well as NIA Reagan scoring criteria. Specifically, the concomitant diagnosis group of AD + TDP-43 showed significantly greater CNN-score for cored plaques than the AD group. Finally, we report that whole tissue computational scores correlate better with CERAD-like categories than focusing on computational scores from a field of view with densest pathology, which is the standard of practice in neuropathological assessment per CERAD guidelines. Together these findings validate and expand CNN models to be robust to cohort variations and provide additional proof-of-concept for future studies to incorporate machine learning algorithms into neuropathological practice.
Preoperative tumor size measurement in breast cancer patients: which threshold is appropriate on computer-aided detection for breast MRI?
Authors: Song Sung Eun , Seo Bo Kyoung , Cho Kyu Ran , Woo Ok Hee , Park Eun Kyung , Cha Jaehyung , Han Seungju 
Published: April 2020

Abstract
Background
Computer-aided detection (CAD) can detect breast lesions by using an enhancement threshold. Threshold means the percentage of increased signal intensity in post-contrast imaging compared to precontrast imaging. If the pixel value of the enhanced tumor increases above the set threshold, CAD provides the size of the tumor, which is calculated differently depending on the set threshold. Therefore, CAD requires the accurate setting of thresholds. We aimed to compare the diagnostic accuracy of tumor size measurement using MRI and CAD with 3 most commonly used thresholds and to identify which threshold is appropriate on CAD in breast cancer patients.

Methods
A total of 130 patients with breast cancers (80 invasive cancers and 50 ductal carcinoma in situ [DCIS]) who underwent preoperative MRI with CAD and surgical treatment were included. Tumor size was manually measured on first contrast-enhanced MRI and acquired by CAD using 3 different thresholds (30, 50, and 100%) for each tumor. Tumor size measurements using MRI and CAD were compared with pathological sizes using Spearman correlation analysis. For comparison of size discrepancy between imaging and pathology, concordance was defined as estimation of size by imaging within 5 mm of the pathological size. Concordance rates were compared using Chi-square test.

Results
For both invasive cancers and DCIS, correlation coefficient rho (r) between tumor size on imaging and pathology was highest at CAD with 30% threshold, followed by MRI, CAD with 50% threshold, and CAD with 100% threshold (all p <  0.05). For invasive cancers, the concordance rate of 72.5% at CAD with 30% threshold showed no difference with that of 62.5% at MRI (p = 0.213). For DCIS, the concordance rate of 30.0% at CAD with 30% threshold showed no difference with that of 36.0% at MRI (p = 0.699). Compared to MRI, higher risk of underestimation was noted when using CAD with 50% or 100% threshold for invasive cancers and when using CAD with 100% threshold for DCIS.

Conclusion
For CAD analysis, 30% threshold is the most appropriate threshold whose accuracy is comparable to manual measurement on MRI for tumor size measurement. However, clinicians should be aware of the higher risk of underestimation when using CAD with 50% threshold for tumor staging in invasive cancers.
Groundwater NO3 concentration and its potential health effects in Beni Moussa perimeter (Tadla plain, Morocco)
Authors: Barakat Ahmed 
Published: April 2020

AbstractIn this research, the concentrations of nitrates were investigated in well water sampled from the irrigated perimeter of Beni Moussa (Tadla plain, Morocco), and human health risks via ingestion and dermal pathways for individuals in different age brackets were assessed using the chronic daily intake, the dermal absorbed dose and hazard index (HI).The results showed that the groundwater NO3 contents were between 4.20 to 80.46 mg L− 1, with an average of 32.11 mg L− 1, indicating anthropogenic inputs caused by the infiltration of nitrates not consumed by plants or surface industrial and domestic wastewater into the shallow aquifer. Compared to the Moroccan standard, 17.78%, 40.00%, 37.78% and 4.44% of sampled wells showed poor, fair, good or excellent quality, respectively. For non-carcinogenic risk, the oral ingestion of nitrate appeared to be the main exposure pathway for local human receptors causing the high non-carcinogenic risk, and the dermal exposure met within the accepted precautionary criterion. Infants in the study area are more likely to experience adverse effects to higher nitrate level in groundwater (3.04E-01 < HI < 1.80E+ 00), followed by female (2.39E-01 < HI < 1.41E+ 00), then male (2.22E-01 < HI < 1.31E+ 00) and finally children (2.08E-01 < HI < 1.23E+ 00). The resulting spatial variation in HI values was greatly influenced by human activities and population density.The results of this study could help to shape effective environmental management measures for enhancing the groundwater quality and ensuring safe drinking water.
Negativity about the outcomes of extreme prematurity a persistent problem - a survey of health care professionals across the North Queensland region
Authors: Ireland Susan , Larkins Sarah , Ray Robin , Woodward Lynn 
Published: April 2020

Abstract
Background
Extremely preterm babies are at risk of significant mortality and morbidity due to their physiological immaturity. At periviable gestations decisions may be made to either provide resuscitation and intensive care or palliation based on assessment of the outlook for the baby and the parental preferences. Health care professionals (HCP) who counsel parents will influence decision making depending on their individual perceptions of the outcome for the baby. This paper aims to explore the knowledge and attitudes towards extremely preterm babies of HCP who care for women in pregnancy in a tertiary, regional and remote setting in North Queensland.

Methods
A cross sectional electronic survey of HCP was performed. Perceptions of survival, severe disability and intact survival data were collected for each gestational age from 22 to 27 completed weeks gestation. Free text comment enabled qualitative content analysis.

Results
Almost all 113 HCP participants were more pessimistic than the actual outcome data suggests. HCP caring for women antenatally were the most pessimistic for survival (p = 0.03 at 23 weeks, p = 0.02 at 25,26 and 27 weeks), severe disability (p = 0.01 at 24 weeks) and healthy outcomes (p = 0.01 at 24 weeks), whilst those working in regional and remote centres were more negative than those in tertiary unit for survival (p = 0.03 at 23,24,25 weeks). Perception became less negative as gestational age increased.

Conclusion
Pessimism of HCP may be negatively influencing decision making and will negatively affect the way in which parents perceive the chances of a healthy outcome for their offspring.
Study protocol for a cluster randomised controlled feasibility trial evaluating personalised care planning for older people with frailty: PROSPER V2 27/11/18
Authors: Heaven Anne , Bower Peter , Cundill Bonnie , Farrin Amanda , Foster Marilyn , Foy Robbie , Hartley Suzanne , Hawkins Rebecca , Hulme Claire , Humphrey Sara , Lawton Rebecca , Parker Catriona , Pendleton Neil , West Robert , Young John , Clegg Andrew 
Published: April 2020

Abstract
Background
Frailty is characterised by increased vulnerability to falls, disability, hospitalisation and care home admission. However, it is relatively reversible in the early stages. Older people living with frailty often have multiple health and social issues which are difficult to address but could benefit from proactive, person-centred care. Personalised care planning aims to improve outcomes through better self-management, care coordination and access to community resources.

Methods
This feasibility cluster randomised controlled trial aims to recruit 400 participants from 11 general practice clusters across Bradford and Leeds in the north of England. Eligible patients will be aged over 65 with an electronic frailty index score of 0.21 (identified via their electronic health record), living in their own homes, without severe cognitive impairment and not in receipt of end of life care. After screening for eligible patients, a restricted 1:1 cluster-level randomisation will be used to allocate practices to the PROSPER intervention, which will be delivered over 12 weeks by a personal independence co-ordinator worker, or usual care. Following initial consent, participants will complete a baseline questionnaire in their own home including measures of health-related quality of life, activities of daily living, depression and health and social care resource use. Follow-up will be at six and 12 months. Feasibility outcomes relate to progression criteria based around recruitment, intervention delivery, retention and follow-up. An embedded process evaluation will contribute to iterative intervention optimisation and logic model development by examining staff training, intervention implementation and contextual factors influencing delivery and uptake of the intervention.

Discussion
Whilst personalised care planning can improve outcomes in long-term conditions, implementation in routine settings is poor. We will evaluate the feasibility of conducting a cluster randomised controlled trial of personalised care planning in a community population based on frailty status. Key objectives will be to test fidelity of trial design, gather data to refine sample size calculation for the planned definitive trial, optimise data collection processes and optimise the intervention including training and delivery.

Trial registration
ISRCTN12363970 – 08/11/18.