Plasma Neurofilament Light Chain and Glial Fibrillary Acidic Protein as Biomarkers of Cognitive Decline in People Living with HIV.

Background: This study examined the relationship between neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) and cognition in people living with HIV (PLWH) at baseline and over time.

Methods: Plasma and clinical data were available from PLWH aged ≥45 years with HIV RNA <200 copies/mL enrolled in the AIDS Clinical Trials Group HAILO cohort study. We measured plasma NfL and GFAP using a single molecule array platform.

Tuberculosis Preventive Treatment for Pregnant People With Human Immunodeficiency Virus in South Africa: A Modeling Analysis of Clinical Benefits and Risks.

Background: Although prior studies of tuberculosis-preventive treatment (TPT) for pregnant people with human immunodeficiency virus (PPWH) report conflicting adverse pregnancy outcome (APO) risks, international guidelines recommend TPT for PPWH.

Methods: We used a microsimulation model to evaluate 5 TPT strategies among PPWH receiving antiretroviral therapy in South Africa: No TPT; 6 months of isoniazid (6H) or 3 months of isoniazid-rifapentine (3HP) during pregnancy (Immediate 6H or Immediate 3HP) or post partum (Deferred 6H or Deferred 3HP). The primary outcomes were maternal, fetal/infant, and combined deaths from causes potentially influenced by TPT (maternal tuberculosis, maternal hepatotoxicity, stillbirth, low birth weight [LBW], and infant tuberculosis).

Harm to myself or others? A qualitative study of the preferences of people who smoke for messages to be included in cigarette pack inserts.

Introduction: Tobacco package inserts [TPIs] are a novel channel to transmit smoking cessation messages. Research has shown associations between inserts, intentions to quit and increased self-efficacy. In Israel, TPIs have been legislated, but not yet implemented.

Disparities in Tobacco Smoking and Risk of Cardiovascular Disease in People With Low Socioeconomic Status or Serious Psychological Distress: A Simulation Analysis.

Introduction: High tobacco smoking prevalence in people with low SES or serious psychological distress in the U.S. may increase cardiovascular disease risk among these marginalized subpopulations.

First-in-human clinical outcomes with NG-350A, an anti-CD40 expressing tumor-selective vector designed to remodel immunosuppressive tumor microenvironments.

Background: Tumor-selective oncolytic viral vectors are promising anticancer therapeutics; however, challenges with dosing and potency in advanced/metastatic cancers have limited efficacy and usage. NG-350A is a next-generation blood-stable adenoviral vector engineered to express an agonist anti-cluster of differentiation (CD)40 antibody without affecting tumor-selectivity and oncolytic potency.

Methods: Intravenous and intratumoral (IT) administration of NG-350A was assessed in a phase Ia/Ib study in patients with metastatic/advanced epithelial tumors (NCT03852511).

PF-06952229, a selective TGF-β-R1 inhibitor: preclinical development and a first-in-human, phase I, dose-escalation study in advanced solid tumors.

Background: PF-06952229 is a selective small-molecule inhibitor of transforming growth factor-β (TGF-β) receptor 1. We evaluated its antitumor activity in preclinical studies and its safety, tolerability, pharmacokinetics, and pharmacodynamics in a phase I study (NCT03685591).

Patients And Methods: In vitro and in vivo preclinical studies were conducted.

Leveraging neighborhood representations of single-cell data to achieve sensitive DE testing with miloDE.

Single-cell RNA-sequencing enables testing for differential expression (DE) between conditions at a cell type level. While powerful, one of the limitations of such approaches is that the sensitivity of DE testing is dictated by the sensitivity of clustering, which is often suboptimal. To overcome this, we present miloDE-a cluster-free framework for DE testing (available as an open-source R package).

Lymphocyte-Directed Immunomodulation Remits Thymoma-Associated Autoimmune Pneumonitis.

Background: Thymoma presents with several autoimmune manifestations and is associated with secondary autoimmune regulator (AIRE) deficiency. Pneumonitis has recently been described as an autoimmune manifestation associated with thymoma presenting with similar clinical, radiographic, histological, and autoantibody features as seen in patients with inherited AIRE deficiency who suffer from Autoimmune PolyEndocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED) syndrome.

Objectives: To treat two patients with biopsy-proven thymoma-associated pneumonitis with lymphocyte-directed immunomodulation.

Autoantibodies to type I interferons in patients with systemic mastocytosis.

Background: Autoantibodies to type I interferons have been identified in association with a variety of inflammatory and autoimmune diseases. Type I interferons have demonstrated inhibitory effects on mast cell proliferation and degranulation. Systemic mastocytosis (SM) is a disease characterized by increased mast cell burden and mediator release.

Validation of Patient-Reported Outcomes in Patients With Nonmetastatic Breast Cancer Receiving Comprehensive Nodal Irradiation in the RadComp Trial.

Purpose: Our purpose was to evaluate the measurement properties of patient-reported outcome (PRO) measures used in the ongoing RadComp pragmatic randomized clinical trial (PRCT).

Methods And Materials: The deidentified and blinded data set included 774 English-speaking female participants who completed their 6-month posttreatment assessment. Eleven PRO measures were evaluated, including the Trial Outcome Index from the Functional Assessment of Cancer Therapy-Breast (FACT-B), Satisfaction with Breast Cosmetic Outcomes, the BREAST-Q, and selected Patient-Reported Outcomes Measurement Information System (PROMIS) measures.

Integrated longitudinal multiomics study identifies immune programs associated with acute COVID-19 severity and mortality.

BACKGROUNDPatients hospitalized for COVID-19 exhibit diverse clinical outcomes, with outcomes for some individuals diverging over time even though their initial disease severity appears similar to that of other patients. A systematic evaluation of molecular and cellular profiles over the full disease course can link immune programs and their coordination with progression heterogeneity.METHODSWe performed deep immunophenotyping and conducted longitudinal multiomics modeling, integrating 10 assays for 1,152 Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study participants and identifying several immune cascades that were significant drivers of differential clinical outcomes.

Anti-Interleukin-23 Autoantibodies in Adult-Onset Immunodeficiency.

Background: Autoantibodies against interleukin-12 (anti-interleukin-12) are often identified in patients with thymoma, but opportunistic infections develop in only some of these patients. Interleukin-12 (with subunits p40 and p35) shares a common subunit with interleukin-23 (subunits p40 and p19). In a patient with disseminated infection, the identification of both anti-interleukin-23 and anti-interleukin-12 prompted further investigation.

Oro-Respiratory Dysbiosis and Its Modulatory Effect on Lung Mucosal Toxicity during Exposure or Co-Exposure to Carbon Nanotubes and Cigarette Smoke.

The oro-respiratory microbiome is impacted by inhalable exposures such as smoking and has been associated with respiratory health conditions. However, the effect of emerging toxicants, particularly engineered nanoparticles, alone or in co-exposure with smoking, is poorly understood. Here, we investigated the impact of sub-chronic exposure to carbon nanotube (CNT) particles, cigarette smoke extract (CSE), and their combination.

Sustainability of an Opt-Out Electronic-Health Record-Based Tobacco Treatment Consult Service at a Large Safety-Net Hospital: A 6-Year Analysis.

Introduction: Our safety-net hospital implemented a hospital-based tobacco treatment intervention in 2016. We previously showed the intervention, an "opt-out" Electronic Health Record (EHR)-based Best Practice Alert (BPA)+ order-set that triggers consultation to an inpatient Tobacco Treatment Consult (TTC) service for all patients who smoke, improves smoking abstinence. We now report on sustainability, 6 years after inception.

The Potential of Real-Time Behavior and Well-Being Assessments to Improve Medical Student Wellness.

Problem: Medical students experience psychological distress more frequently than age-matched peers. Tracking medical student well-being has typically been limited to once- or twice-per-year questionnaires. Ongoing, real-time assessment of student behavior and well-being could facilitate individualized, timely interventions.

Features of acute COVID-19 associated with post-acute sequelae of SARS-CoV-2 phenotypes: results from the IMPACC study.

Post-acute sequelae of SARS-CoV-2 (PASC) is a significant public health concern. We describe Patient Reported Outcomes (PROs) on 590 participants prospectively assessed from hospital admission for COVID-19 through one year after discharge. Modeling identified 4 PRO clusters based on reported deficits (minimal, physical, mental/cognitive, and multidomain), supporting heterogenous clinical presentations in PASC, with sub-phenotypes associated with female sex and distinctive comorbidities.