Protective antibodies target cryptic epitope unmasked by cleavage of malaria sporozoite protein.

The most advanced monoclonal antibodies (mAbs) and vaccines against malaria target the central repeat region or closely related sequences within the circumsporozoite protein (PfCSP). Here, using an antigen-agnostic strategy to investigate human antibody responses to whole sporozoites, we identified a class of mAbs that target a cryptic PfCSP epitope that is only exposed after cleavage and subsequent pyroglutamylation (pGlu) of the newly formed N terminus. This pGlu-CSP epitope is not targeted by current anti-PfCSP mAbs and is not included in the licensed malaria vaccines.

Multiarm-Assisted Design of Dendron-like Degradable Ionizable Lipids Facilitates Systemic mRNA Delivery to the Spleen.

Lipid nanoparticles (LNPs) have emerged as pivotal vehicles for messenger RNA (mRNA) delivery to hepatocytes upon systemic administration and to antigen-presenting cells following intramuscular injection. However, achieving systemic mRNA delivery to non-hepatocytes remains challenging without the incorporation of targeting ligands such as antibodies, peptides, or small molecules. Inspired by comb-like polymeric architecture, here we utilized a multiarm-assisted design to construct a library of 270 dendron-like degradable ionizable lipids by altering the structures of amine heads and multiarmed tails for optimal mRNA delivery.

An injury-induced mesenchymal-epithelial cell niche coordinates regenerative responses in the lung.

Severe lung injury causes airway basal stem cells to migrate and outcompete alveolar stem cells, resulting in dysplastic repair. We found that this "stem cell collision" generates an injury-induced tissue niche containing keratin 5 epithelial cells and plastic Pdgfra mesenchymal cells. Single-cell analysis revealed that the injury-induced niche is governed by mesenchymal proliferation and Notch signaling, which suppressed Wnt/Fgf signaling in the injured niche.

Dynamic behavior and lineage plasticity of the pulmonary venous endothelium.

Repair of the pulmonary vascular bed and the origin of new vasculature remain underexplored despite the critical necessity to meet oxygen demands after injury. Given their critical role in angiogenesis in other settings, we investigated the role of venous endothelial cells in endothelial regeneration after adult lung injury. Here we identified Slc6a2 as a marker of pulmonary venous endothelial cells and generated a venous-specific, inducible Cre mouse line.

Photodynamic therapy for decolonization of the shoulder dermis.

Introduction: is a common source of infection in shoulder surgery. 5-Aminolevulinic acid (5-ALA) is a naturally occurring metabolite of that creates an exothermic reaction when activated by blue light. The purpose of this study was to evaluate the efficacy of preoperative photodynamic therapy using topical 5-ALA to decrease colonization.

Potent AMA1-specific human monoclonal antibody against Plasmodium vivax Pre-erythrocytic and Blood Stages.

New therapeutics are necessary for preventing Plasmodium vivax malaria due to easy transmissibility and dormancy in the liver that increases the clinical burden due to recurrent relapse. In this manuscript we characterize 12 Pv Apical Membrane Antigen 1 (PvAMA1) specific human monoclonal antibodies from Peripheral Blood Mononuclear Cells of a Pv-exposed individual. PvAMA1 is essential for sporozoite and merozoite invasion, making it a unique therapeutic target.

Stress-Resilience Impacts Psychological Wellbeing: Evidence from Brain-Gut Microbiome Interactions.

The brain-gut-microbiome (BGM) system plays an influential role on mental health. We characterized BGM patterns related to resilience using fecal samples and multimodal MRI. Data integration analysis using latent components showed the high resilience phenotype was associated with lower depression and anxiety symptoms, higher frequency of bacterial transcriptomes (related to environmental adaptation, genetic propagation, energy metabolism, anti-inflammation), increased metabolites (N-acetylglutamate; dimethylglycine), and cortical signatures (increased resting state functional connectivity between reward circuits and sensorimotor networks; decreased grey matter volume and white matter tracts within the emotion regulation network).

Measuring Growth, Resistance, and Recovery after Artemisinin Treatment of Plasmodium falciparum in a single semi-high-throughput Assay.

Background: Artemisinin partial resistance (ART-R) has spread throughout Southeast Asia and mutations in , the molecular marker of resistance, are widely reported in East Africa. Effective assays and robust phenotypes are crucial for monitoring populations for the emergence and spread of resistance. The recently developed extended Recovery Ring-stage Survival Assay used a qPCR-based readout to reduce the labor intensiveness for phenotyping of ART-R and improved correlation with the clinical phenotype of ART-R.

Nationally Connected Network of Trainers Empowers Fishers as Medical First Responders: A Case Study in Collaboration and Capacity Building.

Immediate access to advanced medical care in the event of an emergency or injury is not equitable across socioeconomic, occupational, and environmental conditions. Research has shown that basic first aid techniques, when standardized and provided to the public, can significantly improve victim survival in a traumatic event. The Fishing First Aid & Safety Training (FFAST) considers these factors to provide accessible, low, or no cost training across coastal regions of the United States that is adapted specifically for commercial fisheries.

MalKinID: A Classification Model for Identifying Malaria Parasite Genealogical Relationships Using Identity-by-Descent.

Pathogen genomics is a powerful tool for tracking infectious disease transmission. In malaria, identity-by-descent (IBD) is used to assess the genetic relatedness between parasites and has been used to study transmission and importation. In theory, IBD can be used to distinguish genealogical relationships to reconstruct transmission history or identify parasites for quantitative-trait-locus experiments.

Management of periprosthetic humerus fractures after shoulder arthroplasty.

Background: The purpose of this retrospective study was to analyze time to fracture union, complications, and outcomes of postoperative periprosthetic humerus fractures after primary shoulder arthroplasty.

Methods: Retrospective review of patients who sustained a postoperative periprosthetic humerus fracture after primary shoulder arthroplasty at a single institution. Fractures were classified according to the Worland Classification system.

Can Transcriptomics Elucidate the Role of Regulation in Invasion Success?

When a species invades a novel environment, it must bridge the environment-phenotype mismatch in its new range to persist. Contemporary invasion biology research has focused on the role that trait variation and adaptation, and their underlying genomic factors, play in a species' adaptive potential, and thus facilitating invasion. Empirical studies have provided valuable insights into phenotypes that persist and arise in novel environments, coupled with 'omics tools that further the understanding of the contributions of genomic architecture in species establishment.

Experiences of discrimination are associated with microbiome and transcriptome alterations in the gut.

Background: Discrimination is a recognized psychosocial stressor that has been linked to various negative health outcomes. This study explored the impact of discrimination on gut health, specifically focusing on microbiome changes, predicted metagenomic differences, transcriptomic profiles, and the potential for using a multi-omic approach to predict discrimination to identify discrimination status for an individual. Methods: We conducted a comprehensive investigation involving male and premenopausal female participants, using the Everyday Discrimination Scale to classify them into either high or low discrimination.

A conserved Plasmodium nuclear protein is critical for late liver stage development.

Malaria, caused by Plasmodium parasites, imposes a significant health burden and live-attenuated parasites are being pursued as vaccines. Here, we report on the creation of a genetically attenuated parasite by the deletion of Plasmodium LINUP, encoding a liver stage nuclear protein. In the rodent parasite Plasmodium yoelii, LINUP expression was restricted to liver stage nuclei after the onset of liver stage schizogony.

Early postoperative pain is similar after arthroscopic rotator cuff repair vs. short-stay shoulder arthroplasty: a prospective study.

Background: One of the barriers to counseling patients for shoulder arthroplasty (TSA) is the anticipated pain after surgery. This can be contrasted with the common perception of arthroscopic rotator cuff repair (RCR) surgery being less painful because of the less invasive nature of the procedure. We conducted a prospective study comparing postoperative pain levels and narcotic consumption after TSA to those after RCR.

Improving Stroke Outcome Prediction Using Molecular and Machine Learning Approaches in Large Vessel Occlusion.

: Predicting stroke outcomes in acute ischemic stroke (AIS) can be challenging, especially for patients with large vessel occlusion (LVO). Available tools such as infarct volume and the National Institute of Health Stroke Scale (NIHSS) have shown limited accuracy in predicting outcomes for this specific patient population. The present study aimed to confirm whether sudden metabolic changes due to blood-brain barrier (BBB) disruption during LVO reflect differences in circulating metabolites and RNA between small and large core strokes.

Combinatorial design of siloxane-incorporated lipid nanoparticles augments intracellular processing for tissue-specific mRNA therapeutic delivery.

Systemic delivery of messenger RNA (mRNA) for tissue-specific targeting using lipid nanoparticles (LNPs) holds great therapeutic potential. Nevertheless, how the structural characteristics of ionizable lipids (lipidoids) impact their capability to target cells and organs remains unclear. Here we engineered a class of siloxane-based ionizable lipids with varying structures and formulated siloxane-incorporated LNPs (SiLNPs) to control in vivo mRNA delivery to the liver, lung and spleen in mice.

A quality assessment tool for focused abdominal sonography for trauma examinations using artificial intelligence.

Background: Current tools to review focused abdominal sonography for trauma (FAST) images for quality have poorly defined grading criteria or are developed to grade the skills of the sonographer and not the examination. The purpose of this study is to establish a grading system with substantial agreement among coders, thereby enabling the development of an automated assessment tool for FAST examinations using artificial intelligence (AI).

Methods: Five coders labeled a set of FAST clips.

Cardiovascular Disease Mortality Trends, 2010-2022: An Update with Final Data.

Introduction: Age-adjusted mortality rates (AAMR) for cardiovascular diseases (CVD) increased in 2020 and 2021, and provisional data indicated an increase in 2022, resulting in substantial excess CVD deaths during the COVID-19 pandemic. Updated estimates using final data for 2022 are needed.

Methods: The National Vital Statistics System's final Multiple Cause of Death files were analyzed in 2024 to calculate AAMR from 2010 to 2022 and excess deaths from 2020 to 2022 for U.

Frontal alpha asymmetry dynamics: A window into active self-regulatory processes.

Frontal Alpha Asymmetry (FAA) has been studied since the late 1970s as a neural correlate of emotion regulation and motivational processes. FAA is often viewed through a dispositional lens reflecting individual differences in positive or negative emotionality and biases toward approach or avoidance motivational processes. However, FAA also shifts in response to context-specific conditions that elicit approach or avoidance responses, indicating FAA reflects active, ongoing self-regulatory processes.

Disruption of immune responses by type 1 diabetes exacerbates SARS-CoV-2 mediated lung injury.

COVID-19 commonly presents as pneumonia, with those most severely affected progressing to respiratory failure. Patient responses to SARS-CoV-2 infection are varied, with comorbidities acting as major contributors to varied outcomes. Focusing on one such major comorbidity, we assessed whether pharmacological induction of type 1 diabetes mellitus (T1DM) would increase the severity of lung injury in a murine model of COVID-19 pneumonia utilizing wild-type mice infected with mouse-adapted SARS-CoV-2.

Changes in blood pressure measurement prevalence among United States adults with hypertension before and during the COVID-19 pandemic.

Background: The Coronavirus Disease 2019 (COVID-19) pandemic disrupted health care, with particularly profound effects on persons with chronic conditions like hypertension.

Objectives: In this study, we examined changes in the prevalence of blood pressure (BP) measurements by a healthcare professional among adults aged ≥ 18 years with hypertension before and during the COVID-19 pandemic in the United States (US).

Methods: This study utilized the National Health Interview Survey data from April to December of the 2019 and 2021 modules of the survey.