Anti-HIV-1 HSPC-based gene therapy with safety kill switch to defend against and attack HIV-1 infection.

Hematopoietic stem/progenitor cell (HSPC)-based anti-HIV-1 gene therapy holds promise to provide life-long remission following a single treatment. Here we report a multi-pronged anti-HIV-1 HSPC-based gene therapy designed to defend against and attack HIV-1 infection. We developed a lentiviral vector capable of co-expressing three anti-HIV-1 genes.

Leveraging Real-World Evidence to Define Severe RSV Lower Respiratory Tract Disease in Adults.

Introduction: As no standard case definitions for respiratory syncytial virus-associated lower respiratory tract disease (RSV-LRTD) in adults are available, this study analyzed definitions for severe RSV-LRTD from previously published data in hospital and community cohorts of adults with RSV-associated symptoms.

Methods: The frequency, sensitivity, and specificity of acute respiratory disease symptoms among hospitalized and community cohorts of adults with RSV were analyzed. RSV-LRTD signs/symptoms assessed included shortness of breath (dyspnea), cough and/or fever, wheezing/rales/rhonchi (abnormal lung sounds by auscultation), sputum production, tachypnea, hypoxemia, and pleuritic chest pain.

Implantation of MSC spheroid-derived 3D decellularized ECM enriched with the MSC secretome ameliorates traumatic brain injury and promotes brain repair.

Traumatic brain injury (TBI) presents substantial clinical challenges, as existing treatments are unable to reverse damage or effectively promote brain tissue regeneration. Although implantable biomaterials have been proposed to support tissue repair by mitigating the adverse microenvironment in injured brains, many fail to replicate the complex composition and architecture of the native extracellular matrix (ECM), resulting in only limited therapeutic outcomes. This study introduces an innovative approach by developing a mesenchymal stem cell (MSC) spheroid-derived three-dimensional (3D) decellularized ECM (dECM) that is enriched with the MSC-derived matrisome and secretome, offering a promising solution for TBI treatment and brain tissue regeneration.

Descriptive Analysis of Types and Diagnoses Associated with Lower Extremity Amputation: Analysis of the US Veterans Health Administration Database 2019-2023.

Introduction: Veterans in the US have higher rates of lower extremity amputation (LEA) compared to the general population and these rates have increased between 2008 and 2018. There is limited data which directly evaluate the potential underlying comorbidities associated with LEA in the veterans' population especially with the most recent data. Such information is critical to help inform clinical management strategies to reduce the risk of amputations among our veterans.

Population pharmacokinetics and exposure-response relationships of maribavir in transplant recipients with cytomegalovirus infection.

Maribavir is approved for management of post-transplant cytomegalovirus (CMV) infections refractory and/or resistant to CMV therapies at a dose of 400 mg twice daily (BID). Population pharmacokinetic (PopPK) and exposure-response analyses were conducted to support the appropriateness of 400 mg BID dosing. A PopPK model was developed using non-linear mixed-effects modeling with pooled maribavir plasma concentration-time data from phase 1 and 2 studies (from 100 mg up to 1200 mg as single or repeated doses) and the phase 3 SOLSTICE study (400 mg BID).

Interpersonal emotion regulation and depressive symptoms in parent-adolescent dyads: A daily-diary investigation.

Deficient parental extrinsic (IER, how people regulate others' emotions) is a known risk factor for adolescent depression. Although IER and depression development are transactional, dyadic processes, previous work has almost exclusively focused on how parental IER is associated with adolescent depression. The association between parental IER and adolescent depression, and the associations between adolescent IER and adolescent and parental depression have received little attention.

Safety and immunogenicity of an mRNA-based RSV vaccine in Japanese older adults aged ≥60 years: A phase 1, randomized, observer-blind, placebo-controlled trial.

Background: Respiratory syncytial virus (RSV) represents a global health concern, including in older adults. This study assessed the safety and immunogenicity of mRNA-1345, an investigational mRNA RSV vaccine, in adults aged ≥60 years of Japanese descent.

Methods: In this phase 1, randomized, observer-blind, placebo-controlled study, participants were randomized to receive one injection of mRNA-1345 100 μg or placebo.

Allele-specific CRISPR-Cas9 editing inactivates a single nucleotide variant associated with collagen VI muscular dystrophy.

The application of allele-specific gene editing tools can expand the therapeutic options for dominant genetic conditions, either via gene correction or via allelic gene inactivation in situations where haploinsufficiency is tolerated. Here, we used allele-targeted CRISPR-Cas9 guide RNAs (gRNAs) to introduce inactivating frameshifting indels at an SNV in the gene (c.868G>A; G290R), a variant that acts as dominant negative and that is associated with a severe form of congenital muscular dystrophy.

Nonidealities in CO Electroreduction Mechanisms Revealed by Automation-Assisted Kinetic Analysis.

In electrocatalysis, mechanistic analysis of reaction rate data often relies on the linearization of relatively simple rate equations; this is the basis for typical Tafel and reactant order dependence analyses. However, for more complex reaction phenomena, such as surface coverage effects or mixed control, these common linearization strategies will yield incomplete or uninterpretable results. Cohesive kinetic analysis, which is often used in thermocatalysis and involves quantitative model fitting for data collected over a wide range of reaction conditions, requires more data but also provides a more robust strategy for interrogating reaction mechanisms.

Nutrition classification schemes for plant-based meat analogues: Drivers to assess nutritional quality and identity profile.

Changes in dietary patterns promoted by the emergence of alternative food systems are becoming increasingly common. The decrease in the consumption of animal-derived products promoted exponential growth in plant-based product demand and, consequently, the availability of several meat analogues for this consumer market. Plant-based meat analogues (PBMAs) were developed to mimic the physical and sensory characteristics of meats and their derivatives.

In situ via Contact to hBN-Encapsulated Air-Sensitive Atomically Thin Semiconductors.

Establishing reliable electrical contacts to atomically thin materials is a prerequisite for both fundamental studies and applications yet remains a challenge. In particular, the development of contact techniques for air-sensitive monolayers has lagged behind, despite their unique properties and significant potential for applications. Here, we present a robust method to create contacts to device layers encapsulated within hexagonal boron nitride (hBN).

Parameterization of Physiologically Based Biopharmaceutics Models: Workshop Summary Report.

This Article shares the proceedings from the August 29th, 2023 (day 1) workshop "Physiologically Based Biopharmaceutics Modeling (PBBM) Best Practices for Drug Product Quality: Regulatory and Industry Perspectives". The focus of the day was on model parametrization; regulatory authorities from Canada, the USA, Sweden, Belgium, and Norway presented their views on PBBM case studies submitted by industry members of the IQ consortium. The presentations shared key questions raised by regulators during the mock exercise, regarding the PBBM input parameters and their justification.

Immune memory shapes human polyclonal antibody responses to H2N2 vaccination.

Influenza A virus subtype H2N2, which caused the 1957 influenza pandemic, remains a global threat. A recent phase 1 clinical trial investigating a ferritin nanoparticle vaccine displaying H2 hemagglutinin (HA) in H2-naive and H2-exposed adults enabled us to perform comprehensive structural and biochemical characterization of immune memory on the breadth and diversity of the polyclonal serum antibody response elicited. We temporally map the epitopes targeted by serum antibodies after vaccine prime and boost, revealing that previous H2 exposure results in higher responses to the variable HA head domain.

Identification of triacylglycerol remodeling mechanism to synthesize unusual fatty acid containing oils.

Typical plant membranes and storage lipids are comprised of five common fatty acids yet over 450 unusual fatty acids accumulate in seed oils of various plant species. Plant oils are important human and animal nutrients, while some unusual fatty acids such as hydroxylated fatty acids (HFA) are used in the chemical industry (lubricants, paints, polymers, cosmetics, etc.).

Optimized allele-specific silencing of the dominant-negative G293R substitution causing collagen VI-related dystrophy.

Collagen VI-related dystrophies (COL6-RDs) are a group of severe, congenital-onset muscular dystrophies for which there is no effective causative treatment. Dominant-negative mutations are common in , , and 3 genes, encoding the collagen α1, α2, and α3 (VI) chains. They act by incorporating into the hierarchical assembly of the three α (VI) chains and consequently produce a dysfunctional collagen VI extracellular matrix, while haploinsufficiency for any of the genes is not associated with disease.

The Impact of COVID-19, Mental Health Distress, and School-Based Sociocultural Protective Factors among Elementary-Aged Children and their Caregivers.

Given the individual and systemic stress endured by children and families during the COVID-19 pandemic, research examining culturally responsive school experiences and supports to enhance resilience is critical. This study examined the relationship between caregivers' perceptions of COVID-19 impact, mental health distress among children and caregivers, and school-based sociocultural protective factors, including culturally responsive practices in schools and the relationships between teachers and caregivers, concurrently and longitudinally. Data were collected from caregivers of elementary-aged children at two-time points from March to April 2020 ( = 174) and one year later in 2021 ( = 114).

Phase 1 trial evaluating safety and pharmacokinetics of HIV-1 broadly neutralizing mAbs 10E8VLS and VRC07-523LS.

BACKGROUNDBroadly neutralizing monoclonal antibodies (bNAbs) represent a promising strategy for HIV-1 immunoprophylaxis and treatment. 10E8VLS and VRC07-523LS are bNAbs that target the highly conserved membrane-proximal external region (MPER) and the CD4-binding site of the HIV-1 viral envelope glycoprotein, respectively.METHODSIn this phase 1, open-label trial, we evaluated the safety and pharmacokinetics of 5 mg/kg 10E8VLS administered alone, or concurrently with 5 mg/kg VRC07-523LS, via s.

Real-world clinical outcomes and healthcare costs in patients with Crohn's disease treated with vedolizumab versus ustekinumab in the United States.

Objective: To compare real-world treatment persistence, dose escalation, rates of opportunistic or serious infections, and healthcare costs in patients with Crohn's disease (CD) receiving vedolizumab (VDZ) vs ustekinumab (UST) in the United States.

Methods: A retrospective observational study in adults with CD initiated on VDZ or UST on/after 26 September 2016, was performed using the IBM Truven Health MarketScan databases (1 January 2009-30 September 2018). Rates of treatment persistence, dose escalation, opportunistic or serious infection-related encounters, and healthcare costs per patient per month (PPPM) were evaluated.

Allele-specific CRISPR/Cas9 editing inactivates a single nucleotide variant associated with collagen VI muscular dystrophy.

The application of allele-specific gene editing tools can expand the therapeutic options for dominant genetic conditions, either via gene correction or via allelic gene inactivation in situations where haploinsufficiency is tolerated. Here, we used allele-targeted CRISPR/Cas9 guide RNAs (gRNAs) to introduce inactivating frameshifting indels at a single nucleotide variant in the gene (c.868G>A; G290R), a variant that acts as dominant negative and that is associated with a severe form of congenital muscular dystrophy.

Opposing diet, microbiome, and metabolite mechanisms regulate inflammatory bowel disease in a genetically susceptible host.

Inflammatory bowel diseases (IBDs) are chronic conditions characterized by periods of spontaneous intestinal inflammation and are increasing in industrialized populations. Combined with host genetics, diet and gut bacteria are thought to contribute prominently to IBDs, but mechanisms are still emerging. In mice lacking the IBD-associated cytokine, interleukin-10, we show that a fiber-deprived gut microbiota promotes the deterioration of colonic mucus, leading to lethal colitis.

A scalable and cost-efficient rRNA depletion approach to enrich RNAs for molecular biology investigations.

Transcriptomics analyses play pivotal roles in understanding the complex regulatory networks that govern cellular processes. The abundance of rRNAs, which account for 80%-90% of total RNA in eukaryotes, limits the detection and investigation of other transcripts. While mRNAs and long noncoding RNAs have poly(A) tails that are often used for positive selection, investigations of poly(A) RNAs, such as circular RNAs, histone mRNAs, and small RNAs, typically require the removal of the abundant rRNAs for enrichment.

A winged relative of ice-crawlers in amber bridges the cryptic extant Xenonomia and a rich fossil record.

Until the advent of phylogenomics, the atypical morphology of extant representatives of the insect orders Grylloblattodea (ice-crawlers) and Mantophasmatodea (gladiators) had confounding effects on efforts to resolve their placement within Polyneoptera. This recent research has unequivocally shown that these species-poor groups are closely related and form the clade Xenonomia. Nonetheless, divergence dates of these groups remain poorly constrained, and their evolutionary history debated, as the few well-identified fossils, characterized by a suite of morphological features similar to that of extant forms, are comparatively young.