Shir

BACKGROUND: Distal Xq28 duplication, or int22h1/int22h2-mediated Xq28 duplication syndrome, leads to cognitive impairment, neurobehavioral issues, and facial dysmorphisms. Existing literature has limited information on clinical traits and penetrance. METHODS: We identified cases of distal Xq28 duplication (chrX: 154,126,575-154,709,680, GRCh37/hg19) through a review of clinical records and microarray reports from five centers, encompassing both postnatal and prenatal cases, with no prior family knowledge of the duplication...

Epigenetic defects caused by hereditary or de novo mutations are implicated in various human diseases. It remains uncertain whether correcting the underlying mutation can reverse these defects in patient cells. Here we show by the analysis of myotonic dystrophy type 1 (DM1)-related locus that in mutant human embryonic stem cells (hESCs), DNA methylation and H3K9me3 enrichments are completely abolished by repeat excision (CTG2000 expansion), whereas in patient myoblasts (CTG2600 expansion), repeat deletion fails to do so...

Pseudomonas aeruginosa is a ubiquitous Gram-negative opportunistic pathogen with remarkable phylogenetic and phenotypic variabilities. In this work, we applied classical molecular networking analysis to secondary metabolite profiling data from seven Pseudomonas aeruginosa strains, including five clinical isolates from the lung secretions of people with cystic fibrosis (CF). We provide three vignettes illustrating how secondary metabolite profiling aids in the identification of rare genomics traits in P. aeruginosa ...

This paper proposes an innovative approach to improve the performance of grid-connected photovoltaic (PV) systems operating in environments with variable atmospheric conditions. The dynamic nature of atmospheric parameters poses challenges for traditional control methods, leading to reduced PV system efficiency and reliability. To address this issue, we introduce a novel integration of fuzzy logic and sliding mode control methodologies. Fuzzy logic enables the PV system to effectively handle imprecise and uncertain atmospheric data, allowing for decision-making based on qualitative inputs and expert knowledge...

BACKGROUND: Recent studies suggest that participation in recreational and even competitive sports is generally safe for patients with implantable cardioverter-defibrillators (ICDs). However, these studies included only patients with implanted transvenous ICD (TV-ICD). Nowadays, subcutaneous ICD (S-ICD) is a safe and effective alternative and is increasingly implanted in younger ICD candidates. Data on the safety of sport participation for patients with implanted S-ICD systems is urgently needed...

A growing number out-of-hospital cardiac arrest (OHCA) registries have been developed across the globe. A few of these are national, while others cover larger geographical regions. These registries have common objectives; continuous quality improvement, epidemiological research and providing infrastructure for clinical trials. OHCA registries make performance comparison across Emergency Medical Services systems possible for benchmarking, hypothesis generation and further research. Changes in OHCA incidence and outcomes provide insights about the effects of secular trends or health services interventions...

BACKGROUND: Clinical practice guidelines on limitation of life-sustaining treatments (LST) in the intensive care unit (ICU), in the form of withholding or withdrawal of LST, state that there is no ethical difference between the two. Such statements are not uniformly accepted worldwide, and there are few studies on LST limitation in Asia. This study aimed to evaluate the predictors and outcomes of withholding and withdrawal of LST in Singapore, focusing on the similarities and differences between the two approaches...

Mutations in the SCN8A gene, encoding the voltage-gated sodium channel NaV 1.6, are associated with a range of neurodevelopmental syndromes. The p.(Gly1625Arg) (G1625R) mutation was identified in a patient diagnosed with Developmental epileptic encephalopathy (DEE). While most of the characterized DEE-associated SCN8A mutations were shown to cause a gain-of-channel function, we show that the G1625R variant, positioned within the S4 segment of domain IV, results in complex effects. Voltage-clamp analyses of NaV 1...

BACKGROUND: Primary progressive aphasia (PPA) defines a group of neurodegenerative disorders characterised by language decline. Three PPA variants correlate with distinct underlying pathologies: semantic variant PPA (svPPA) with transactive response DNA-binding protein of 43 kD (TDP-43) proteinopathy, agrammatic variant PPA (agPPA) with tau deposition and logopenic variant PPA (lvPPA) with Alzheimer's disease (AD). Our objectives were to differentiate PPA variants using clinical and neuroimaging features, assess progression and evaluate structural MRI and a novel 18-F fluorodeoxyglucose positron emission tomography (FDG-PET) image decomposition machine learning algorithm for neuropathology prediction...

Heart rate variability (HRV),a measure of the fluctuations in the intervals between consecutive heartbeats, is an indicator of changes in the autonomic nervous system. A chronic reduction in HRV has been repeatedly linked to clinical depression. However, the chronological and mechanistic aspects of this relationship, between the neural, physiological, and psychopathological levels, remain unclear. In this review we present evidence by which changes in HRV might precede the onset of depression. We describe several pathways that can facilitate this relationship...

Individuals exhibiting restrained eating behaviors demonstrate increased inhibitory control when exposed to food-related stimuli, indicating the presence of an automatic food-inhibition association. Existing literature proposes that this association contributes to the devaluation of food within this population. Efforts to disrupt this association by promoting the complete elimination of the inhibition of food responses have resulted in increased food consumption but have also led to heightened food-related anxiety in individuals with restrained eating behaviors...

Integration renewable energy sources into current power generation systems necessitates accurate forecasting to optimize and preserve supply-demand restrictions in the electrical grids. Due to the highly random nature of environmental conditions, accurate prediction of PV power has limitations, particularly on long and short periods. Thus, this research provides a new hybrid model for forecasting short PV power based on the fusing of multi-frequency information of different decomposition techniques that will allow a forecaster to provide reliable forecasts...

Risk sharing agreements (RSAs) and managed access agreements have emerged as tools to overcome evidentiary uncertainty and contain costs of pharmaceuticals; however, Canada has relatively little experience with these health policy instruments. This article describes one of the few examples of national RSAs. Enzyme replacement therapies (ERT) were introduced in Canada to treat Fabry disease in the early 2000s through an RSA. Based on qualitative interviews with key participating actors, this article explains how this RSA ensured continuity of treatment for patients already on ERT, and collected robust real-world evidence to secure treatment for future Fabry patients...

Dairy production systems display a wide range of greenhouse gas (GHG) emission characteristics influenced by factors like geographical location, farm size, herd composition, milk yield, management practices, and existing infrastructure. Effective national GHG mitigation plans for the dairy industry should incorporate strategies that account for the diversity within this system. This paper aims to introduce a multi-scale framework to assess the GHG mitigation potential within the Israeli dairy system. It begins by analyzing the GHG intensity per unit of milk produced by a representative sample of 145 farms (20 % of the national dairy farms)...

BACKGROUND: Coronary microvascular disease (CMD) is common in patients with and without obstructive coronary artery disease, and is associated with adverse clinical outcomes. Respiratory-related variables are associated with pulmonary and systemic microvascular dysfunction, while evidence regarding their relationship with CMD is limited. We aim to evaluate respiratory-related variables as risk factors of CMD. METHODS: This is an observational, single-center study enrolling consecutive patients undergoing invasive evaluation of coronary microvascular function in the catheterization laboratory...

Many adult lung diseases involve dysregulated lung repair. Deciphering the molecular and cellular mechanisms that govern intrinsic lung repair is essential to develop new treatments to repair/regenerate the lungs. Aberrant Wnt signalling is associated with lung diseases including emphysema, idiopathic pulmonary fibrosis and pulmonary arterial hypertension but how Wnt signalling contributes to these diseases is still unclear. There are several alternative pathways that can be stimulated upon Wnt ligand binding, one of these is the Planar Cell Polarity (PCP) pathway which induces actin cytoskeleton remodelling...

No abstract text is available yet for this article.

Successful immunotherapy relies on triggering complex responses involving T cell dynamics in tumors and the periphery. Characterizing these responses remains challenging using static human single-cell atlases or mouse models. To address this, we developed a framework for in vivo tracking of tumor-specific CD8+ T cells over time and at single-cell resolution. Our tools facilitate the modeling of gene program dynamics in the tumor microenvironment (TME) and the tumor-draining lymph node (tdLN). Using this approach, we characterize two modes of anti-programmed cell death protein 1 (PD-1) activity, decoupling induced differentiation of tumor-specific activated precursor cells from conventional type 1 dendritic cell (cDC1)-dependent proliferation and recruitment to the TME...

Substantial attention has been drawn over the past few years by high step-up dc-dc converters owing to their applications in a wide range. Apart from renewable energy applications, high voltage/ high pulse converters are efficiently used in water treatment applications. The converter suggested a combination of Quadratic and SEPIC converters with a diode-capacitor cell. This topology generates high-voltage repetitive pulses with a single semiconductor switch and reduced component count. The stress across the components is less than the high-gain converters reported in the literature...

According to cybernetic approaches, emotion regulation is motivated by the desire to reduce discrepancies between experienced and desired emotions. Yet, this assumption has rarely been tested directly in healthy or unhealthy populations. In two ecological momentary assessment studies, we monitored motivated emotion regulation in daily life in participants who varied in the severity of their depressive symptoms (Study 1; N = 173) and in clinically depressed and nondepressed participants (Study 2; N = 120). Across studies, associations between motivation in emotion regulation and discrepancies between experienced and desired emotions differed by depression...