A Comprehensive Atlas of AAV Tropism in the Mouse.

Gene therapy with Adeno-Associated Virus (AAV) vectors requires knowledge of their tropism within the body. Here we analyze the tropism of ten naturally occurring AAV serotypes (AAV3B, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAVrh8, AAVrh10 and AAVrh74) following systemic delivery into male and female mice. A transgene expressing ZsGreen and Cre recombinase was used to identify transduction in a cell-dependent manner based on fluorescence.

The Diagnostic Journey of Dysautonomia Patients: Insights from a Patient-Reported Outcome Study.

Dysautonomia refers to any disorder involving altered function of the autonomic nervous system. Dysautonomia can be debilitating as it often affects multiple organ systems. The diagnostic journey for individuals affected by dysautonomia can be hindered by symptom overlap with other conditions and by limited access to autonomic specialists.

COVID-19-Associated Encephalopathy: A Case Series Demonstrating the Rapid Deterioration of Mental Status and a Review of the Literature.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is known for its severe inflammatory response, often leading to multi-organ dysfunction. Among the less-recognized complications is COVID-19-associated encephalopathy, particularly in the elderly, where it contributes significantly to morbidity and mortality. This report explores the rapid neurocognitive decline observed in six hospitalized patients with COVID-19, with or without pre-existing neurological conditions.

Evaluation of a self-screening tool and patient alert cards to help patients identify and manage severe adverse drug reactions.

Background: Few studies have examined the use of self-screening tools and patient alert cards (PAC) for screening adverse drug reactions (ADRs).

Aim: To evaluate the benefits of self-screening tools and PAC for screening ADRs.

Method: A prospective study of outpatients was conducted at a tertiary care teaching hospital.

Variability in Vaccine Response and Trajectory in Early Childhood and Association with Demographic Variables, Antibiotic Exposure and Infection Proneness.

Introduction: We sought to explore the variability of antibody responses to multiple vaccines during early life in individual children, assess the trajectory of each child longitudinally, determine the associations of demographic variables and antibiotic exposures with vaccine-induced immunity, and link vaccine responsiveness to infection proneness.

Methods: In 357 prospectively-recruited children, age six through 36 months, antibody levels to 13 routine vaccine antigens were measured in sera at multiple time points and normalized to their respective protective thresholds to categorize children into four groups: very low, low, normal, and high vaccine responder. Demographic variables and frequency of antibiotic exposure data were collected.

Examining the Feasibility and Acceptability of Identifying Signs of Social Anxiety, in University Students Aged 18-25, While Watching 360° Immersive Films.

Timely, accurate assessment and treatment for social anxiety disorder (SAD) in young people is crucial. There is potential for the adoption of tailored virtual reality interventions for a complementary diagnostic tool using heart rate monitoring as a response indicator. This study examined the feasibility and acceptability of this concept by exposing healthy individuals, aged 18-25, to developed 360° immersive films while collecting heart rate sensor data.

3D-Printable Elastomers for Real-Time Autonomous Self-Healing in Soft Devices.

Photocurable self-healing elastomers are promising candidates for producing complex soft devices that can mend damage. However, the practicality of these materials is limited by reliance on external stimuli, custom synthesis, manual realignment, and multihour healing cycles. This paper introduces a tough 3D-printable hybrid acrylate/thiol-ene elastomer (prepared with commercially available precursors) that exhibits nearly instantaneous damage repair in the absence of external stimuli.

Polygenic score distribution differences across European ancestry populations: implications for breast cancer risk prediction.

Background: The 313-variant polygenic risk score (PRS) provides a promising tool for clinical breast cancer risk prediction. However, evaluation of the PRS across different European populations which could influence risk estimation has not been performed.

Methods: We explored the distribution of PRS across European populations using genotype data from 94,072 females without breast cancer diagnosis, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 223,316 females without breast cancer diagnosis from the UK Biobank.

Integrated Metagenomic and Metabolomic Analysis of In Vitro Murine Gut Microbial Cultures upon Bisphenol S Exposure.

Background: The gut microbiota are an important interface between the host and the environment, mediating the host's interactions with nutritive and non-nutritive substances. Dietary contaminants like Bisphenol A (BPA) may disrupt the microbial community, leaving the host susceptible to additional exposures and pathogens. BPA has long been a controversial and well-studied contaminant, so its structural analogues like Bisphenol S (BPS) are replacing it in consumer products, but have not been well studied.

Adjuvant therapy with pembrolizumab in renal cell carcinoma: real-world experiences from a retrospective, multi-institutional cohort.

Introduction: Adjuvant pembrolizumab versus placebo significantly improved disease-free survival (DFS) in renal cell carcinoma (RCC) patients at high risk of recurrence following nephrectomy in KEYNOTE-564 trial (NCT03142334). The objective of this study was to evaluate efficacy and safety of adjuvant pembrolizumab in a real-world setting.

Methods: In this multicenter retrospective study, RCC patients receiving adjuvant pembrolizumab between 01/22 and 10/23 at seven tertiary referral centers were included.

The pharmacological basis for nonpeptide agonism of the GLP-1 receptor by orforglipron.

Orally bioavailable, synthetic nonpeptide agonists (NPAs) of the glucagon-like peptide-1 receptor (GLP-1R) may offer an effective, scalable pharmacotherapy to address the metabolic disease epidemic. One of the first molecules in the emerging class of GLP-1R NPAs is orforglipron, which is in clinical development for treating type 2 diabetes and obesity. Here, we characterized the pharmacological properties of orforglipron in comparison with peptide-based GLP-1R agonists and other NPAs.

Evaluation of deprescribing services in frail patients: a systematic review.

Background: Deprescribing, a process of dose reduction or withdrawal of inappropriate medication that no longer has benefit, is a proposed intervention in the care of older adults living with frailty.

Objective/aim: To evaluate the safety, effectiveness, and clinical impact of deprescribing services in frail patients.

Methods: A systematic literature search was performed in November 2023 using Scopus, CINAHL PLUS (EBSCO), MEDLINE (OVID and EMBASE), and Cochrane Library.

The Meaning of Being a 'Good Nurse' in the ICU During the COVID-19 Pandemic.

Intensive care unit (ICU) nurses were at the forefront of patient care during the coronavirus (COVID-19) pandemic. To date, no studies have explored what it meant to be a 'good nurse' in this unique and challenging context. As such, the aim of this study was to construct the meaning of the 'good nurse' in ICUs during a pandemic.

Drug utilisation study in hospitalised chronic kidney disease patients, using World Health Organisation prescribing indicators: an observational study.

Background: Chronic kidney disease (CKD) is associated with comorbidities and altered pharmacokinetics, making appropriate prescribing, and monitoring necessary to minimise drug-related problems (DRPs). Therefore, this study aimed to describe the drug-utilisation pattern in hospitalised CKD patients.

Methods: An observational study was conducted in hospitalised adult (≥18 years old) CKD patients in the UK using WHO prescribing indicators, from November 2021 to April 2022 in a large teaching hospital in England from admission until discharge.

Introduction and accuracy assessment of Nicolab's StrokeViewer in a developing stroke thrombectomy UK service. a service development/improvement project.

Aim: The aim of this study was to evaluate the implementation of artificial intelligence (AI) software in a quaternary stroke centre as well as assess the accuracy and efficacy of StrokeViewer software in large vessel occlusion detection and its potential impact on radiological workflow.

Materials And Methods: Data were collected during two separate three-month periods comparing the accuracy rate of StrokeViewer in detection of large vessel occlusion to that of a junior registrar. During the first three months, 37 cases were identified and during the second leg, 47.

HepB-CpG vs HepB-Alum Vaccine in People With HIV and Prior Vaccine Nonresponse: The BEe-HIVe Randomized Clinical Trial.

Importance: Nonresponse to hepatitis B vaccine is common among people with HIV, resulting in vulnerability to infection with hepatitis B virus (HBV).

Objective: To compare the seroprotection response achieved with a 2-dose (noninferiority, 10% margin) and a 3-dose hepatitis B vaccine with a cytosine phosphoguanine adjuvant (HepB-CpG vaccine) vs a conventional 3-dose hepatitis B vaccine with an aluminum hydroxide adjuvant (HepB-alum vaccine) in people with HIV and prior nonresponse to HepB-alum vaccine.

Design, Setting, And Participants: This phase 3, open-label, randomized clinical trial included people with HIV receiving antiretroviral therapy (CD4 cell count ≥100 cells/μL and HIV RNA <1000 copies/mL) without past or present serological evidence of having HBV or a response to hepatitis B vaccine.

Aqueous copper geochemistry shapes the sediment microbial resistome in a recovering stream.

Aqueous metals are pervasive contaminants associated with historical mining. We produced and examined 16 metagenomes from a contaminated creek to investigate how anthropogenic metal contamination shapes the functional profiles of microbial communities. We then incorporated the metagenomic profiles and concurrently collected geochemical context into a multivariate model to examine correlations between stream geochemistry and microbial functional potential.

Application of machine learning algorithms to identify serological predictors of COVID-19 severity and outcomes.

Background: Critically ill hospitalized patients with COVID-19 have greater antibody titers than those with mild to moderate illness, but their association with recovery or death from COVID-19 has not been characterized.

Methods: In a cohort study of 178 COVID-19 patients, 73 non-hospitalized and 105 hospitalized patients, mucosal swabs and plasma samples were collected at hospital enrollment and up to 3 months post-enrollment (MPE) to measure virus RNA, cytokines/chemokines, binding antibodies, ACE2 binding inhibition, and Fc effector antibody responses against SARS-CoV-2. The association of demographic variables and more than 20 serological antibody measures with intubation or death due to COVID-19 was determined using machine learning algorithms.

Cotranslational molecular condensation of cochaperones and assembly factors facilitates axonemal dynein biogenesis.

Axonemal dynein, the macromolecular machine that powers ciliary motility, assembles in the cytosol with the help of dynein axonemal assembly factors (DNAAFs). These DNAAFs localize in cytosolic foci thought to form via liquid-liquid phase separation. However, the functional significance of DNAAF foci formation and how the production and assembly of multiple components are so efficiently coordinated, at such enormous scale, remain unclear.

Translating insights into therapies for Long Covid.

Long Covid is defined by a wide range of symptoms that persist after the acute phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Commonly reported symptoms include fatigue, weakness, postexertional malaise, and cognitive dysfunction, with many other symptoms reported. Symptom range, duration, and severity are highly variable and partially overlap with symptoms of myalgic encephalomyelitis/chronic fatigue syndrome and other post-acute infectious syndromes, highlighting opportunities to define shared mechanisms of pathogenesis.

An International Delphi Consensus on the Management of Pollen-Food Allergy Syndrome: A Work Group Report of the AAAAI Adverse Reactions to Foods Committee.

Background: Pollen-food allergy syndrome (PFAS) is common among patients with allergic rhinitis. Treatment recommendations for patients with PFAS remain variable.

Objective: To develop consensus recommendation statements for managing patients with PFAS.

Cell aggregation mediated by deletion in modulates fungal colonization and host immune responses in the skin.

is an emerging multi-drug-resistant fungal pathogen that colonizes the skin and causes invasive infections in hospitalized patients. Multi-cellular aggregative phenotype is widely reported in the isolates, but its role in skin colonization and host immune response is not yet known. In this study, we generated aggregative phenotype by deleting the gene in and determined the fungal colonization and host immune response using an intradermal mouse model of skin infection.