Intranasally administrated fusion-inhibitory lipopeptides block SARS-CoV-2 infection in mice and enable long-term protective immunity.

We have assessed antiviral activity and induction of protective immunity of fusion-inhibitory lipopeptides derived from the C-terminal heptad-repeat domain of SARS-CoV-2 spike glycoprotein in transgenic mice expressing human ACE2 (K18-hACE2). The lipopeptides block SARS-CoV-2 infection in cell lines and lung-derived organotypic cultures. Intranasal administration in mice allows the maintenance of homeostatic transcriptomic immune profile in lungs, prevents body-weight loss, decreases viral load and shedding, and protects mice from death caused by SARS-CoV-2 variants.

Illuminating the multidimensional contributions of small-scale fisheries.

Sustainable development aspires to "leave no one behind". Even so, limited attention has been paid to small-scale fisheries (SSF) and their importance in eradicating poverty, hunger and malnutrition. Through a collaborative and multidimensional data-driven approach, we have estimated that SSF provide at least 40% (37.

Massively parallel characterization of transcriptional regulatory elements.

The human genome contains millions of candidate cis-regulatory elements (cCREs) with cell-type-specific activities that shape both health and many disease states. However, we lack a functional understanding of the sequence features that control the activity and cell-type-specific features of these cCREs. Here we used lentivirus-based massively parallel reporter assays (lentiMPRAs) to test the regulatory activity of more than 680,000 sequences, representing an extensive set of annotated cCREs among three cell types (HepG2, K562 and WTC11), and found that 41.

De novo designed proteins neutralize lethal snake venom toxins.

Snakebite envenoming remains a devastating and neglected tropical disease, claiming over 100,000 lives annually and causing severe complications and long-lasting disabilities for many more. Three-finger toxins (3FTx) are highly toxic components of elapid snake venoms that can cause diverse pathologies, including severe tissue damage and inhibition of nicotinic acetylcholine receptors, resulting in life-threatening neurotoxicity. At present, the only available treatments for snakebites consist of polyclonal antibodies derived from the plasma of immunized animals, which have high cost and limited efficacy against 3FTxs.

Delayed onset of ocean acidification in the Gulf of Maine.

The Gulf of Maine holds significant ecological and economic value for fisheries and communities in north-eastern North America. However, there is apprehension regarding its vulnerability to the effects of increasing atmospheric CO. Substantial recent warming and the inflow of low alkalinity waters into the Gulf of Maine have raised concerns about the impact of ocean acidification on resident marine calcifiers (e.

A human single-neuron dataset for object recognition.

Object recognition is fundamental to how we interact with and interpret the world around us. The human amygdala and hippocampus play a key role in object recognition, contributing to both the encoding and retrieval of visual information. Here, we recorded single-neuron activity from the human amygdala and hippocampus when neurosurgical epilepsy patients performed a one-back task using naturalistic object stimuli.

Digital health for early psychosis in Ghana: patient and caregiver needs and preferences.

In West Africa, the long-term consequences of poor early psychosis recovery include poverty, neglect, and community ostracization. To understand the potential for digital health approaches to support early psychosis care in Ghana, we conducted a survey study among early psychosis patients and their caregivers about mental health needs, technology use and access, and interest in digital mental health. Hospital staff at Accra Psychiatric Hospital reviewed hospital medical records from January 2023 - December 2023 identifying young adults (≥18 years old) who had experienced psychosis symptoms for the first time within the prior five years.

Morphological and functional convergence of visual projection neurons from diverse neurogenic origins in Drosophila.

The Drosophila visual system is a powerful model to study the development of neural circuits. Lobula columnar neurons-LCNs are visual output neurons that encode visual features relevant to natural behavior. There are ~20 classes of LCNs forming non-overlapping synaptic optic glomeruli in the brain.

A Systematic Review of Evaluated Labor Market Initiatives Addressing Precarious Employment: Findings and Public Health Implications.

Precarious employment (PE) is a major determinant of population health and contributor to health and social inequities. The purpose of this article is to synthesize and critically appraise available evidence on labor market initiatives addressing PE identified through a systematic review. Of the 21 initiatives reviewed, grouped into four categories-labor market policies, legislation, and reforms; union strategies; apprenticeships and other youth programs; social protection programs-10 showed consistently positive outcomes and 11 a combination of negative, mixed, or inconclusive outcomes.

Leveraging descriptor learning and functional map-based shape matching for automated anatomical Landmarking in mouse mandibles.

Geometric morphometrics is used in the biological sciences to quantify morphological traits. However, the need for manual landmark placement hampers scalability, which is both time-consuming, labor-intensive, and open to human error. The selected landmarks embody a specific hypothesis regarding the critical geometry relevant to the biological question.

Effectiveness of Data-Driven Gating FDG PET/CT for Abdominal Region.

This study aimed to validate the effectiveness of MotionFree (MF) in the abdominal region using 2 different PET/CT scanners to determine how to use MF efficiently. All 198 patients underwent respiratory-gated F-FDG PET/CT with MF. Imaging was performed using Discovery MI (DMI) and Discovery IQ (DIQ) PET/CT scanners, and all data were divided into 2 groups in each category (abdominal: upper and lower abdomen, lesion size, <20 mm and ≥20 mm; scanner group: DMI and DIQ).

Psychometric Evaluation of the Scleroderma Skin Questionnaire: A Novel Patient Reported Outcome for Skin Disease in Patients with Systemic Sclerosis.

Objective: To evaluate the psychometric properties of the Scleroderma Skin Questionnaire (SSQ), a novel patient-reported outcome (PRO) to assess systemic sclerosis (SSc) related skin symptoms.

Methods: The SSQ was administered to 799 adults (mean age 52.7; 82% female) enrolled in the SSc Collaborative National Quality and Efficacy Registry (CONQUER).

Effect of Characteristic Inflammatory and Structural Pelvic Magnetic Resonance Imaging Lesions on Expert Assessment of Axial Juvenile Spondyloarthritis.

Objective: To evaluate the influence of pelvic magnetic resonance imaging (MRI) findings on axial disease assessment in juvenile spondyloarthritis (JSpA).

Methods: This was a cross-sectional study of patients with JSpA with suspected axial disease. Three experts reviewed each case and rated their confidence (-3 to +3) in the presence of axial disease, first with clinical data and second with clinical and MRI data.

Engineering vaginal film platform for mucoadhesion and sustained drug release for HIV-1 prevention.

User adherence contributes to the effectiveness of topical pre-exposure prophylactic products designed to protect against human immunodeficiency virus type 1 (HIV-1) infection. Long-acting approaches that do not require daily or coitally-dependent use could potentially improve user adherence. This study aims to develop a long-acting vaginal film to deliver an integrase inhibitor, MK-2048, for prevention of HIV-1 infection.

The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study.

Purpose: To assess the association between neoadjuvant therapy and overall survival (OS) in patients with left-sided resectable pancreatic cancer (RPC) compared to upfront surgery.

Background: Left-sided pancreatic cancer is associated with worse OS compared to right-sided pancreatic cancer. Although neoadjuvant therapy is currently seen as not effective in patients with RPC, current randomized trials included mostly patients with right-sided RPC.

Application of Artificial Intelligence to Analyze Data from Randomized Controlled Trials: An Example from DECAAF-II.

Background: Causal machine learning (ML) provides an efficient way of identifying heterogeneous treatment effect groups from hundreds of possible combinations, especially for randomized trial data.

Objective: The aim of this paper is to illustrate the potential of applying causal ML on the DECAAF II trial data. We proposed a causal ML model to predict the treatment response heterogeneity.

Examining changes in fatal violence against women after bail reform in New Jersey.

Introduction Cash bail reforms that end pretrial detention due to the inability to afford bail have been highly debated across the US. A major concern cited by bail reform opponents is that reducing pretrial detention will increase community violence, particularly violence against women. The objective of this study was to assess if New Jersey's cash bail reform was associated with changes in rates of fatal violence against women.

Infrainguinal bypass for limb salvage has comparable mortality and affords a better chance of home discharge than amputation among octogenarians.

Background: Infrainguinal bypass for chronic limb-threatening ischemia (CTLI) in octogenarians is considered a high-risk procedure due to the presumed associated frailty of the patient population. However, the alternative which is major amputation may not be a better option. This study retrospectively compares the outcomes of bypass versus major amputation for functionally independent and partially dependent patients.

Beyond Redox Regulation: Novel Roles of TXNIP in the Pathogenesis and Therapeutic Targeting of Kidney Disease.

Cellular stress conditions, such as oxidative and endoplasmic reticulum (ER) stresses contribute to development of various kidney diseases. Oxidative stress is prompted by reactive oxygen species (ROS) accumulation and delicately mitigated by glutathione and thioredoxin (Trx) antioxidant systems. Initially identified as a Trx-binding partner, thioredoxin interacting protein (TXNIP) is significantly upregulated and activated by oxidative and ER stresses.

Rethinking the rise of early onset gastrointestinal cancers: a call to action.

Since the early 1990s, there has been a dramatic rise in gastrointestinal cancers diagnosed in patients under age 50 for reasons that remain poorly understood. The most significant change has been the increase in incidence rates of early-onset colorectal cancer, especially rates of left-sided colon and rectal cancers. Increases in gastric, pancreatic, and other gastrointestinal cancer diagnoses have further contributed to this trend.