Network analysis combined with genome-wide association study helps identification of genes related to amino acid contents in soybean.

Background: Additional to total protein content, the amino acid (AA) profile is important to the nutritional value of soybean seed. The AA profile in soybean seed is a complex quantitative trait controlled by multiple interconnected genes and pathways controlling the accumulation of each AA. With a total of 621 soybean germplasm, we used three genome-wide association study (GWAS)-based approaches to investigate the genomic regions controlling the AA content and profile in soybean.

Inactivation of GSK3β by Ser phosphorylation prevents thymocyte necroptosis and impacts Tcr repertoire diversity.

The assembly of Tcrb and Tcra genes require double negative (DN) thymocytes to undergo multiple rounds of programmed DNA double-strand breaks (DSBs), followed by their efficient repair. However, mechanisms governing cell cycle checkpoints and specific survival pathways during the repair process remain unclear. Here, we report high-resolution scRNA-seq analyses of individually sorted mouse DN3 and DN4 thymocytes, which reveals a G2M cell cycle checkpoint, in addition to the known G1 checkpoint, during Tcrb and Tcra recombination.

Quality of life in early breast cancer patients after adjuvant accelerated partial-breast irradiation (APBI) in randomized trial.

Accelerated partial breast irradiation (APBI) represents a valid option for adjuvant therapy of selected early breast cancer (BC). This single-institution prospective randomized study compares the health-related quality of life (HRQoL) between women treated with the highly conformal-external beam APBI technique and those with the more commonly used moderately hypofractionated whole breast irradiation (hypo-WBI). Eligible patients were women over 50 years with early BC (G1/2 DCIS ≤ 25 mm or G1/2 invasive non-lobular luminal-like HER2 negative carcinoma ≤ 20 mm) after breast-conserving surgery with negative margins.

The impact of an interactive online informational and peer support application (app) for patients with low anterior resection syndrome (LARS) on quality of life: a multicenter randomized controlled trial.

Introduction: Low Anterior Resection Syndrome (LARS) describes bowel dysfunction post-restorative proctectomy (RP) and is associated with poor quality of life (QoL). The aim of this study was to assess the impact of an interactive online informational and peer support App on participants' QoL (primary outcome), LARS, and emotional distress (secondary outcomes).

Methods: A multicentre, randomized, parallel-group trial was conducted across five Canadian colorectal surgery practices.

Prospective association of tobacco retailer density and neighbourhood walkability with youth vaping initiation in California, USA.

Background: Tobacco retailer density might influence youth e-cigarette use due to increased access and exposure to point-of-sale marketing. There is a need for longitudinal investigations on the association of tobacco retailer density with youth e-cigarette use, with consideration of contextual factors such as neighbourhood walkability that could enhance retailer exposure.

Methods: Five semi-annual waves (Fall 2021-Fall 2023) of a Southern California school-based cohort of youth who never vaped at baseline (n=3401; mean baseline age=15 years [range=12-17]) were merged with spatial data on tobacco retailers corresponding to each school year.

Cardiovascular events observed among patients in the etrasimod clinical programme: an integrated safety analysis of patients with moderately to severely active ulcerative colitis.

Objective: Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P) receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). S1P receptor expression on cardiac cells is involved in cardiac conduction. We report cardiovascular treatment-emergent adverse events (TEAEs) associated with S1P receptor modulators and other cardiovascular events in the etrasimod UC clinical programme.

Neuromodulation Strategies in Lennox-Gastaut Syndrome: Practical Clinical Guidance from the Pediatric Epilepsy Research Consortium.

Lennox-Gastaut syndrome (LGS) is a severe developmental and epileptic encephalopathy characterized by multiple drug-resistant seizure types, cognitive impairment, and distinctive electroencephalographic patterns. Neuromodulation techniques, including vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation (RNS), have emerged as important treatment options for patients with LGS who do not respond adequately to antiseizure medications. This review, developed with input from the Pediatric Epilepsy Research Consortium (PERC) LGS Special Interest Group, provides practical guidance for clinicians on the use of these neuromodulation approaches in patients with LGS.

Fate of Semilunar Valves From Discarded Hearts at the Time of Pediatric Heart Retransplantation.

Background: Partial heart transplantation (PHT) is a novel procedure for children in need of a growing valve replacement option. One challenge is identifying suitable donor valves. Semilunar heart valves from patients receiving a retransplant may be a source, however their functionality and growth potential especially at the time of retransplant are unknown.

Electrophysiological Studies in Combination With Interim-Positron Emission Tomography Scan for Prevention of Severe Brentuximab-Vedotin-Induced Neurotoxicity.

Brentuximab-vedotin (BV)-induced neurotoxicity (BVIN), a frequent adverse event caused by this monoclonal antibody, is the primary reason for dose modification or drug discontinuation, and is characterized by sensory, motor, and/or autonomic peripheral nerve dysfunctions. Although reversible, BVIN can persist for months or years after treatment and negatively affect quality of life (QoL). Currently, BVIN is managed by dose adjustment or drug interruption, leading to an increased risk of disease relapse.

Association Between Early Immunosuppression Center Variability and One-Year Outcomes After Pediatric Liver Transplant.

Background: Despite the existence of institutional protocols, liver transplant centers often have variability in early immunosuppression practices. We aimed to measure within-center variability in early immunosuppression after pediatric liver transplant (LT) and examine its association with one-year outcomes.

Methods: We analyzed pediatric LTs from 2013 to 2018 in the United Network for Organ Sharing registry, with data aggregated by center.

Prevention of Infections Among Pediatric Solid Organ Transplant Recipients With Asplenia or Hyposplenism.

Pediatric solid organ transplant (SOT) recipients with splenic dysfunction are at increased risk for infections, and tailored guidance on the management of asplenia/hyposplenism among SOT recipients is often lacking. The purpose of this article is to provide practice recommendations via a frequently asked questions (FAQs) format that focuses on three main domains: the identification of asplenia/hyposplenism among SOT recipients/candidates, prophylactic strategies for mitigating the risk of invasive disease associated with splenic dysfunction in the context of transplantation, and the provision of appropriate patient counseling on the risks associated with asplenia/hyposplenism. Answers to the FAQs are based on international expert opinion informed by practices for managing splenic dysfunction and associated data in other populations with asplenia.

Sepsis-induced NET formation requires MYD88 but is independent of GSDMD and PAD4.

Neutrophils are peripheral blood-circulating leukocytes that play a pivotal role in host defense against bacterial pathogens which upon activation, they release web-like chromatin structures called neutrophil extracellular traps (NETs). Here, we analyzed and compared the importance of myeloid differentiation factor 88 (MYD88), peptidyl arginine deiminase 4 (PAD4), and gasdermin D (GSDMD) for NET formation in vivo following sepsis and neutrophilia challenge. Injection of lipopolysaccharide (LPS)/E.

Tapinarof Improved Outcomes and Sleep for Patients and Families in Two Phase 3 Atopic Dermatitis Trials in Adults and Children.

Introduction: Tapinarof is a topical aryl hydrocarbon receptor (AhR) agonist in development for the treatment of atopic dermatitis (AD). In two phase 3 trials (ADORING 1 and 2), tapinarof cream 1% once daily (QD) demonstrated significant efficacy and was well tolerated in patients down to age 2 years with AD. Here, we evaluate patient-reported outcomes (PROs), including family impact, with tapinarof in ADORING 1 and 2.

Image Guidance is Associated with Improved Freedom From Recurrence After Superficial Radiation Therapy for Nonmelanoma Skin Cancer.

Purpose: This is the first study to quantify the 2-year freedom from recurrence for individuals with nonmelanoma skin cancer (NMSC) such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and squamous carcinoma in situ (SCCIS) treated with image guided superficial radiation therapy (IGSRT) versus SRT without image guidance.

Methods And Materials: This retrospective cohort study evaluates the 2-year freedom recurrence rate of NMSCs treated by IGSRT (March 2016 to January 2022) and compares it to existing data on NMSCs treated by SRT via 1 sample proportion tests. Individuals >18 years old with biopsy-proven SCC, SCCIS, and/or BCC treated with IGSRT were included in the study, and 1602 patients/2880 treated lesions were followed until January 14, 2022.

A mini review of leveraging biobanking in the identification of novel biomarkers in neurological disorders: insights from a rapid single-cell sequencing pipeline.

Recent successes in the identification of biomarkers and therapeutic targets for diagnosing and managing neurological diseases underscore the critical need for cutting-edge biobanks in the conduct of high-caliber translational neuroscience research. Biobanks dedicated to neurological disorders are particularly timely, given the increasing prevalence of neurological disability among the rising aging population. Translational research focusing on disorders of the central nervous system (CNS) poses distinct challenges due to the limited accessibility of CNS tissue pre-mortem.

The sequence-structure-function relationship of intrinsic ERα disorder.

The oestrogen receptor (ER or ERα), a nuclear hormone receptor that drives most breast cancer, is commonly activated by phosphorylation at serine 118 within its intrinsically disordered N-terminal transactivation domain. Although this modification enables oestrogen-independent ER function, its mechanism has remained unclear despite ongoing clinical trials of kinase inhibitors targeting this region. By integration of small-angle X-ray scattering and nuclear magnetic resonance spectroscopy with functional studies, we show that serine 118 phosphorylation triggers an unexpected expansion of the disordered domain and disrupts specific hydrophobic clustering between two aromatic-rich regions.

Bidirectional histone monoaminylation dynamics regulate neural rhythmicity.

Histone H3 monoaminylations at Gln5 represent an important family of epigenetic marks in brain that have critical roles in permissive gene expression. We previously demonstrated that serotonylation and dopaminylation of Gln5 of histone H3 (H3Q5ser and H3Q5dop, respectively) are catalysed by transglutaminase 2 (TG2), and alter both local and global chromatin states. Here we found that TG2 additionally functions as an eraser and exchanger of H3 monoaminylations, including H3Q5 histaminylation (H3Q5his), which displays diurnally rhythmic expression in brain and contributes to circadian gene expression and behaviour.

Bioactive Secondary Metabolites from Bauhinia variegata Linn. Roots: Isolation, Characterization, and Cytotoxic Evaluation.

Introduction: This study aims to isolate and characterize potential cytotoxic compounds from the roots of Bauhinia variegata Linn. (Caesalpiniaceae) and evaluate their activity against human cancer cell lines. Five compounds, namely β-sitosterol (1), piperine (2), piperolein B (3), retrofractamide A (4), and dehydropipernonaline (5), were isolated from B.

An Azomethine Derivative, 1-(4-nitrophenyl)-N-phenylmethanimine (BCS2) Ameliorated 7,12-dimethylbenz(a)anthracene-induced Mammary Carcinoma through Nrf2-Keap1-HO-1 Pathway.

Aims: The aim of this study is the evaluation of an Azomethine derivative, BCS2, for its antioxidant and anti-tumor activities against mammary carcinoma through the Nrf2- Keap1-HO-1 pathway.

Background: The global prevalence of breast cancer is rising at an alarming rate. The facilitation of abnormal cell proliferation in mammary carcinoma occurs due to the disruption of signaling pathways that balance pro- and antioxidant status, thereby producing oxidative stress that disrupts genomic stability.

Artificial Intelligence, Machine Learning and Big Data in Radiation Oncology.

This review explores the applications of artificial intelligence and machine learning (AI/ML) in radiation oncology, focusing on computer vision (CV) and natural language processing (NLP) techniques. We examined CV-based AI/ML in digital pathology and radiomics, highlighting the prospective clinical studies demonstrating their utility. We also reviewed NLP-based AI/ML applications in clinical documentation analysis, knowledge assessment, and quality assurance.

First pass effect in patients with large core infarcts undergoing mechanical thrombectomy: subgroup analysis of the prospective international ASSIST registry.

Background: Studies have described a first pass effect (FPE) where patients with successful recanalization after one pass experience better outcomes. Few studies have evaluated this in patients with large core infarctions.

Objective: To determine whether patients with large core infarcts undergoing mechanical thrombectomy in which first pass reperfusion is achieved experience improved outcomes compared with those who undergo more than one pass.