Long-term safety of lentiviral or gammaretroviral gene-modified T cell therapies.

Long-term risks of gene therapy are not fully understood. In this study, we evaluated safety outcomes in 783 patients over more than 2,200 total patient-years of observation from 38 T cell therapy trials. The trials employed integrating gammaretroviral or lentiviral vectors to deliver engineered receptors to target HIV-1 infection or cancer.

A Randomized, Blinded, Vehicle-Controlled Dose-Ranging Study to Evaluate and Characterize Remdesivir Efficacy Against Ebola Virus in Rhesus Macaques.

Ebola virus (EBOV) causes severe disease in humans, with mortality as high as 90%. The small-molecule antiviral drug remdesivir (RDV) has demonstrated a survival benefit in EBOV-exposed rhesus macaques. Here, we characterize the efficacy of multiple intravenous RDV dosing regimens on survival of rhesus macaques 42 days after intramuscular EBOV exposure.

DDX50 cooperates with STAU1 to effect stabilization of pro-differentiation RNAs.

Glucose binding can alter protein oligomerization to enable differentiation. Here, we demonstrate that glucose binding is a general capacity of DExD/H-box RNA helicases, including DDX50, which was found to be essential for the differentiation of diverse cell types. Glucose binding to conserved DDX50 ATP binding sequences altered protein conformation and dissociated DDX50 dimers.

Tumor Lysis Syndrome in Acute Myeloid Leukemia Patients Treated With a Venetoclax Based Regimen.

Venetoclax with hypomethylating agents (HMA) is the standard of care for acute myeloid leukemia (AML) in patients ineligible for intensive chemotherapy and is associated with tumor lysis syndrome (TLS). TLS prophylaxis and the use of Cairo Bishop versus Howard diagnostic criteria are not standardized. Here we report TLS prophylaxis and incidence in a retrospective cohort of 100 consecutive AML patients treated with venetoclax and HMA.

SARS-CoV-2 resistance analyses from the Phase 3 PINETREE study of remdesivir treatment in nonhospitalized participants.

Remdesivir inhibits the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp; Nsp12). Here, we conducted viral resistance analyses from the Phase 3 PINETREE trial of remdesivir in nonhospitalized participants at risk of severe COVID-19. Nasopharyngeal swabs (collected at baseline [Day 1], Days 2, 3, 7, and 14) were eligible for analysis if their viral load was above the lower limit of quantification for the RT-qPCR assay (2228 copies/mL).

Imaging of electric-field-induced domain structure in DyMnO nanocrystals.

Multiferroic materials that exhibit interacting and coexisting properties, like ferroelectricity and ferromagnetism, possess significant potential in the development of novel technologies that can be controlled through the application of external fields. They also exhibit varying regions of polarity, known as domains, with the interfaces that separate the domains referred to as domain walls. In this study, using three-dimensional (3D) bragg coherent diffractive imaging (BCDI), we investigate the dynamics of multiferroic domain walls in a single hexagonal dysprosium manganite (h-DyMnO ) nanocrystal under varying applied electric field.

Lisocabtagene Maraleucel for Relapsed/Refractory Large B-Cell Lymphoma: A Cell Therapy Consortium Real-World Analysis.

Lisocabtagene maraleucel (liso-cel) is an autologous CD19-directed CAR T cell therapy approved for the treatment of relapsed/refractory large B-cell lymphoma (LBCL). We present a multicenter retrospective study evaluating safety, efficacy, and resource utilization of liso-cel in the standard-of-care setting. Patients received commercial liso-cel at 7 US medical centers and patient selection, toxicity management, and disease assessment followed institutional practices.

Repurposing an epithelial sodium channel inhibitor as a therapy for murine and human skin inflammation.

Inflammatory skin disease is characterized by a pathologic interplay between skin cells and immunocytes and can result in disfiguring cutaneous lesions and systemic inflammation. Immunosuppression is commonly used to target the inflammatory component; however, these drugs are often expensive and associated with side effects. To identify previously unidentified targets, we carried out a nonbiased informatics screen to identify drug compounds with an inverse transcriptional signature to keratinocyte inflammatory signals.

Disease-Linked Regulatory DNA Variants and Homeostatic Transcription Factors in Epidermis.

Identifying noncoding single nucleotide variants ( SNVs ) in regulatory DNA linked to polygenic disease risk, the transcription factors ( TFs ) they bind, and the target genes they dysregulate is a goal in polygenic disease research. Massively parallel reporter gene analysis ( MPRA ) of 3,451 SNVs linked to risk for polygenic skin diseases characterized by disrupted epidermal homeostasis identified 355 differentially active SNVs ( daSNVs ). daSNV target gene analysis, combined with daSNV editing, underscored dysregulated epidermal differentiation as a pathomechanism shared across common polygenic skin diseases.

Inconsistent Reporting and Definitions of Time-to-Event Endpoints in CAR T Clinical Trials: A Review.

Clinical trials evaluating chimeric antigen receptor T-cell therapy (CAR T) commonly report time-to-event (TTE) endpoints. However, definitions are not necessarily comparable across studies and variability can lead to misinterpretation of results or inappropriate comparisons across products and studies. Amid the rapidly increasing number of published CAR T trials-many of which were used for regulatory approval-this study aims to summarize the variation in the use and reporting of TTE endpoints in CAR T trials.

Glucose binds and activates NSUN2 to promote translation and epidermal differentiation.

Elevations in intracellular glucose concentrations are essential for epithelial cell differentiation by mechanisms that are not fully understood. Glucose has recently been found to directly bind several proteins to alter their functions to enhance differentiation. Among the newly identified glucose-binding proteins is NSUN2, an RNA-binding protein that we identified as indispensable for epidermal differentiation.

TET2 regulates early and late transitions in exhausted CD8 T cell differentiation and limits CAR T cell function.

CD8 T cell exhaustion hampers control of cancer and chronic infections and limits chimeric antigen receptor (CAR) T cell efficacy. Targeting in CAR T cells provides therapeutic benefit; however, TET2's role in exhausted T cell (T) development is unclear. In chronic lymphocytic choriomeningitis virus (LCMV) infection, TET2 drove conversion from stem cell-like T progenitors toward terminally differentiated and effector (T)-like T.

Imaging in-operando LiCoO nanocrystallites with Bragg coherent X-ray diffraction.

Although the LiCoO (LCO) cathode material has been widely used in commercial lithium ion batteries (LIB) and shows high stability, LIB's improvements have several challenges that still need to be overcome. In this paper, we have studied the in-operando structural properties of LCO within battery cells using Bragg Coherent X-ray Diffraction Imaging to identify ways to optimise the LCO batteries' cycling. We have successfully reconstructed the X-ray scattering phase variation (a fingerprint of atomic displacement) within a  ≈ (1.

Multisystemic Resilience and Anxious-Depressed Symptoms in Black Youth Exposed to Maternal Syndemics: A Mixed-Method Study.

We explored associations between multisystemic resilience and anxious-depressed symptoms in Black families experiencing maternal syndemics (i.e., co-occurring epidemics of substance abuse, violence, HIV/AIDS), using a sequential explanatory study design.

Climate Change, Racism, and Food Insecurity: Cyclical Impacts of Stressors Exacerbate Health Disparities.

Introduction: Disadvantaged populations have higher rates of chronic disease, including heart disease, cancer, and diabetes. Race, ethnicity, lower socioeconomic status, and poverty all contribute to these disproportionate rates. Other factors, including systemic racism, climate change, poor diet, lack of food access, and epigenetic influences, that are distributed and experienced differently across vulnerable populations also play a significant role in the development of chronic diseases.

Cytokine-mediated CAR T therapy resistance in AML.

Acute myeloid leukemia (AML) is a rapidly progressive malignancy without effective therapies for refractory disease. So far, chimeric antigen receptor (CAR) T cell therapy in AML has not recapitulated the efficacy seen in B cell malignancies. Here we report a pilot study of autologous anti-CD123 CAR T cells in 12 adults with relapsed or refractory AML.

A retrospective characterization of pediatric facemasks marketed in the United States and implications for future designs.

Background: Device manufacturers who seek to market their pediatric facemasks in the United States (U.S.), as part of anthropometric data requirement, need to demonstrate their mask designs are expected to fit the intended user population.

Geographic Variations in Urban-Rural Particulate Matter (PM) Concentrations in the United States, 2010-2019.

Fine particulate matter 2.5 (PM) is a widely studied pollutant with substantial health impacts, yet little is known about the urban-rural differences across the United States. Trends of PM in urban and rural census tracts between 2010 and 2019 were assessed alongside sociodemographic characteristics including race/ethnicity, poverty, and age.

Clinical Management of Hospitalized Patients With High-Consequence Infectious Diseases in England.

Infectious disease physicians in England have been diagnosing and managing occasional cases of viral hemorrhagic fever since 1971, including the United Kingdom's first case of Ebola virus disease in 1976. Specialist isolation facilities to provide safe and effective care have been present since that time. Following the emergence of Middle East respiratory syndrome (MERS) in 2012, and the avian influenza A (H7N9) outbreak in 2013, and the 2014-2016 Ebola virus disease outbreak in West Africa, clinical and public health preparedness and response pathways in England have been strengthened for these types of diseases, now called high-consequence infectious diseases (HCIDs).

Slice-specific B shimming improves the repeatability of multishot DWI at 7 T.

Purpose: Compared with lower field strengths, DWI at 7 T faces the combined challenges of increased distortion and blurring due to B inhomogeneity, and increased signal dropouts due to B inhomogeneity. This study addresses the B limitations using slice-specific static parallel transmission (pTx) in a multi-shot, readout-segmented EPI diffusion imaging sequence.

Methods: DWI was performed in 7 healthy subjects using MRI at 7 T and readout-segmented EPI.

Optimizing the post-CAR T monitoring period in recipients of axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel.

CD19-directed chimeric antigen receptor T-cell (CAR T) therapies, including axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), and lisocabtagene maraleucel (liso-cel), have transformed the treatment landscape for B-cell non-Hodgkin lymphoma, showcasing significant efficacy but also highlighting toxicity risks such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The US Food and Drug Administration has mandated patients remain close to the treatment center for 4 weeks as part of a Risk Evaluation and Mitigation Strategy to monitor and manage these toxicities, which, although cautious, may add to cost of care, be burdensome for patients and their families, and present challenges related to patient access and socioeconomic disparities. This retrospective study across 9 centers involving 475 patients infused with axi-cel, tisa-cel, and liso-cel from 2018 to 2023 aimed to assess CRS and ICANS onset and duration, as well as causes of nonrelapse mortality (NRM) in real-world CAR T recipients.