bluuebunny/crossref_metadata_2025_split huggingface dataset:
Magnetic resonance imaging (MRI) of normal human placentae
Authors: Lo Glen , Jacques Angela , Dickinson Jan E. 
Published: June 2022

AbstractIntroductionThe MRI appearances of the human placenta in the absence of maternal or fetal pathology have not been extensively studied, with only a few studies reporting findings in the uncomplicated pregnancy. The purpose of this study is to review the placental MRI appearances in low‐risk pregnancies in a prospective study.MethodsA prospective observational study of placental MRI in low‐risk pregnancies was initially planned, however recruitment was terminated early due to the COVID19 pandemic. The protocol was subsequently modified to compare the placental appearances in the enrolled cohort with pregnancies having had MRI for non‐placental pathologies. The data from the two groups were then pooled to assess the range of normal placental appearances.ResultsEighty‐three pregnancies were prospectively assessed with MRI at a median gestation of 29 weeks (range 14–39) from a mixed group of prospective cases (n = 28) and retrospectively recruited obstetric MRI (n = 55). Placental thickness in the third trimester ranged from 18 to 35 mm. T2 heterogeneity was seen in 75% (25/33) at second trimester and by the third trimester 50% (25/50) were moderately or markedly heterogenous. T2 dark bands (>6 mm) were seen in 9% (3/33) and 20% (10/50) of second and third trimester pregnancies, respectively. Undetectable myometrium or loss of the subplacental myometrial plane was present in 15% (5/33) of second and 38% (19/50) of third trimester placentae.ConclusionThis qualitative study of normal placental MRI appearances expands the current knowledge base by confirming they vary, evolve with gestation, and can overlap with signs of placenta accreta spectrum.
Meta‐analysis confirmed genetic susceptibility conferred by multiple risk variants from CTLA4 and SERPINA1 in granulomatosis with polyangiitis
Authors: Banerjee Pratibha , Kumar Uma , Khetarpal Preeti , Senapati Sabyasachi 
Published: June 2022

AbstractBackgroundGranulomatosis with polyangiitis (GPA) is a rare systemic autoimmune disease. Smaller sample size and complex nature of the disease pathogenesis has made it challenging to perform well‐powered genetic investigations. We performed a systematic review based meta‐analysis in GPA to investigate the genetic susceptibility conferred by non‐human leukocyte antigen (non‐HLA) candidate genes.MethodsA systematic review was performed using web‐based literature search and eligible studies were included following inclusion‐exclusion criteria. Studies were evaluated for their quality of evidence and study outcome was assessed using the Newcastle‐Ottawa Scale and Grades of Research, Assessment, Development and Evaluation tools. Reviewer's agreement was accessed through Cohen's κ value. Meta‐analyses were performed using RevMan 5 tool. Meta‐odds ratio (meta‐OR) and Z test P value were evaluated to estimate the genetic susceptibility for each of the variants.ResultsEighteen studies were found eligible and 7 genetic variants from only 4 genes, namely CTLA4, PRTN3, SERPINA1 and PTPN22 could be studied for meta‐analysis. rs231775‐G (49‐G) (Meta‐OR = 1.42 [1.14‐1.76]; P = .001) of CTLA4 and rs7151526‐A (Meta‐OR = 2.70 [1.51‐4.85]; P = .0008) of SERPINA1 were confirmed to be predisposing alleles, and rs5742909‐C (318‐C) (Meta‐OR = 0.65 [0.44‐0.97]; P =.03) of CTLA4 was found to be protective for GPA. In concordance with the genetic association of rs7151526‐A, serological marker for the same variant “Z” allele of SERPINA1 was found to be predisposing (Meta‐OR = 12.60 [5.01‐31.68]; P < .00001) for GPA.ConclusionGenetic variants confirmed in this study play critical roles in T‐cell mediated immune function and could be significantly implicated in GPA. Molecular pathology studies are warranted to confirm their role. These markers could be used for efficient patient classification and disease management.
Lifelong cytomegalovirus and early‐LIFE irradiation synergistically potentiate age‐related defects in response to vaccination and infection
Authors: Pugh Jason L. , Coplen Christopher P. , Sukhina Alona S. , Uhrlaub Jennifer L. , Padilla‐Torres Jose , Hayashi Tomonori , Nikolich‐Žugich Janko 
Published: June 2022

AbstractWhile whole‐body irradiation (WBI) can induce some hallmarks of immune aging, (re)activation of persistent microbial infection also occurs following WBI and may contribute to immune effects of WBI over the lifespan. To test this hypothesis in a model relevant to human immune aging, we examined separate and joint effects of lifelong latent murine cytomegalovirus (MCMV) and of early‐life WBI over the course of the lifespan. In late life, we then measured the response to a West Nile virus (WNV) live attenuated vaccine, and lethal WNV challenge subsequent to vaccination. We recently published that a single dose of non‐lethal WBI in youth, on its own, was not sufficient to accelerate aging of the murine immune system, despite widespread DNA damage and repopulation stress in hematopoietic cells. However, 4Gy sub‐lethal WBI caused manifest reactivation of MCMV. Following vaccination and challenge with WNV in the old age, MCMV‐infected animals experiencing 4Gy, but not lower, dose of sub‐lethal WBI in youth had reduced survival. By contrast, old irradiated mice lacking MCMV and MCMV‐infected, but not irradiated, mice were both protected to the same high level as the old non‐irradiated, uninfected controls. Analysis of the quality and quantity of anti‐WNV immunity showed that higher mortality in MCMV‐positive WBI mice correlated with increased levels of MCMV‐specific immune activation during WNV challenge. Moreover, we demonstrate that infection, including that by WNV, led to MCMV reactivation. Our data suggest that MCMV reactivation may be an important determinant of increased late‐life mortality following early‐life irradiation and late‐life acute infection.
Rejuvenation of neutrophils and their extracellular vesicles is associated with enhanced aged fracture healing
Authors: Zhang Xin , Baht Gurpreet Singh , Huang Rong , Chen Yu‐Hsiu , Molitoris Kristin Happ , Miller Sara E. , Kraus Virginia Byers 
Published: June 2022

AbstractTissue repair is negatively affected by advanced age. Recent evidence indicates that hematopoietic cell‐derived extracellular vesicles (EVs) are modulators of regenerative capacity. Here, we report that plasma EVs carrying specific surface markers indicate the degree of age‐associated immunosenescence; moreover, this immunosenescence phenotype was accentuated by fracture injury. The number of CD11b+Ly6CintermediateLy6Ghigh neutrophils significantly decreased with age in association with defective tissue regeneration. In response to fracture injury, the frequencies of neutrophils and associated plasma EVs were significantly higher in fracture calluses than in peripheral blood. Exposure of aged mice to youthful circulation through heterochronic parabiosis increased the number of neutrophils and their correlated Ly6G+ plasma EVs, which were associated with improved fracture healing in aged mice of heterochronic parabiosis pairs. Our findings create a foundation for utilizing specific immune cells and EV subsets as potential biomarkers and therapeutic strategies to promote resilience to stressors during aging.
Prices, taxes and alcohol use: a systematic umbrella review
Authors: Guindon G. Emmanuel , Zhao Kevin , Fatima Tooba , Garasia Sophiya , Quinn Nicholas , Baskerville N. Bruce , Paraje Guillermo 
Published: June 2022

AbstractAimTo measure the impact of taxes and prices on alcohol use with particular attention to the different context of rising alcohol consumption in low‐ and middle‐income countries.MethodsSystematic review: we searched MEDLINE, Embase, EconLit and LILACS, grey literature, hand‐searched five specialty journals and examined references of relevant studies. We considered all reviews that included studies that quantitatively examined the relationship between alcohol prices or taxes and alcohol use. At least two reviewers independently screened the articles and extracted the characteristics, methods and main results and assessed the quality of each included study. We identified 30 reviews.ResultsThere was overwhelming evidence that higher alcohol prices and taxes were associated with lower total alcohol consumption and that price responsiveness varied by beverage type. Total own‐price elasticities of alcohol demand were consistently negative and substantial enough to be policy meaningful; total own‐price elasticities for beer, wine and spirits were found to be approximately −0.3, −0.6 and −0.65. Reviews generally concluded that higher taxes and prices were associated with lower heavy episodic drinking and heavy drinking, although the magnitude of these associations was generally unclear. Reviews provided no evidence that alcohol price responsiveness differed by socioeconomic status, mixed and contradictory evidence with respect to age and sex and limited evidence that price responsiveness in low‐ and middle‐income countries was approximately the same as in high‐income countries.ConclusionsTaxes are effective in reducing alcohol use. Moreover, increasing the price of alcohol by increasing taxes can also be expected to increase tax revenue, because the demand for alcohol is most certainly inelastic.
Analysis of alopecia areata surveys suggests a threshold for improved patient-reported outcomes
Authors: Renert-Yuval Yael , Correa da Rosa Joel , Garcet Sandra , Pavel Ana B. , Bares Jennifer , Chima Margot , Hawkes Jason E. , Gilleaudeau Patricia , Sullivan-Whalen Mary , Singer Giselle K. , Krueger James G. , Guttman-Yassky Emma 
Published: June 2022

Summary

Background
Although alopecia areata (AA) greatly impacts patients’ quality of life (QoL), there is no adequate validation of AA-targeted QoL surveys in clinical trials, hindering sufficient representation of patient-reported outcomes.

Objectives
Better understanding of patient-reported outcomes may guide treatment goals and future clinical trials.

Methods
In a recent randomized controlled trial testing dupilumab in AA, patients were administered the Alopecia Areata Quality of Life Index (AA-QLI) and the Alopecia Areata Symptom Impact Scale (AASIS) surveys, specifically evaluating QoL in patients with AA. An in-depth analysis was performed to assess the utility of these questionnaires in this patient population, both at baseline and after treatment, and to determine a threshold for improved patient-reported outcomes.

Results
While AASIS correlated with baseline Severity of Alopecia Tool (SALT) scores and with therapeutic response, AA-QLI showed no correlation with AA severity before or after treatment. Itch strongly correlated with serum IgE levels across both surveys. Using various approaches to estimate a discriminative threshold for decreased impact of AA on QoL (by AASIS) following treatment, a SALT score of 20 points or less post-treatment was associated with improved patient-reported outcomes, including both AA-related symptoms and items within the daily activities/feelings domain such as ‘feeling sad’ and ‘feeling anxious or worry’.

Conclusions
AASIS is better than AA-QLI to assess patient-reported outcomes. SALT ≤ 20 following treatment should be considered as a threshold for meaningful therapeutic outcome and as a clinical endpoint in future clinical trials for AA.
What is already known about this topic? Alopecia areata greatly compromises quality of life, and affected patients have increased prevalences of depression, anxiety and social phobia.Despite the significant negative impact of the disease on patients’ wellbeing, validation of targeted questionnaires in alopecia areata is lacking, and a therapeutic response threshold for improved patient-reported outcomes is unknown.
What does this study add? This study investigated the utility of two different alopecia areata-targeted questionnaires – Alopecia Areata Quality of Life Index and Alopecia Areata Symptom Impact Scale (AASIS) – in a clinical trial setting.AASIS was found to correlate strongly with alopecia areata severity and clinical response.
What are the clinical implications of this work? Patients with ≤ 20% scalp hair loss after treatment reported improvement in multiple quality-of-life items, suggesting this as a meaningful therapeutic outcome that may guide clinicians and improve the development of future clinical trials.
Applying educational theory to medical education research
Authors: Melvin Anna , Patel Rakesh S. 
Published: June 2022

Abstract
Applying educational theory to medical education research is no different to the way theory drives research and practice in other domains. However, the practical application of theory to research in medical education can often be challenging for many different reasons. This article seeks to help researchers by exploring some important questions about educational theory, including what theory is, why it is important, and how it can be used in medical education research.
Long term oncological outcomes for laparoscopic versus open surgery for rectal cancer – A population‐based nationwide noninferiority study
Authors: Dehlaghi Jadid Kaveh , Cao Yang , Petersson Josefin , Angenete Eva , Matthiessen Peter 
Published: June 2022

AbstractAimThe aim of this work was to compare the 5‐year overall survival in a national cohort of patients undergoing curative abdominal resection for rectal cancer by laparoscopic (LAP) or open (OPEN) surgery.MethodAll patients diagnosed with clinical Stage I–III rectal cancer and who underwent LAP or OPEN abdominal curative surgery in Sweden between 2010 and 2016 were retrieved from the Swedish Colorectal Cancer Registry. A noninferiority study design was employed with a statistical power of 90%, a one‐side type I error of 2.5% and a noninferiority margin of 2%. The analyses were performed as intention‐to‐treat and the relationship between surgical technique and overall mortality within 5 years was analysed. Multilevel regression models with the patients matched by propensity scores adjusted for patient‐ and tumour‐related variables were used.ResultsA total of 8410 Stage I–III cancer patients were included. This group underwent 2094 LAP (24.9%) and 6316 OPEN (75.1%) procedures and were followed until 31 December 2020. Multivariable Cox regression demonstrated that 5‐year overall survival was higher in the LAP group [hazard ratio (HR) 0.877; 95% CI 0.775–0.993]. [Correction added on 21 November 2022, after first online publication: In the preceding sentence, the CI value for LAP group has been corrected from “0.877” to “0.775” in this version.] The outcome was similar when multiple imputation and propensity score matching were employed. When cT4 patients were excluded there was no difference (HR 0.885; 95% CI 0.790–1.033). At 5‐years’ follow‐up local recurrence was not different, at 2.9% for the LAP group and 3.6% for the OPEN group (p = 0.075), while metastatic disease was more frequent in the OPEN group (19.6% compared with 15.6% for LAP; p < 0.001).ConclusionThis study demonstrated that the LAP technique was not inferior to OPEN surgery with regard to overall 5‐year survival. These results support the use of laparoscopic surgery.
Pursuing best practices for minimizing wild bee captures to support biological research
Authors: Montero‐Castaño Ana , Koch Jonathan Berenguer Uhuad , Lindsay Thuy‐Tien Thai , Love Byron , Mola John M. , Newman Kiera , Sharkey Janean K. 
Published: June 2022

AbstractBees are important pollinators of wild and domesticated flowering plant species. Over the last 30 years, an increasing number of scientific articles have been published on the ecology and conservation of wild bees. To achieve research goals, many studies have pursued the lethal take of wild bees. Although the impact of lethal take for scientific pursuits is likely negligible compared to the negative impacts of human‐mediated phenomena such as climate change, urbanization, and agricultural intensification, it is important to evaluate the history of lethal take on scientific endeavors. In our study, we evaluated a random sample of 30 years of scientific publications on wild bees. Across 1426 surveyed publications, 536 reported the lethal take of wild bees. We found that 61% of these studies lethally captured wild bees primarily for species identification. Furthermore, we determined passive sampling of wild bees resulted in substantially more lethal collections than active methods per study. However, combined approaches of passive and active collection resulted in the greatest lethal take of wild bees per study. Finally, we determined that 64% of the studies did not provide deposition information for their samples, hindering additional research that could be done with them. The increasing availability of video and photographic devices and artificial intelligence approaches to identification, the development of low and noninvasive molecular methods, and the ease of sharing information, allow for a timely discussion on alternative routes and potentially new best practices in bee research. We focus our discussion on alternative methods for minimizing lethal captures for identification purposes and through passive methods, and for maximizing the utility of the data collected. Finally, we provide a framework for continued engagement among researchers and managers to develop strategies that can contribute to reducing our impact on wild bee communities and making the most of collected specimens.
Delivering paediatric precision medicine: Genomic and environmental considerations along the causal pathway of childhood neurodevelopmental disorders
Authors: Woolfenden Sue , Farrar Michelle A. , Eapen Valsamma , Masi Anne , Wakefield Claire E. , Badawi Nadia , Novak Iona , Nassar Natasha , Lingam Raghu , Dale Russell C. 
Published: June 2022

Precision medicine refers to treatments that are targeted to an individual's unique characteristics. Precision medicine for neurodevelopmental disorders (such as cerebral palsy, attention‐deficit/hyperactivity disorder, obsessive–compulsive disorder, Tourette syndrome, and autism spectrum disorder) in children has predominantly focused on advances in genomic sequencing technologies to increase our ability to identify single gene mutations, diagnose a multitude of rare neurodevelopmental disorders, and gain insights into pathogenesis. Although targeting specific gene variants with high penetrance will help some children with rare disease, this approach will not help most children with neurodevelopmental disorders. A ‘pathway’ driven approach targeting the cumulative influence of psychosocial, epigenetic, or cellular factors is likely to be more effective. To optimize the therapeutic potential of precision medicine, we present a biopsychosocial integrated framework to examine the ‘gene–environment neuroscience interaction’. Such an approach would be supported through harnessing the power of big data, transdiagnostic assessment, impact and implementation evaluation, and a bench‐to‐bedside scientific discovery agenda with ongoing clinician and patient engagement.What this paper addsPrecision medicine has predominantly focused on genetic risk factors.The impact of environmental risk factors, particularly inflammatory, metabolic, and psychosocial risks, is understudied.A holistic biopsychosocial model of neurodevelopmental disorder causal pathways is presented.The model will provide precision medicine across the full spectrum of neurodevelopmental disorders.
Do subsidies on seed and fertilizer lead to child labour? Evidence from Malawi
Authors: Frempong Raymond Boadi 
Published: June 2022

SummaryMotivationSub‐Saharan African governments have subsidized farm inputs—fertilizer and seed especially—to increase food production by small‐scale farmers to improve food security. A potential drawback of such schemes is that they may encourage farmers to put their children to work in the fields, harming their education.PurposeDid the Malawi Farm Input Subsidy Programme that began in 2005/2006 increase child labour on the holdings of beneficiary smallholders?Methods and approachThe article analyses data from the Malawi Integrated Household Panel Survey to examine the effect of seed and fertilizer subsidies on child labour. The study employs a correlated‐random‐effects‐control function regression, using district coupon allocation as an instrumental variable for coupons received by households.FindingsThere was statistically significant evidence that the Farm Input Subsidy Programme (FISP) increased child labour. The effect, however, was relatively small. At the sample mean, it was estimated that the programme led to a 12 percentage point increase in the likelihood that children would work on the farm and that the children would work an additional 72 minutes a week on the fields. The FISP, however, did not affect the enrolment of children in school.Effects varied socially: children in male‐headed, uneducated, and smallholder households were the most affected.Policy implicationsAlthough the observed effects are not large, they are unwelcome. Two policy corrections could eliminate them. One, the award of subsidy coupons could be made conditional on children's school performance. Two, given that the effects barely applied in households where parents had been to school, agricultural training should stress the importance of children attending school and not working in the fields.
Making space for freshwater biodiversity in low‐income fishing economies
Authors: Brummett Randall E. 
Published: June 2022

AbstractGlobally, freshwater biodiversity and the food system that it underpins are under enormous threat. Historically damaged by overfishing, environmental deterioration (e.g., pollution, damming, water extraction and watershed modification) is now destroying canonical ecosystem structure. Under pressure to secure the food supply and create jobs, local politicians are reluctant to enforce rules that would reduce fishing pressure and threaten the already vulnerable economies of many fishing communities. Aquaculture can directly address food supply but has in the past been troubled with its own negative environmental footprint. New technology is available to solve these problems. Modern aquaculture, as a commercial alternative to capture fishing can take advantage of existing infrastructure to grow more food, but more importantly, create new and better jobs in places where few alternatives exist, making economic and local political space for policies that operate for both food production and the protection of aquatic biodiversity. This opinion seeks to revise the current vision of aquaculture as a competitor and threat to inland fisheries, arguing rather that the way to approach the biodiversity crisis in freshwater is to create economic alternatives to fishing and environmental abuse so that poor people can afford to care about nature.
Effets de la pandémie sur la sécurité et la santé des gens de mer, ces travailleurs clés du secteur maritime
Authors: SHAN Desai 
Published: June 2022

RésuméSi la pandémie a bouleversé le monde du travail, elle n'a pas entièrement paralysé le commerce international, ce moteur essentiel de l'activité économique, ni le transport maritime, dont dépend l'acheminement de plus de 90 pour cent des marchandises mondiales. Cependant, en raison des restrictions destinées à freiner la propagation du virus, les gens de mer ont souvent été empêchés de quitter leur navire et de rentrer chez eux. L'autrice analyse la crise de la sécurité et de la santé au travail qui en a résulté pour ces travailleurs clés du secteur maritime, en s'appuyant sur des entretiens avec 29 d'entre eux.