Sequence variants in HECTD1 result in a variable neurodevelopmental disorder.

Dysregulation of genes encoding the homologous to E6AP C-terminus (HECT) E3 ubiquitin ligases has been linked to cancer and structural birth defects. One member of this family, the HECT-domain-containing protein 1 (HECTD1), mediates developmental pathways, including cell signaling, gene expression, and embryogenesis. Through GeneMatcher, we identified 14 unrelated individuals with 15 different variants in HECTD1 (10 missense, 3 frameshift, 1 nonsense, and 1 splicing variant) with neurodevelopmental disorders (NDDs), including autism, attention-deficit/hyperactivity disorder, and epilepsy.

Assessing the role of education level on climate change belief, concern and action: a multinational survey of healthcare professionals in nephrology.

Background: Climate change poses a significant risk to kidney health, and countries with lower national wealth are more vulnerable. Yet, citizens from lower-income countries demonstrate less concern for climate change than those from higher-income countries. Education is a key covariate.

Fibroblast transcriptomics uncovers pathogenic genomic variants in individuals with exome-negative childhood onset epilepsy.

Objective: This study aims to improve genetic diagnosis in childhood onset epilepsy with neurodevelopmental problems by utilizing RNA sequencing of fibroblasts to identify pathogenic variants that may be missed by exome sequencing and copy number variation analysis.

Methods: We enrolled 41 individuals with childhood onset epilepsy and neurodevelopmental problems who previously had inconclusive genetic testing. Fibroblast samples were cultured and analyzed using RNA sequencing to detect aberrant expression, aberrant splicing, and monoallelic expression using the Detection of RNA Outlier Pipeline (DROP) pipeline.

Improving the binding affinity of plastic degrading cutinase with polyethylene terephthalate (PET) and polyurethane (PU); an in-silico study.

Plastic pollution is a worrying problem, and its degradation is a laborious process. Although enzymatic plastic breakdown is a sustainable method, drawbacks such as numerous plastic kinds of waste make the degradation challenging. Therefore, a multi-plastic degrading (MPD) enzyme becomes necessary.

Molecular mechanisms of nitric oxide regulating high photosynthetic performance of wheat plants in waterlogging at flowering.

Nitric oxide (NO) positively contributes to maintaining a high photosynthetic rate in waterlogged-wheat plants by maintaining high stomatal conductance (g), mesophyll conductance (g), and electron transport rates in PSII (J). However, the molecular mechanisms underlying the synergistic regulation of photosynthetic characteristics during wheat waterlogging remain unclear. Pot experiments were conducted with two cultivars: Yangmai15 (YM15: high waterlogging-tolerance capacity) and Yangmai24 (YM24: conventional waterlogging-tolerance capacity).

What Next for the Science of Patient Preference? Interoperability, Standardization, and Transferability.

Using patient preference information (PPI) to incorporate patient voices into the drug development lifecycle can help align therapies with the needs and values of patients. However, several barriers have limited the use of PPI, including a lack of clarity on its use by decision-makers, a need for greater decision-maker trust in PPI, and a lack of time, budgets, and access to specialist expertise. The value proposition for PPI could be enhanced by making it FAIR: Findable, Accessible, Interoperable, and Reusable.

Residual Mitral Regurgitation Interacts With Transmitral Mean Pressure Gradient to Modify the Association With Mortality Following Transcatheter Edge-to-Edge Repair.

Background: The association, if any, between the transmitral mean pressure gradient (TMPG) after mitral transcatheter edge-to-edge repair and 1-year mortality is controversial in patients undergoing mitral transcatheter edge-to-edge repair with the MitraClip system. We sought to estimate the association between intraoperatively measured residual mitral regurgitation (rMR) and TMPG and 1-year mortality among patients undergoing mitral transcatheter edge-to-edge repair to facilitate decisions on additional devices.

Methods: In patients with severe secondary (functional) MR, we analyzed registry data using generalized estimating equations.

Long-chain acyl-CoA synthetase regulates systemic lipid homeostasis via glycosylation-dependent lipoprotein production.

Interorgan lipid transport is crucial for organism development and the maintenance of physiological function. Here, we demonstrate that long-chain acyl-CoA synthetase (dAcsl), which catalyzes the conversion of fatty acids into acyl-coenzyme As (acyl-CoAs), plays a critical role in regulating systemic lipid homeostasis. dAcsl deficiency in the fat body led to the ectopic accumulation of neutral lipids in the gut, along with significantly reduced lipoprotein contents in both the fat body and hemolymph.

Solventless Dual-Cure Liquid Resins Via Circular Use of Phthalic Anhydride for Recyclable Composite Applications.

Fiber-reinforced composites (FRCs) possess a remarkable strength-to-weight ratio, making them ideal light-weighing alternative materials of metals used in automotive, aerospace, and outdoor equipment applications, but their recycling is challenging. Chemically recyclable thermoset polymers can enable fiber recovery and reuse; however, challenges remain in the separation and purification of depolymerized small molecules for efficient polymer recycling. To this end, a series of liquid resins for chemically recyclable polymer networks is designed based on phthalic anhydride, a widely produced and inexpensive chemical.

Impact of cariprazine on body weight and blood pressure among adults with bipolar I disorder, schizophrenia, or major depressive disorder in a real-world setting.

Background: Atypical antipsychotics are a common treatment for serious mental illness, but many are associated with adverse effects, including weight gain and cardiovascular issues, and real-world experience may differ from clinical trial data. Cariprazine has previously demonstrated a favorable safety and tolerability profile in clinical trials. Here, we evaluated the effects of cariprazine on body weight and blood pressure for bipolar I disorder (BP-I), schizophrenia, or as adjunctive treatment for major depressive disorder (MDD) using real-world data.

Rome Foundation Working Team Report on overlap in disorders of gut-brain interaction.

In patients with disorders of gut-brain interaction (DGBI), overlapping non-gastrointestinal conditions such as fibromyalgia, headaches, gynaecological and urological conditions, sleep disturbances and fatigue are common, as is overlap among DGBI in different regions of the gastrointestinal tract. These overlaps strongly influence patient management and outcome. Shared pathophysiology could explain this scenario, but details are not fully understood.

Recombinant XBB.1.5 boosters induce robust neutralization against KP.2- and KP.3-included JN.1 sublineages.

The newly emerged variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) demonstrate resistance to present therapeutic antibodies as well as the capability to evade vaccination-elicited antibodies. JN.1 sublineages were demonstrated as one of the most immune-evasive variants, showing higher neutralization resistance compared to XBB.

Combinatorial phenotypic landscape enables bacterial resistance to phage infection.

Success of phage therapies is limited by bacterial defenses against phages. While a large variety of anti-phage defense mechanisms has been characterized, how expression of these systems is distributed across individual cells and how their combined activities translate into protection from phages has not been studied. Using bacterial single-cell RNA sequencing, we profiled the transcriptomes of ~50,000 cells from cultures of a human pathobiont, , infected with a lytic bacteriophage.

Case report: A successful case of targeted immunotherapy for locally advanced pancreatic cancer under non-surgical conditions.

Introduction: Locally advanced pancreatic cancer (LAPC) is a borderline unresectable malignancy that presents significant treatment challenges. The management of LAPC remains a complex issue, particularly in patients who are not eligible for surgical resection.

Case: Here, we report the case of a 60-year-old woman diagnosed with LAPC through pathological biopsy who subsequently underwent targeted immunotherapy following the failure of a gemcitabine, oxaliplatin, and S-1 (G&S) chemotherapy regimen.

Capsule network approach for monkeypox (CAPSMON) detection and subclassification in medical imaging system.

In response to the pressing need for the detection of Monkeypox caused by the Monkeypox virus (MPXV), this study introduces the Enhanced Spatial-Awareness Capsule Network (ESACN), a Capsule Network architecture designed for the precise multi-class classification of dermatological images. Addressing the shortcomings of traditional Machine Learning and Deep Learning models, our ESACN model utilizes the dynamic routing and spatial hierarchy capabilities of CapsNets to differentiate complex patterns such as those seen in monkeypox, chickenpox, measles, and normal skin presentations. CapsNets' inherent ability to recognize and process crucial spatial relationships within images outperforms conventional CNNs, particularly in tasks that require the distinction of visually similar classes.

Targeting EBV Episome for Anti-Cancer Therapy: Emerging Strategies and Challenges.

As a ubiquitous human pathogen, the Epstein-Barr virus (EBV) has established lifelong persistent infection in about 95% of the adult population. The EBV infection is associated with approximately 200,000 human cancer cases and 140,000 deaths per year. The presence of EBV in tumor cells provides a unique advantage in targeting the viral genome (also known as episome), to develop anti-cancer therapeutics.

Innovative Solid Lipid Nanoparticle-Enriched Hydrogels for Enhanced Topical Delivery of L-Glutathione: A Novel Approach to Anti-Ageing.

Skin ageing, driven predominantly by oxidative stress from reactive oxygen species (ROS) induced by environmental factors like ultraviolet A (UVA) radiation, accounts for approximately 80% of extrinsic skin damage. L-glutathione (GSH), a potent antioxidant, holds promise in combating UVA-induced oxidative stress. However, its instability and limited penetration through the stratum corneum hinder its topical application.

Exploring the Potential of Selenium-Containing Amine (Se-AMA) to Enhance Photosynthesis and Leaf Water Content: New Avenues for Carbonic Anhydrase Modulation in .

Global changes and growing demands have led to the development of new molecular approaches to improve crop physiological performances. Carbonic anhydrase (CA) enzymes, ubiquitous across various life kingdoms, stand out for their critical roles in plant photosynthesis and water relations. We hypothesize that the modulators of human CAs could affect plant physiology.

Hereditary Pancreatic Cancer: Advances in Genetic Testing, Early Detection Strategies, and Personalized Management.

: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with a five-year survival rate of approximately 13% for advanced stages. While the majority of PDAC cases are sporadic, a significant subset is attributable to hereditary and familial predispositions, accounting for approximately 25% of cases. This article synthesizes recent advancements in the understanding, detection, and management of hereditary pancreatic cancer (PC).

Exploring CAR T-Cell Dynamics: Balancing Potent Cytotoxicity and Controlled Inflammation in CAR T-Cells Derived from Systemic Sclerosis and Myositis Patients.

Systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and idiopathic inflammatory myositis (IIM) are autoimmune diseases managed with long-term immunosuppressive therapies. Hu19-CD828Z, a fully human anti-CD19 chimeric antigen receptor (CAR) with a CD28 costimulatory domain, is engineered to potently deplete B-cells. In this study, we manufactured Hu19-CD828Z CAR T-cells from peripheral blood of SLE, IIM, and SSc patients and healthy donors (HDs).

SLC25A38 is required for mitochondrial pyridoxal 5'-phosphate (PLP) accumulation.

Many essential proteins require pyridoxal 5'-phosphate, the active form of vitamin B6, as a cofactor for their activity. These include enzymes important for amino acid metabolism, one-carbon metabolism, polyamine synthesis, erythropoiesis, and neurotransmitter metabolism. A third of all mammalian pyridoxal 5'-phosphate-dependent enzymes are localized in the mitochondria; however, the molecular machinery involved in the regulation of mitochondrial pyridoxal 5'-phosphate levels in mammals remains unknown.

Prediction of Cyclic O Molecules Stabilized by Helium under Pressure.

Oxygen usually exists in the form of diatomic molecules at ambient conditions. At high pressure, it undergoes a series of phase transitions from diatomic O to O cluster and ultimately dissociates into a polymeric O spiral chain structure. Intriguingly, the commonly found cyclic hexameric molecules in other group VIA elements (e.

Signal peptidase SpsB coordinates staphylococcal cell cycle, surface protein septal trafficking, and LTA synthesis.

Unlabelled: Cell wall-anchored surface proteins of Gram-positive bacteria, harboring a highly conserved YSIRK/G-S signal peptide (SP), are deposited at cell division septum and anchored to septal peptidoglycan. The mechanisms supporting YSIRK protein septal trafficking remain elusive. Previously, we identified that LtaS-mediated lipoteichoic acid (LTA) synthesis restricts septal trafficking of YSIRK+ proteins in .

Properties, Antioxidant and Antibacterial Activity of Southern Meagre Fish () Skin Gelatin Reinforced with Clove Bud Extract.

The properties of biopolymer films prepared using Southern meagre fish () skin gelatin blends, both with and without clove bud extract (CE) at concentrations of 0.3% and 0.7%, were investigated.

Fabrication with Characterization of Single-Walled Carbon Nanotube Thin Film Transistor (CNT-TFT) by Spin Coating Method for Flat Panel Display.

Background: Thin Film Transistors (TFTs) are increasingly prevalent electrical components in display products, ranging from smartphones to diagonal flat panel TVs. The limitations in existing TFT technologies, such as high-temperature processing, carrier mobility, lower ON/OFF ratio, device mobility, and thermal stability, result in the search for new semiconductor materials with superior properties.

Objective: The main objective of this present work is to fabrícate the efficient Single-Walled Carbon Nanotube Thin Film Transistor (TFT) for flat panel display.