bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a scale assessing retired older adults’ attitudes to volunteering
Authors: Dana Liyuwork Mitiku , Jongenelis Michelle I. , Jackson Ben , Newton Robert U. , Pettigrew Simone 
Published: March 2021

AbstractObjectiveGiven positive attitudes to volunteering are likely to be associated with support for volunteering and individual participation, this study aimed to develop and test a 10‐item ‘attitudes to formal volunteering’ scale for retired older adults that could be used to inform intervention efforts.MethodA sample of 801 Australian retirees (62% female; mean age: 71.9 years) completed a survey that included the attitude scale, demographic items and questions assessing engagement in volunteering.ResultsA principal component analysis identified two factors (general attitude to volunteering and attitude to participating in volunteering) that together accounted for 64% of the variance in attitude scores. A confirmatory factor analysis indicated the two‐factor model was an excellent fit to the data. Cronbach's alphas for both factors were >0.80, and both were positively associated with volunteering engagement.ConclusionThe proposed scale is a potentially useful instrument for measuring attitudes to volunteering among retired older adults.
Loneliness in older age: What is it, why is it happening and what should we do about it in Australia?
Authors: Ogrin Rajna , Cyarto Elizabeth V. , Harrington Karra D. , Haslam Catherine , Lim Michelle H. , Golenko Xanthe , Bush Matiu , Vadasz Danny , Johnstone Georgina , Lowthian Judy A. 
Published: March 2021

AbstractLoneliness is an important health issue facing older people due to its association with poor quality of life and poor health outcomes. This paper aimed to clarify key issues around loneliness among older adults and draw attention to innovative programs and the translation of emerging research into practice. Loneliness is a mismatch between a person's actual and desired social connections, experienced as negative emotions. Older adults are vulnerable to loneliness because of changes associated with ageing. As such, identifying as older is often seen as a burden, negatively impacting self‐esteem, sense of purpose and relevance, culminating in loneliness. Interventions combatting loneliness can target individuals, relationships, communities or societies. We advocate for an intersectoral approach to support healthy ageing and reduce loneliness. This will require further research to evaluate new approaches with loneliness as the primary outcome, and additional funding to translate evidence into an integrated multi‐level approach to addressing loneliness.
Neoliberalism and the Crisis in Higher Education: The Cost of Ideology
Authors: Mintz Beth 
Published: March 2021

AbstractA number of factors have contributed to the crisis in higher education, including the long‐term transformation in funding. In this article, I argue that neoliberalism can explain many of the processes leading to our changing commitment to colleges and universities and the cost increases that this change has produced. A number of neoliberal assumptions firmly rooted in conventional wisdom have contributed to a “student‐as‐customer” phenomenon, which is, itself, a cost driver. I look at the development of the student as customer as a vehicle for exploring tuition increases. I also examine the tension between education as a public and a private good and the marketization of higher education as crucial drivers of these transformations. In doing so, I emphasize that the student as customer has been created by the changes in the way we think about, organize, and fund education, rather than any fundamental change in young people.
Nanoarchitectures for efficient IgE cross‐linking on effector cells to study amoxicillin allergy
Authors: Tesfaye Amene , Rodríguez‐Nogales Alba , Benedé Sara , Fernández Tahía D. , Paris Juan L. , Rodriguez Maria J. , Jiménez‐Sánchez Isabel M. , Bogas Gador , Mayorga Cristobalina , Torres María J. , Montañez María I. 
Published: March 2021

AbstractBackgroundAmoxicillin (AX) is nowadays the β‐lactam that more frequently induces immediate allergic reactions. Nevertheless, diagnosis of AX allergy is occasionally challenging due to risky in vivo tests and non‐optimal sensitivity of in vitro tests. AX requires protein haptenation to form multivalent conjugates with increased size to be immunogenic. Knowing adduct structural features for promoting effector cell activation would help to improve in vitro tests. We aimed to identify the optimal structural requirement in specific cellular degranulation to AX using well‐precised nanoarchitectures of different lengths.MethodWe constructed eight Bidendron Antigens (BiAns) based on polyethylene glycol (PEG) linkers of different lengths (600–12,000 Da), end‐coupled with polyamidoamine dendrons that were terminally multi‐functionalized with amoxicilloyl (AXO). In vitro IgE recognition was studied by competitive radioallergosorbent test (RAST) and antibody–nanoarchitecture complexes by transmission electron microscopy (TEM). Their allergenic activity was evaluated using bone marrow‐derived mast cells (MCs) passively sensitized with mouse monoclonal IgE against AX and humanized RBL‐2H3 cells sensitized with polyclonal antibodies from sera of AX‐allergic patients.ResultsAll BiAns were recognized by AX‐sIgE. Dose‐dependent activation responses were observed in both cellular assays, only with longer structures, containing spacers in the range of PEG 6000–12,000 Da. Consistently, greater proportion of immunocomplexes and number of antibodies per complex for longer BiAns were visualized by TEM.ConclusionsBiAns are valuable platforms to study the mechanism of effector cell activation. These nanomolecular tools have demonstrated the importance of the adduct size to promote effector cell activation in AX allergy, which will impact for improving in vitro diagnostics.
Hypertension affects the treatment of wet age‐related macular degeneration
Authors: Wang Ting , Xia Jun , Yuan Meng , Wu Xiaohang , Zhu Yi , Chen Chuan , Bergunder Sean J. , Liu Zhenzhen , Chen Wenben , Huang Kai , Lin Haotian 
Published: March 2021

AbstractPurposeDue to population ageing as well as the high prevalence of hypertension and age‐related macular degeneration (AMD) in elderly individuals, and the relationship between hypertension and AMD is unclear. Our research aimed to investigate the association between hypertension, wet AMD (wAMD) and the treatment strategy of wAMD patients affected by hypertension.MethodsData of wAMD patients at Zhongshan Ophthalmic Center, Sun Yat‐sen University, between 1 January 2002 and 30 June 2019, were extracted from the electronic healthcare information system. wAMD patients were divided into subgroups by hypertension status, age, sex, the need for vitrectomy surgery and the number of anti‐VEGF drug intravitreal injections that these were divided in 1–3 vs. >3 (available time from 1 January 2012 to 30 June 2019).ResultsA total of 3096 wAMD patients (41.7% female, 58.3% male) with an age range of 50–96 years (68.7 (SD 9.42) years) were included. wAMD was significantly associated with hypertension (p < 0.001). After adjustment for sex and age, Cox regression model showed a significant association between hypertension in wAMD patients and the number of injections (RR = 1.31, 95% CI: 1.13–1.50, p < 0.001). There was no significant association between hypertension and the need for vitrectomy (p = 0.82).Conclusionswet AMD was associated with hypertension status, and after the regular series of three injections, wAMD patients with hypertension were more likely to receive anti‐VEGF drug intravitreal injections than those without hypertension. These results may facilitate prospective research on the prevention of wAMD and contribute to the management of wAMD patients.
Antithyroid drug use during pregnancy and the risk of birth defects in offspring: systematic review and meta‐analysis of observational studies with methodological considerations
Authors: Morales Daniel R. , Fonkwen Lionel , Nordeng Hedvig M. E. 
Published: March 2021

AimsMaternal antithyroid drug (ATD) use during pregnancy has been associated with an increased risk of birth defects in offspring. Uncertainty remains on the size of this risk and how it compares to untreated hyperthyroidism due to methodological limitations of previous studies.MethodsSystematic review of MEDLINE and EMBASE identifying observational studies examining ATD use during pregnancy and risk of birth defects by 28 August 2020. Data were extracted on study characteristics, effect estimates and comparator groups. Adjusted effect estimates were pooled using a random‐effects generic inverse variance method and absolute risk calculated.ResultsSeven cohort studies and 1 case–control study involving 6 212 322 pregnancies and 388 976 birth defects were identified reporting regression effect estimates. Compared to an unexposed population comparison, the association between ATD use during pregnancy and birth defects in offspring was: adjusted risk ratio (aRR) 1.16 95% confidence interval (CI) 1.08–1.25 for propylthiouracil (PTU); aRR 1.28 95%CI 1.06–1.54 for methimazole/carbimazole (MMI/CMZ); aRR 1.51, 95%CI 1.16–1.97 for both MMI/CMZ and PTU; and aRR 1.15 95%CI 1.02–1.29 for untreated hyperthyroidism. The excess risk of any and major birth defects per 1000, respectively, was: 10.2 and 1.3 for PTU; 17.8 and 2.3 for MMI/CMZ; 32.5 and 4.1 for both MMI/CMZ and PTU; and 9.6 and 1.2 for untreated hyperthyroidism.ConclusionsWhen appropriately analysed the risk of birth defects associated with ATD use in pregnancy is attenuated. Although still elevated, the risk of birth defects is smallest with PTU compared to MMI/CMZ and may be similar to that of untreated hyperthyroidism.
Population pharmacokinetics and genetics of oral meltdose tacrolimus (Envarsus) in stable adult liver transplant recipients
Authors: Martial Lisa C. , Biewenga Maaike , Ruijter Bastian N. , Keizer Ron , Swen Jesse J. , van Hoek Bart , Moes Dirk Jan A. R. 
Published: March 2021

AimsMeltdose tacrolimus (Envarsus) is marketed as a formulation with a more consistent exposure. Due to the narrow therapeutic window, therapeutic drug monitoring is essential to maintain adequate exposure. The primary objective of this study was to develop a population pharmacokinetic (PK) model of Envarsus among liver transplant patients and select a limited sampling strategy (LSS) for AUC estimation. The secondary objective was to investigate potential covariates including CYP3A/IL genotype suitable for initial dose optimization when converting to Envarsus.MethodsAdult liver transplant patients were converted from prolonged release tacrolimus (Advagraf) to Envarsus and blood samples were obtained using whole blood and dried blood spot sampling. Subsequently the population PK parameters were estimated using nonlinear‐mixed effect modelling. Demographic factors, and recipient and donor CYP3A4, CYP3A5, IL‐6, ‐10 and ‐18 genotype were tested as potential covariates to explain interindividual variability.ResultsFifty‐five patients were included. A 2‐compartment model with delayed absorption was the most suitable to describe population PK parameters. The population PK parameters were as follows: clearance, 3.27 L/h; intercompartmental clearance, 9.6 L/h; volume of distribution of compartments 1 and 2, 95 and 500 L, respectively. No covariates were found to significantly decrease interindividual variability. The best 3‐point LSS was t = 0,4,8 with a median bias of 1.8% (−12.5–12.5).ConclusionsThe LSS can be used to adequately predict the AUC. No clinically relevant covariates known to influence the PK of Envarsus, including CYP3A status, were identified and therefore do not seem useful for initial dose optimization.
A transformation‐free linear regression for compositional outcomes and predictors
Authors: Fiksel Jacob , Zeger Scott , Datta Abhirup 
Published: March 2021

AbstractCompositional data are common in many fields, both as outcomes and predictor variables. The inventory of models for the case when both the outcome and predictor variables are compositional is limited, and the existing models are often difficult to interpret in the compositional space, due to their use of complex log‐ratio transformations. We develop a transformation‐free linear regression model where the expected value of the compositional outcome is expressed as a single Markov transition from the compositional predictor. Our approach is based on estimating equations thereby not requiring complete specification of data likelihood and is robust to different data‐generating mechanisms. Our model is simple to interpret, allows for 0s and 1s in both the compositional outcome and covariates, and subsumes several interesting subcases of interest. We also develop permutation tests for linear independence and equality of effect sizes of two components of the predictor. Finally, we show that despite its simplicity, our model accurately captures the relationship between compositional data using two datasets from education and medical research.
On polygenic risk scores for complex traits prediction
Authors: Zhao Bingxin , Zou Fei 
Published: March 2021

AbstractPolygenic risk scores (PRS) have gained substantial attention for complex traits prediction in genome‐wide association studies (GWAS). Motivated by the polygenic model of complex traits, we study the statistical properties of PRS under the high‐dimensional but sparsity free setting where the triplet with being the sample size, the number of assayed single‐nucleotide polymorphisms (SNPs), and the number of assayed causal SNPs, respectively. First, we derive asymptotic results on the out‐of‐sample (prediction) R‐squared for PRS. These results help understand the widespread observed gap between the in‐sample heritability (or partial R‐squared due to the genetic features) estimate and the out‐of‐sample R‐squared for most complex traits. Next, we investigate how features should be selected (e.g., by a p‐value threshold) for constructing optimal PRS. We reveal that the optimal threshold depends largely on the genetic architecture underlying the complex trait and the sample size of the training GWAS, or the ratio. For highly polygenic traits with a large ratio, it is difficult to separate causal and null SNPs and stringent feature selection in principle often leads to poor PRS prediction. We numerically illustrate the theoretical results with intensive simulation studies and real data analysis on 33 complex traits with a wide range of genetic architectures in the UK Biobank database.
External validation of International Prognostic Score for asymptomatic early stage chronic lymphocytic leukaemia and proposal of an alternative score
Authors: Smolej Lukáš , Turcsányi Peter , Kubová Zuzana , Zuchnická Jana , Mihályová Jana , Šimkovič Martin , Vodárek Pavel , Krčméryová Mária , Móciková Heidi , Brejcha Martin , Špaček Martin ,   Czech CLL Study Group
Published: March 2021

SummaryMost patients with chronic lymphocytic leukaemia (CLL) are nowadays diagnosed without any symptoms and do not require therapy. A prognostic score identifying patients within this large group who are at high risk of disease progression would be highly beneficial. The recently published International Prognostic Score for Early asymptomatic patients (IPS‐E) uses combination of absolute lymphocyte count (ALC) >15 × 109/l, palpable lymphadenopathy, and unmutated immunoglobulin heavy‐chain variable‐region (IGHV) gene to predict the time to first‐line therapy (TTFT). Patients at low, intermediate, and high risk had estimated 5‐year TTFT of 8%, 28%, and 61%. We performed an external validation of the IPS‐E score using an unselected, consecutive group of 130 Binet A patients. The 5‐year TTFT was 11%, 36%, and 78% (C‐statistic 0·74). Furthermore, we propose an alternative system (AIPS‐E) using cytogenetic aberrations instead of palpable lymphadenopathy. This system yielded 5‐year TTFT of 14%, 40%, and 72%. These results were externally validated in 388 Binet A patients from five Czech centres; the 5‐year TTFT was 16%, 37%, and 80% (C‐statistic 0·74). In conclusion, we have successfully validated the IPS‐E score for patients with early stage CLL. In addition, we propose a modified scoring system, the AIPS‐E, combining IGHV, fluorescence in situ hybridisation, and ALC.
Beneficial intergenerational effects of exercise on brain and cognition: a multilevel meta‐analysis of mean and variance
Authors: Yang Yefeng , Lagisz Malgorzata , Foo Yong Zhi , Noble Daniel W. A. , Anwer Hamza , Nakagawa Shinichi 
Published: March 2021

ABSTRACTPhysical exercise not only helps to improve physical health but can also enhance brain development and cognition. Recent reports on parental (both maternal and paternal) effects raise the possibility that parental exercise may provide benefits to offspring through intergenerational inheritance. However, the general magnitude and consistency of parental exercise effects on offspring is still controversial. Additionally, empirical research has long overlooked an important aspect of exercise: its effects on variability in neurodevelopmental and cognitive traits. Here, we compiled data from 52 studies involving 4786 rodents (412 effect sizes) to quantify the intergenerational transmission of exercise effects on brain and cognition. Using a multilevel meta‐analytic approach, we found that, overall, parental exercise showed a tendency for increasing their offspring's brain structure by 12.7% (albeit statistically non‐significant) probably via significantly facilitating neurogenesis (16.5%). Such changes in neural anatomy go in hand with a significant 20.8% improvement in neurobehaviour (improved learning and memory, and reduced anxiety). Moreover, we found parental exercise significantly reduces inter‐individual differences (i.e. reduced variance in the treatment group) in progeny's neurobehaviour by 10.2% (coefficient of variation ratio, lnCVR), suggesting the existence of an individual by intervention interaction. The positive effects of exercise are modulated by several covariates (i.e. moderators), such as the exercised parent's sex, offspring's sex, and age, mode of exercise, and exercise timing. In particular, parental forced exercise is more efficient than voluntary exercise at significantly improving offspring neurobehaviour (26.0%) and reducing its variability (14.2%). We observed larger effects when parental exercise started before pregnancy. However, exercising only during pregnancy also had positive effects. Mechanistically, exercise significantly upregulated brain‐derived neurotrophic factor (BDNF) by 28.9%, vascular endothelial growth factor (VEGF) by 35.8%, and significantly decreased hippocampal DNA methylation by 3.5%, suggesting that brain growth factor cascades and epigenetic modifications can moderate the transmission of parental exercise effects. Collectively, by coupling mean with variance effects, our analyses draw a more integrated picture of the benefits that parental exercise has on offspring: not only does it improve offspring brain development and cognitive performance, but it also reduces inter‐individual differences in cognition‐related traits. We advocate that meta‐analysis of variation together with the mean of a trait provides novel insights for old controversies as well as emerging new questions, opening up a new era for generating variance‐based hypotheses.
VPS33B interacts with NESG1 to suppress cell growth and cisplatin chemoresistance in ovarian cancer
Authors: Ning Yingxia , Zeng Zhaoyang , Deng Yuao , Feng Weifeng , Huang Lun , Liu Huiling , Lin Jiazhi , Zhang Chen , Fan Yue , Liu Longyang 
Published: March 2021

AbstractThe pathogenesis and cisplatin chemoresistance of ovarian cancer (OC) are still unclear. Vacuolar protein sorting‐associated 33B (VPS33B) has not been reported in OC to date. In this study, immunohistochemistry was used to detect VPS33B protein expression between OC and ovarian tissues. MTT, EdU, colony formation, cell cycle, in vivo tumorigenesis, western blot, ChIP, EMSA, co‐immunoprecipitation (CoIP), qRT‐PCR, and microconfocal microscopy were used to explore the function and molecular mechanisms of VPS33B in OC cells. The results of the present study demonstrated that VPS33B protein expression was obviously reduced in OC compared with that in ovarian tissues. Overexpressed VPS33B suppressed cell cycle transition, cell growth, and chemoresistance to cisplatin in vitro and in vivo. Analysis of the mechanism indicated that overexpressed VPS33B regulated the epidermal growth factor receptor (EGFR)/PI3K/AKT/c‐Myc/p53/miR‐133a‐3p feedback loop and reduced the expression of the cell cycle factor CDK4. Nasopharyngeal epithelium‐specific protein 1 (NESG1) as a tumor suppressor not only interacted with VPS33B, but was also induced by VPS33B by the attenuation of PI3K/AKT/c‐Jun‐mediated transcription inhibition. Overexpressed NESG1 further suppressed cell growth by mediating VPS33B‐modulated signals in VPS33B‐overexpressing OC cells. Finally, NESG1 induced VPS33B expression by reducing the inhibition of PI3K/AKT/c‐Jun‐mediated transcription. Our study is the first to demonstrate that VPS33B serves as a tumor suppressor, and VPS33B can interact with NESG1 to suppress cell growth and promote cisplatin sensitivity by regulating the EGFR/PI3K/AKT/c‐Myc/p53/miR‐133a‐3p feedback loop in OC cells.
Identification of cancer driver genes using Sleeping Beauty transposon mutagenesis
Authors: Takeda Haruna , Jenkins Nancy A. , Copeland Neal G. 
Published: March 2021

AbstractCancer genome sequencing studies have identified driver genes for a variety of different cancers and helped to understand the genetic landscape of human cancer. It is still challenging, however, to identify cancer driver genes with confidence simply from genetic data alone. In vivo forward genetic screens using Sleeping Beauty (SB) transposon mutagenesis provides another powerful genetic tool for identifying candidate cancer driver genes in wild‐type and sensitized mouse tumors. By comparing cancer driver genes identified in human and mouse tumors, cancer driver genes can be identified with additional confidence based upon comparative oncogenomics. This review describes how SB mutagenesis works in mice and focuses on studies that have identified cancer driver genes in the mouse gastrointestinal tract.
Examining the Effects of Changes in Classroom Quality on Within‐Child Changes in Achievement and Behavioral Outcomes
Authors: Watts Tyler W. , Nguyen Tutrang , Carr Robert C. , Vernon‐Feagans Lynne , Blair Clancy 
Published: March 2021

This study examines whether changes in classroom quality predict within‐child changes in achievement and behavioral problems in elementary school (ages spanning approximately 6–11 years old). Drawing on data from a longitudinal study of children in predominantly low‐income, nonurban communities (n = 1,078), we relied on child fixed effects modeling, which controlled for stable factors that could bias the effects of classroom quality. In general, we found that changes in classroom quality had small and statistically nonsignificant effects on achievement and behavior. However, we found that moving into a high‐quality classroom, particularly those rated as high in Classroom Organization, had positive effects on achievement and behavior for children with significant exposure to poverty in early life.