bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mapping the genetic landscape of early-onset Alzheimer’s disease in a cohort of 36 families
Authors: Mol Merel O. , van der Lee Sven J. , Hulsman Marc , Pijnenburg Yolande A. L. , Scheltens Phillip ,   Netherlands Brain Bank, Seelaar Harro , van Swieten John C. , Kaat Laura Donker , Holstege Henne , van Rooij Jeroen G. J. 
Published: June 2022

AbstractBackgroundMany families with clinical early-onset Alzheimer’s disease (EOAD) remain genetically unexplained. A combination of genetic factors is not standardly investigated. In addition to monogenic causes, we evaluated the possible polygenic architecture in a large series of families, to assess if genetic testing of familial EOAD could be expanded.MethodsThirty-six pedigrees (77 patients) were ascertained from a larger cohort of patients, with relationships determined by genetic data (exome sequencing data and/or SNP arrays). All families included at least one AD patient with symptom onset <70 years. We evaluated segregating rare variants in known dementia-related genes, and other genes or variants if shared by multiple families.APOEwas genotyped and duplications inAPPwere assessed by targeted test or using SNP array data. We computed polygenic risk scores (PRS) compared with a reference population-based dataset, by imputing SNP arrays or exome sequencing data.ResultsIn eight families, we identified a pathogenic variant, including the genesAPP,PSEN1,SORL1, and an unexpectedGRNframeshift variant.APOE-ε4 homozygosity was present in eighteen families, showing full segregation with disease in seven families. Eight families harbored a variant of uncertain significance (VUS), of which six includedAPOE-ε4 homozygous carriers. PRS was not higher in the families combined compared with the population mean (beta 0.05,P= 0.21), with a maximum increase of 0.61 (OR = 1.84) in theGRNfamily. Subgroup analyses indicated lower PRS in sixAPP/PSEN1families compared with the rest (beta −0.22 vs. 0.10;P= 0.009) and lowerAPOEburden in all eight families with monogenic cause (beta 0.29 vs. 1.15,P= 0.010). Nine families remained without a genetic cause or risk factor identified.ConclusionBesides monogenic causes, we suspect a polygenic disease architecture in multiple families based onAPOEand rare VUS. The risk conveyed by PRS is modest across the studied families. Families without any identified risk factor render suitable candidates for further in-depth genetic evaluation.
Autism-associated protein POGZ controls ESCs and ESC neural induction by association with esBAF
Authors: Sun Xiaoyun , Cheng Linxi , Sun Yuhua 
Published: June 2022

Abstract
Background
The POGZ gene has been found frequently mutated in neurodevelopmental disorders (NDDs), particularly autism spectrum disorder (ASD) and intellectual disability (ID). However, little is known about its roles in embryonic stem cells (ESCs), neural development and diseases.

Methods
We generated Pogz−/− ESCs and directed ESC differentiation toward a neural fate. We performed biochemistry, ChIP-seq, ATAC-seq, and bioinformatics analyses to understand the role of POGZ.

Results
We show that POGZ is required for the maintenance of ESC identity and the up-regulation of neural genes during ESC differentiation toward a neural fate. Genome-wide binding analysis shows that POGZ is primarily localized to gene promoter and enhancer regions. POGZ functions as both a transcriptional activator and repressor, and its loss leads to deregulation of differentiation genes, including neural genes. POGZ physically associates with the SWI-SNF (esBAF) chromatin remodeler complex, and together they modulate enhancer activities via epigenetic modifications such as chromatin remodeling and histone modification. During ESC neural induction, POGZ-mediated recruitment of esBAF/BRG1 and H3K27ac are important for proper expression of neural progenitor genes.

Limitations
The genotype and allele relevant to human neurodevelopmental disorders is heterozygous loss of function. This work is designed to study the effects of loss of POGZ function on ESCs and during ESC neural induction. Also, this work lacks of in vivo validation using animal models.

Conclusions
The data suggest that POGZ is both a transcription factor and a genome regulator, and its loss leads to defects in neural induction and neurogenesis.
The inhibition of tamoxifen on UGT2B gene expression and enzyme activity in rat liver contribute to the estrogen homeostasis dysregulation
Authors: Hao Zhixiang , Xu Jiahao , Zhao Han , Zhou Wei , Liu Zhao , He Shiqing , Yin Xiaoxing , Zhang Bei , Wang Zhongjian , Zhou Xueyan 
Published: June 2022

Abstract
Background
Tamoxifen treatment may induce dysregulation of estrogen homeostasis, leading to the occurrence of related adverse reactions. However, the potential mechanisms are still unclear. The purpose of the present study was to uncover whether tamoxifen treatment would act on estrogen metabolism-related biological enzymes and the regulatory effect on estrogen homeostasis to clarify the key factors and potential mechanisms of adverse reactions caused by long-term use of tamoxifen.

Method
Female SD rats were administrated with tamoxifen CMC-Na solution (p.o.) once daily for four weeks and then housed at room temperature. Serum, breast, liver, uterus, and ovarian tissues were obtained, and the effects of tamoxifen administration on estrogen homeostasis, the expression, and activity of estrogen metabolic enzyme were evaluated.

Results
Compared with the control group, the estrogen homeostasis was disturbed and the expression and activity of UGT2B1 (homology with human UGT2B7) were significantly reduced in the rats administrated with tamoxifen. The inhibitory effect of tamoxifen on UGT2B7 was dominated by hydrophobic and π-π stacking interactions, resulting in a concentration-dependent inhibition of UGT2B7 activity by tamoxifen and the imbalance of ligand-activated transcription factors, leading to abnormal regulation of UGT2B and disturbance of estrogen homeostasis, which in turn led to adverse reactions of tamoxifen.

Conclusion
We established links between estrogen metabolism and tamoxifen administration and we proposed that the UGT2B inhibition was involved in the disturbance of estrogen homeostasis and the occurrence of tamoxifen-related adverse reactions.
Fairness in assessment practices in online education: Iranian University English teachers’ perceptions
Authors: Azizi Zeinab 
Published: June 2022

AbstractAlthough fairness in assessment practices (APs) in traditional classes has gained noticeable attention in recent years, it has remained unexplored in online education (OE). Thus, this study explores Iranian university English teachers’ perceptions of fair APs in OE. For this purpose, 21 university English teachers from Lorestan University and Ayatollah Borujerdi University, Iran, were selected using a purposive sampling method. They were invited to express their conceptions of fair APs by completing a reflective written statement questionnaire. The collected data were subjected to a thematic coding analysis. The results yielded three overarching categories: distributive justice (i.e., equality should be considered, equity is of paramount importance, and assessment practices should be tied with students’ needs), procedural justice (i.e., voices of students should be heard, both consistency and flexibility are required, and assessment procedures should be transparent), and interactional justice (i.e., interpersonal justice is crucial and informational justice should be considered). The study concludes by proposing a range of implications for different testing stakeholders.
Breakfast skipping and its relationship with academic performance in Ethiopian school-aged children, 2019
Authors: Abebe Lulu , Mengistu Nebiyu , Tesfaye Tinsae Shemelise , Kabthymer Robel Hussen , Molla Wondwosen , Tarekegn Desalegn , Wudneh Aregahegn , Shonor Misrak Negash , Yimer Solomon 
Published: June 2022

AbstractBreakfast skipping and its relationship with academic achievement among primary school children were investigated in this study. A cross-sectional study was conducted among 848 primary school children. Breakfast skipping was analyzed using a 2-item questionnaire. A 19-item Social Academic and Emotional Behavior Risk Screening questionnaire was used to collect data on children’s behavior. The prevalence of breakfast skipping was found to be 38.1%. Living in a rural area (AOR = 5.2; 95% CI: 3.54, 7.71); having illiterate parents (AOR = 6.66; 95% CI 3.0, 14.7); having parents with a primary education level (AOR 5.18, 95% CI: 2.25, 11.94); living with guardians or other relatives (AOR = 4.06; 95%CI: 2.1, 7.9); and having lower academic achievement (AOR = 2.76; 95% CI: 1.44, 5.29) were factors associated with skipping breakfast.In conclusion, breakfast skipping has been identified as a significant public health concern that requires an immediate response from stakeholders. It is recommended to intervene based on the identified factors.
Comparing self-reported and measured hypertension and hypercholesterolaemia at standard and more stringent diagnostic thresholds: the cross-sectional 2010–2015 Busselton Healthy Ageing study
Authors: Burvill Angela J , Murray Kevin , Knuiman Matthew W , Hung Joseph 
Published: June 2022

Abstract
Background
Population health behaviour and risk factor surveys most often rely on self-report but there is a lack of studies assessing the validity of self-report using Australian data. This study investigates the sensitivity, specificity and agreement of self-reported hypertension and hypercholesterolaemia with objective measures at standard and more stringent diagnostic thresholds; and factors associated with sensitivity and specificity of self-report at different thresholds.

Methods
This study was a secondary analysis of a representative community-based cross-sectional sample of 5,092 adults, aged 45–69 years, residing in Busselton, Western Australia, surveyed in 2010–2015. Participants completed a self-administered questionnaire. Blood pressure and serum cholesterol levels were measured.

Results
At currently accepted diagnostic thresholds, sensitivities of self-reported hypertension and hypercholesterolaemia were 58.5% and 39.6%, respectively and specificities were >90% for both. Agreement using Cohen’s kappa coefficient was 0.562 and 0.223, respectively. At two higher diagnostic thresholds, sensitivities of self-reported hypertension and hypercholesterolaemia improved by an absolute 14–23% and 15–25%, respectively and specificities remained >85%. Agreement was substantial for hypertension (kappa = 0.682–0.717) and moderate for hypercholesterolaemia (kappa = 0.458–0.533). Variables that were independently associated with higher sensitivity and lower specificity of self-report were largely consistent across thresholds and included increasing age, body mass index, worse self-rated health, diabetes and family history of hypertension.

Conclusions
Self-reported hypertension and hypercholesterolaemia often misclassify individuals’ objective status and underestimate objective prevalences, at standard diagnostic thresholds, which has implications for surveillance studies that rely on self-reported data. Self-reports of hypertension, however, may be reasonable indicators of those with blood pressures ≥160/100 mmHg or those taking anti-hypertensive medications. Self-reported hypercholesterolaemia data should be used with caution at all thresholds.
Effect of carbohydrate-restricted diets and intermittent fasting on obesity, type 2 diabetes mellitus, and hypertension management: consensus statement of the Korean Society for the Study of obesity, Korean Diabetes Association, and Korean Society of Hypertension
Authors: Choi Jong Han , Cho Yoon Jeong , Kim Hyun-Jin , Ko Seung-Hyun , Chon Suk , Kang Jee-Hyun , Kim Kyoung-Kon , Kim Eun Mi , Kim Hyun Jung , Song Kee-Ho , Nam Ga Eun , Kim Kwang Il ,   Committee of Clinical Practice Guidelines, Korean Society for the Study of Obesity (KSSO), Committee of Clinical Practice Guidelines and Committee of Food and Nutrition, Korean Diabetes Association (KDA), Policy Committee of Korean Society of Hypertension (KSH), Policy Development Committee of National Academy of Medicine of Korea (NAMOK)
Published: June 2022

Abstract
Background
Carbohydrate-restricted diets and intermittent fasting (IF) have been rapidly gaining interest among the general population and patients with cardiometabolic disease, such as overweight or obesity, diabetes, and hypertension. However, there are limited expert recommendations for these dietary regimens. This study aimed to evaluate the level of scientific evidence on the benefits and harms of carbohydrate-restricted diets and IF to make responsible recommendations.

Methods
A meta-analysis and systematic literature review of 66 articles on 50 randomized controlled clinical trials (RCTs) of carbohydrate-restricted diets and ten articles on eight RCTs of IF was performed.

Results
Based on the analysis, the following recommendations are suggested. In adults with overweight or obesity, a moderately-low carbohydrate or low carbohydrate diet (mLCD) can be considered as a dietary regimen for weight reduction. In adults with type 2 diabetes, mLCD can be considered as a dietary regimen for improving glycemic control and reducing body weight. In contrast, a very-low carbohydrate diet (VLCD) and IF are recommended against in patients with diabetes. Furthermore, no recommendations are suggested for VLCD and IF in adults with overweight or obesity, and carbohydrate-restricted diets and IF in patients with hypertension.

Conclusion
Here, we describe the results of our analysis and the evidence for these recommendations.
Character strengths as protective factors against behavior problems in early adolescent
Authors: Qin Cheng , Cheng Xiaotong , Huang Yuyan , Xu Shuang , Liu Kezhi , Tian Mingyuan , Liao Xiaoyuan , Zhou Xinyi , Xiang Bo , Lei Wei , Chen Jing 
Published: June 2022

AbstractCharacter strengths could effectively prevent negative psychological outcomes in adults. However, there was little research conducted among early adolescents. The present study aimed to explore character strengths that were independently related to fewer behavior problems in early adolescents. In total, 521 early adolescents (mean age 10.92 ± 0.04, range 10–12 years) were recruited from primary schools in Sichuan, China. Character strengths were measured using the Values in Action Inventory of Strengths for Youth (VIA-Youth). Behavior problems were measured using the Conners Parent Symptom Questionnaire (PSQ). The results showed that behavior problems were negatively correlated with character strengths (r= −0.14 to −0.3,p< 0.05 Bonferroni corrected). Character strengths explained a significant proportion of additional variance (14–22%) in five types of behavior problems after controlling the effect of demographic factors (residence, left-behind experiences, maternal education level). Moreover, several specific character strengths showed an independent contribution (β= −0.34 to −0.14 for self-regulation, perseverance, zest, humility, and leadership;β= 0.21 to 0.34, for hope; allp< 0.05) to behavior problems. Our study revealed that character strengths were protective factors against behavior problems in early adolescents.
Adaptive local discontinuous Galerkin methods with semi-implicit time discretizations for the Navier-Stokes equations
Authors: Meng Xiangyi , Xu Yan 
Published: June 2022

AbstractIn this paper, we present a mesh adaptation algorithm for the unsteady compressible Navier-Stokes equations under the framework of local discontinuous Galerkin methods coupled with implicit-explicit Runge-Kutta or spectral deferred correction time discretization methods. In both of the two high order semi-implicit time integration methods, the convective flux is treated explicitly and the viscous and heat fluxes are treated implicitly. The remarkable benefits of such semi-implicit temporal discretizations are that they can not only overcome the stringent time step restriction compared with time explicit methods, but also avoid the construction of the large Jacobian matrix as is done for fully implicit methods, thus are relatively easy to implement. To save computing time as well as capture the flow structures of interest accurately, a local mesh refinement (h-adaptive) technique, in which we present detailed criteria for selecting candidate elements and complete strategies to refine and coarsen them, is also applied for the Navier-Stokes equations. Numerical experiments are provided to illustrate the high order accuracy, efficiency and capabilities of the semi-implicit schemes in combination with adaptive local discontinuous Galerkin methods for the Navier-Stokes equations.
Opportunities and Challenges for PBPK Model of mAbs in Paediatrics and Pregnancy
Authors: Gill Katherine L. , Jones Hannah M. 
Published: June 2022

AbstractNew drugs may in some cases need to be tested in paediatric and pregnant patients. However, it is difficult to recruit such patients and there are many ethical issues around their inclusion in clinical trials. Modelling and simulation can help to plan well-designed clinical trials with a reduced number of participants and to bridge gaps where recruitment is difficult. Physiologically based pharmacokinetic (PBPK) models for small molecule drugs have been used to aid study design and dose adjustments in paediatrics and pregnancy, with several publications in the literature. However, published PBPK models for monoclonal antibodies (mAb) in these populations are scarce. Here, the current status of mAb PBPK models in paediatrics and pregnancy is discussed. Seven mAb PBPK models published for paediatrics were found, which report good prediction accuracy across a wide age range. No mAb PBPK models for pregnant women have been published to date. Current challenges to the development of such PBPK models are discussed, including gaps in our knowledge of relevant physiological processes and availability of clinical data to verify models. As the availability of such data increases, it will help to improve our confidence in the PBPK model predictive ability. Advantages for using PBPK models to predict mAb PK in paediatrics and pregnancy are discussed. For example, the ability to incorporate ontogeny and gestational changes in physiology, prediction of maternal, placental and foetal exposure and the ability to make predictions fromin vitroand preclinical data prior to clinical data being available.
Enhanced ferroelectricity by strain gradient in few-layer HfO2thin films
Authors: Chen Jianwen , Zhao Wei , Song Wenjing , Cao Wang , Ding Jianwen 
Published: June 2022

Abstract
Due to the great potential in reducing the size of ferroelectric memory cells and the good compatibility with traditional silicon process, the ferroelectricity of few-layer HfO2 thin films has received huge attention, but its microscopic mechanism is still unclear. Based on first-principles calculations, the ferroelectricity of few-layer HfO2 thin films in the presence of both strain and strain gradient has been investigated systematically. It is shown that the orthorhombic ferroelectric phase exists stably with the strain between −7% and 3%, and the ferroelectric polarization decreases monotonically with the strain increasing, which is consistent with previous studies. In particular, the ferroelectric polarization increases monotonically with the strain gradient increasing within the strain less than −2.5%, which is due to the fact that the strain gradient further separates the positive and negative centers. Our findings provide possible theoretical explanations for recent experimental results and technical guidance for the design of ultra-thin ferroelectric devices.
Natural history study and statistical modeling of disease progression in a preclinical model of myotubular myopathy
Authors: Buono Suzie , Monseur Arnaud , Menuet Alexia , Robé Anne , Koch Catherine , Laporte Jocelyn , Thielemans Leen , Depla Marion , Cowling Belinda S. 
Published: June 2022

ABSTRACT
Generating reliable preclinical data in animal models of disease is essential in therapy development. Here, we performed statistical analysis and joint longitudinal–survival modeling of the progressive phenotype observed in Mtm1−/y mice, a reliable model for myotubular myopathy. Analysis of historical data was used to generate a model for phenotype progression, which was then confirmed with phenotypic data from a new colony of mice derived via in vitro fertilization in an independent animal house, highlighting the reproducibility of disease phenotype in Mtm1−/y mice. These combined data were used to refine the phenotypic parameters analyzed in these mice and improve the model generated for expected disease progression. The disease progression model was then used to test the therapeutic efficacy of Dnm2 targeting. Dnm2 reduction by antisense oligonucleotides blocked or postponed disease development, and resulted in a significant dose-dependent improvement outside the expected disease progression in untreated Mtm1−/y mice. This provides an example of optimizing disease analysis and testing therapeutic efficacy in a preclinical model, which can be applied by scientists testing therapeutic approaches using neuromuscular disease models in different laboratories.
This article has an associated First Person interview with the joint first authors of the paper.
Association between the body mass index, waist circumference, and body fat percentage with erosive esophagitis in adults with obesity after sleeve gastrectomy
Authors: Zevallos-Ventura Alba S. , de la Cruz-Ku Gabriel , Runzer-Colmenares Fernando M. , Pinto-Elera Jesús , Toro-Huamanchumo Carlos J. 
Published: June 2022

Background: High anthropometric indexes before sleeve gastrectomy (SG) are associated with an increased risk of erosive esophagitis (EE) in bariatric surgery candidates. Reasons that explain how these indexes influence the development of esophageal pathology after surgery remains unclear. Objectives: To assess the association between the body mass index (BMI), waist circumference (WC), and body fat percentage (BFP) with the development of EE in adults with obesity three months after SG. Setting: Clínica Avendaño, Lima, Peru. Methods: Retrospective cohort using a database including adults with obesity who underwent SG during 2017-2020. All the patients included had an endoscopy before and after the surgery. Sociodemographic, clinical and laboratory characteristics were compared according to BMI, WC and BFP, as well as by the development of de novo esophagitis. The association was evaluated by crude and adjusted generalized linear models with the log-Poisson family. Results: From a total of 106 patients, 23 (21.7%) developed EE. We did not find significant differences in sociodemographic, clinical and laboratory characteristics between patients with de novo EE compared to those who did not develop EE. After adjustment, BMI (aRR = 0.59, 95% CI = 0.18-1.40), BFP (aRR = 0.41, 95% CI = 0.15-1.19) and WC (aRR = 0.91, 95% CI = 0.69-1.16) were not associated with the development of EE three months post SG. Conclusions: We found no association between preoperative anthropometric indexes and the development of de novo EE; therefore, morbid obesity should not be a criterion to exclude the patients to undergo SG as primary surgery because of the risk of developing EE.