The Critical Roles of Phosphatidylethanolamine-Binding Proteins in Legumes.

Legumes, characterized by their ability to form symbiotic relationships with nitrogen-fixing bacteria, play crucial roles in agriculture, ecology and human nutrition. Phosphatidylethanolamine-binding proteins (PEBPs) are the key genetic players that contribute to the diverse biological functions of legumes. In this review, we summarize the current understanding of important roles of PEBP genes in legumes, including flowering, inflorescence architecture, seed development and nodulation.

Association of Major Histocompatibility Complex Polymorphism With Acute Phase Response in Broiler Chicken.

Background: Stress associated with changes in host immunity occurs in response to altered environmental conditions, endogenous imbalances, infectious agents and harmful stimuli. The importance of genetic diversity in chickens has increased due to individual immune differences towards resistance and susceptibility to various stimuli.

Objectives: This study aimed to investigate the association of major histocompatibility complex (MHC) polymorphism with acute phase response (APR) in Ross 308 broiler chickens.

Association Between Delay to First Shock and Successful First-Shock Ventricular Fibrillation Termination in Patients With Witnessed Out-of-Hospital Cardiac Arrest.

Background: In patients with out-of-hospital cardiac arrest who present with an initial shockable rhythm, a longer delay to the first shock decreases the probability of survival, often attributed to cerebral damage. The mechanisms of this decreased survival have not yet been elucidated. Estimating the probability of successful defibrillation and other factors in relation to the time to first shock may guide prehospital care systems to implement policies that improve patient survival by decreasing time to first shock.

Does the Vaccination against Tick-Borne Encephalitis Offer Good Value for Money for Incidence Rates below the WHO Threshold for Endemicity? A Case Study for Germany.

Unlabelled: Tick-borne encephalitis (TBE) is a viral infection affecting the central nervous system (CNS) with potential long-term consequences including neurological sequelae. Vaccination is critical to reduce TBE morbidity and mortality, as no antiviral treatment is available. The World Health Organization (WHO) defines areas with an incidence of ≥5 cases/100,000 PPY as highly endemic and recommends that vaccination is offered to all individuals in these areas.

Variability of Hepatitis C Treatment Cascade Outcomes among People Who Inject Drugs across Geographically Diverse Clinics in the US: The HERO Study.

Heterogeneity of outcomes across different clinical trial study sites is often inevitable. Understanding how outcomes differ by site is important for planning future programs and studies. We examined the extent of heterogeneity of hepatitis C virus (HCV) treatment cascade outcomes among persons who inject drugs (PWIDs) across sixteen clinical sites utilized in the HERO Study-a pragmatic randomized trial of HCV treatment support.

Preclinical Profile of the HIV-1 Maturation Inhibitor VH3739937.

The HIV-1 maturation inhibitor (MI) VH3739937 (VH-937) inhibits cleavage between capsid and spacer peptide 1 and exhibits an oral half-life in humans compatible with once-weekly dosing. Here, the antiviral properties of VH-937 are described. VH-937 exhibited potent antiviral activity against all HIV-1 laboratory strains, clinical isolates, and recombinant viruses examined, with half-maximal effective concentration (EC) values ≤ 5.

Robustness Assessment of Oncology Dose-Finding Trials Using the Modified Fragility Index.

Objectives: The sample sizes of phase I trials are typically small; some designs may lead to inaccurate estimation of the maximum tolerated dose (MTD). The objective of this study was to propose a metric assessing whether the MTD decision is sensitive to enrolling a few additional subjects in a phase I dose-finding trial.

Methods: Numerous model-based and model-assisted designs have been proposed to improve the efficiency and accuracy of finding the MTD.

Strategies to Target Chemoradiotherapy Resistance in Small Cell Lung Cancer.

Small cell lung cancer (SCLC) is a lethal form of lung cancer with few treatment options and a high rate of relapse. While SCLC is initially sensitive to first-line DNA-damaging chemo- and radiotherapy, relapse disease is almost universally therapy-resistant. As a result, there has been interest in understanding the mechanisms of therapeutic resistance in this disease.

Coupling Habitat Radiomic Analysis with the Diversification of the Tumor ecosystem: Illuminating New Strategy in the Assessment of Postoperative Recurrence of Non-Muscle Invasive Bladder Cancer.

Rationale And Objectives: Non-muscle-invasive bladder cancer (NMIBC) is highly recurrent, with each recurrence potentially progressing to muscle-invasive cancer, affecting patient prognosis. Intratumoral heterogeneity plays a crucial role in NMIBC recurrence. This study investigated a novel habitat-based radiomic analysis for stratifying NMIBC recurrence risk.

Terpenoids from the Soft Coral Collected in the South China Sea.

The chemical investigation of the South China Sea soft coral has resulted in the isolation of seven new terpenoids, including two new meroterpenoids, namely sinudenoids F-G (-), and five new cembranes, namely sinudenoids H-L (-). Their structures and absolute configurations were elucidated based on extensive analyses of spectroscopic data, single-crystal X-ray diffraction, comparison with the literature data, and quantum chemical calculations. Among them, sinudenoid F () and sinudenoid G () are rare meroterpenoids featuring a methyl benzoate core.

Clinician and Visitor Activity Patterns in an Intensive Care Unit Room: A Study to Examine How Ambient Monitoring Can Inform the Measurement of Delirium Severity and Escalation of Care.

The early detection of the acute deterioration of escalating illness severity is crucial for effective patient management and can significantly impact patient outcomes. Ambient sensing technology, such as computer vision, may provide real-time information that could impact early recognition and response. This study aimed to develop a computer vision model to quantify the number and type (clinician vs.

Pharmacokinetics of Vancomycin in Healthy Korean Volunteers and Monte Carlo Simulations to Explore Optimal Dosage Regimens in Patients with Normal Renal Function.

: To date, population pharmacokinetic (PK) studies of vancomycin on healthy Korean adults have not been conducted. This study aimed to investigate the PK properties of vancomycin in healthy volunteers and to identify optimal dosing regimens based on the area under the concentration-time curve (AUC) in adult patients with normal renal function. : We conducted a prospective clinical study, analysing PK samples from 12 healthy participants using noncompartmental analysis and non-linear mixed-effects modelling.

Transcription factor TCF1 binds to RORγt and orchestrates a regulatory network that determines homeostatic Th17 cell state.

T helper (Th) 17 cells encompass a spectrum of cell states, including cells that maintain homeostatic tissue functions and pro-inflammatory cells that can drive autoimmune tissue damage. Identifying regulators that determine Th17 cell states can identify ways to control tissue inflammation and restore homeostasis. Here, we found that interleukin (IL)-23, a cytokine critical for inducing pro-inflammatory Th17 cells, decreased transcription factor T cell factor 1 (TCF1) expression.

Incremental Prognostic Value of Cardiac MRI Feature Tracking and T1 Mapping in Arrhythmogenic Right Ventricular Cardiomyopathy.

Purpose To explore the role of cardiac MRI feature tracking (FT) and T1 mapping in predicting sustained ventricular arrhythmias (VA) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and to investigate their possible incremental value beyond ARVC risk score. Materials and Methods The retrospective study analyzed 91 patients with ARVC (median age, 36 years [IQR, 27-50 years]; 60 male, 31 female) who underwent cardiac MRI examinations between November 2010 and March 2022. The primary end point was the first occurrence of sustained VA after cardiac MRI to first VA, with censoring of patients who were alive without VA at last follow-up.

Asia-inclusive drug development leveraging principles of ICH E5 and E17 guidelines: Case studies illustrating quantitative clinical pharmacology as a foundational enabler.

With the International Conference on Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) E17 guidelines in effect from 2018, the design of Asia-inclusive multiregional clinical trials (MRCTs) has been streamlined, thereby enabling efficient simultaneous global development. Furthermore, with the recent regulatory reforms in China and its drug administration joining the ICH as a full regulatory member, early participation of China in the global clinical development of novel investigational drugs is now feasible. This would also allow for inclusion of the region in the geographic footprint of pivotal MRCTs leveraging principles of the ICH E5 and E17.

Isocyanide Substituent Influences Reductive Elimination versus Migratory Insertion in Reaction with an [Fe(μ-H)] Complex.

Iron hydrides are proposed reactive intermediates for N and CO conversion in industrial and biological processes. Here, we report a reactivity study of a low-coordinate di(μ-hydrido)diiron(II) complex, Fe(μ-H), where is a bis(β-diketiminate) cyclophane, with isocyanides, which have electronic structures related to N and CO. The reaction outcome is influenced by the isocyanide substituent, with 2,6-xylyl isocyanide leading to H loss, to form a bis(μ-1,1-isocyanide)diiron(I) complex, whereas all of the other tested isocyanides insert into the Fe-H bond to give (μ-1,2-iminoformyl) complexes.

Temperature and water availability induce chronic stress responses in zebra finches (Taeniopygia guttata).

Animals initiate physiological mechanisms to re-establish homeostasis following environmental stress. To understand how bird physiology responds to abiotic stress, we quantified changes in haematological markers of chronic stress response and body condition of male zebra finches (Taeniopygia guttata) acclimated for 18 weeks to hot and cool temperatures (daytime temperature: 40°C and 23°C) with water available ad libitum or restricted during half of the active phase. Ambient temperature induced greater chronic stress than restricted water availability.

Preclinical and first-in-human evaluation of AL002, a novel TREM2 agonistic antibody for Alzheimer's disease.

Background: Variants of the gene triggering receptor expressed on myeloid cells-2 (TREM2) increase the risk of Alzheimer's disease (AD) and other neurodegenerative disorders. Signaling by TREM2, an innate immune receptor expressed by microglia, is thought to enhance phagocytosis of amyloid beta (Aβ) and other damaged proteins, promote microglial proliferation, migration, and survival, and regulate inflammatory signaling. Thus, TREM2 activation has potential to alter the progression of AD.