bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between circulating 25-hydroxyvitamin D and cardiometabolic risk factors in adults in rural and urban settings
Authors: Mba Camille M. , Koulman Albert , Forouhi Nita G. , Sharp Stephen J. , Imamura Fumiaki , Jones Kerry , Meadows Sarah R. , Assah Felix , Mbanya Jean Claude , Wareham Nick J. 
Published: July 2022

Abstract
Background
An inverse association between vitamin D status and cardiometabolic risk has been reported but this relationship may have been affected by residual confounding from adiposity and physical activity due to imprecise measures of these variables. We aimed to investigate the relationship between serum 25-hydroxyvitamin D (25(OH)D) and cardiometabolic risk factors, with adjustment for objectively-measured physical activity and adiposity.

Methods
This was a population-based cross-sectional study in 586 adults in Cameroon (63.5% women). We assessed markers of glucose homoeostasis (fasting blood glucose (BG), 2 h post glucose load BG, HOMA-IR)) and computed a metabolic syndrome score by summing the sex‐specific z‐scores of five risk components measuring central adiposity, blood pressure, glucose, HDL cholesterol and triglycerides.

Results
Mean±SD age was 38.3 ± 8.6 years, and serum 25(OH)D was 51.7 ± 12.5 nmol/L. Mean 25(OH)D was higher in rural (53.4 ± 12.8 nmol/L) than urban residents (50.2 ± 12.1 nmol/L), p = 0.002. The prevalence of vitamin D insufficiency (<50 nmol/L) was 45.7%. There was an inverse association between 25(OH)D and the metabolic syndrome score in unadjusted analyses (β = −0.30, 95% CI −0.55 to −0.05), which became non-significant after adjusting for age, sex, smoking status, alcohol intake and education level. Serum 25(OH)D was inversely associated with fasting BG (−0.21, −0.34 to −0.08)), which remained significant after adjustment for age, sex, education, smoking, alcohol intake, the season of data collection, BMI and physical activity (−0.17, −0.29 to −0.06). There was an inverse association of 25(OH)D with 2-h BG (−0.20, −0.34 to −0.05) and HOMA-IR (−0.12, −0.19 to −0.04) in unadjusted analysis, but these associations became non-significant after adjustment for potential confounders.

Conclusion
Vitamin D insufficiency was common in this population. This study showed an inverse association between vitamin D status and fasting glucose that was independent of potential confounders, including objectively measured physical activity and adiposity, suggesting a possible mechanism through insulin secretion.
Factors associated with MRI success in children cooled for neonatal encephalopathy and controls
Authors: Woodward Kathryn , Spencer Arthur P. C. , Jary Sally , Chakkarapani Ela 
Published: July 2022

AbstractObjectiveTo investigate if an association exists between motion artefacts on brain MRI and comprehension, co-ordination, or hyperactivity scores in children aged 6–8 years, cooled for neonatal encephalopathy (cases) and controls.MethodsCase children (n = 50) without cerebral palsy were matched with 43 controls for age, sex, and socioeconomic status. Children underwent T1-weighted (T1w), diffusion-weighted image (DWI) brain MRI and cognitive, behavioural, and motor skills assessment. Stepwise multivariable logistic regression assessed associations between unsuccessful MRI and comprehension (including Weschler Intelligence Scale for Children (WISC-IV) verbal comprehension, working memory, processing speed and full-scale IQ), co-ordination (including Movement Assessment Battery for Children (MABC-2) balance, manual dexterity, aiming and catching, and total scores) and hyperactivity (including Strengths and Difficulties Questionnaire (SDQ) hyperactivity and total difficulties scores).ResultsCases had lower odds of completing both T1w and DWIs (OR: 0.31, 95% CI 0.11–0.89). After adjusting for case-status and sex, lower MABC-2 balance score predicted unsuccessful T1w MRI (OR: 0.81, 95% CI 0.67–0.97,p = 0.022). Processing speed was negatively correlated with relative motion on DWI (r = −0.25,p = 0.026) and SDQ total difficulties score was lower for children with successful MRIs (p = 0.049).ConclusionsMotion artefacts on brain MRI in early school-age children are related to the developmental profile.ImpactChildren who had moderate/severe neonatal encephalopathy are less likely to have successful MRI scans than matched controls.Motion artefact on MRI is associated with lower MABC-2 balance scores in both children who received therapeutic hypothermia for neonatal encephalopathy and matched controls, after controlling for case-status and sex.Exclusion of children with motion artefacts on brain MRI can introduce sampling bias, which impacts the utility of neuroimaging to understand the brain–behaviour relationship in children with functional impairments.
Fathers’ sensitive parenting enhanced by prenatal video-feedback: a randomized controlled trial using ultrasound imaging
Authors: Buisman Renate S. M. , Alyousefi-van Dijk Kim , de Waal Noor , Kesarlal Ashwina R. , Verhees Martine W. F. T. , van IJzendoorn Marinus H. , Bakermans-Kranenburg Marian J. 
Published: July 2022

AbstractBackgroundThe aim of this study was to evaluate an interaction-based prenatal parenting intervention program aimed at promoting parental sensitivity and involvement in expectant fathers using ultrasound images: Prenatal Video-Feedback Intervention to Promote Positive Parenting (VIPP-PRE).MethodsIn this randomized controlled trial, 73 first-time, healthy expectant fathers were enrolled. Participants were randomly assigned to the VIPP-PRE intervention (n = 39) or a dummy intervention (n = 34). Parental sensitivity was coded from video-recorded 10-min interactions with an infant simulator at a prenatal pretest and with fathers’ own infant at a postnatal posttest. Prenatal and postnatal involvement was assessed via an application on participants’ smartphones.ResultsFathers receiving VIPP-PRE demonstrated increased sensitivity across the perinatal period, relative to fathers receiving a dummy intervention. Fathers’ involvement with the infant increased significantly from the prenatal to postnatal period, regardless of the intervention.ConclusionsPrenatal video-feedback using ultrasound imaging of the unborn child has the potential to promote the quality of parenting in an important, but understudied, population and period: men in the transition to fatherhood. Future research should examine the long-term effectiveness of VIPP-PRE and its effectiveness in increasing parenting quality in at-risk families.ImpactThis study identifies a brief and focused prenatal intervention using assisted interactions between the father and his baby by means of ultrasound imaging as a promising strategy to improve sensitive fathering in the early postnatal phase.Our study shows that pregnancy provides a window of opportunity for promoting prenatal involvement and bonding in expectant fathers, with potential long-term benefits for the future father–child relationship.Ultrasound measures are currently used to monitor fetal growth and development, but our results suggest that they may also create an opportunity for stimulating father–infant interaction to promote postnatal caregiving quality.
Using machine learning to impact on long-term clinical care: principles, challenges, and practicalities
Authors: Ashton James J. , Young Aneurin , Johnson Mark J. , Beattie R. Mark 
Published: July 2022

AbstractThe rise of machine learning in healthcare has significant implications for paediatrics. Long-term conditions with significant disease heterogeneity comprise large portions of the routine work performed by paediatricians. Improving outcomes through discovery of disease and treatment prediction models, alongside novel subgroup clustering of patients, are some of the areas in which machine learning holds significant promise. While artificial intelligence has percolated into routine use in our day to day lives through advertising algorithms, song or movie selections and sifting of spam emails, the ability of machine learning to utilise highly complex and dimensional data has not yet reached its full potential in healthcare. In this review article, we discuss some of the foundations of machine learning, including some of the basic algorithms. We emphasise the importance of correct utilisation of machine learning, including adequate data preparation and external validation. Using nutrition in preterm infants and paediatric inflammatory bowel disease as examples, we discuss the evidence and potential utility of machine learning in paediatrics. Finally, we review some of the future applications, alongside challenges and ethical considerations related to application of artificial intelligence.ImpactMachine learning is a widely used term; however, understanding of the process and application to healthcare is lacking.This article uses clinical examples to explore complex machine learning terms and algorithms.We discuss limitations and potential future applications within paediatrics and neonatal medicine.
Mesenchymal stem cell therapy in perinatal arterial ischemic stroke: systematic review of preclinical studies
Authors: Lehnerer Verena , Roidl Anna , Romantsik Olga , Guzman Raphael , Wellmann Sven , Bruschettini Matteo 
Published: July 2022

Abstract
Background
Perinatal arterial ischemic stroke (PAIS) is a neurologic disorder leading to long-term complications. Mesenchymal stem cells (MSCs) have emerged as a novel therapeutic agent. This systematic review aims to determine the effects of stem cell-based interventions for the treatment of PAIS in preclinical studies.

Methods
We included all controlled studies on MSCs in neonatal animals with PAIS. Functional outcome was the primary outcome. The literature search was performed in February 2021.

Results
In the 20 included studies, MSCs were most frequently delivered via intracerebral injection (n = 9), 3 days after the induction of PAIS (n = 8), at a dose ranging from 5 × 104 to 5 × 106 cells. The meta-analysis showed an improvement on the cylinder rearing test (MD: −10.62; 95% CI: −14.38 to −6.86) and on the water maze test (MD: 1.31 MD; 95% CI: 0.80 to 1.81) in animals treated with MSCs compared to the control group animals.

Conclusion
MSCs appear to improve sensorimotor and cognitive performance in PAIS-injured animals; however, the certainty of the evidence is low. Registration of the protocol of preclinical studies, appropriate sample size calculation, rigorous randomization, and reporting of the data on animal sex and survival are warranted.
PROSPERO registration number: CRD42021239642.

Impact

This is the first systematic review and meta-analysis of preclinical studies investigating the effects of MSCs in an experimental model of PAIS.

MSCs appear to improve sensorimotor and cognitive performance in PAIS-injured neonatal animals.

The certainty of the evidence is low due to high or unclear risk of bias in most domains.
Functional isolation, culture and cryopreservation of adult human primary cardiomyocytes
Authors: Zhou Bingying , Shi Xun , Tang Xiaoli , Zhao Quanyi , Wang Le , Yao Fang , Hou Yongfeng , Wang Xianqiang , Feng Wei , Wang Liqing , Sun Xiaogang , Wang Li , Hu Shengshou 
Published: July 2022

AbstractCardiovascular diseases are the most common cause of death globally. Accurately modeling cardiac homeostasis, dysfunction, and drug response lies at the heart of cardiac research. Adult human primary cardiomyocytes (hPCMs) are a promising cellular model, but unstable isolation efficiency and quality, rapid cell death in culture, and unknown response to cryopreservation prevent them from becoming a reliable and flexible in vitro cardiac model. Combing the use of a reversible inhibitor of myosin II ATPase, (-)-blebbistatin (Bleb), and multiple optimization steps of the isolation procedure, we achieved a 2.74-fold increase in cell viability over traditional methods, accompanied by better cellular morphology, minimally perturbed gene expression, intact electrophysiology, and normal neurohormonal signaling. Further optimization of culture conditions established a method that was capable of maintaining optimal cell viability, morphology, and mitochondrial respiration for at least 7 days. Most importantly, we successfully cryopreserved hPCMs, which were structurally, molecularly, and functionally intact after undergoing the freeze-thaw cycle. hPCMs demonstrated greater sensitivity towards a set of cardiotoxic drugs, compared to human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Further dissection of cardiomyocyte drug response at both the population and single-cell transcriptomic level revealed that hPCM responses were more pronouncedly enriched in cardiac function, whereas hiPSC-CMs responses reflected cardiac development. Together, we established a full set of methodologies for the efficient isolation and prolonged maintenance of functional primary adult human cardiomyocytes in vitro, unlocking their potential as a cellular model for cardiovascular research, drug discovery, and safety pharmacology.
Enhancing exposure therapy for posttraumatic stress disorder (PTSD): a randomized clinical trial of virtual reality and imaginal exposure with a cognitive enhancer
Authors: Difede JoAnn , Rothbaum Barbara O. , Rizzo Albert A. , Wyka Katarzyna , Spielman Lisa , Reist Christopher , Roy Michael J. , Jovanovic Tanja , Norrholm Seth D. , Cukor Judith , Olden Megan , Glatt Charles E. , Lee Francis S. 
Published: July 2022

AbstractPosttraumatic stress disorder (PTSD) is a significant public health issue. Yet, there are limited treatment options and no data to suggest which treatment will work for whom. We tested the efficacy of virtual reality exposure (VRE) or prolonged imaginal exposure (PE), augmented with D-cycloserine (DCS) for combat-related PTSD. As an exploratory aim, we examined whether brain-derived neurotrophic factor (BDNF) and fatty acid amide hydrolase (FAAH) moderated treatment response. Military personnel with PTSD (n = 192) were recruited into a multisite double-blind randomized controlled trial to receive nine weeks of VRE or PE, with DCS or placebo. Primary outcome was the improvement in symptom severity. Randomization was stratified by comorbid depression (MDD) and site. Participants in both VRE and PE showed similar meaningful clinical improvement with no difference between the treatment groups. A significant interaction (p = 0.45) suggested VRE was more effective for depressed participants (CAPS difference M = 3.51 [95% CI 1.17–5.86],p = 0.004, ES = 0.14) while PE was more effective for nondepressed participants (M = −8.87 [95% CI −11.33 to −6.40],p < 0.001, ES = −0.44). The main effect of DCS vs. placebo was not significant. Augmentation by MDD interaction (p = 0.073) suggested that depressed participants improved more on placebo (M = −8.43 [95% CI −10.98 to −5.88],p < 0.001, ES = −0.42); DCS and placebo were equally effective for nondepressed participants. There was an apparent moderating effect of BDNF Val66Met polymorphism on DCS augmentation (ES = 0.67). Met66 allele carriers improved more on DCS (ES = −0.25). FAAH 385 A carriers improved more than non-carriers (ES = 0.33), particularly those with MDD (ES = 0.62). This study provides a step toward precision therapeutics for PTSD by demonstrating that comorbid MDD and genetic markers may help guide treatment selection.ClinicalTrials.gov Identifier: NCT01352637.
A self-amplifying USP14-TAZ loop drives the progression and liver metastasis of pancreatic ductal adenocarcinoma
Authors: Zhao Chunle , Gong Jun , Bai Yu , Yin Taoyuan , Zhou Min , Pan Shutao , Liu Yuhui , Gao Yang , Zhang Zhenxiong , Shi Yongkang , Zhu Feng , Zhang Hang , Wang Min , Qin Renyi 
Published: July 2022

AbstractWith a 5-year survival rate of approximately 10%, pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal solid malignancies in humans. A poor understanding of the underlying biology has resulted in a lack of effective targeted therapeutic strategies. Tissue microarray and bioinformatics analyses have revealed that the downstream transcriptional coactivator of the Hippo pathway, transcriptional coactivator with PDZ-binding motif (TAZ), might be a therapeutic target in PDAC. Since pharmacological inhibition of TAZ is challenging, we performed unbiased deubiquitinase (DUB) library screening to explore the pivotal regulators of TAZ ubiquitination as potential targets in PDAC models. We found that USP14 contributed to Yes-associated protein (YAP)/TAZ transcriptional activity and stabilized TAZ but not YAP. Mechanistically, USP14 catalyzed the K48-linked deubiquitination of TAZ to promote TAZ stabilization. Moreover, TAZ facilitated the transcription of USP14 by binding to the TEA domain transcription factor (TEAD) 1/4 response element in the promoter of USP14. USP14 was found to modulate the expression of TAZ downstream target genes through a feedback mechanism and ultimately promoted cancer progression and liver metastasis in PDAC models in vitro and in vivo. In addition, depletion of USP14 led to proteasome-dependent degradation of TAZ and ultimately arrested PDAC tumour growth and liver metastasis. A strong positive correlation between USP14 and TAZ expression was also detected in PDAC patients. The small molecule inhibitor of USP14 catalytic activity, IU1, inhibited the development of PDAC in subcutaneous xenograft and liver metastasis models. Overall, our data strongly suggested that the self-amplifying USP14-TAZ loop was a previously unrecognized mechanism causing upregulated TAZ expression, and identified USP14 as a viable therapeutic target in PDAC.
Hypoxia aggravates ferroptosis in RPE cells by promoting the Fenton reaction
Authors: Henning Yoshiyuki , Blind Ursula Sarah , Larafa Safa , Matschke Johann , Fandrey Joachim 
Published: July 2022

AbstractOxidative stress and hypoxia in the retinal pigment epithelium (RPE) have long been considered major risk factors in the pathophysiology of age-related macular degeneration (AMD), but systematic investigation of the interplay between these two risk factors was lacking. For this purpose, we treated a human RPE cell line (ARPE-19) with sodium iodate (SI), an oxidative stress agent, together with dimethyloxalylglycine (DMOG) which leads to stabilization of hypoxia-inducible factors (HIFs), key regulators of cellular adaptation to hypoxic conditions. We found that HIF stabilization aggravated oxidative stress-induced cell death by SI and iron-dependent ferroptosis was identified as the main cell death mechanism. Ferroptotic cell death depends on the Fenton reaction where H2O2 and iron react to generate hydroxyl radicals which trigger lipid peroxidation. Our findings clearly provide evidence for superoxide dismutase (SOD) driven H2O2 production fostering the Fenton reaction as indicated by triggered SOD activity upon DMOG + SI treatment as well as by reduced cell death levels upon SOD2 knockdown. In addition, iron transporters involved in non-transferrin-bound Fe2+ import as well as intracellular iron levels were also upregulated. Consequently, chelation of Fe2+ by 2’2-Bipyridyl completely rescued cells. Taken together, we show for the first time that HIF stabilization under oxidative stress conditions aggravates ferroptotic cell death in RPE cells. Thus, our study provides a novel link between hypoxia, oxidative stress and iron metabolism in AMD pathophysiology. Since iron accumulation and altered iron metabolism are characteristic features of AMD retinas and RPE cells, our cell culture model is suitable for high-throughput screening of new treatment approaches against AMD.
Reduced miR-184-3p expression protects pancreatic β-cells from lipotoxic and proinflammatory apoptosis in type 2 diabetes via CRTC1 upregulation
Authors: Grieco Giuseppina E. , Brusco Noemi , Fignani Daniela , Nigi Laura , Formichi Caterina , Licata Giada , Marselli Lorella , Marchetti Piero , Salvini Laura , Tinti Laura , Po Agnese , Ferretti Elisabetta , Sebastiani Guido , Dotta Francesco 
Published: July 2022

AbstractThe loss of functional β-cell mass in type 2 diabetes (T2D) is associated with molecular events that include β-cell apoptosis, dysfunction and/or dedifferentiation. MicroRNA miR-184-3p has been shown to be involved in several β-cell functions, including insulin secretion, proliferation and survival. However, the downstream targets and upstream regulators of miR-184-3p have not been fully elucidated. Here, we show reduced miR-184-3p levels in human T2D pancreatic islets, whereas its direct target CREB regulated transcription coactivator 1 (CRTC1) was increased and protects β-cells from lipotoxicity- and inflammation-induced apoptosis. Downregulation of miR-184-3p in β-cells leads to upregulation of CRTC1 at both the mRNA and protein levels. Remarkably, the protective effect of miR-184-3p is dependent on CRTC1, as its silencing in human β-cells abrogates the protective mechanism mediated by inhibition of miR-184-3p. Furthermore, in accordance with miR-184-3p downregulation, we also found that the β-cell-specific transcription factor NKX6.1, DNA-binding sites of which are predicted in the promoter sequence of human and mouse MIR184 gene, is reduced in human pancreatic T2D islets. Using chromatin immunoprecipitation analysis and mRNA silencing experiments, we demonstrated that NKX6.1 directly controls both human and murine miR-184 expression. In summary, we provide evidence that the decrease in NKX6.1 expression is accompanied by a significant reduction in miR-184-3p expression and that reduction of miR-184-3p protects β-cells from apoptosis through a CRTC1-dependent mechanism.
Facet nanoarchitectonics of visible-light driven Ag3PO4 photocatalytic micromotors: Tuning motion for biofilm eradication
Authors: Rojas Daniel , Kuthanova Michaela , Dolezelikova Kristyna , Pumera Martin 
Published: July 2022

AbstractThe customized design of micro-/nanomotors represents one of the main research topics in the field of micro-/nanomotors; however, the effects of different crystal facets on micromotor movement are often neglected. In this work, self-propelled amorphous, cubic, and tetrahedral Ag3PO4 particles were synthetized using a scalable precipitation method. Their programmable morphologies exhibited different motion properties under fuel-free and surfactant-free conditions and visible light irradiation. Differences in these motion properties were observed according to morphology and correlated with photocatalytic activity. Moreover, Ag3PO4 micromotors are inherently fluorescent, which allows fluorescence-based tracking. Furthermore, bacterial biofilms represent a major concern in modern society since most of them are antibiotic resistant. The as-prepared self-propelled particles exhibited morphologically dependent antibiofilm activities toward gram-positive and gram-negative bacteria. The enhanced diffusion of the particles promoted biofilm removal in comparison with static control experiments, realizing the possibility of a new class of light-driven biofilm-eradicating micromotors that do not require the use of both H2O2 and UV light.