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.

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.

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.

Research Attitudes Questionnaire scores and retention in a recruitment registry.

Background: Recruitment registries are maximally effective when registrants are retained to the point of referral. The Research Attitudes Questionnaire (RAQ) has previously been shown to predict research participation behaviors, including Alzheimer's disease clinical trial completion.

Objective: To test the hypothesis that RAQ score is associated with retention behaviors in a local recruitment registry.

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).

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.

Progressive natural killer cell dysfunction in advanced-stage clear-cell renal cell carcinoma and association with clinical outcomes.

Background: Natural killer (NK) cells are important contributors to antitumor immunity in clear-cell renal cell carcinoma (ccRCC). However, their phenotype, function, and association with clinical outcomes in ccRCC remain poorly understood.

Materials And Methods: We analyzed single-cell RNA sequencing data from 13 primary tumors, 1 localized tumor extension, and 1 metastasis from ccRCC patients at different clinical stages.

Nivolumab to restore T-cell fitness in CAR-T refractory multiple myeloma.

Efficacy and durability remain central shortcomings of T-cell based therapies in multiple myeloma (MM). Here, we employ blood-based transcriptional T-cell profiling to define impaired T-cell fitness as putative biomarker associated with sensitivity to PD1 inhibition in CAR-T refractory MM patients.

Current developments in T-cell receptor therapy for Acute Myeloid Leukaemia.

T-cell receptor (TCR) therapies are a promising modality for the treatment of cancers, with significant efforts being directed towards acute myeloid leukaemia (AML), a particularly challenging disease. Chimeric antigen receptor (CAR) T-cells targeting single surface antigens have shown remarkable efficacy for B-cell lymphoblastic leukaemia, lymphomas and multiple myeloma. However, AML presents formidable obstacles to the effectiveness of CAR T-cells due to the widespread expression of heterogenous leukaemia immunophenotypes and surface antigen targets additionally present on normal myeloid cells.

Effect of Improved Provider Communication and Adherence to Guidelines on PrEP Initiation in Kisumu Kenya.

Introduction: Adolescent girls and young women (AGYW) in Kenya have low pre-exposure prophylaxis (PrEP) initiation rates in part due to stigmatizing interactions with health care providers. Our recent randomized clinical trial of a standardized patient actor (SP) training intervention for providers found higher quality PrEP delivery at intervention sites, however it was unclear whether improved service quality improved PrEP initiation.

Methods: This analysis used routine records from facilities participating in the randomized trial which aimed to improve provider communication and adherence to Kenyan guidelines when offering PrEP to AGYW.

Using internet-assisted geocoding of 1940 census addresses to reconstruct enumeration districts for use with redlining and longitudinal health datasets.

Many historical administrative documents, such as the 1940 census, have been digitized and thus could be merged with geographic data. Merged data could reveal social determinants of health, health and social policy milieu, life course events, and selection effects otherwise masked in longitudinal datasets. However, most exact boundaries of 1940 census enumeration districts have not yet been georeferenced.

Summon a demon and bind it: A grounded theory of LLM red teaming.

Engaging in the deliberate generation of abnormal outputs from Large Language Models (LLMs) by attacking them is a novel human activity. This paper presents a thorough exposition of how and why people perform such attacks, defining LLM red-teaming based on extensive and diverse evidence. Using a formal qualitative methodology, we interviewed dozens of practitioners from a broad range of backgrounds, all contributors to this novel work of attempting to cause LLMs to fail.

Outcomes and complications of vertebral body tethering by patient gender.

Purpose: Non-fusion surgical options for pediatric scoliosis management such as vertebral body tethering (VBT) offer an alternative to spinal fusion. With this study, we aim to evaluate the postoperative outcomes in boys versus girls who have undergone VBT. Our hypothesis is that girls and boys will have similar outcomes by 2-year follow-up.

HIV Prevention in Syringe Service Programs Since the Start of COVID-19: Where Do We Go From Here?

Purpose: This narrative review addresses post-2020, specific, complex challenges for use of and adherence to pre-exposure prophylaxis (PrEP) for HIV prevention among out-of-treatment people who use drugs (PWUD) at syringe services programs (SSPs).

Recent Findings: The COVID-19 pandemic and its associated changes to the provision of healthcare have significantly impacted HIV prevention, especially for PWUD. Through a synthesis of literature and clinical experience, we (1) characterize the operational changes imposed by the pandemic on SSPs that shaped the current HIV prevention landscape; (2) describe three levels of current challenges for PWUD, including consumer attitudes, non-medical and medical provider attitudes, and structural and scalability barriers; (3) characterize current models for PrEP in SSPs; and (4) offer practical recommendations for HIV prevention in harm reduction programs.

Hypomorphic RAG2 Deficiency Promotes Selection of Self-Reactive B Cells.

Reduced function or hypomorphic variants in recombination-activating genes (RAG) 1 or 2 result in a broad clinical phenotype including common variable immunodeficiency (CVID) and even adult-onset disease. Milder RAG variants are less characterized. Here we describe the longitudinal course of a milder combined RAG deficiency in 3 of 7 siblings sharing the same RAG2 mutations over a 50-year study.

Screening for Structural Heart Defects: A Single-Center Retrospective Cost Analysis for Fetal Echocardiography in Adults with Congenital Heart Disease.

Fetal echocardiography (FE) is recommended for parents with congenital heart disease (pCHD) due to a 3-6% recurrence risk of congenital heart disease (CHD). This study aimed to evaluate the cost of FE for detecting neonatal CHD in pCHD. FE data were collected between 12/2015 and 12/2022.

Ranolazine effectively improves clinical symptoms in patients with slow flow coronary arteries: a randomized, double-blind, placebo-controlled clinical trial.

The coronary slow flow phenomenon (CSF) causes persistent chest pains that can affect patients' quality of life. We aimed to examine the ranolazine impacts on clinical symptoms in CSF patients. The present randomized, double-blind, placebo-controlled trial consisted of 44 patients with CSF.