mRNA vaccines encoding membrane-anchored RBDs of SARS-CoV-2 mutants induce strong humoral responses and can overcome immune imprinting.

We investigated mRNA vaccines encoding a membrane-anchored receptor-binding domain (RBD), each a fusion of a variant RBD, the transmembrane (TM) and cytoplasmic tail fragments of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. In naive mice, RBD-TM mRNA vaccines against SARS-CoV-2 variants induced strong humoral responses against the target RBD. Multiplex surrogate viral neutralization (sVNT) assays revealed broad neutralizing activity against a range of variant RBDs.

Clinical Potential of Novel Microbial Therapeutic LP51 Based on Xerosis-Microbiome Index.

Xerosis, characterized by dry, rough skin, causes discomfort and aesthetic concerns, necessitating effective treatment. Traditional treatments often show limited efficacy, prompting the need for innovative therapies. This study highlights the efficacy of microbiome therapeutic LP51, derived from a healthy vaginal microbiome, in improving xerosis.

A vaccine platform targeting lung-resident memory CD4 T-cells provides protection against heterosubtypic influenza infections in mice and ferrets.

Lung tissue-resident memory T (T) cells induced by influenza vaccination are crucial for heterosubtypic immunity upon re-exposure to the influenza virus, enabling rapid and robust responses upon reactivation. To enhance the efficacy of influenza vaccines, we induce the generation of lung T cells following intranasal vaccination with a commercial influenza vaccine adjuvanted with NexaVant (NVT), a TLR3 agonist-based adjuvant. We demonstrate that intranasal immunization with the NVT-adjuvanted vaccine provides improved protection against influenza virus infections by inducing the generation of CD4 T cells in the lungs in a type I interferon-dependent manner.

Risk of Contrast-Induced Acute Kidney Injury in Computed Tomography: A 16 Institutional Retrospective Cohort Study.

Objectives: Concern about contrast-induced acute kidney injury (CI-AKI) may delay the timely administration of contrast media for computed tomography (CT). The precise causative effect of iodinated contrast media on CI-AKI and its relevant risk factors remains an area of ongoing investigation. Therefore, this study aimed to determine the risk of CI-AKI following contrast-enhanced CT and its predisposing risk factors.

Arthroscopic Partial Repair of Large to Massive Rotator Cuff Tears Shows Clinical Outcomes and Survivorship at Minimum 10-Year Follow-Up Comparable to Those of Arthroscopic Complete Repair.

Purpose: To compare the survival rate (revision surgery) and clinical and radiologic outcomes of arthroscopic partial versus complete repair for large to massive rotator cuff tears over a minimum 10-year follow-up period.

Methods: We conducted a retrospective analysis of patients who underwent arthroscopic partial or complete repair of large to massive rotator cuff tears between 2008 and 2013, with minimum 10-year follow-up. Functional outcomes were measured using the visual analog scale pain score, Subjective Shoulder Value, American Shoulder and Elbow Surgeons score, University of California, Los Angeles shoulder score, and passive range of motion preoperatively and at the last follow-up.

Nationwide, Couple-Based Genetic Carrier Screening.

Background: Genomic sequencing technology allows for identification of reproductive couples with an increased chance, as compared with that in the general population, of having a child with an autosomal recessive or X-linked genetic condition.

Methods: We investigated the feasibility, acceptability, and outcomes of a nationwide, couple-based genetic carrier screening program in Australia as part of the Mackenzie's Mission project. Health care providers offered screening to persons before pregnancy or early in pregnancy.

Deep learning algorithm for predicting left ventricular systolic dysfunction in atrial fibrillation with rapid ventricular response.

Aims: Although evaluation of left ventricular ejection fraction (LVEF) is crucial for deciding the rate control strategy in patients with atrial fibrillation (AF), real-time assessment of LVEF is limited in outpatient settings. We aimed to investigate the performance of artificial intelligence-based algorithms in predicting LV systolic dysfunction (LVSD) in patients with AF and rapid ventricular response (RVR).

Methods And Results: This study is an external validation of a pre-existing deep learning algorithm based on residual neural network architecture.

Breast ultrasound knobology and the knobology of twinkling for marker detection.

Breast ultrasound utilizes various scanning techniques to acquire optimal images for diagnostic evaluation. During interventional procedures, such as ultrasound-guided biopsies or preoperative localizations, knowledgeable and purposeful scanning adjustments are critical for successfully identifying the targeted mass or biopsy marker or clip. While most ultrasound scanning parameters are similar across different vendors, detailed descriptions specifically addressing the scanning parameters-often referred to as "knobology"- for breast ultrasound is at best limited in the literature.

Saturation profiling of drug-resistant genetic variants using prime editing.

Methods to characterize the functional effects of genetic variants of uncertain significance (VUSs) have been limited by incomplete coverage of the mutational space. In clinical oncology, drug resistance arising from VUSs can prevent optimal treatment. Here we introduce PEER-seq, a high-throughput method based on prime editing that can evaluate the functional effects of single-nucleotide variants (SNVs).

PD-L1 Expression Varies in Thyroid Cancer Types and Is Associated with Decreased Progression Free Survival (PFS) in Patients with Anaplastic Thyroid Cancer.

Background: Thyroid cancer (TC) remains a significant clinical challenge worldwide, with a subset of patients facing aggressive disease progression and therapeutic resistance. Immune checkpoint inhibitors targeting programmed death-ligand 1 (PD-L1) have emerged as promising therapeutic approaches for various malignancies, yet their efficacy in TC remains uncertain. The objective of this study was to investigate PD-L1 expression in aggressive TC and its association with histological subtypes, molecular mutation, and progression-free survival.

Epidemiologic Study of Myasthenia Gravis in the Elderly US Population: A Longitudinal Analysis of the Medicare Claims Database, 2006-2019.

Background And Objectives: Epidemiologic studies suggest increasing incidence and prevalence of myasthenia gravis (MG) among the elderly population outside the United States. We aimed to provide an estimation of MG incidence and prevalence and their trend among the Medicare Fee-For-Service (FFS)-covered elderly US population.

Methods: We performed a retrospective longitudinal study using Medicare claims data (2006-2019).

Description and phylogenetic position of a new species, J.E.Jang, K.H.Lee & H.Y.Gil (Saxifragaceae), from the southern islands of South Korea.

We describe a new species, J.E.Jang, K.

Vaginal lactobacilli produce anti-inflammatory β-carboline compounds.

The optimal vaginal microbiome is a Lactobacillus-dominant community. Apart from Lactobacillus iners, the presence of Lactobacillus species is associated with reduced vaginal inflammation and reduced levels of pro-inflammatory cytokines. Loss of Lactobacillus-dominance is associated with inflammatory conditions, such as bacterial vaginosis (BV).

Clinical Utility of Donor-Derived Cell-Free DNA in Heart Transplant Recipients With Multi-Organ Transplants.

Background: Donor-derived cell-free DNA (dd-cfDNA) has emerged as a reliable, noninvasive method for the surveillance of allograft rejection in heart transplantation (HT) patients, but its utility in multi-organ transplants (MOT) is unknown. We describe our experience using dd-cfDNA in simultaneous MOT recipients.

Methods: A single-center retrospective review of all HT recipients between 2018 and 2022 that had at least one measurement of dd-cfDNA collected.

A Systematic Search and Review of Registered Pharmacological Therapies Investigated to Improve Outcomes after a Stroke.

Introduction: Stroke burden is largely due to long-term impairments requiring prolonged care and loss of productivity. We aim to identify and assess studies of different registered pharmacological therapies as treatments for improving post-stroke impairments and/or disabilities.

Methods: In a systematic search and review (PROSPERO registration: CRD42022376973), studies of treatments that have been investigated as recovery-enhancing or recovery-promoting treatments in adult patients who had suffered a stroke will be searched for, screened, and reviewed based on the following: participants (P): adult humans, aged 18 years or older, diagnosed with stroke; interventions (I): registered or marketed pharmacological therapies that have been investigated as recovery-enhancing or recovery-promoting treatments in stroke; comparators (C): active or placebo or no comparator; outcomes (O): stroke-related neurological impairments and functional/disability assessments.

The reovirus variant RP116 is oncolytic in immunocompetent models and generates reduced neutralizing antibodies to Type 3 Dearing.

The mammalian reovirus Type 3 Dearing (T3D) is a naturally occurring oncolytic virus. We previously identified a T3D variant isolated from persistently infected cancer cells that has a premature stop codon mutation in the gene, generating a truncated σ1-attachment protein that lacks the globular head. We now report on the molecular characterization of this variant, named RP116, and assess its antitumor potential in human cancer cells and syngeneic mouse models.

In Vitro Self-Circularization Methods Based on Self-Splicing Ribozyme.

In vitro circular RNA (circRNA) preparation methods have been gaining a lot of attention recently as several reports suggest that circRNAs are more stable, with better performances in cells and in vivo, than linear RNAs in various biomedical applications. Self-splicing ribozymes are considered a major in vitro circRNA generation method for biomedical applications due to their simplicity and efficiency in the circularization of the gene of interest. This review summarizes, updates, and discusses the recently developed self-circularization methods based on the self-splicing ribozyme, such as group I and II intron ribozymes, and the pros and cons of each method in preparing circRNA in vitro.

Durvalumab after Chemoradiotherapy in Limited-Stage Small-Cell Lung Cancer.

Background: Adjuvant therapy with durvalumab, with or without tremelimumab, may have efficacy in patients with limited-stage small-cell lung cancer who do not have disease progression after standard concurrent platinum-based chemoradiotherapy.

Methods: In a phase 3, double-blind, randomized, placebo-controlled trial, we assigned patients to receive durvalumab at a dose of 1500 mg, durvalumab (1500 mg) plus tremelimumab at a dose of 75 mg (four doses only), or placebo every 4 weeks for up to 24 months. Randomization was stratified according to disease stage (I or II vs.

Prediction of Axial Length From Macular Optical Coherence Tomography Using Deep Learning Model.

Purpose: The purpose of this study was to develop a deep learning model for predicting the axial length (AL) of eyes using optical coherence tomography (OCT) images.

Methods: We retrospectively included patients with AL measurements and OCT images taken within 3 months. We utilized a 5-fold cross-validation with the ResNet-152 architecture, incorporating horizontal OCT images, vertical OCT images, and dual-input images.