Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma.

Background: Polyclonal autologous T cells that are epigenetically reprogrammed through mTOR inhibition and IFN-α polarization (RAPA-201) represent a novel approach to the adoptive T cell therapy of cancer. Ex vivo inhibition of mTOR results causes a shift towards T central memory (T) whereas ex vivo IFN-α promotes type I cytokines, with each of these functions known to enhance the adoptive T cell therapy of cancer. Rapamycin-resistant T cells polarized for a type II cytokine phenotype were previously evaluated in the allogeneic transplantation context.

Optimizing Diabetes-in-Pregnancy Outcomes Requires a Care Continuum.

This study aimed to assess the strengths, limitations, opportunities, and threats presented by diabetes-in-pregnancy. We review the improvements in maternal and fetal mortality since the advent of insulin therapy, evaluate current health challenges, and identify opportunities for preventing increased mortality due to diabetes-in-pregnancy. Prior to 1922, women with type 1 diabetes mellitus (T1DM) of childbearing age were discouraged from becoming pregnant as the maternal and fetal/neonatal mortality rates were extremely high.

Safety and Immunogenicity of Omicron Protein Vaccines in mRNA-Vaccinated Adolescents: A Phase 3, Randomised Trial.

Objectives: Safety and immunogenicity assessment of updated monovalent and bivalent SARS-CoV-2 vaccines in adolescents.

Methods: This phase 3, double-blinded study randomised 12-<18-year-old participants, who received ≥2 prior doses of an approved/authorised mRNA-based COVID-19 vaccine, 1:1 to receive NVX-CoV2601 (XBB.1.

Sex-Based Bias in Artificial Intelligence-Based Segmentation Models in Clinical Oncology.

Artificial intelligence (AI) advancements have accelerated applications of imaging in clinical oncology, especially in revolutionizing the safe and accurate delivery of state-of-the-art imaging-guided radiotherapy techniques. However, concerns are growing over the potential for sex-related bias and the omission of female-specific data in multi-organ segmentation algorithm development pipelines. Opportunities exist for addressing sex-specific data as a source of bias, and improving sex inclusion to adequately inform the development of AI-based technologies to ensure their fairness, generalizability and equitable distribution.

Utilization of AF4 for characterizing complex nanomaterial drug products: Reexamining sample recovery and its impact on particle size distribution as a quality attribute.

Asymmetrical flow field-flow fractionation (AF4) with multi-detection has continued to gain wider acceptance for characterizing complex drug products. An important quality attribute for these products is the measurement of the particle size distribution (PSD). Current limitations of established procedures (e.

Probabilistic Approaches for Risk Assessment and Regulatory Criteria Development: Current Applications, Gaps, and Opportunities.

Traditional ecological and human health risk assessment often relies on deterministic frameworks that preclude the presence of variability or uncertainty among input parameters characterizing exposure, effects, and risk. To promote increased realism and generate more robust risk management decisions, probabilistic risk assessment (PRA) has been introduced as a foundational grouping of techniques that seeks to broadly characterize variability among its components. While multiple methods exist (e.

Deciphering the dose-dependent effects of thymoquinone on cellular proliferation and transcriptomic changes in A172 glioblastoma cells.

Glioblastoma multiforme (GBM), the most prevalent primary malignant brain tumor in adults, exhibits a dismal 6.9% five-year survival rate post-diagnosis. Thymoquinone (TQ), the most abundant bioactive compound in Nigella sativa, has been extensively researched for its anticancer properties across various human cancers.

Sex Differences in Early/Unplanned Separation Among US Service Members With a History of Mild Traumatic Brain Injury.

Objective: To investigate the incidence of early/unplanned (E/U) separations following mild traumatic brain injury (mTBI) and assess whether sex impacts the hazard of separation.

Setting: Military Health System (MHS).

Participants: Active duty service members (N = 75,730) with an initial mTBI diagnosis in military records between January 2011 and January 2018.

Association between Delayed Broad-Spectrum Gram-negative Antibiotics and Clinical Outcomes: How Much Does Getting It Right with Empiric Antibiotics Matter?

Background: Clinicians often start unnecessarily broad-spectrum empiric Gram-negative antibiotics out of the concern that delaying effective therapy could lead to a worse clinical outcome. This study examined the consequences of delayed initiation of broad-spectrum Gram-negative antibiotics.

Methods: In a retrospective cohort of adult inpatients from 928 US hospitals, we compared clinical outcomes after (1) empiric narrow-spectrum antibiotics escalated to broad-spectrum antibiotics (delayed broad-spectrum therapy, DBT) and (2) empiric broad-spectrum antibiotics continued for at least 5 days (early broad-spectrum therapy, EBT) using Win Ratios.

An Automated Approach for Domain-Specific Knowledge Graph Generation─Graph Measures and Characterization.

In 2020, nearly 3 million scientific and engineering papers were published worldwide (White, K. Publications Output: U.S.

Brain Function Outcomes of Recent and Lifetime Cannabis Use.

Importance: Cannabis use has increased globally, but its effects on brain function are not fully known, highlighting the need to better determine recent and long-term brain activation outcomes of cannabis use.

Objective: To examine the association of lifetime history of heavy cannabis use and recent cannabis use with brain activation across a range of brain functions in a large sample of young adults in the US.

Design, Setting, And Participants: This cross-sectional study used data (2017 release) from the Human Connectome Project (collected between August 2012 and 2015).

CRM1 regulates androgen receptor stability and impacts DNA repair pathways in prostate cancer, independent of the androgen receptor.

Among the known nuclear exportins, CRM1 is the most studied prototype. Dysregulation of CRM1 occurs in many cancers, hence, understanding the role of CRM1 in cancer can help in developing synergistic therapeutics. The study investigates how CRM1 affects prostate cancer growth and survival.

The swinging sclera technique for evisceration.

Purpose: To present a modified evisceration technique with a full-thickness horizontal sclerotomy and assess post-operative motility and long-term outcomes.

Methods: This is a retrospective chart review of patients who underwent evisceration with a single surgeon (TJM). The standard initial steps of evisceration were performed.

Open-Source Large Language Models in Radiology: A Review and Tutorial for Practical Research and Clinical Deployment.

Integrating large language models (LLMs) into health care holds substantial potential to enhance clinical workflows and care delivery. However, LLMs also pose serious risks if integration is not thoughtfully executed, with complex challenges spanning accuracy, accessibility, privacy, and regulation. Proprietary commercial LLMs (eg, GPT-4 [OpenAI], Claude 3 Sonnet and Claude 3 Opus [Anthropic], Gemini [Google]) have received much attention from researchers in the medical domain, including radiology.

Characterization of spike S1/S2 processing and entry pathways of lentiviral pseudoviruses bearing seasonal human coronaviruses NL63, 229E, and HKU1 spikes.

Although much has been learned about the entry mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many details of the entry mechanisms of seasonal human coronaviruses (HCoVs) remain less well understood. In the present study, we used 293T cell lines stably expressing angiotensin converting enzyme (ACE2), aminopeptidase N (APN), or transmembrane serine protease 2 (TMPRSS2), which support high-level transduction of lentiviral pseudoviruses bearing spike proteins of seasonal HCoVs, HCoV-NL63, -229E, or -HKU1, respectively, to compare spike processing and virus entry pathways among these viruses. Our results showed that the entry of HCoV-NL63, -229E, and -HKU1 pseudoviruses into cells is sensitive to endosomal acidification inhibitors (chloroquine and NHCl), indicating entry via the endocytosis route.

Inhibiting NLRP3 enhances cellular autophagy induced by outer membrane vesicles from .

The bacterium is able to invade lung epithelial cells and survive intracellularly. During this process, it secretes outer membrane vesicles (OMVs), however, it is currently unclear how OMVs from (PA-OMVs) affect lung epithelial cells and their impact on oxidative stress, autophagy, and other physiological activities of lung epithelial cells. In this study, we found that PA-OMVs activated oxidative stress and autophagy in cells.

Policy Recommendations to Support Equitable Access to Long-Acting Injectables for Human Immunodeficiency Virus Prevention and Treatment: A Policy Paper of the Infectious Diseases Society of America and the HIV Medicine Association.

Long-acting injectables (LAIs) for HIV prevention and treatment could dramatically improve health outcomes and health equity for people with HIV and those who could benefit from pre-exposure prophylaxis. Despite widespread acceptability and demand by providers and potential users of LAIs, implementation has been extremely limited since the introduction of cabotegravir/rilpivirine, the first LAI for HIV treatment, in January 2021, and long-acting cabotegravir, the first LAI for HIV prevention, in December 2021. We report results of a provider survey, conducted by the HIV Medicine Association, which identified LAI implementation barriers related to health insurance processes, staffing and administrative support, drug costs and acquisition, and access for individuals who are uninsured.

Temporal Genomic Analysis of Homogeneous Tumor Models Reveals Key Regulators of Immune Evasion in Melanoma.

In this study, we find that Mif expression is associated with tumor growth and aggressiveness, specifically in tumors with low heterogeneity. These findings could facilitate the development of new strategies to treat patients with homogeneous, high MIF-expressing tumors that are unresponsive to immune checkpoint therapy.

Electrocatalysis: From Planar Surfaces to Nanostructured Interfaces.

The reactions critical for the energy transition center on the chemistry of hydrogen, oxygen, carbon, and the heterogeneous catalyst surfaces that make up electrochemical energy conversion systems. Together, the surface-adsorbate interactions constitute the electrochemical interphase and define reaction kinetics of many clean energy technologies. Practical devices introduce high levels of complexity where surface roughness, structure, composition, and morphology combine with electrolyte, pH, diffusion, and system level limitations to challenge our ability to deconvolute underlying phenomena.