A trivalent mucosal vaccine encoding phylogenetically inferred ancestral RBD sequences confers pan-Sarbecovirus protection in mice.

The continued emergence of SARS-CoV-2 variants and the threat of future Sarbecovirus zoonoses have spurred the design of vaccines that can induce broad immunity against multiple coronaviruses. Here, we use computational methods to infer ancestral phylogenetic reconstructions of receptor binding domain (RBD) sequences across multiple Sarbecovirus clades and incorporate them into a multivalent adenoviral-vectored vaccine. Mice immunized with this pan-Sarbecovirus vaccine are protected in the upper and lower respiratory tracts against infection by historical and contemporary SARS-CoV-2 variants, SARS-CoV, and pre-emergent SHC014 and Pangolin/GD coronavirus strains.

Tracking Insulin- and Glucagon-Expressing Cells In Vitro and In Vivo Using a Double-Reporter Human Embryonic Stem Cell Line.

Differentiation protocols used to generate stem cell-derived islet cells yield heterogenous cell populations. We generated a human embryonic stem cell line that reports insulin- and glucagon-expressing cells in vitro and in vivo without altering their differentiation or function. We showed some insulin- and glucagon-expressing bihormonal cells are cell-autonomously fated to become α-like cells.

Coffee consumption is associated with intestinal Lawsonibacter asaccharolyticus abundance and prevalence across multiple cohorts.

Although diet is a substantial determinant of the human gut microbiome, the interplay between specific foods and microbial community structure remains poorly understood. Coffee is a habitually consumed beverage with established metabolic and health benefits. We previously found that coffee is, among >150 items, the food showing the highest correlation with microbiome components.

Probing novel epitopes on the Plasmodium falciparum circumsporozoite protein for vaccine development.

RTS,S and R21 are the only vaccines recommended by the WHO to protect children from Plasmodium falciparum (Pf) clinical malaria. Both vaccines target the Pf sporozoite surface protein circumsporozoite protein (CSP). Recent studies showed that human antibodies neutralize Pf sporozoites most efficiently when simultaneously binding to the PfCSP NANP repeat and the NPDP junction domain.

Ex-vivo antioxidant, enzyme inhibitory properties and computational analysis unveil the molecular mechanism of cardiac and penile phosphodiesterase-5 inhibition by bacterial strain HOKA1 extract as an aphrodisiac's agent.

The study uses in-vitro antioxidant, ex-vivo enzyme kinetics and in-silico approach using standard protocols to understand their inhibitory mechanism better. The study revealed that bacterial strain HOKA1 isolated from Oniru beach, grown in nutrient agar supplemented with sodium chloride (30%NaCl). Moreso, the bacterial strain HOKA1 extract showed better antioxidant capability and greatly reduced the penile and cardiac cGMP with the highest penile and cardiac concentration between 0.

Routine Spironolactone in Acute Myocardial Infarction.

Background: Mineralocorticoid receptor antagonists have been shown to reduce mortality in patients after myocardial infarction with congestive heart failure. Whether routine use of spironolactone is beneficial after myocardial infarction is uncertain.

Methods: In this multicenter trial with a 2-by-2 factorial design, we randomly assigned patients with myocardial infarction who had undergone percutaneous coronary intervention to receive either spironolactone or placebo and either colchicine or placebo.

Association of the Universal Designated Hitter Rule With Changes to Injuries in Major League Baseball Pitchers.

Background: In 2022, Major League Baseball (MLB) implemented the universal designated hitter (DH) rule, thus allowing the pitcher to focus solely on defense while the DH, who bats for the pitcher, focuses solely on offense.

Purpose/hypothesis: The purpose of our study was to determine if implementation of the universal DH rule affected the incidence of injuries in MLB pitchers when compared with before implementation. It was hypothesized that the shift to the universal DH rule would be associated with a decrease in the rate of offense-related pitcher injuries.

Stratified analysis identifies HIF-2 as a therapeutic target for highly immune-infiltrated melanomas.

While immune-checkpoint blockade (ICB) has revolutionized treatment of metastatic melanoma over the last decade, the identification of broadly applicable robust biomarkers has been challenging, driven in large part by the heterogeneity of ICB regimens and patient and tumor characteristics. To disentangle these features, we performed a standardized meta-analysis of eight cohorts of patients treated with anti-PD-1 (n=290), anti-CTLA-4 (n=175), and combination anti-PD-1/anti-CTLA-4 (n=51) with RNA sequencing of pre-treatment tumor and clinical annotations. Stratifying by immune-high vs -low tumors, we found that surprisingly, high immune infiltrate was a biomarker for response to combination ICB, but not anti-PD-1 alone.

Potent neutralization by a RBD antibody with broad specificity for SARS-CoV-2 JN.1 and other variants.

SARS-CoV-2 continues to be a public health burden, driven in-part by its continued antigenic diversification and resulting emergence of new variants. By increasing herd immunity, current vaccines have improved infection outcomes for many. However, prophylactic and treatment interventions that are not compromised by viral evolution of the Spike protein are still needed.

Multiomics biomarkers were not superior to clinical variables for pan-cancer screening.

Background: Cancer screening tests are considered pivotal for early diagnosis and survival. However, the efficacy of these tests for improving survival has recently been questioned. This study aims to test if cancer screening could be improved by biomarkers in peripheral blood based on multi-omics data.

Accuracy and Readability of ChatGPT on Potential Complications of Interventional Radiology Procedures: AI-Powered Patient Interviewing.

Rationale And Objectives: It is crucial to inform the patient about potential complications and obtain consent before interventional radiology procedures. In this study, we investigated the accuracy, reliability, and readability of the information provided by ChatGPT-4 about potential complications of interventional radiology procedures.

Materials And Methods: Potential major and minor complications of 25 different interventional radiology procedures (8 non-vascular, 17 vascular) were asked to ChatGPT-4 chatbot.

Lessons on Telemedicine in Rheumatology: Thinking beyond the Coronavirus Disease 2019 Pandemic.

During the COVID-19 pandemic, telemedicine was rapidly deployed to meet the clinical needs of patients with rheumatic diseases worldwide. Rheumatologists were forced to care for patients with all rheumatic diseases, regardless of disease activity, and limited evidence was available to guide provider decision-making regarding telemedicine appropriateness for outpatient rheumatology encounters. As the COVID-19 pandemic progressed, the ongoing provision of rheumatology telemedicine care in the U.

Bortezomib for rituximab-refractory immune-mediated thrombotic thrombocytopenic purpura in the caplacizumab era: an Italian multicenter study.

Background: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) patients are not responsive to standard rituximab in approximately 10% to 15% of cases, and oral immunosuppressants showed controversial results with significant toxicity. Targeting plasma cells with bortezomib appears promising, but the available evidence is scarce and stems only from isolated reports in the precaplacizumab era.

Objectives: To evaluate the safety and efficacy of bortezomib in rituximab-refractory iTTP patients.

A Population Pharmacokinetic Study to Evaluate Doxorubicin Exposure Across All Age Groups.

Background: The effect of age on doxorubicin pharmacokinetics remains inconclusive, especially in patients at the extremes of the age spectrum. We developed a population pharmacokinetic model to further investigate the impact of age on the pharmacokinetics of doxorubicin.

Methods: A three-compartment model, incorporating allometric scaling was developed to describe doxorubicin pharmacokinetics across all ages.

Head Kinematics Associated with Off-Field Head Injury Assessment (HIA1) Events in a Season of English Elite-Level Club Men's and Women's Rugby Union Matches.

Objectives: The purpose of this study was to investigate head kinematic variables in elite men's and women's rugby union and their ability to predict player removal for an off-field (HIA1) head injury assessment.

Methods: Instrumented mouthguard (iMG) data were collected for 250 men and 132 women from 1865 and 807 player-matches, respectively, and synchronised to video-coded match footage. Head peak resultant linear acceleration (PLA), peak resultant angular acceleration (PAA) and peak change in angular velocity (dPAV) were extracted from each head acceleration event (HAE).

Occurrence and ultrastructural surface of Blastocystis isolated from water sources in Kedah and Penang, Malaysia.

Blastocystis is a ubiquitous waterborne parasite that has been implicated in some disease conditions including colorectal cancer and irritable bowel syndrome, and its surface coat characteristics have been associated with its pathogenicity. Although the morphology of Blastocystis isolates from human and animal sources have been studied, there is a paucity of data on the surface ultrastructure of Blastocystis isolated from water sources. Therefore, this study aimed to determine the occurrence and the ultrastructural surface of Blastocystis isolates from several water sources in Kedah and Penang, Malaysia.

Reliability of ultrasound assessment of the rectus femoris muscle thickness: intra-rater, inter-rater, and inter-day analysis accounting for age and sex.

Background: The rectus femoris muscle plays an important role in maintaining lower limb stability and biomechanical control during basic physical activities. Both reduced quadriceps strength and decreased muscle thickness of the rectus femoris, as measured by ultrasound, are associated with an increased risk of falls in older adults. We estimated the relative and absolute intra-rater, inter-rater, and inter-day reliability of the procedure.

Electrocapacitive removal of Na and Cd ions from contaminated aqueous solution using FeO-poly (3,4-ethylenedioxythiophene) poly(styrene sulfonate) modified chitosan nanosheets.

Chitosan nanosheets (NS) stabilized on poly (3,4-ethylenedioxythiophene): poly(styrene sulfonate) (PEDOT: PSS) was functionalized using FeO to capacitively remove chloride ions and toxic cadmium ions at optimized pH, concentration, and number of charging cycles. The synthesis procedure was investigated by Fourier transform infrared spectroscopy (FTIR), X-Ray Diffractometer (XRD), Transmission Electron Microscope (TEM), Scanning Electron Microscope - Energy Dispersive X-ray Spectroscopy (SEM-EDS), and Brunauer-Emmett-Teller (BET). The analyses confirms increase in surface area of the nanocomposite from 41 to 132 m/g and a decrease in crystallinity from 75.

Machine Learning Algorithms to Predict the Risk of Rupture of Intracranial Aneurysms: a Systematic Review.

Purpose: Subarachnoid haemorrhage is a potentially fatal consequence of intracranial aneurysm rupture, however, it is difficult to predict if aneurysms will rupture. Prophylactic treatment of an intracranial aneurysm also involves risk, hence identifying rupture-prone aneurysms is of substantial clinical importance. This systematic review aims to evaluate the performance of machine learning algorithms for predicting intracranial aneurysm rupture risk.

Prognostic implication of DPD quantification in transthyretin cardiac amyloidosis.

Aims: Quantification of cardiac [99mTc]-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) uptake enhances diagnostic capabilities and may facilitate prognostic stratification in patients with transthyretin cardiac amyloidosis (ATTR-CA). This study aimed to evaluate the association of quantitative left ventricular (LV) DPD uptake with myocardial structure and function, and their implications on outcome in ATTR-CA.

Methods And Results: Consecutive ATTR-CA patients (n = 100) undergoing planar DPD scintigraphy with Perugini grade 2 or 3, alongside quantitative DPD single-photon emission computed tomography/computed tomography imaging and speckle-tracking echocardiography between 2019 and 2023, were included and divided into two cohorts based on median DPD retention index (low DPD uptake: ≤5.