Miracle-dz/UniFAR-FTUs huggingface dataset:
Understanding the new BRD4‐related syndrome: Clinical and genomic delineation with an international cohort study

BRD4 is part of a multiprotein complex involved in loading the cohesin complex onto DNA, a fundamental process required for cohesin‐mediated loop extrusion and formation of Topologically Associating Domains. Pathogenic variations in this complex have been associated with a growing number of syndromes, collectively known as cohesinopathies, the most classic being Cornelia de Lange syndrome. However, no cohort study has been conducted to delineate the clinical and molecular spectrum of BRD4‐related disorder. We formed an international collaborative study, and collected 14 new patients, including two fetuses. We performed phenotype and genotype analysis, integrated prenatal findings from fetopathological examinations, phenotypes of pediatric patients and adults. We report the first cohort of patients with BRD4‐related disorder and delineate the dysmorphic features at different ages. This work extends the phenotypic spectrum of cohesinopathies and characterize a new clinically relevant and recognizable pattern, distinguishable from the other cohesinopathies.
NFC como alternativa para mejorar el desarrollo de videojuegos en dispositivos móviles

La aparicion de nuevas alternativas de interaccion puede llevar a generar videojuegos cada vez mas interesantes, este es el caso de la interaccion con el telefono movil, especialmente la tecnologia NFC. Sin embargo no existe un referente para conocer que tipos de videojuegos serian los mas apropiados para desarrollar con NFC. Por tanto, este articulo aporta una revision de varias fuentes para determinar el estado actual de videojuegos con NFC para futuras referencias de generadores de contenido y emprendedores en el campo de los videojuegos; como contribuciones se tiene una revision en varias fuentes a nivel comercial, bibliografico y de tiendas de aplicaciones para generar el estado actual y el esquema de posibles videojuegos con los cuales NFC podria interactuar, determinando las categorias de videojuegos mas apropiadas para desarrollar con dicha tecnologia y proponiendo algunas caracteristicas que NFC permite implementar.
Leveraging big data bioinformatics approaches to extract knowledge from Staphylococcus aureus public omics data

Abstract Staphylococcus aureus is a notorious pathogen posing challenges in the medical industry due to drug resistance and biofilm formation. The horizon of knowledge on S. aureus pathogenesis has expanded with the advancement of data-driven bioinformatics techniques. Mining information from sequenced genomes and their expression data is an economic approach that alleviates wastage of resources and redundancy in experiments. The current review covers how big data bioinformatics has been used in the analysis of S. aureus from publicly available –omics data to uncover mechanisms of infection and inhibition. Particularly, advances in the past two decades in biomarker discovery, host responses, phenotype identification, consolidation of information, and drug development are discussed highlighting the challenges and shortcomings. Overall, the review summarizes the diverse aspects of scrupulous re-analysis of S. aureus proteomic and transcriptomic expression datasets retrieved from public repositories in terms of the efforts taken, benefits offered, and follow-up actions. The detailed review thus serves as a reference and aid for (i) Computational biologists by briefing the approaches utilized for bacterial omics re-analysis concerning S. aureus and (ii) Experimental biologists by elucidating the potential of bioinformatics in biological research to generate reliable postulates in a prompt and economical manner.
The cost-effectiveness of a resilience-based psychosocial intervention for HIV prevention among MSM in India

Objective: MSM in India are at a high risk for HIV infection given psychosocial challenges, sexual orientation stress, and stigma. We examined the cost-effectiveness of a novel resilience-based psychosocial intervention for MSM in India. Design: We parameterized a validated microsimulation model (CEPAC) with India-specific data and results from a randomized trial and examined two strategies for MSM: status quo HIV care (SQ), and a trial-based psychosocial intervention (INT) focused on building resilience to stress, improving mental health, and reducing condomless anal sex (CAS). Methods: We projected lifetime clinical and economic outcomes for MSM without HIV initially. Intervention effectiveness, defined as reduction in self-reported CAS, was estimated at 38%; cost was $49.37/participant. We used a willingness-to-pay threshold of US$2100 (2019 Indian per capita GDP) per year of life saved (YLS) to define cost-effectiveness. We also assessed the 5-year budget impact of offering this intervention to 20% of Indian MSM. Results: Model projections showed the intervention would avert 2940 HIV infections among MSM over 10 years. Over a lifetime horizon, the intervention was cost-effective (ICER = $900/YLS). Results were most sensitive to intervention effectiveness and cost; the intervention remained cost-effective under plausible ranges of these parameters. Offering this intervention in the public sector would require an additional US$28 M over 5 years compared with SQ. Conclusion: A resilience-based psychosocial intervention integrated with HIV risk reduction counseling among MSM in India would reduce HIV infections and be cost-effective. Programs using this approach should be expanded as a part of comprehensive HIV prevention in India.
Population pharmacokinetics analysis of guselkumab in healthy subjects and patients with psoriatic arthritis, plaque psoriasis and palmoplantar pustulosis

Aims: Guselkumab, a monoclonal antibody that binds to the p19 subunit of interleukin 23, is approved for the treatment of plaque psoriasis (PsO) and psoriatic arthritis (PsA), palmoplantar pustulosis (PPP), generalized pustular psoriasis, and erythrodermic psoriasis in various countries. The purpose of this analysis was to develop a comprehensive population pharmacokinetic (PK) model for guselkumab to determine whether PK differs across different disease populations and healthy subjects.
Multimodal, Multiscale Insights into Hippocampal Seizures Enabled by Transparent, Graphene-Based Microelectrode Arrays

Visual Abstract Hippocampal seizures are a defining feature of mesial temporal lobe epilepsy (MTLE). Area CA1 of the hippocampus is commonly implicated in the generation of seizures, which may occur because of the activity of endogenous cell populations or of inputs from other regions within the hippocampal formation. Simultaneously observing activity at the cellular and network scales in vivo remains challenging. Here, we present a novel technology for simultaneous electrophysiology and multicellular calcium imaging of CA1 pyramidal cells (PCs) in mice enabled by a transparent graphene-based microelectrode array (Gr MEA). We examine PC firing at seizure onset, oscillatory coupling, and the dynamics of the seizure traveling wave as seizures evolve. Finally, we couple features derived from both modalities to predict the speed of the traveling wave using bootstrap aggregated regression trees. Analysis of the most important features in the regression trees suggests a transition among states in the evolution of hippocampal seizures.
Quantitative MRI Characterization of the Extremely Preterm Brain at Adolescence: Atypical versus Neurotypical Developmental Pathways.

Background Extremely preterm (EP) birth is associated with higher risks of perinatal white matter (WM) injury, potentially causing abnormal neurologic and neurocognitive outcomes. MRI biomarkers distinguishing individuals with and without neurologic disorder guide research on EP birth antecedents, clinical correlates, and prognoses. Purpose To compare multiparametric quantitative MRI (qMRI) parameters of EP-born adolescents with autism spectrum disorder, cerebral palsy, epilepsy, or cognitive impairment (ie, atypically developing) with those without (ie, neurotypically developing), characterizing sex-stratified brain development. Materials and Methods This prospective multicenter study included individuals aged 14-16 years born EP (Extremely Low Gestational Age Newborns-Environmental Influences on Child Health Outcomes Study, or ELGAN-ECHO). Participants underwent 3.0-T MRI evaluation from 2017 to 2019. qMRI outcomes were compared for atypically versus neurotypically developing adolescents and for girls versus boys. Sex-stratified multiple regression models were used to examine associations between spatial entropy density (SEd) and T1, T2, and cerebrospinal fluid (CSF)-normalized proton density (nPD), and between CSF volume and T2. Interaction terms modeled differences in slopes between atypically versus neurotypically developing adolescents. Results A total of 368 adolescents were classified as 116 atypically (66 boys) and 252 neurotypically developing (125 boys) participants. Atypically versus neurotypically developing girls had lower nPD (mean, 557 10 × percent unit [pu] ± 46 [SD] vs 573 10 × pu ± 43; P = .04), while atypically versus neurotypically developing boys had longer T1 (814 msec ± 57 vs 789 msec ± 82; P = .01). Atypically developing girls versus boys had lower nPD and shorter T2 (eg, in WM, 557 10 × pu ± 46 vs 580 10 × pu ± 39 for nPD [P = .006] and 86 msec ± 3 vs 88 msec ± 4 for T2 [P = .003]). Atypically versus neurotypically developing boys had a more moderate negative association between T1 and SEd (slope, -32.0 msec per kB/cm3 [95% CI: -49.8, -14.2] vs -62.3 msec per kB/cm3 [95% CI: -79.7, -45.0]; P = .03). Conclusion Atypically developing participants showed sexual dimorphisms in the cerebrospinal fluid-normalized proton density (nPD) and T2 of both white matter (WM) and gray matter. Atypically versus neurotypically developing girls had lower WM nPD, while atypically versus neurotypically developing boys had longer WM T1 and more moderate T1 associations with microstructural organization in WM. © RSNA, 2022 Online supplemental material is available for this article.
Plin5 inhibits proliferation and migration of vascular smooth muscle cell through interacting with PGC-1α following vascular injury

ABSTRACT Abnormal proliferation and migration of vascular smooth muscle cell (VSMC) is a hallmark of vascular neointima hyperplasia. Perilipin 5 (Plin5), a regulator of lipid metabolism, is also confirmed to be involved in vascular disorders, such as microvascular endothelial dysfunction and atherosclerosis. To investigate the regulation and function of plin5 in the phenotypic alteration of VSMC, -an animal model of vascular intima hyperplasia was established in C57BL/6 J and Plin5 knockdown (Plin5 ±) mice by wire injure. Immunohistochemical staining was used to analyze neointima hyperplasia in artery. Ki-67, dihydroethidium immunofluorescence staining and wound healing assay were used to measure proliferation, reactive oxygen species (ROS) generation and migration of VSMC, respectively. Plin5 was downregulated in artery subjected to vascular injury and in VSMC subjected to platelet-derived growth factor (PDGF)-BB. Plin5 knockdown led to accelerated neointima hyperplasia, excessive proliferation and migration of VSMC after injury. In vitro, we observed increased ROS content in VSMC isolated from Plin5 ± mice. Antioxidative N-acetylcysteine (NAC) inhibited VSMC proliferation and migration induced by PDGF-BB or plin5 knockdown. More importantly, plin5-peroxlsome proliferator-activated receptor-γ coactivator (PGC)-1α interaction was also attenuated in VSMC after knockdown of plin5. Overexpression of PGC-1α suppressed PDGF-BB-induced ROS generation, proliferation, and migration in VSMC isolated from Plin5 ± mice. These data suggest that plin5 serves as a potent regulator of VSMC proliferation, migration, and neointima hyperplasia by interacting with PGC-1α and affecting ROS generation. Graphical abstract
Solving Biobjective Distributed Flow-Shop Scheduling Problems With Lot-Streaming Using an Improved Jaya Algorithm

A distributed flow-shop scheduling problem with lot-streaming that considers completion time and total energy consumption is addressed. It requires to optimally assign jobs to multiple distributed factories and, at the same time, sequence them. A biobjective mathematic model is first developed to describe the considered problem. Then, an improved Jaya algorithm is proposed to solve it. The Nawaz–Enscore–Ham (NEH) initializing rule, a job-factory assignment strategy, the improved strategies for makespan and energy efficiency are designed based on the problem’s characteristic to improve the Jaya’s performance. Finally, experiments are carried out on 120 instances of 12 scales. The performance of the improved strategies is verified. Comparisons and discussions show that the Jaya algorithm improved by the designed strategies is highly competitive for solving the considered problem with makespan and total energy consumption criteria.
Global Navigation Satellite Systems Applications in Different Modes of Transport

Nowadays (July 2016) we can distinguish four modes of transport – air, maritime, rail and road. In each mode the continuous knowledge of the current user’s position is one of the most important parameters of safety and economy of the transport. The information about position can be obtained from satellite navigation systems SNS (GPS, GLONASS) and based augmentation systems SBAS (WAAS, EGNOS, MSAS, GAGAN). Two next global SNSs and one SBAS are under construction. This paper gives the reply to some questions: in which mode these systems are the most frequently used and why, which system is preferred in separate mode and individual region of the world, which kind of the receiver, one or more systems, are most popular. The comparison of SNSs applications, the capability of SNS receivers and supported constellations by theses receivers and additionally the detailed analysis of SNS receiver survey designed for each mode of transport are presented in this paper also. keYWOrDs global satellite navigation systems (GNSS), mode of transport, GNSS market and applications
Biallelic Variants in the Ectonucleotidase ENTPD1 Cause a Complex Neurodevelopmental Disorder with Intellectual Disability, Distinct White Matter Abnormalities, and Spastic Paraplegia

Human genomics established that pathogenic variation in diverse genes can underlie a single disorder. For example, hereditary spastic paraplegia is associated with >80 genes, with frequently only few affected individuals described for each gene. Herein, we characterize a large cohort of individuals with biallelic variation in ENTPD1, a gene previously linked to spastic paraplegia 64 (Mendelian Inheritance in Man # 615683).
Timolol 0.5% ophthalmic solution influences cardiac function in healthy cats

Objectives The aim of this study was to ascertain the effect of a drop of timolol 0.5% ophthalmic solution on the systolic function of the left ventricle (LV) and left atrium (LA), and to confirm if timolol helped appraisal of diastolic function by reducing heart rate (HR) and separating the transmitral outflow waves from tissue Doppler imaging (TDI). Methods A total of 41 client-owned healthy cats underwent two echocardiograms 20 mins apart. The timolol group (33 cats) received a drop of timolol solution after the first examination. Standard and speckle-tracking echocardiography evaluated the LV and LA function of both groups at the two time points evaluated. Results Timolol reduced HR (19%), and fractional shortening from LV (20.3%) and LA (16.6%). Septal S' decreased by 51% (from 7.7 to 5.2 cm/s) and lateral S’ dropped by 43.1% (7.3 to 5.1 cm/s). Most longitudinal techniques did not change after timolol, including the mitral annular plane systolic excursion from the interventricular annulus, tricuspid annular plane systolic excursion, LV longitudinal strain and LV tissue motion annular displacement. The isovolumic relaxation time increased by 15.2% (from 54 to 64.6 ms), with most cats presenting this variable above the reference (>60 ms). Timolol did not support diastolic assessment, enabling evaluation in only 2/11 cats when using lateral TDI and 1/9 cats using septal TDI. Regarding side effects, miosis occurred in 18 cats (54.5%). Conclusions and relevance Timolol reduced systolic function, decreasing standard echocardiographic variables. Regarding diastolic evaluation, although timolol decreased HR, it did not separate the mitral diastolic waves, as expected.
‘This is not what I want for my children’: agency and parenting in Danish asylum centres

Abstract Background Children of asylum-seeking families constitute a particularly vulnerable group, and there is growing interest in understanding how asylum-seeking parents can be supported to safeguard the health, wellbeing and growth of their children. In this study, we examine the capabilities of asylum-seeking parents to act on the support and advice provided by child health nurses in Danish asylum centres. Methods We draw on semi-structured qualitative interviews with 11 asylum-seeking families (corresponding to 15 parents) living in two asylum centres run by the Danish Red Cross. Results The findings illustrate that asylum-seeking parents’ agentic capabilities to take care of their children are tightly constrained by their housing constrictions and living conditions, insufficient money allowances, regular relocations and juridical status as asylum-seekers. These physical and organizational structures and the pervasive uncertainty related to being asylum-seekers inhibited parents from acting on advice from child health nurses, and from providing their children with a safe, healthy and stable environment. Conclusions Asylum-seeking parents face the task of taking care of their children within particular physical, organizational and juridical structures, which tightly constrain their ability to parent their children well, or to follow advice provided by child health nurses.
An individualised psychosocial intervention program for persons with MND/ALS and their families in low resource settings

Motor Neuron Disease (MND) leads to significant psychosocial distress for the person with the illness and caregivers. Psychosocial factors influence the management and quality of life to a significant degree. Objective To develop individualised psychosocial intervention program for people with MND and their families in India. Methods People with MND and healthcare staff were constructively involved in co-designing the intervention program in four phases adapted from the MRC framework: 1. A detailed need assessment phase where 30 participants shared their perceptions of psychosocial needs 2. Developing the intervention module (synthesis of narrative review, identified needs); 3. Feasibility testing of the intervention program among seven participants; 4. Feedback from participants on the feasibility (acceptance, practicality adaptation). The study adopted an exploratory research design. Results Intervention program of nine sessions, addressing psychosocial challenges through the different stages of progression of the illness and ways to handle the challenges, specific to the low resource settings, was developed and was found to be feasible. People with MND and families who participated in the feasibility study shared the perceived benefit through feedback interviews. Conclusion MND has changing needs and challenges. Intervention programme was found to be feasible to be implemented among larger group to establish efficacy.
Neural and Cognitive Underpinnings of Counterintuitive Science and Math Reasoning in Adolescence

Abstract Reasoning about counterintuitive concepts in science and math is thought to require suppressing naive theories, prior knowledge, or misleading perceptual cues through inhibitory control. Neuroimaging research has shown recruitment of pFC regions during counterintuitive reasoning, which has been interpreted as evidence of inhibitory control processes. However, the results are inconsistent across studies and have not been directly compared with behavior or brain activity during inhibitory control tasks. In this fMRI study, 34 adolescents (aged 11–15 years) answered science and math problems and completed response inhibition tasks (simple and complex go/no-go) and an interference control task (numerical Stroop). Increased BOLD signal was observed in parietal (Brodmann's area 40) and prefrontal (Brodmann's area 8, 45/47) cortex regions in counterintuitive problems compared with control problems, where no counterintuitive reasoning was required, and in two parietal clusters when comparing correct counterintuitive reasoning to giving the incorrect intuitive response. There was partial overlap between increases in BOLD signal in the complex response inhibition and interference control tasks and the science and math contrasts. However, multivariate analyses suggested overlapping neural substrates in the parietal cortex only, in regions typically associated with working memory and visuospatial attentional demands rather than specific to inhibitory control. These results highlight the importance of using localizer tasks and a range of analytic approach to investigate to what extent common neural networks underlie performance of different cognitive tasks and suggests visuospatial attentional skills may support counterintuitive reasoning in science and math.
Evaluating the Sleep Treatment Education Program (STEP-1): A single-session educational workshop addressing insomnia in cancer survivors

Abstract Insomnia is a common late effect of cancer, affecting as many as 27% of cancer survivors. Although cognitive behavioral therapy for insomnia (CBT-I) is highly effective, treatment-associated burdens and limited availability of providers result in few survivors receiving this treatment. To address this gap, we developed the Sleep Treatment Education Program-1 (STEP-1), a single-session intervention addressing insomnia after cancer. As a preliminary evaluation of STEP-1’s potential to improve survivors’ insomnia, STEP-1 was delivered to a convenience sample of 34 cancer survivors as an educational workshop in person or by videoconference. Participants completed the Insomnia Severity Index (ISI) at the workshop and at 1-month follow-up; items assessing participants’ intentions to implement program suggestions and satisfaction were also collected. At 1-month follow-up, mean insomnia symptoms on the ISI were significantly lower compared to baseline (9.73 vs 15.73; d = 1.38, P < .001); the reduction in mean ISI scores did not significantly differ between in-person and videoconference participants (5.82 vs 6.33; P = .78). These results, along with positive indicators of program engagement and satisfaction, support the potential efficacy of STEP-1 to meet survivors’ needs for insomnia care. Particularly when delivered by videoconference, STEP-1 has the potential to dramatically improve access and uptake for insomnia treatment in cancer survivors. Results also more generally support development of low-intensity, self-management insomnia interventions for cancer survivors and potentially other populations.
Sarcoplasmic reticulum calcium handling in unbranched, immediately post‐necrotic fast‐twitch mdx fibres is similar to wild‐type littermates

What is the central question of this study? What are the early effects of dystrophin deficiency on sarcoplasmic reticulum Ca2+ handling in the mdx mouse? What is the main finding and its importance? In the mdx mouse, Ca2+ handling by the sarcoplasmic reticulum is little affected by the absence of dystrophin when looking at fibres without branches that have recently regenerated after massive myonecrosis. This has important implications for our understanding of Ca2+ pathology in the mdx mouse.