bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autoantigen presentation by splenic dendritic cells is required for RBC‐specific autoimmunity
Authors: Richards Amanda L. , Qiu Annie , Zotti Flavia Dei , Sheldon Kathryn , Usaneerungrueng Chomkan , Gruber David R. , Hudson Krystalyn E. 
Published: November 2020

AbstractBackgroundFailure of humoral tolerance to red blood cell (RBC) antigens may lead to autoimmune hemolytic anemia (AIHA), a severe and sometimes fatal disease. Previous studies have shown that although tolerance is robust in HOD mice, autoantibodies are generated upon adoptive transfer of OTII CD4+ T cells, which are specific for an epitope contained within the HOD antigen. These data imply that antigen‐presenting cells (APCs) are presenting RBC‐derived autoantigen(s) and are capable of driving T‐cell activation. Given that multiple APCs participate in erythrophagocytosis, we used a transgenic approach to determine which cellular subsets were required for autoantigen presentation and subsequent autoreactive T‐cell activation.Study Design and MethodsHOD mice, which express an RBC‐specific antigen consisting of hen egg lysozyme, ovalbumin, and human blood group molecule Duffy, were bred with IAbfl/fl and Cre‐expressing transgenic animals to generate mice that lack I‐Ab expression on particular cell subsets. OTII CD4+ T cell proliferation was assessed in vivo in HOD+I‐Abfl/flxCre+ mice and in vitro upon coculture with sorted APCs.ResultsAnalysis of HOD+I‐Abfl/flxCre+ mice demonstrated that splenic conventional dendritic cells (DCs), but not macrophages or monocytes, were required for autoantigen presentation to OTII CD4+ T cells. Subsequent in vitro coculture experiments revealed that both CD8+ and CD8− DC subsets participate in erythrophagocytosis, present RBC‐derived autoantigen and stimulate autoreactive T‐cell proliferation.ConclusionThese data suggest that if erythrocyte T‐cell tolerance fails, DCs are capable of initiating autoimmune responses. As such, targeting DCs may be a fruitful strategy for AIHA therapies.
Effectiveness of non-pharmacological interventions for managing agitation during post-traumatic amnesia following traumatic brain injury: a systematic review protocol
Authors: Carrier Sarah L. , Hicks Amelia J. , Ponsford Jennie L. , McKay Adam 
Published: November 2020

ABSTRACT

Objective:
To synthesize current evidence on the effects and harms of non-pharmacological interventions for managing agitation during post-traumatic amnesia in adults who have sustained a traumatic brain injury.

Introduction:
Agitation is one of the most disruptive and clinically significant sequelae observed during post-traumatic amnesia. Patients who experience agitation during this period demonstrate reduced engagement in rehabilitation and poorer long-term functional outcomes. Agitation also poses a risk to staff and patient safety. Research for the effects of pharmacological intervention for managing agitation during this period is inconclusive. Thus, synthesis of the research for non-pharmacological interventions for reducing agitation during post-traumatic amnesia is essential for improving long-term outcomes for survivors of traumatic brain injury.

Inclusion criteria:
Studies will be considered if they include participants aged 16 years and older who exhibit agitated behaviors during post-traumatic amnesia after sustaining a traumatic brain injury (irrespective of severity or mechanism). Studies will be considered if they evaluate any non-pharmacological intervention for reducing agitation, with all types of comparators accepted. Primary outcomes of interest include a change in agitation severity and any adverse effects.

Methods:
Key information sources include MEDLINE Ovid SP interface, PubMed, CINAHL, Excerpta Medica Database, PsycINFO, and Cochrane CENTRAL. Studies published in English will be included, irrespective of publication year. Two independent reviewers will be involved in study selection and data extraction. Eligible studies will be critically appraised for methodological quality. Studies will be pooled with statistical meta-analysis where possible; otherwise findings will be reported in narrative form.

Systematic review registration number:
PROSPERO CRD42020186802
Consistency of variety of machine learning and statistical models in predicting clinical risks of individual patients: longitudinal cohort study using cardiovascular disease as exemplar
Authors: Li Yan , Sperrin Matthew , Ashcroft Darren M , van Staa Tjeerd Pieter 
Published: November 2020

AbstractObjectiveTo assess the consistency of machine learning and statistical techniques in predicting individual level and population level risks of cardiovascular disease and the effects of censoring on risk predictions.DesignLongitudinal cohort study from 1 January 1998 to 31 December 2018.Setting and participants3.6 million patients from the Clinical Practice Research Datalink registered at 391 general practices in England with linked hospital admission and mortality records.Main outcome measuresModel performance including discrimination, calibration, and consistency of individual risk prediction for the same patients among models with comparable model performance. 19 different prediction techniques were applied, including 12 families of machine learning models (grid searched for best models), three Cox proportional hazards models (local fitted, QRISK3, and Framingham), three parametric survival models, and one logistic model.ResultsThe various models had similar population level performance (C statistics of about 0.87 and similar calibration). However, the predictions for individual risks of cardiovascular disease varied widely between and within different types of machine learning and statistical models, especially in patients with higher risks. A patient with a risk of 9.5-10.5% predicted by QRISK3 had a risk of 2.9-9.2% in a random forest and 2.4-7.2% in a neural network. The differences in predicted risks between QRISK3 and a neural network ranged between –23.2% and 0.1% (95% range). Models that ignored censoring (that is, assumed censored patients to be event free) substantially underestimated risk of cardiovascular disease. Of the 223 815 patients with a cardiovascular disease risk above 7.5% with QRISK3, 57.8% would be reclassified below 7.5% when using another model.ConclusionsA variety of models predicted risks for the same patients very differently despite similar model performances. The logistic models and commonly used machine learning models should not be directly applied to the prediction of long term risks without considering censoring. Survival models that consider censoring and that are explainable, such as QRISK3, are preferable. The level of consistency within and between models should be routinely assessed before they are used for clinical decision making.
Mortality due to cancer treatment delay: systematic review and meta-analysis
Authors: Hanna Timothy P , King Will D , Thibodeau Stephane , Jalink Matthew , Paulin Gregory A , Harvey-Jones Elizabeth , O’Sullivan Dylan E , Booth Christopher M , Sullivan Richard , Aggarwal Ajay 
Published: November 2020

Abstract

Objective
To quantify the association of cancer treatment delay and mortality for each four week increase in delay to inform cancer treatment pathways.

Design
Systematic review and meta-analysis.

Data sources
Published studies in Medline from 1 January 2000 to 10 April 2020.

Eligibility criteria for selecting studies
Curative, neoadjuvant, and adjuvant indications for surgery, systemic treatment, or radiotherapy for cancers of the bladder, breast, colon, rectum, lung, cervix, and head and neck were included. The main outcome measure was the hazard ratio for overall survival for each four week delay for each indication. Delay was measured from diagnosis to first treatment, or from the completion of one treatment to the start of the next. The primary analysis only included high validity studies controlling for major prognostic factors. Hazard ratios were assumed to be log linear in relation to overall survival and were converted to an effect for each four week delay. Pooled effects were estimated using DerSimonian and Laird random effect models.

Results
The review included 34 studies for 17 indications (n=1 272 681 patients). No high validity data were found for five of the radiotherapy indications or for cervical cancer surgery. The association between delay and increased mortality was significant (P<0.05) for 13 of 17 indications. Surgery findings were consistent, with a mortality risk for each four week delay of 1.06-1.08 (eg, colectomy 1.06, 95% confidence interval 1.01 to 1.12; breast surgery 1.08, 1.03 to 1.13). Estimates for systemic treatment varied (hazard ratio range 1.01-1.28). Radiotherapy estimates were for radical radiotherapy for head and neck cancer (hazard ratio 1.09, 95% confidence interval 1.05 to 1.14), adjuvant radiotherapy after breast conserving surgery (0.98, 0.88 to 1.09), and cervix cancer adjuvant radiotherapy (1.23, 1.00 to 1.50). A sensitivity analysis of studies that had been excluded because of lack of information on comorbidities or functional status did not change the findings.

Conclusions
Cancer treatment delay is a problem in health systems worldwide. The impact of delay on mortality can now be quantified for prioritisation and modelling. Even a four week delay of cancer treatment is associated with increased mortality across surgical, systemic treatment, and radiotherapy indications for seven cancers. Policies focused on minimising system level delays to cancer treatment initiation could improve population level survival outcomes.
Multilevel modelling and multiple group analysis of disparities in continuity of care and viral suppression among adolescents and youths living with HIV in Nigeria
Authors: Badejo Okikiolu , Noestlinger Christiana , Jolayemi Toyin , Adeola Juliette , Okonkwo Prosper , Van Belle Sara , Wouters Edwin , Laga Marie 
Published: November 2020

IntroductionSubstantial disparities in care outcomes exist between different subgroups of adolescents and youths living with HIV (AYLHIV). Understanding variation in individual and health facility characteristics could be key to identifying targets for interventions to reduce these disparities. We modelled variation in AYLHIV retention in care and viral suppression, and quantified the extent to which individual and facility characteristics account for observed variations.MethodsWe included 1170 young adolescents (10–14 years), 3206 older adolescents (15–19 years) and 9151 young adults (20–24 years) who were initiated on antiretroviral therapy (ART) between January 2015 and December 2017 across 124 healthcare facilities in Nigeria. For each age group, we used multilevel modelling to partition observed variation of main outcomes (retention in care and viral suppression at 12 months after ART initiation) by individual (level one) and health facility (level two) characteristics. We used multiple group analysis to compare the effects of individual and facility characteristics across age groups.ResultsFacility characteristics explained most of the observed variance in retention in care in all the age groups, with smaller contributions from individual-level characteristics (14%–22.22% vs 0%–3.84%). For viral suppression, facility characteristics accounted for a higher proportion of variance in young adolescents (15.79%), but not in older adolescents (0%) and young adults (3.45%). Males were more likely to not be retained in care (adjusted OR (aOR)=1.28; p<0.001 young adults) and less likely to achieve viral suppression (aOR=0.69; p<0.05 older adolescent). Increasing facility-level viral load testing reduced the likelihood of non-retention in care, while baseline regimen TDF/3TC/EFV or NVP increased the likelihood of viral suppression.ConclusionsDifferences in characteristics of healthcare facilities accounted for observed disparities in retention in care and, to a lesser extent, disparities in viral suppression. An optimal combination of individual and health services approaches is, therefore, necessary to reduce disparities in the health and well-being of AYLHIV.
Attitudes towards the New Zealand Government’s Smokefree 2025 goal associated with smoking and vaping in university students aged 18 to 24 years: results of a 2018 national cross-sectional survey
Authors: Wamamili Ben , Wallace-Bell Mark , Richardson Ann , Grace Randolph C , Coope Pat 
Published: November 2020

ObjectiveIn March 2011, New Zealand (NZ) launched an aspirational goal to reduce smoking prevalence to 5% or less by 2025 (Smokefree 2025 goal). Little is known about university students’ awareness of, support for and perceptions about this goal. We sought to narrow the knowledge gap.SettingUniversity students in NZ.MethodsWe analysed data from a 2018 cross-sectional survey of university students across NZ. Logistic regression analysis examined the associations between responses about the Smokefree goal with smoking and vaping, while controlling for age, sex and ethnicity. Confidence intervals (95% CI) were reported where appropriate.ParticipantsThe sample comprised 1476 students: 919 (62.3%) aged 18 to 20 and 557 (37.7%) aged 21 to 24 years; 569 (38.6%) male and 907 (61.4%) female; 117 (7.9%) Māori and 1359 (92.1%) non-Māori. Of these, 10.5% currently smoked (ie, smoked at least monthly) and 6.1% currently vaped (ie, used an e-cigarette or vaped at least once a month).ResultsOverall awareness of the Smokefree goal was 47.5% (95% CI: 44.9 to 50.1); support 96.9% (95% CI: 95.8 to 97.8); belief that it can be achieved 88.8% (95% CI: 86.8 to 90.7) and belief that e-cigarettes/vaping can help achieve it 88.1% (95% CI: 86.0 to 89.9).Dual users of tobacco cigarettes and e-cigarettes had greater odds of being aware of the Smokefree goal (OR=3.07, 95% CI: 1.19 to 7.92), current smokers had lower odds of supporting it (OR=0.13, 95% CI: 0.06 to 0.27) and of believing that it can be achieved (OR=0.15, 95% CI: 0.09 to 0.24) and current vapers had greater odds of believing that e-cigarettes/vaping can help to achieve it (OR=8.57, 95% CI: 1.18 to 62.52) compared with non-users.ConclusionsThe results suggest strong overall support for the Smokefree goal and belief that it can be achieved and that e-cigarettes/vaping can help achieve it. Smoking and vaping were associated with high awareness of the Smokefree goal, but lower support and optimism that it can be achieved.
Prevalence of general and abdominal obesity in 2015–2016 and 8-year longitudinal weight and waist circumference changes in adults and elderly: the Tromsø Study
Authors: Løvsletten Ola , Jacobsen Bjarne K , Grimsgaard Sameline , Njølstad Inger , Wilsgaard Tom , Løchen Maja-Lisa , Eggen Anne Elise , Hopstock Laila Arnesdatter 
Published: November 2020

ObjectivesTo describe the prevalence of general (body mass index (BMI) ≥30 kg/m2) and abdominal (waist circumference women >88 cm, men >102 cm) obesity in Tromsø 7 (2015–2016), and the secular change from Tromsø 6 (2007–2008). Furthermore, to study longitudinal changes in body weight and waist circumference from Tromsø 6 to Tromsø 7.SettingA population study in Tromsø, Norway.ParticipantsThe cross-sectional analyses included 20 855 participants in Tromsø 7 (aged ≥40 years) and 12 868 in Tromsø 6 (aged ≥30 years). The longitudinal analyses included 8592 participants with repeated measurements, aged 35–79 in Tromsø 6.Outcome measuresMean age-specific and sex-specific BMI, waist circumference, prevalence of general and abdominal overweight and obesity, as well as longitudinal changes in body weight and waist circumference according to sex and birth cohort.ResultsOver 8 years, the age-adjusted prevalence of general obesity increased (p<0.0001) from 20.1% to 23.0% in women and from 20.7% to 25.2% in men. The age-adjusted prevalence of abdominal obesity did not increase in women (from 54.7% to 53.4%), and the increase in men was modest (from 36.8% to 38.6%, p=0.003). Longitudinal analyses showed an increase in body weight, by 1.1 kg (95% CI 0.9 to 1.2) in women and 0.7 kg (95% CI 0.6 to 0.9) in men, and also waist circumference, by 1.3 cm (95% CI 1.0 to 1.5) in women and 1.4 cm (95% CI 1.2 to 1.6) in men. There were inverse relationships (p<0.001) between age at baseline and change in weight and waist circumference.ConclusionsRepeated cross-sectional analyses showed that the prevalence of general obesity increased, whereas the increase in abdominal obesity was less marked. Longitudinal analyses showed increases in both body weight and waist circumference. The youngest age groups have the largest increase.
Expanding the upper age limit for cervical cancer screening: a protocol for a nationwide non-randomised intervention study
Authors: Tranberg Mette , Petersen Lone Kjeld , Elfström Klara Miriam , Hammer Anne , Blaakær Jan , Bennetsen Mary Holten , Jensen Jørgen Skov , Andersen Berit 
Published: November 2020

IntroductionCervical cancer screening ceases between the ages of 60 and 65 in most countries. Yet, a relatively high proportion of cervical cancers are diagnosed in women above the screening age. This study will evaluate if screening of women aged 65–69 years may result in increased detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) compared with women not invited to screening. Invited women may choose between general practitioner (GP)-based screening or cervico-vaginal self-sampling. Furthermore, the study will assess if self-sampling is superior to GP-based screening in reaching long-term unscreened women.Methods and analysisThis population-based non-randomised intervention study will include 10 000 women aged 65–69 years, with no record of a cervical cytology sample or screening invitation in the 5 years before inclusion. Women who have opted-out of the screening programme or have a record of hysterectomy or cervical amputation are excluded. Women residing in the Central Denmark Region (CDR) are allocated to the intervention group, while women residing in the remaining four Danish regions are allocated to the reference group. The intervention group is invited for human papillomavirus-based screening by attending routine screening at the GP or by requesting a self-sampling kit. The reference group receives standard care which is the opportunity to have a cervical cytology sample obtained at the GP or by a gynaecologist. The study started in April 2019 and will run over the next 4.5 years. The primary outcome will be the proportion of CIN2+ detected in the intervention and reference groups. In the intervention group, the proportion of long-term unscreened women attending GP-based screening or self-sampling will be compared.Ethics and disseminationThe study has been submitted to the Ethical Committee in the CDR which deemed that the study was not notifiable to the Committee and informed consent is therefore not required. The study is approved by the Danish Data Protection Regulation and the Danish Patient Safety Authority. Results will be disseminated in peer-reviewed journals.Trial registration numberNCT04114968.
Social and physical neighbourhood characteristics and loneliness among older adults: results from the MINDMAP project
Authors: Timmermans Erik , Motoc Irina , Noordzij J Mark , Beenackers Marielle A , Wissa Rita , Sarr Aliou , Gurer Asli , Fabre Guillaume , Ruiz Milagros , Doiron Dany , Oude Groeniger Joost , Deeg Dorly , Van Lenthe Frank J , Huisman Martijn 
Published: November 2020

BackgroundLoneliness is associated with several adverse mental and physical health outcomes in older adults. Previous studies have shown that a variety of individual-level and perceived area-level characteristics are associated with loneliness. This study examined the associations of objectively measured social and physical neighbourhood characteristics with loneliness.MethodsWe used cross-sectional data from 1959 older adults (63–98 years) who participated in the Longitudinal Ageing Study Amsterdam (LASA; wave 2011/12) and the Health and Living Conditions of the Population of Eindhoven and Surroundings study (GLOBE; wave 2014) in the Netherlands. Study-specific loneliness scores were harmonised across both cohort studies and divided into tertiles denoting low, medium and high levels of loneliness. Objectively measured neighbourhood characteristics, including area-level percentages of low educated residents, social security beneficiaries and unoccupied dwellings, average income, crime levels and land use mix, were linked to individual-level data. Multinomial logistic regression analyses were conducted to examine the associations of interest.ResultsThere was no statistical evidence for an association of the included neighbourhood characteristics with loneliness. Although not statistically significant, the observed associations suggested that participants living in neighbourhoods with more heterogeneous land use mix were less likely to have a medium and high level of loneliness than those living in more homogeneous neighbourhoods in terms of land use mix (ORmedium=0.54, 95% CI=0.18–1.67; ORhigh=0.67, 95% CI=0.21–2.11).ConclusionThe results indicate that the included objectively measured social and physical neighbourhood characteristics are not associated with loneliness in old age.
The effect of circuit resistance training on plasma levels of amino acids, alpha-hydroxybutyrate, mannose, and urinary levels of glycine conjugated adducts in obese adolescent boys
Authors: Rasooli Seyed Ali , Fathi Rozita , Golzar Farhad Ahmadi-Kani , Baghersalimi Masoumeh 
Published: November 2020

Few studies have examined the improving effects of exercise on the association between metabolites of impaired protein metabolism and insulin resistance in obese children. Therefore, this study aims to investigate the effect of circuit resistance training (CRT) on plasma levels of amino acids, alpha-hydroxybutyrate (α-HB), mannose, and urinary levels of glycine conjugated adducts in obese adolescent boys. Forty obese adolescent boys (body mass index above the 95th percentile) with an age range of 14–17 years were randomly divided into the CRT group (n = 20) and control group (n = 20). The CRT program (3 times/week, 70%–80% of 1-repetition maximum) was performed for 8 weeks. The results indicated that the body composition and plasma levels of glucose, insulin resistance, valine, mannose, lysine, and the sum of branched-chain amino acids (BCAA) were decreased because of CRT. The plasma levels of asparagine, glycine, serine, and urinary levels of glycine conjugated adduct also increased in the CRT group. Although α-HB level decreased during CRT, it had no significant difference from that of the control group. It can be concluded that the improvement in obesity complications including insulin resistance in obese adolescent boys after CRT may be due to decrease in plasma levels of mannose and BCAA and increase urinary metabolites. Novelty: CRT improves glucose metabolism and insulin resistance in obese adolescent boys. CRT decreases plasma levels of mannose and BCAA and normalizes other amino acids. CRT increases urinary levels of glycine conjugated adducts.
Ḥaḍāna Practices in Tunisia: Between Women’s Rights and the Best Interest of the Child, 1956–2019
Authors: Voorhoeve Maaike 
Published: November 2020

Abstract
This article examines how Tunisian judges since independence deal with childcare cases upon divorce. As a legal ethnographic study of ḥaḍāna (child custody) in contemporary Tunisia, this study aims to contribute to the existing literature on judicial practice in Muslim contexts. The article aims to reveal these judges’ understandings of child custody, of women’s and men’s roles in childcare, and of the rights and interests of children and how this understanding developed over time.