bluuebunny/crossref_metadata_2025_split huggingface dataset:
Home-based screening tools for amblyopia: a systematic review protocol
Authors: Sii Samantha , Chean Chung Shen , Kuht Helen J , Thomas Mervyn G , Rufai Sohaib R 
Published: August 2021

IntroductionAmblyopia is an important public health concern associated with functional vision loss and detrimental impact on the physical and mental well-being of children. The gold standard for diagnosis of amblyogenic conditions currently involves screening by orthoptists and/or ophthalmologists. The bloom of technology enables the use of home-based screening tools to detect these conditions at an early stage by the layperson in community, which could reduce the burden of screening in the community, especially during restrictions associated with the COVID-19 pandemic. Here, we propose a systematic review aiming to evaluate the accuracy and reliability of home-based screening tools compared with the existing gold standard.Methods and analysisWe aim to search for studies involving home-based screening tools for amblyopia among children aged under 18 years. Oxford Centre for Evidence-Based Medicine Level 4 evidence and above will be included, without language or time restrictions. The following platforms will be searched from inception to 31 August 2021: PubMed, Medline, The Cochrane Library, Embase, Web of Science Core Collection and Clinicaltrials.gov. Two independent reviewers will identify studies for inclusion based on a screening questionnaire. The search and screening will start on 14 August 2021 until 1 October 2021. We aim to complete our data analysis by 30 November 2021. Risk of bias will be assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool for diagnostic accuracy studies only. Our primary outcome measure is the diagnostic accuracy of home-based screening tools, while secondary outcome measures include validity, feasibility, reproducibility and cost-effectiveness, where available.Ethics and disseminationEthical approval is not necessary as no primary data will be collected. The findings will be disseminated through presentations at scientific meetings and peer-reviewed journal publication.PROSPERO registration numberCRD42021233511.
Home-based rehabilitation programme compared with traditional physiotherapy for patients at risk of poor outcome after knee arthroplasty: the CORKA randomised controlled trial
Authors: Barker Karen L , Room Jonathan , Knight Ruth , Dutton Susan , Toye Francine , Leal Jose , Kenealy Nicola , Maia Schlüssel Michael , Collins Gary , Beard David , Price Andrew James , Underwood Martin , Drummond Avril , Lamb Sarah 
Published: August 2021

ObjectivesTo evaluate whether a home-based rehabilitation programme for people assessed as being at risk of a poor outcome after knee arthroplasty offers superior outcomes to traditional outpatient physiotherapy.DesignA prospective, single-blind, two-arm randomised controlled superiority trial.Setting14 National Health Service physiotherapy departments in the UK.Participants621 participants identified at high risk of a poor outcome after knee arthroplasty using a bespoke screening tool.InterventionsA multicomponent home-based rehabilitation programme delivered by rehabilitation assistants with supervision from qualified therapists versus usual care outpatient physiotherapy.Main outcome measuresThe primary outcome was the Late-Life Function and Disability Instrument (LLFDI) at 12 months. Secondary outcomes were the Oxford Knee Score (a disease-specific measure of function), Knee injury and Osteoarthritis Outcome Score Quality of Life subscale, Physical Activity Scale for the Elderly, 5 dimension, 5 level version of Euroqol (EQ-5D-5L) and physical function assessed using the Figure of 8 Walk test, 30 s Chair Stand Test and Single Leg Stance.Results621 participants were randomised between March 2015 and January 2018. 309 were assigned to CORKA (Community Rehabilitation after Knee Arthroplasty) home-based rehabilitation, receiving a median five treatment sessions (IQR 4–7). 312 were assigned to usual care, receiving a median 4 sessions (IQR 2–6). The primary outcome, LLFDI function total score at 12 months, was collected for 279 participants (89%) in the home-based CORKA group and 287 participants (92%) in the usual care group. No clinically or statistically significant difference was found between the groups (intention-to-treat adjusted difference=0.49 points; 95% CI −0.89 to 1.88; p=0.48). There were no statistically significant differences between the groups on any of the patient-reported or physical secondary outcome measures at 6 or 12 months.There were 18 participants in the intervention group reporting a serious adverse event (5.8%), only one directly related to the intervention, all other adverse events recorded throughout the trial related to underlying chronic medical conditions.ConclusionsThe CORKA intervention was not superior to usual care. The trial detected no significant differences, clinical or statistical, between the two groups on either primary or secondary outcomes. CORKA offers an evaluation of an intervention utilising a different service delivery model for this patient group.Trial registration numberISRCTN13517704.
Comprehensive non-invasive prenatal screening for pregnancies with elevated risks of genetic disorders: protocol for a prospective, multicentre study
Authors: Xu Chenming , Cai Xiaoqiang , Chen Songchang , Luo Qiong , Xi Hui , Zhang Dan , Wang Hua , Wu Yanting , Huang He-Feng , Zhang Jinglan 
Published: August 2021

IntroductionChromosomal abnormalities and monogenic disorders account for ~15%–25% of recognisable birth defects. With limited treatment options, preconception and prenatal screening were developed to reduce the incidence of such disorders. Currently, non-invasive prenatal screening (NIPS) for common aneuploidies is implemented worldwide with superiority over conventional serum or sonographic screening approaches. However, the clinical validity for the screening of frequent chromosome segmental copy number variations and monogenic disorders still awaits to be proved.Methods and analysisThis study is a multicentre, prospective study. The participants were recruited from three tertiary hospitals in China starting from 10 April 2021. The study is expected to conclude before 10 October 2022. Pregnant women with abnormal prenatal screening results indicated for invasive prenatal diagnosis or those who decide to terminate their pregnancies due to abnormal ultrasound findings will be evaluated for enrolment. Cell-free DNA extracted from the maternal plasma will be used for an analytically validated comprehensive NIPS test developed by Beijing BioBiggen Technology Co. (Beijing, China). The diagnostic results from prenatal or postnatal specimens as well as the pregnancy outcome data will be collected to examine the clinical sensitivity, specificity, positive and negative predictive values of the test.Ethics and disseminationThis study was approved by the Obstetrics and Gynecology Hospital of Fudan University (2020-178). Results of this study will be disseminated to public through scientific conferences and a peer-reviewed journal. Written informed consents will be obtained from participants.Trial registration numberChiCTR2100045739.
Partner loss and its effect on frailty trajectories: results from the 13-year follow-up Survey of Health, Ageing and Retirement in Europe (SHARE)
Authors: Oberndorfer Moritz , Mogg Christina , Haider Sandra , Grabovac Igor , Drgac Deborah , Dorner Thomas 
Published: August 2021

BackgroundFrailty is a geriatric syndrome closely linked to a variety of adverse health outcomes. Thus, it is important to identify factors associated with the development of frailty. It was the aim of this study to examine, if, and to what extent partner loss, a highly stressful life event, affects frailty trajectories of community dwelling adults aged 50 or older.MethodsUsing six waves of panel data from the Survey of Health, Ageing and Retirement in Europe (SHARE), we investigated the effect of partner loss on frailty trajectories estimating growth curve models. Our sample included 183 502 observations of 83 494 community-dwelling individuals aged 50 or older from 21 European countries collected between 2004 and 2017. Frailty was measured using the validated sex-specific SHARE-Frailty-Instrument including muscular weakness, unintended weight loss, decrease in walking capacity, low physical activity and exhaustion.ResultsOur sample contained 79 874 participants who lived in a partnership during their entire observational period and 3620 participants who lost their partner during their observational period. Both men (β=0.184 (95% CI: −0.017 to 0.386), p=0.073) and women (β=0.237 (95% CI: 0.106 to 0.369), p<0.001) showed initial effects of partner loss on frailty, but while only women gradually recovered over time (β=−0.023 (95% CI: −0.039 to −0.008), p=0.002), among men, the effect of partner loss persisted (β<0.001 (95% CI: −0.029 to 0.029), p=0.998).ConclusionThis study revealed that partner loss is followed by elevated frailty. However, while women’s frailty tended to recover from partner loss over time, men’s frailty remained elevated. Notable individual differences in the response of frailty trajectories to partner loss suggest the existence of effect modifiers.
IL-7 expands lymphocyte populations and enhances immune responses to sipuleucel-T in patients with metastatic castration-resistant prostate cancer (mCRPC)
Authors: Pachynski Russell K , Morishima Chihiro , Szmulewitz Russell , Harshman Lauren , Appleman Leonard , Monk Paul , Bitting Rhonda L , Kucuk Omer , Millard Frederick , Seigne John D , Fling Steven P , Maecker Holden T , Duault Caroline , Ramchurren Nirasha , Hess Bruce , D’Amico Leonard , Lacroix Andreanne , Kaiser Judith C , Morre Michel , Grégoire Anne , Cheever Martin , Yu Evan Y , Fong Lawrence 
Published: August 2021

BackgroundSipuleucel-T (sip-T) is a Food and Drug Administration (FDA)-approved autologous cellular immunotherapy for metastatic castration-resistant prostate cancer (mCRPC). We hypothesized that combining sip-T with interleukin (IL)-7, a homeostatic cytokine that enhances both B and T cell development and proliferation, would augment and prolong antigen-specific immune responses against both PA2024 (the immunogen for sip-T) and prostatic acid phosphatase (PAP).MethodsFifty-four patients with mCRPC treated with sip-T were subsequently enrolled and randomized 1:1 into observation (n=26) or IL-7 (n=28) arms of a phase II clinical trial (NCT01881867). Recombinant human (rh) IL-7 (CYT107) was given weekly×4. Immune responses were evaluated using flow cytometry, mass cytometry (CyTOF), interferon (IFN)-γ ELISpot,3H-thymidine incorporation, and ELISA.ResultsTreatment with rhIL-7 was well tolerated. For the rhIL-7-treated, but not observation group, statistically significant lymphocyte subset expansion was found, with 2.3–2.6-fold increases in CD4+T, CD8+T, and CD56brightNK cells at week 6 compared with baseline. No significant differences in PA2024 or PAP-specific T cell responses measured by IFN-γ ELISpot assay were found between rhIL-7 and observation groups. However, antigen-specific T cell proliferative responses and humoral IgG and IgG/IgM responses significantly increased over time in the rhIL-7-treated group only. CyTOF analyses revealed pleiotropic effects of rhIL-7 on lymphocyte subsets, including increases in CD137 and intracellular IL-2 and IFN-γ expression. While not powered to detect clinical outcomes, we found that 31% of patients in the rhIL-7 group had prostate specific antigen (PSA) doubling times of >6 months, compared with 14% in the observation group.ConclusionsTreatment with rhIL-7 led to a significant expansion of CD4+ and CD8+ T cells, and CD56brightnatural killer (NK) cells compared with observation after treatment with sip-T. The rhIL-7 treatment also led to improved antigen-specific humoral and T cell proliferative responses over time as well as to increased expression of activation markers and beneficial cytokines. This is the first study to evaluate the use of rhIL-7 after sip-T in patients with mCRPC and demonstrates encouraging results for combination approaches to augment beneficial immune responses.
Adjuvant nivolumab for stage III/IV melanoma: evaluation of safety outcomes and association with recurrence-free survival
Authors: Mandalá Mario , Larkin James , Ascierto Paolo A , Del Vecchio Michele , Gogas Helen , Cowey C Lance , Arance Ana , Dalle Stéphane , Schenker Michael , Grob Jean-Jacques , Chiarion-Sileni Vanna , Marquez-Rodas Ivan , Butler Marcus O , Di Giacomo Anna Maria , Lutzky Jose , De La Cruz-Merino Luis , Atkinson Victoria , Arenberger Petr , Hill Andrew , Fecher Leslie , Millward Michael , Khushalani Nikhil I , de Pril Veerle , Lobo Maurice , Weber Jeffrey 
Published: August 2021

BackgroundSeveral therapeutic options are now available in the adjuvant melanoma setting, mandating an understanding of their benefit‒risk profiles in order to make informed treatment decisions. Herein we characterize adjuvant nivolumab select (immune-related) treatment-related adverse events (TRAEs) and evaluate possible associations between safety and recurrence-free survival (RFS) in the phase III CheckMate 238 trial.MethodsPatients with resected stage IIIB–C or IV melanoma received nivolumab 3 mg/kg every 2 weeks (n=452) or ipilimumab 10 mg/kg every 3 weeks for four doses and then every 12 weeks (n=453) for up to 1 year or until disease recurrence, unacceptable toxicity, or consent withdrawal. First-occurrence and all-occurrence select TRAEs were analyzed within discrete time intervals: from 0 to 3 months of treatment, from >3–12 months of treatment, and from the last dose (regardless of early or per-protocol treatment discontinuation) to 100 days after the last dose. Possible associations between select TRAEs and RFS were investigated post randomization in 3-month landmark analyses and in Cox model analyses (including a time-varying covariate of select TRAE), within and between treatment groups.ResultsFrom the first nivolumab dose to 100 days after the last dose, first-occurrence select TRAEs were reported in 67.7% (306/452) of patients. First-occurrence select TRAEs were reported most frequently from 0 to 3 months (48.0%), during which the most common were pruritus (15.5%) and diarrhea (15.3%). Most select TRAEs resolved within 6 months. There was no clear association between the occurrence (or not) of select TRAEs and RFS by landmark analysis or by Cox model analysis within treatment arms or comparing nivolumab to the ipilimumab comparator arm.ConclusionResults of this safety analysis of nivolumab in adjuvant melanoma were consistent with its established safety profile. In the discrete time intervals evaluated, most first-occurrence TRAEs occurred early during treatment and resolved. No association between RFS and select TRAEs was evident.Trial registration numberNCT02388906.
International initiative for a curated SDHB variant database improving the diagnosis of hereditary paraganglioma and pheochromocytoma
Authors: Ben Aim Laurene , Maher Eamonn R , Cascon Alberto , Barlier Anne , Giraud Sophie , Ercolino Tonino , Pigny Pascal , Clifton-Bligh Roderick J , Mirebeau-Prunier Delphine , Mohamed Amira , Favier Judith , Gimenez-Roqueplo Anne-Paule , Schiavi Francesca , Toledo Rodrigo A , Dahia Patricia L , Robledo Mercedes , Bayley Jean Pierre , Burnichon Nelly 
Published: August 2021

BackgroundSDHB is one of the major genes predisposing to paraganglioma/pheochromocytoma (PPGL). Identifying pathogenic SDHB variants in patients with PPGL is essential to the management of patients and relatives due to the increased risk of recurrences, metastases and the emergence of non-PPGL tumours. In this context, the ‘NGS and PPGL (NGSnPPGL) Study Group’ initiated an international effort to collect, annotate and classify SDHB variants and to provide an accurate, expert-curated and freely available SDHB variant database.MethodsA total of 223 distinct SDHB variants from 737 patients were collected worldwide. Using multiple criteria, each variant was first classified according to a 5-tier grouping based on American College of Medical Genetics and NGSnPPGL standardised recommendations and was then manually reviewed by a panel of experts in the field.ResultsThis multistep process resulted in 23 benign/likely benign, 149 pathogenic/likely pathogenic variants and 51 variants of unknown significance (VUS). Expert curation reduced by half the number of variants initially classified as VUS. Variant classifications are publicly accessible via the Leiden Open Variation Database system (https://databases.lovd.nl/shared/genes/SDHB).ConclusionThis international initiative by a panel of experts allowed us to establish a consensus classification for 223 SDHB variants that should be used as a routine tool by geneticists in charge of PPGL laboratory diagnosis. This accurate classification of SDHB genetic variants will help to clarify the diagnosis of hereditary PPGL and to improve the clinical care of patients and relatives with PPGL.
Quantitative analysis of unruptured intracranial aneurysm wall thickness and enhancement using 7T high resolution, black blood magnetic resonance imaging
Authors: Liu Xinke , Feng Junqiang , Li Zhixin , Zhang Zihao , Zhang Qiang , Jiang Yuhua , Huo Xiaochuan , Chai Xubin , Wu Yue , Kong Qingle , Liu Peng , Ge Huijian , Jin Hengwei , An Jing , Jiang Peng , Saloner David A , Li Youxiang , Zhu Chengcheng 
Published: August 2021

BackgroundThis study was performed to quantify intracranial aneurysm wall thickness (AWT) and enhancement using 7T MRI, and their relationship with aneurysm size and type.Methods27 patients with 29 intracranial aneurysms were included. Three-dimensional T1 weighted pre‐ and post-contrast fast spin echo with 0.4 mm isotropic resolution was used. AWT was defined as the full width at half maximum on profiles of signal intensity across the aneurysm wall on pre-contrast images. Enhancement ratio (ER) was defined as the signal intensity of the aneurysm wall over that of the brain parenchyma. The relationships between AWT, ER, and aneurysm size and type were investigated.Results7T MRI revealed large variations in AWT (range 0.11–1.24 mm). Large aneurysms (>7 mm) had thicker walls than small aneurysms (≤7 mm) (0.49±0.05 vs 0.41±0.05 mm, p<0.001). AWT was similar between saccular and fusiform aneurysms (p=0.546). Within each aneurysm, a thicker aneurysm wall was associated with increased enhancement in 28 of 29 aneurysms (average r=0.65, p<0.05). Thicker walls were observed in enhanced segments (ER >1) than in non-enhanced segments (0.53±0.09 vs 0.38±0.07 mm, p<0.001).ConclusionImproved image quality at 7T allowed quantification of intracranial AWT and enhancement. A thicker aneurysm wall was observed in larger aneurysms and was associated with stronger enhancement.
Learning from experience: what the emerging global marine assessment community can learn from the social processes of other global environmental assessments
Authors: Fawkes Kyle , Ferse Sebastian , Scheffers Anja , Cummins Valerie 
Published: August 2021

Abstract
In recent decades, international assessments of the ocean have evolved from specialized, technical evaluations of the state of the marine environment to more integrated and thematically extensive science-policy platforms. As assessment programmes such as the UN Regular Process blossom on the global stage and subsume responsibility for tracking progress on sustainable development, there is a need to consider how their processes wield influence and effectively translate knowledge into action. In the present paper, we undertake a comprehensive review of the literature on global environmental assessments (GEAs) and extract key principles that can be applied to global assessments of the marine environment. We were particularly inspired to identify how social processes could be arranged to best distill, communicate, and produce actionable knowledge. While we look to the advice of experts in the literature, we highlight specific examples from the Intergovernmental Panel on Climate Change (IPCC), Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES), and the Global Environment Outlook (GEO). From this review, knowledge coproduction, multilevel collaboration, and futures thinking emerged as the dominant principles of influential and action-oriented assessments. We conclude the paper by contextualizing how these principles may be operationalized for Global Marine Assessments in the future.
Prostate-Specific Antigen Kinetics Effects on Outcomes of Low-Volume Metastatic Prostate Cancer Patients Receiving Androgen Deprivation Therapy
Authors: Lin Yen-Chi , Lin Po-Hung , Shao I-Hung , Chu Yuan-Cheng , Kan Hung-Cheng , Liu Chung-Yi , Yu Kai-Jie , Chang Ying-Hsu , Pang See-Tong , Huang Jhen-Ling , Chuang Cheng-Keng 
Published: August 2021

Background. The present study aimed to analyse factors influencing the effects of androgen deprivation therapy (ADT) in patients with newly diagnosed metastatic castration-naïve prostate cancer (mCNPC), especially in low-volume disease (LVD), according to subclassification of metastatic prostate cancer established by the CHAARTED trial. Materials and Methods. We reviewed 648 patients with newly diagnosed mCNPC receiving ADT at Chang Gung Memorial Hospital from January 2007 to December 2016. Basic characteristics and PSA kinetics profile were subsequently evaluated. Results. 48.3% of LVD patients progressed to castration-resistant prostate cancer (mCRPC). Among them, CRPC group had significantly shorter time to PSA nadir (TTN) and faster time from PSA nadir to CRPC (TFNTC) (

p

< 0.001) compared to non-CRPC group. PSA doubling time (PSADT) < 4 months tended to be associated with faster disease progression and shorter overall survival (OS). Among all patients with metastatic prostate cancer, those with shorter TTN <9 months, higher nadir PSA level ≥1 ng/mL, and shorter PSADT <3 months had increased tendency for biochemical progression. Conclusions. PSADT is an effective clinical predictor for disease progression and survival in LVD. Other PSA kinetics including TTN and TFNTC, though not the major predictors for disease progression or OS in LVD, might be the predictors for disease control status.