Intranasal oxytocin for apathy in people with frontotemporal dementia (FOXY): a multicentre, randomised, double-blind, placebo-controlled, adaptive, crossover, phase 2a/2b superiority trial.

Background: No treatments exist for apathy in people with frontotemporal dementia. Previously, in a randomised double-blind, placebo-controlled, dose-finding study, intranasal oxytocin administration in people with frontotemporal dementia improved apathy ratings on the Neuropsychiatric Inventory over 1 week and, in a randomised, double-blind, placebo-controlled, crossover study, a single dose of 72 IU oxytocin increased blood-oxygen-level-dependent signal in limbic brain regions. We aimed to determine whether longer treatment with oxytocin improves apathy in people with frontotemporal dementia.

OXCT1 succinylation and activation by SUCLA2 promotes ketolysis and liver tumor growth.

Ketone bodies generated in hepatocytes in the adult liver are used for nonhepatic tissues as an energy source. However, ketolysis is reactivated in hepatocellular carcinoma (HCC) cells with largely unelucidated mechanisms. Here, we demonstrate that 3-oxoacid CoA-transferase 1 (OXCT1), a rate-limiting enzyme in ketolysis, interacts with SUCLA2 upon IGF1 stimulation in HCC cells.

Structures and mRNP remodeling mechanism of the TREX-2 complex.

mRNAs are packaged with proteins into messenger ribonucleoprotein complexes (mRNPs) in the nucleus. mRNP assembly and export are of fundamental importance for all eukaryotic gene expression. Before export to the cytoplasm, mRNPs undergo dynamic remodeling governed by the DEAD-box helicase DDX39B (yeast Sub2).

A forward genetic screen identifies potassium channel essentiality in SHH medulloblastoma maintenance.

Distinguishing tumor maintenance genes from initiation, progression, and passenger genes is critical for developing effective therapies. We employed a functional genomic approach using the Lazy Piggy transposon to identify tumor maintenance genes in vivo and applied this to sonic hedgehog (SHH) medulloblastoma (MB). Combining Lazy Piggy screening in mice and transcriptomic profiling of human MB, we identified the voltage-gated potassium channel KCNB2 as a candidate maintenance driver.

Two-in-one strategy to enhance the stability of TiCT in transition metal ion solutions.

Although MXenes have attracted significant attention across diverse fields, they exhibit a pronounced susceptibility to oxidation in aqueous environments, with oxidation significantly accelerated in the presence of transition metal ions (TMI) such as Fe and Cu. This limitation impedes the synthesis of transition metal compounds/MXene-based composites and their potential for functional applications. In this study, we elucidate the mechanism of accelerated oxidation of TiCT is that Fe promotes the electron loss in TiCT, thus leading to an increased production of hydroxyl radicals (OH) to oxidize TiCT.

The Anatomy of Gossip: Dissecting Dynamics and Impacts in Surgical Residency.

Background: Gossip, defined by social scientists as "evaluative talk about an absent third party," is anecdotally pervasive yet poorly understood in surgical residency programs. Gossip is known to have both positive and negative impacts. This study sought to deconstruct the role of gossip in surgical residency and evaluate its impact through the lens of surgical residents.

Immunology of Biliary Atresia.

Biliary atresia is a progressive neonatal cholangiopathy that leads to liver failure. Characterized by inflammation-mediated liver injury, the immune system plays a critical role in the pathogenesis of this disease. Though several types of immune cells and mediators have been implicated in animal models of biliary atresia, emerging literature reflects the complex interplay of components of the immune response that contributes to disease progression in humans.

Influence of prosthetic foot selection on walking performance during various load carriage conditions.

Background: Ambulatory individuals with lower limb amputations often face challenges with body support, body propulsion, and balance control. Carrying an infant, toddler, backpack, or other load can exacerbate these challenges and highlights the importance of prescribing the most suitable prosthetic foot. The aim of this study was to examine the influence of five different prosthetic feet on walking performance during various load carriage conditions.

Binding a C-appended rhenium-(Bispyridine) carbonyl complex to β-Lactoglobulin: Effects of pH & cysteine modification on calyx affinity.

Due to its commercial availability and well-defined structure, the interaction between bovine protein β-lactoglobulin (βLG) and a wide variety of non-native ligands - including transition metal complexes - has been explored, but its application as an artificial metalloenzyme scaffold is limited. This protein is hypothesized to transport fatty acids and other nutrients during juvenile development, and it binds hydrophobic ligands inside a binding pocket constructed upon an 8-stranded β-barrel, called the 'calyx'. Herein, we compare the binding behavior of two rhenium(anthracene-bispyridine) ('Anth-py') tricarbonyl complexes, one with a 12‑carbon chain appended to the ligand scaffold ('Anth-py') to βLG.

HemaScope: A Tool for Analyzing Single-cell and Spatial Transcriptomics Data of Hematopoietic Cells.

Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) techniques hold great value in evaluating the heterogeneity and spatial characteristics of hematopoietic cells within tissues. These two techniques are highly complementary, with scRNA-seq offering single-cell resolution and ST retaining spatial information. However, there is an urgent demand for well-organized and user-friendly toolkits capable of handling single-cell and spatial information.

Adjuvant radiation therapy improves outcome of patients with surgical resected adrenocortical carcinoma.

Purpose: Adrenocortical carcinoma (ACC) is a rare malignancy known for high rates of recurrence and poor prognosis. Previous studies revealed controversial roles of adjuvant radiation therapy (RT) in patient management. This study aimed to investigate the role of adjuvant RT in postoperative ACC patients.

Polysomnography in a Private Tertiary Hospital in Tanzania: Subjects' Characteristics and Sleep Disorders.

Background And Objectives: Huge clinical and research gaps exist concerning the epidemiology, natural history, availability, and accessibility of care for sleep disorders in sub-Saharan Africa (SSA). This study aimed to profile the characteristics of patients referred for polysomnography and the frequencies of sleep disorders encountered at the new sleep laboratory in Dar es Salaam, Tanzania.

Materials And Methods: This retrospective hospital-based descriptive observational study was conducted at the Aga Khan Hospital Dar es Salaam.

2024 White Paper on Recent Issues in Bioanalysis: Three Way-Cross Validation; Urine Clinical Analysis; Automated Methods; Regulatory Queries on Plasma Protein Binding; Automated Biospecimen Management; ELN Migration; Ultra-Sensitivity Mass Spectrometry ( - Recommendations on Advanced Strategies for Mass Spectrometry Assays, Chromatography, Sample Preparation and BMV/Regulated Bioanalysis - Regulatory Agencies' Inputs on Regulated Bioanalysis/BMV).

The 18 Workshop on Recent Issues in Bioanalysis (18 WRIB) took place in San Antonio, TX, USA on May 6-10, 2024. Over 1100 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 18 WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.

2024 White Paper on Recent Issues in Bioanalysis: Evolution of Immunogenicity Assessment beyond ADA/NAb; Regulated Genomic/NGS Assays; Hypersensitivity Reactions; Minimum Noise Reduction; False Positive Range; Modernized Vaccine Approaches; NAb/TAb Correlation - Recommendations on Advanced Strategies for Molecular Assays and Immunogenicity of Gene Therapy, Cell Therapy, Vaccine; Biotherapeutics Immunogenicity Assessment & Clinical Relevance - Regulatory Agencies' Input on Immunogenicity/Technologies of Biotherapeutics, Gene, Cell & Vaccine Therapies).

The 18 Workshop on Recent Issues in Bioanalysis (18 WRIB) took place in San Antonio, TX, USA on May 6-10, 2024. Over 1100 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 18 WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.

2024 White paper on recent issues in bioanalysis: Impact of LDT in US and IVDR in EU; AI/ML for High Parameter Flow Cytometry; The rise of Olink Technology; CDx for AAV Gene Therapies; Integrative Bioanalysis by Multiple Platforms; Super Sensitive ADA/NAb LBA ( - Recommendations on Advanced Strategies for Biomarkers, IVD/CDx Assays (BAV), Cell Based Assays (CBA), and Ligand-Binding Assays (LBA) - Regulatory Agencies' Input on Biomarkers, IVD/CDx, and Biomarker Assay Validation).

The 18th Workshop on Recent Issues in Bioanalysis (18th WRIB) took place in San Antonio, TX, USA on May 6-10, 2024. Over 1100 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 18th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.

Herpesvirus Infections After Chimeric Antigen Receptor T-Cell Therapy and Bispecific Antibodies: A Review.

In this narrative review, we explore the burden and risk factors of various herpesvirus infections in patients receiving chimeric antigen receptor T-cell (CAR-T) therapy or bispecific antibodies (BsAb) for the treatment of hematologic malignancies. Antiviral prophylaxis for herpes simplex/varicella zoster viruses became part of the standard of care in this patient population. Breakthrough infections may rarely occur, and the optimal duration of prophylaxis as well as the timing of recombinant zoster immunization remain to be explored.

Repurposing Drugs for Synergistic Combination Therapies to Counteract Monkeypox Virus Tecovirimat Resistance.

The ongoing monkeypox (mpox) disease outbreak has spread to multiple countries in Central Africa and evidence indicates it is driven by a more virulent clade I monkeypox virus (MPXV) strain than the clade II strain associated with the 2022 global mpox outbreak, which led the WHO to declare this mpox outbreak a public health emergency of international concern. The FDA-approved small molecule antiviral tecovirimat (TPOXX) is recommended to treat mpox cases with severe symptoms, but the limited efficacy of TPOXX and the emergence of TPOXX resistant MPXV variants has challenged this medical practice of care and highlighted the urgent need for alternative therapeutic strategies. In this study we have used vaccinia virus (VACV) as a surrogate of MPXV to assess the antiviral efficacy of combination therapy of TPOXX together with mycophenolate mofetil (MMF), an FDA-approved immunosuppressive agent that we have shown to inhibit VACV and MPXV, or the N-myristoyltransferase (NMT) inhibitor IMP-1088.

A Comprehensive Review of the Development and Therapeutic Use of Antivirals in Flavivirus Infection.

Flaviviruses are a diverse group of viruses primarily transmitted through hematophagous insects like mosquitoes and ticks. Significant expansion in the geographic range, prevalence, and vectors of flavivirus over the last 50 years has led to a dramatic increase in infections that can manifest as hemorrhagic fever or encephalitis, leading to prolonged morbidity and mortality. Millions of infections every year pose a serious threat to worldwide public health, encouraging scientists to develop a better understanding of the pathophysiology and immune evasion mechanisms of these viruses for vaccine development and antiviral therapy.

eEF-2K Deficiency Boosts the Virus-Specific Effector CD8 T Cell Responses During Viral Infection.

In this study, we revealed a critical role of eukaryotic elongation factor-2 kinase (eEF-2K), a negative regulator of protein synthesis, in regulating T cells during vaccinia virus (VACV) infection. We found that eEF-2K-deficient (eEF-2K⁻/⁻) mice exhibited a significantly higher proportion of VACV-specific effector CD8 T cells without compromising the development of VACV-specific memory CD8 T cells. RNA sequencing demonstrated that eEF-2K⁻/⁻ VACV-specific effector CD8 T cells had enhanced functionality, which improves their capacity to combat viral infection during the effector phase.

Metabolite Profiling and Association Analysis of Leaf Tipburn in Heat-Tolerant Bunching Onion Varieties.

The bunching onion is an important leafy vegetable, prized for its distinctive flavor and color. It is consumed year-round in Japan, where a stable supply is essential. However, in recent years, the challenges posed by climate change and global warming have resulted in adverse effects on bunching onions, including stunted growth, discoloration, and the development of leaf tipburn, threatening both crop quality and yield.

Dietary Interventions, Supplements, and Plant-Derived Compounds for Adjunct Vitiligo Management: A Review of the Literature.

Vitiligo is a chronic autoimmune pigmentation disorder shaped by a complex interplay of genetic predispositions and environmental triggers. While conventional therapies-phototherapy, corticosteroids, and immunosuppressants-can be effective, their benefits are often partial and temporary, with recurrence common once treatment stops. As such, there is increasing interest in exploring complementary approaches that may offer a more sustainable impact.

Food Insecurity and Coping Mechanisms: Impact on Maternal Mental Health and Child Malnutrition.

Background: Household food insecurity (HFI) is a serious public health concern in Lebanon. Adverse mental health issues have been reported among food insecure households in addition to physical and nutritional complications. Caregivers in food insecure families tend to adopt different coping mechanisms to mitigate the effects of food insecurity (FI) on their children.

Improving Cooking Skills, Lifestyle Behaviors, and Clinical Outcomes for Adults at Risk for Cardiometabolic Disease: Protocol for a Randomized Teaching Kitchen Multisite Trial (TK-MT).

Background/objectives: This protocol describes a study to investigate the feasibility and preliminary efficacy of a novel Teaching Kitchen Multisite Trial (TK-MT) for adults with cardiometabolic abnormalities. The TK-MT protocol describes a hybrid lifestyle intervention combining in-person and virtual instruction in culinary skills, nutrition education, movement, and mindfulness with community support and behavior change strategies. This 18-month-long randomized controlled trial aims to evaluate the feasibility of implementing a 12-month, 24 class program, assess preliminary study efficacy, and identify barriers and facilitators to implementation.