Safety and immunogenicity of an optimized self-replicating RNA platform for low dose or single dose vaccine applications: a randomized, open label Phase I study in healthy volunteers.

Self-replicating RNA (srRNA) technology, in comparison to mRNA vaccines, has shown dose-sparing by approximately 10-fold and more durable immune responses. However, no improvements are observed in the adverse events profile. Here, we develop an srRNA vaccine platform with optimized non-coding regions and demonstrate immunogenicity and safety in preclinical and clinical development.

Bedside Neuromodulation of Persistent Pain and Allodynia with Caloric Vestibular Stimulation.

Background: Caloric vestibular stimulation (CVS) is a well-established neurological diagnostic technique that also induces many phenomenological modulations, including reductions in phantom limb pain (PLP), spinal cord injury pain (SCIP), and central post-stroke pain.

Objective: We aimed to assess in a variety of persistent pain (PP) conditions (i) short-term pain modulation by CVS relative to a forehead ice pack cold-arousal control procedure and (ii) the duration and repeatability of CVS modulations. The tolerability of CVS was also assessed and has been reported separately.

Impact of Educational Background on Preoperative Disease Severity and Postoperative Outcomes Among Patients With Cervical Spondylotic Myelopathy.

Study Design: Retrospective review of a prospectively maintained database.

Objective: Assess differences in preoperative status and postoperative outcomes among patients of different educational backgrounds undergoing surgical management of cervical spondylotic myelopathy (CSM).

Summary Of Background Data: Patient education level (EL) has been suggested to correlate with health literacy, disease perception, socioeconomic status (SES), and access to health care.

Early cellular and molecular signatures correlate with severity of West Nile virus infection.

Infection with West Nile virus (WNV) drives a wide range of responses, from asymptomatic to flu-like symptoms/fever or severe cases of encephalitis and death. To identify cellular and molecular signatures distinguishing WNV severity, we employed systems profiling of peripheral blood from asymptomatic and severely ill individuals infected with WNV. We interrogated immune responses longitudinally from acute infection through convalescence employing single-cell protein and transcriptional profiling complemented with matched serum proteomics and metabolomics as well as multi-omics analysis.

Large language models encode clinical knowledge.

Large language models (LLMs) have demonstrated impressive capabilities, but the bar for clinical applications is high. Attempts to assess the clinical knowledge of models typically rely on automated evaluations based on limited benchmarks. Here, to address these limitations, we present MultiMedQA, a benchmark combining six existing medical question answering datasets spanning professional medicine, research and consumer queries and a new dataset of medical questions searched online, HealthSearchQA.

Prognostic Value of Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Imaging for Predicting Venous Thromboembolism in Children With Lymphoma.

Background: Positron emission tomography (PET)/computed tomography (CT) imaging can detect changes in arterial inflammation, but has not been used to evaluate chemotherapy-induced venous inflammation or assess risk for venous thromboembolism (VTE) in pediatric oncology. Therefore, the purpose of this study was to evaluate the prognostic value of fluorine-18-fluorodeoxyglucose PET/CT imaging of venous inflammation for predicting VTE occurrence in the 12 months after lymphoma diagnosis in pediatric, adolescent, and young adult patients.

Methods: Pediatric, adolescent, and young adult patients with lymphoma diagnoses (n=71) who underwent whole-body PET/CT imaging at initial staging of disease and first therapeutic follow-up were retrospectively evaluated for serial changes in lower extremity venous uptake of fluorine-18-fluorodeoxyglucose.

The use of the time-to-event index (Tevent) to compare the negative impact of COVID-19 on public health among continents/regions in 2020 and 2021: An observational study.

Background: During the COVID-19 pandemic, how to measure the negative impact caused by COVID-19 on public health (ImpactCOV) is an important issue. However, few studies have applied the bibliometric index, taking both infected days (quantity) and impact (damage) into account for evaluating ImpactCOV thus far. This study aims to verify the proposed the time-to-event index (Tevent) that is viable and applicable in comparison with 11 other indicators, apply the Tevent to compare the ImpactCOVs among groups in continents/countries in 2020 and 2021, and develop an online algorithm to compute the Tevent-index and draw the survival analysis.

Circulating Spike Protein Detected in Post-COVID-19 mRNA Vaccine Myocarditis.

Background: Cases of adolescents and young adults developing myocarditis after vaccination with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-targeted mRNA vaccines have been reported globally, but the underlying immunoprofiles of these individuals have not been described in detail.

Methods: From January 2021 through February 2022, we prospectively collected blood from 16 patients who were hospitalized at Massachusetts General for Children or Boston Children's Hospital for myocarditis, presenting with chest pain with elevated cardiac troponin T after SARS-CoV-2 vaccination. We performed extensive antibody profiling, including tests for SARS-CoV-2-specific humoral responses and assessment for autoantibodies or antibodies against the human-relevant virome, SARS-CoV-2-specific T-cell analysis, and cytokine and SARS-CoV-2 antigen profiling.

Cell-Selective Adeno-Associated Virus-Mediated Gene Regulation Therapy Rescues Mortality and Seizure Phenotypes in a Dravet Syndrome Mouse Model and Is Well Tolerated in Nonhuman Primates.

Dravet syndrome (DS) is a developmental and epileptic encephalopathy caused by monoallelic loss-of-function variants in the gene. encodes for the alpha subunit of the voltage-gated type I sodium channel (Na1.1), the primary voltage-gated sodium channel responsible for generation of action potentials in GABAergic inhibitory interneurons.

Modular evolution of secretion systems and virulence plasmids in a bacterial species complex.

Background: Many named species as defined in current bacterial taxonomy correspond to species complexes. Uncertainties regarding the organization of their genetic diversity challenge research efforts. We utilized the Agrobacterium tumefaciens species complex (a.

Preoperative Breast MRI for Newly Diagnosed Ductal Carcinoma in Situ: Imaging Features and Performance in a Multicenter Setting (ECOG-ACRIN E4112 Trial).

Background There are limited data from clinical trials describing preoperative MRI features and performance in the evaluation of mammographically detected ductal carcinoma in situ (DCIS). Purpose To report qualitative MRI features of DCIS, MRI performance in the identification of additional disease, and associations of imaging features with pathologic, genomic, and surgical outcomes from the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) E4112 trial. Materials and Methods Secondary analyses of a multicenter prospective clinical trial from the ECOG-ACRIN Cancer Research Group included women with DCIS diagnosed with conventional imaging techniques (mammography and US), confirmed via core-needle biopsy (CNB), and enrolled between March 2015 and April 2016 who were candidates for wide local excision (WLE) based on conventional imaging and clinical examination results.

An online time-to-event dashboard comparing the effective control of COVID-19 among continents using the inflection point on an ogive curve: Observational study.

Background: During the COVID-19 pandemic, one of the frequently asked questions is which countries (or continents) are severely hit. Aside from using the number of confirmed cases and the fatality to measure the impact caused by COVID-19, few adopted the inflection point (IP) to represent the control capability of COVID-19. How to determine the IP days related to the capability is still unclear.

A Prospective Study of Neurologic Disorders in Hospitalized Patients With COVID-19 in New York City.

Objective: To determine the prevalence and associated mortality of well-defined neurologic diagnoses among patients with coronavirus disease 2019 (COVID-19), we prospectively followed hospitalized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients and recorded new neurologic disorders and hospital outcomes.

Methods: We conducted a prospective, multicenter, observational study of consecutive hospitalized adults in the New York City metropolitan area with laboratory-confirmed SARS-CoV-2 infection. The prevalence of new neurologic disorders (as diagnosed by a neurologist) was recorded and in-hospital mortality and discharge disposition were compared between patients with COVID-19 with and without neurologic disorders.

Use of Chest Imaging in the Diagnosis and Management of COVID-19: A WHO Rapid Advice Guide.

The World Health Organization (WHO) undertook the development of a rapid guide on the use of chest imaging in the diagnosis and management of coronavirus disease 2019 (COVID-19). The rapid guide was developed over 2 months by using standard WHO processes, except for the use of "rapid reviews" and online meetings of the panel. The evidence review was supplemented by a survey of stakeholders regarding their views on the acceptability, feasibility, impact on equity, and resource use of the relevant chest imaging modalities (chest radiography, chest CT, and lung US).

A structure- and chemical genomics-based approach for repositioning of drugs against VCP/p97 ATPase.

Valosin-containing protein (VCP/p97) ATPase (a.k.a.

Incubation of 2-methylisoborneol synthase with the intermediate analog 2-methylneryl diphosphate.

Incubation of synthetic 2-methylneryl diphosphate (2-MeNPP, 10) with 2-methylisoborneol synthase (MIBS) gave a mixture of products that differed significantly from that derived from the natural substrate (E)-2-methylgeranyl diphosphate (3, 2-MeGPP). The proportion of (-)-2-methylisoborneol (1) decreased from 89 to 17% while that of 2-methylenebornane (4) increased from 10 to 26%, with the relative yields of the isomeric homo-monoterpenes 2-methyl-2-bornene (5) and 1-methylcamphene (6) remaining essentially unchanged (<1% each), as determined by chiral GC-MS analysis. The majority of the product mixture resulting from the MIBS-catalyzed cyclization of 2-MeNPP (10) consisted of the anomalous monocyclic homo-monoterpenes (±)-2-methylllimonene (15, 39%) and 2-methyl-α-terpineol (13, 10%), as well as the acylic derivatives 2-methylnerol (11, 7%) and 2-methyllinalool (14, <1%).

Inhibition of JCPyV infection mediated by targeted viral genome editing using CRISPR/Cas9.

Progressive multifocal leukoencephalopathy (PML) is a debilitating disease resulting from infection of oligodendrocytes by the JC polyomavirus (JCPyV). Currently, there is no anti-viral therapeutic available against JCPyV infection. The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) system (CRISPR/Cas9) is a genome editing tool capable of introducing sequence specific breaks in double stranded DNA.

Septic pulmonary embolism caused by a Klebsiella pneumoniae liver abscess: clinical characteristics, imaging findings, and clinical courses.

Objectives: Septic pulmonary embolism caused by a Klebsiella (K.) pneumoniae liver abscess is rare but can cause considerable morbidity and mortality. However, clinical information regarding this condition is limited.

Characterizing titanium dioxide and zinc oxide nanoparticles in sunscreen spray.

Objective: Numerous commercial products contain titanium dioxide (TiO2 ) and zinc oxide (ZnO) nanoparticles (NPs); however, many of these are not labelled as containing NPs. This study sought to develop an effective means of characterizing TiO2 and ZnO NPs in sunscreen sprays, including the size, shape and composition of the particles as well as their aggregation/agglomeration characteristics.

Methods: Transmission electron microscopy (TEM) coupled with a window-type microchip K-kit/copper grid and X-ray diffraction (XRD) was used to characterize the oxide NPs.

iNOS inhibitory activity of sesquiterpenoids and a monoterpenoid from the rhizomes of Curcuma wenyujin.

Eleven new sesquiterpenoids, wenyujinins A-K (1-11), and a new monoterpenoid, wenyujinin L (12), were isolated from the rhizomes of Curcuma wenyujin. Their structures and relative configurations were elucidated using 1D and 2D NMR, X-ray crystallographic analysis, and HRESIMS data. The absolute configurations of 1, 2, 3, 4, 6, 8, 9, and 10 were determined by comparison of the experimental and calculated ECD spectra.

Blunted proarrhythmic effect of nicorandil in a Langendorff-perfused phase-2 myocardial infarction rabbit model.

Background: Nicorandil (a K(ATP) opener) administration is reported to reduce ventricular arrhythmias 4.8 ± 2.2 hours after myocardial infarction (MI).

Fascin 2b is a component of stereocilia that lengthens actin-based protrusions.

Stereocilia are actin-filled protrusions that permit mechanotransduction in the internal ear. To identify proteins that organize the cytoskeleton of stereocilia, we scrutinized the hair-cell transcriptome of zebrafish. One promising candidate encodes fascin 2b, a filamentous actin-bundling protein found in retinal photoreceptors.

Binding kinetics of biomolecule interaction at ultralow concentrations based on gold nanoparticle enhancement.

Measuring the kinetic constants of protein-protein interactions at ultralow concentrations becomes critical in characterizing biospecific affinity, and exploring the feasibility of clinical diagnosis with respect to detection sensitivity, efficiency and accuracy. In this study, we propose a method that can calculate the binding constants of protein-protein interactions in sandwich assays at ultralow concentrations at the pg/mL level, using a localized surface plasmon coupled fluorescence fiber-optic biosensor (LSPCF-FOB). We discuss a two-compartment model to achieve reaction-limited kinetics under the stagnant conditions of the reaction chamber.