bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induced pluripotent stem cell-derived cells model brain microvascular endothelial cell glucose metabolism
Authors: Weber Callie M. , Moiz Bilal , Zic Sophia M. , Alpízar Vargas Viviana , Li Andrew , Clyne Alisa Morss 
Published: December 2022

AbstractGlucose transport from the blood into the brain is tightly regulated by brain microvascular endothelial cells (BMEC), which also use glucose as their primary energy source. To study how BMEC glucose transport contributes to cerebral glucose hypometabolism in diseases such as Alzheimer’s disease, it is essential to understand how these cells metabolize glucose. Human primary BMEC (hpBMEC) can be used for BMEC metabolism studies; however, they have poor barrier function and may not recapitulate in vivo BMEC function. iPSC-derived BMEC-like cells (hiBMEC) are readily available and have good barrier function but may have an underlying epithelial signature. In this study, we examined differences between hpBMEC and hiBMEC glucose metabolism using a combination of dynamic metabolic measurements, metabolic mass spectrometry, RNA sequencing, and Western blots. hiBMEC had decreased glycolytic flux relative to hpBMEC, and the overall metabolomes and metabolic enzyme levels were different between the two cell types. However, hpBMEC and hiBMEC had similar glucose metabolism, including nearly identical glucose labeled fractions of glycolytic and TCA cycle metabolites. Treatment with astrocyte conditioned media and high glucose increased glycolysis in both hpBMEC and hiBMEC, though hpBMEC decreased glycolysis in response to fluvastatin while hiBMEC did not. Together, these results suggest that hiBMEC can be used to model cerebral vascular glucose metabolism, which expands their use beyond barrier models.
Four-dimensional measurement of root system development using time-series three-dimensional volumetric data analysis by backward prediction
Authors: Teramoto Shota , Uga Yusaku 
Published: December 2022

Abstract
Background
Root system architecture (RSA) is an essential characteristic for efficient water and nutrient absorption in terrestrial plants; its plasticity enables plants to respond to different soil environments. Better understanding of root plasticity is important in developing stress-tolerant crops. Non-invasive techniques that can measure roots in soils nondestructively, such as X-ray computed tomography (CT), are useful to evaluate RSA plasticity. However, although RSA plasticity can be measured by tracking individual root growth, only a few methods are available for tracking individual roots from time-series three-dimensional (3D) images.

Results
We developed a semi-automatic workflow that tracks individual root growth by vectorizing RSA from time-series 3D images via two major steps. The first step involves 3D alignment of the time-series RSA images by iterative closest point registration with point clouds generated by high-intensity particles in potted soils. This alignment ensures that the time-series RSA images overlap. The second step consists of backward prediction of vectorization, which is based on the phenomenon that the root length of the RSA vector at the earlier time point is shorter than that at the last time point. In other words, when CT scanning is performed at time point A and again at time point B for the same pot, the CT data and RSA vectors at time points A and B will almost overlap, but not where the roots have grown. We assumed that given a manually created RSA vector at the last time point of the time series, all RSA vectors except those at the last time point could be automatically predicted by referring to the corresponding RSA images. Using 21 time-series CT volumes of a potted plant of upland rice (Oryza sativa), this workflow revealed that the root elongation speed increased with age. Compared with a workflow that does not use backward prediction, the workflow with backward prediction reduced the manual labor time by 95%.

Conclusions
We developed a workflow to efficiently generate time-series RSA vectors from time-series X-ray CT volumes. We named this workflow 'RSAtrace4D' and are confident that it can be applied to the time-series analysis of RSA development and plasticity.
Ethnic and racial-specific differences in levels of centrosome-associated mitotic kinases, proliferative and epithelial-to-mesenchymal markers in breast cancers
Authors: Rivera-Rivera Yainyrette , Vargas Geraldine , Jaiswal Neha , Núñez-Marrero Angel , Li Jiannong , Chen Dung-Tsa , Eschrich Steven , Rosa Marilin , Johnson Joseph O. , Dutil Julie , Chellappan Srikumar P. , Saavedra Harold I. 
Published: December 2022

AbstractMolecular epidemiology evidence indicates racial and ethnic differences in the aggressiveness and survival of breast cancer. Hispanics/Latinas (H/Ls) and non-Hispanic Black women (NHB) are at higher risk of breast cancer (BC)-related death relative to non-Hispanic white (NHW) women in part because they are diagnosed with hormone receptor-negative (HR) subtype and at higher stages. Since the cell cycle is one of the most commonly deregulated cellular processes in cancer, we propose that the mitotic kinases TTK (or Mps1), TBK1, and Nek2 could be novel targets to prevent breast cancer progression among NHBs and H/Ls. In this study, we calculated levels of TTK, p-TBK1, epithelial (E-cadherin), mesenchymal (Vimentin), and proliferation (Ki67) markers through immunohistochemical (IHC) staining of breast cancer tissue microarrays (TMAs) that includes samples from 6 regions in the Southeast of the United States and Puerto Rico -regions enriched with NHB and H/L breast cancer patients. IHC analysis showed that TTK, Ki67, and Vimentin were significantly expressed in triple-negative (TNBC) tumors relative to other subtypes, while E-cadherin showed decreased expression. TTK correlated with all of the clinical variables but p-TBK1 did not correlate with any of them. TCGA analysis revealed that the mRNA levels of multiple mitotic kinases, including TTK, Nek2, Plk1, Bub1, and Aurora kinases A and B, and transcription factors that are known to control the expression of these kinases (e.g. FoxM1 and E2F1-3) were upregulated in NHBs versus NHWs and correlated with higher aneuploidy indexes in NHB, suggesting that these mitotic kinases may be future novel targets for breast cancer treatment in NHB women.
Extended treatment of multimodal cognitive behavioral therapy in children and adolescents with obsessive–compulsive disorder improves symptom reduction: a within-subject design
Authors: Adam Julia , Goletz Hildegard , Dengs Stefanie , Klingenberger Nora , Könnecke Sonja , Vonderbank Christina , Hautmann Christopher , Hellmich Martin , Plück Julia , Döpfner Manfred 
Published: December 2022

Abstract
Background
Based on the current state of research regarding the treatment in pediatric obsessive–compulsive disorder (OCD), cognitive behavioral therapy (CBT) (in severe cases with additional pharmacotherapy) is considered as the first-line treatment according to internationally recognized guidelines. Research is mostly based on randomized controlled trials (RCTs; efficacy research). Thus, examined treatment conditions, especially the treatment duration, and patients’ characteristics do not necessarily correspond to those found within routine care. Studies showed CBT packages as a whole to be efficacious, but less is known about the effects of individual CBT components. Furthermore, effects on comorbid symptoms or psychosocial impairment have been often neglected and different rater perspectives have been hardly considered in previous research.

Methods
This effectiveness study aimed to examine the effects of multimodal CBT in children, adolescents, and young adults (age 6–20 years) with OCD (n = 38) within routine care. Effects on obsessive–compulsive and co-existing symptoms were evaluated in a within-subject design by comparing changes during the assessment phase with 12-week standard treatment and with individually tailored extended treatment. Additionally, within the standard treatment, non-exposure treatment was compared to exposure treatment. Multi-informant assessment was applied, and the analyses included multilevel modeling and t-tests for pre-post comparisons.

Results
During the standard treatment and extended treatment, obsessive–compulsive symptoms, strain, and functional impairment significantly decreased. Moreover, a significant reduction of overall comorbid symptoms emerged, particularly regarding internalizing symptoms, including anxiety and depression. Comparisons of treatment components indicated that adding exposure with response prevention (ERP) has an additional positive effect. Clinical improvement and remission rates increased considerably when more treatment sessions were provided.

Conclusions
These results suggest that improvement after an initial 12-week course of treatment may not allow for the prediction of non-responders/non-remitters and for the termination of treatment. Overall, the findings show that results from randomized controlled trials are transferrable to routine care.
Trial registration number This study was registered retrospectively at the German Clinical Trials Register (https://drks.de/search/de/trial/DRKS00030050).
Robust and rigorous identification of tissue-specific genes by statistically extending tau score
Authors: Lüleci Hatice Büşra , Yılmaz Alper 
Published: December 2022

Abstract
Objectives
In this study, we aimed to identify tissue-specific genes for various human tissues/organs more robustly and rigorously by extending the tau score algorithm.

Introduction
Tissue-specific genes are a class of genes whose functions and expressions are preferred in one or several tissues restrictedly. Identification of tissue-specific genes is essential for discovering multi-cellular biological processes such as tissue-specific molecular regulations, tissue development, physiology, and the pathogenesis of tissue-associated diseases.

Materials and Methods
Gene expression data derived from five large RNA sequencing (RNA-seq) projects, spanning 96 different human tissues, were retrieved from ArrayExpress and ExpressionAtlas. The first step is categorizing genes using significant filters and tau score as a specificity index. After calculating tau for each gene in all datasets separately, statistical distance from the maximum expression level was estimated using a new meaningful procedure. Specific expression of a gene in one or several tissues was calculated after the integration of tau and statistical distance estimation, which is called as extended tau approach. Obtained tissue-specific genes for 96 different human tissues were functionally annotated, and some comparisons were carried out to show the effectiveness of the extended tau method.

Results and Discussion
Categorization of genes based on expression level and identification of tissue-specific genes for a large number of tissues/organs were executed. Genes were successfully assigned to multiple tissues by generating the extended tau approach as opposed to the original tau score, which can assign tissue specificity to single tissue only.
Evaluation of carotid intima media thickness in children with idiopathic nephrotic syndrome
Authors: Kamel Ashraf Sayed , AlGhawass Mohamed Mohamed Ezzat , Sayed Muhammad Adel , Roby Sara Aly 
Published: December 2022

Abstract
Background
Nephrotic syndrome is the one of the commonest renal disorders in children. Children with nephrotic syndrome (NS) are at a high risk of atherosclerosis due to hyperlipidemia, hypertension. Carotid intima media thickness (CIMT) is a surrogate marker for atherosclerosis. This study aimed to evaluate the carotid intima media thickness in children with nephrotic syndrome and its relation to different risk factors.

Methods
This is an observational case control study that included forty children with nephrotic syndrome and thirty healthy children as controls. The inclusion criteria were: age of 2 years or more with disease duration of minimum of 1 year and glomerular filtration rate > 90 mL/min/1.73m2. CIMT was assessed by ultrasound. Lipid profile, protein/creatinine ratio in urine and kidney function tests were done.

Results
The mean CIMT (mm) was significantly higher in patients with NS (0.477 ± 0.04) compared to controls (0.39 ± 0.03) (P < 0.001) even when compared across different age groups. 60% of patients had received non-steroid immunosuppressive therapy. CIMT was significantly higher in patients receiving non-steroid immunosuppressive therapy than those receiving steroids alone. Subsequently, CIMT had significant positive correlation to duration of the disease (p = 0.05), body mass index (BMI) (p = 0.03), number of relapses (p = 0.01) and diastolic blood pressures (p = 0.003).

Conclusion
Children with NS had significantly higher CIMT than control group. CIMT was positively correlated to disease duration, number of relapses and BMI. It was significantly higher among patients receiving non-steroid immunosuppressive therapy than those receiving steroids alone.
The awareness and acceptance of anti-COVID 19 vaccination in adolescence
Authors: Cupertino Vita , Bozzola Elena , De Luca Giampaolo , Del Giudice Emanuela , De Martino Giuseppe , Cannataro Piero , Tozzi Alberto Eugenio , Corsello Giovanni 
Published: December 2022

Abstract
Background
COVID-19 had devastating effects on children’s and adolescents’ life, including neuropsychological impairment, discontinuation of social life and education.
Since June 2021, antiCOVID19 vaccination has become available to adolescents in Italy up to 12 years and since December 2021 to children aged more than 5 years. The pediatric population represents a challenging target for vaccination. Aim of the study is to perform a survey among adolescents to explore factors associated with COVID 19 immunization and their perceptions about COVID-19 vaccines.

Methods
Italian students aged 10–17 years were invited to participate in an anonymous online survey regarding their immunization against COVID-19 and their opinion on the immunization practice through a web link to the questionnaire. The study period was March-June 2022. Statistical analysis was performed with SPSS v 21.

Results
In the study period, 895 students entered the survey. A total of 87.3% of respondents were immunized against SARS-CoV2. The most important predictors of being immunized against SARS-CoV2 were having both parents immunized (p < 0, 001) and being aged over 12 years. In the unvaccinated group, the decision was mostly influenced by the family (65.8%). Regardless the immunization status, respondents were willing to receive information about COVID 19 vaccination mostly by their family doctor (51.8%) and at school (28.9%).

Conclusions
Parents’ decisions and attitudes strongly affected the immunization status of adolescents.
Students’ willing to receive COVID 19 vaccine information by family doctors and at school, underline the potential role of paediatricians and school educators in contributing to an increased vaccine coverage among the paediatric age.
New roles for AP-1/JUNB in cell cycle control and tumorigenic cell invasion via regulation of cyclin E1 and TGF-β2
Authors: Pérez-Benavente Beatriz , Fathinajafabadi Alihamze , de la Fuente Lorena , Gandía Carolina , Martínez-Férriz Arantxa , Pardo-Sánchez José Miguel , Milián Lara , Conesa Ana , Romero Octavio A. , Carretero Julián , Matthiesen Rune , Jariel-Encontre Isabelle , Piechaczyk Marc , Farràs Rosa 
Published: December 2022

Abstract
Background
JUNB transcription factor contributes to the formation of the ubiquitous transcriptional complex AP-1 involved in the control of many physiological and disease-associated functions. The roles of JUNB in the control of cell division and tumorigenic processes are acknowledged but still unclear.

Results
Here, we report the results of combined transcriptomic, genomic, and functional studies showing that JUNB promotes cell cycle progression via induction of cyclin E1 and repression of transforming growth factor (TGF)-β2 genes. We also show that high levels of JUNB switch the response of TGF-β2 stimulation from an antiproliferative to a pro-invasive one, induce endogenous TGF-β2 production by promoting TGF-β2 mRNA translation, and enhance tumor growth and metastasis in mice. Moreover, tumor genomic data indicate that JUNB amplification associates with poor prognosis in breast and ovarian cancer patients.

Conclusions
Our results reveal novel functions for JUNB in cell proliferation and tumor aggressiveness through regulation of cyclin E1 and TGF-β2 expression, which might be exploited for cancer prognosis and therapy.
Cluster randomised control trial protocol for estimating the effectiveness and cost-effectiveness of a complex intervention to increase care home staff influenza vaccination rates compared to usual practice (FLUCARE)
Authors: Patel Amrish , Sims Erika , Blacklock Jeanette , Birt Linda , Bion Veronica , Clark Allan , Griffiths Alys , Guillard Cecile , Hammond Amber , Holland Richard , Jones Andy , Jones Liz , Katangwe-Chigamba Thando , Pitcher Jennifer , Ruby Po , Scott Sion , Wagner Adam P. , Ahmed Saiqa , Baqir Wasim , Cook Luke , Dean Tony , Wright David 
Published: December 2022

AbstractThe care home staff influenza vaccination rate in England is significantly lower than the 75% World Health Organisation recommendation. This represents a substantial potential for resident harm. Barriers to staff vaccination stem from individual and organisational levels. Existing interventions address some but not all barriers and are not underpinned by behavioural science theory. This study aims to estimate the effectiveness and cost-effectiveness of a theory-informed intervention to improve care home staff vaccination rates compared to routine practice.Set in care homes with both nursing and residential focus, and a range of ownership status, only homes providing long stay care to older people with a staff vaccination rate below 40% are eligible to participate. Participation expressions of interest will be sought using a variety of approaches prior to seeking consent.The primary outcome measure is the proportion of staff vaccinated at 6 months, with secondary outcome measures being proportion vaccinated at 3 months, numbers of staff sick days, general practitioner and nurse visits to care home, care home resident hospitalisations and mortality.Based on the assumptions that the mean cluster (care home) size is 54 staff, a coefficient of variation of 0.48, control vaccination rate is 55%, intervention 75%, intra-cluster correlation coefficient of 0.2 and with 90% power, and 20% attrition, we require 39 care homes per arm.Blocked randomisation will be at the level of care home, stratified by the proportion of non-white care home staff, and implemented by Norwich Clinical Trials Unit.The intervention comprises co-designed information videos and posters, provision of in-house staff vaccination clinics, and incentive scheme and monthly data collection on trial outcomes. Beyond usual practice, the control arm will additionally contribute monthly data.Data will be collected at the start, monthly and at 6 months, and analysis will be blind to allocation. Statistical analysis will use the intention-to-treat principle with the difference in vaccination rates between groups compared using a random effect logistic regression model at the staff-level.This will be the first study to use a theory-informed intervention designed to comprehensively address identified barriers to care home staff influenza vaccination.Trial registration: ISRCTN ISRCTN22729870. Registered on 24 August 22. Secondary identifiers: R209939, IRAS 316820, CPMS 53812.
Novel alendronate-CGS21680 conjugate reduces bone resorption and induces new bone formation in post-menopausal osteoporosis and inflammatory osteolysis mouse models
Authors: Larrañaga-Vera Ane , Toti Kiran S. , Flatow James S. , Haraczy Alexandra J. , Warnick Eugene , Rao Harsha , Gao Zhan-Guo , Sussman Sarah M. , Mediero Aranzazu , Leucht Philipp , Jacobson Kenneth A. , Cronstein Bruce N. 
Published: December 2022

AbstractLoss of bone is a common medical problem and, while it can be treated with available therapies, some of these therapies have critical side effects. We have previously demonstrated that CGS21680, a selective A2A adenosine receptor agonist, prevents bone loss, but its on-target toxicities (hypotension, tachycardia) and frequent dosing requirements make it unusable in the clinic. We therefore generated a novel alendronate-CGS21680 conjugate (MRS7216), to target the agonist to bone where it remains for long periods thereby diminishing the frequency of administration and curtailing side effects. MRS7216 was synthesized from CGS21680 by sequential activation of the carboxylic acid moiety and reacting with an appropriate amino acid (PEG, alendronic acid) under basic conditions. MRS7216 was tested on C57BL/6J (WT) mice with established osteoporosis (OP) and WT or A2A KO mice with wear particle-induced inflammatory osteolysis (OL). Mice were treated weekly with MRS7216 (10mg/kg). Bone formation was studied after in vivo labeling with calcein/Alizarin Red, and μCT and histology analyses were performed. In addition, human primary osteoblasts and osteoclasts were cultured using bone marrow discarded after hip replacement. Receptor binding studies demonstrate that MRS7216 efficiently binds the A2A adenosine receptor. MRS7216-treated OP and OL mice had significant new bone formation and reduced bone loss compared to vehicle or alendronate-treated mice. Histological analysis showed that MRS7216 treatment significantly reduced osteoclast number and increased osteoblast number in murine models. Interestingly, cultured human osteoclast differentiation was inhibited, and osteoblast differentiation was stimulated by the compound indicating that MRS7216 conjugates represent a novel therapeutic approach to treat osteoporosis and osteolysis.
Effect of arm movement and task difficulty level on balance performance in healthy children: are there sex differences?
Authors: Muehlbauer Thomas , Hill Mathew W. , Schedler Simon 
Published: December 2022

Abstract
Objective
In children, studies have shown that balance performance is worse in boys compared to girls and further studies revealed inferior performance when arm movement was restricted during balance assessment. However, it remains unclear whether restriction of arm movement during balance testing differentially affects children’s balance performance (i.e., boys more than girls). Thus, we compared the influence of arm movement on balance performance in healthy boys versus girls (mean age: ~ 11.5 years) while performing balance tasks with various difficulty level.

Results
In nearly all tests, balance performance (i.e., timed one-legged stance, 3-m beam walking backward step number, Lower Quarter Y-Balance test reach distance) was significantly worse during restricted compared to free arm movement but without any differences between sexes or varying levels of task difficulty. These findings indicated that balance performance is negatively affected by restriction of arm movement, but this does not seem to be additionally influenced by children’s sex and the level of task difficulty.