Safety, Tolerability, and Pharmacokinetics of Long-Acting Broadly Neutralizing HIV-1 Monoclonal Antibody VRC07523LS in Newborn Infants Exposed to HIV-1.

Background: Vertical HIV-1 transmission despite antiretroviral therapy may be mitigated by use of long-acting, broadly neutralizing, monoclonal antibodies (bNAb) such as VRC07523LS. The present study was designed to determine the safety and pharmacokinetics of VRC07523LS.

Methods: VRC07523LS, 80 mg/dose, was administered subcutaneously after birth to non-breastfed (Cohort 1; N=11, enrolled in USA) and breastfed (Cohort 2; N=11, enrolled in South Africa and Zimbabwe) infants exposed to HIV-1.

Historic smallpox vaccination and Mpox cross-reactive immunity: Evidence from healthcare workers with childhood and adulthood exposures.

In recent years, human mpox has made multiple resurges, prompting public health professionals to consider factors that lead to the increased risk for the reemergence of other orthopoxviruses. Due to the genetic similarity between orthopoxviruses, vaccinia vaccines used to prevent smallpox transmission are also indicated and have been used for mpox infection prevention and control. In this study, cross-reactive immunity for mpox was observed among individuals with self-reported history of smallpox vaccination.

Differential long-term tamoxifen therapy benefit by menopausal status in breast cancer patients: secondary analysis of a controlled randomized clinical trial.

Background: Estrogen receptor-positive breast cancer patients have a long-term risk of distant metastatic disease, and premenopausal patients have a higher risk. Randomized studies with long-term follow-up are essential to understand treatment benefit. We elucidated the long-term tamoxifen therapy benefit by menopausal status in the Stockholm tamoxifen trials with 20 years complete follow-up.

Equivalent Pain and Opioid Use Between Transabdominal and Retroperitoneal Adrenalectomy.

Introduction: Laparoscopic transabdominal adrenalectomy (LTA) and posterior retroperitoneoscopic adrenalectomy (PRA) are safe, effective surgical approaches. A direct comparison of postoperative pain and narcotic use is needed.

Methods: Adults who had laparoscopic adrenalectomy at a tertiary institution from 2015 to 2021 were identified from a surgical database.

Use of an Ethinyl Estradiol/Etonogestrel Vaginal Ring Alters Vaginal Microbial Communities in Women with HIV.

Background: HIV-1 antiretroviral therapy (ART) alters hormonal contraceptive levels delivered via intravaginal ring (IVR) in a regimen specific manner. We explored the role of the IVR on vaginal microbial communities, vaginal short chain fatty acids (SCFAs), vaginal HIV shedding, and the effect of vaginal microbes on hormone concentrations in cisgender women with HIV (WWH).

Methods: Vaginal microbes were assessed by 16S RNA sequencing of weekly vaginal swabs, vaginal SCFA by mass spectrometry, HIV-1 shedding by nucleic acid amplification on vaginal aspirates, and bacterial vaginosis by Nugent scoring from 74 participants receiving an etonorgestrel/ethinyl estradiol (ENG/EE) intravaginal ring while on no ART (N=25), efavirenz-based ART (N=25), or atazanavir-based ART (N=24).

Natural Variation in HIV-1 Entry Kinetics Map to Specific Residues and Reveal an Interdependence Between Attachment and Fusion.

Unlabelled: HIV-1 entry kinetics reflect the fluid motion of the HIV envelope glycoprotein through at least three major structural configurations that drive virus-cell membrane fusion. The lifetime of each state is an important component of potency for inhibitors that target them. We used the time-of-addition inhibitor assay and a novel analytical strategy to define the kinetics of pre-hairpin exposure (using T20) and co-receptor engagement (via.

A phenotypic screening approach to target p60AmotL2-expressing invasive cancer cells.

Background: Tumor cells have the ability to invade and form small clusters that protrude into adjacent tissues, a phenomenon that is frequently observed at the periphery of a tumor as it expands into healthy tissues. The presence of these clusters is linked to poor prognosis and has proven challenging to treat using conventional therapies. We previously reported that p60AmotL2 expression is localized to invasive colon and breast cancer cells.

NK Cell-Monocyte Cross-talk Underlies NK Cell Activation in Severe COVID-19.

NK cells in the peripheral blood of severe COVID-19 patients exhibit a unique profile characterized by activation and dysfunction. Previous studies have identified soluble factors, including type I IFN and TGF-β, that underlie this dysregulation. However, the role of cell-cell interactions in modulating NK cell function during COVID-19 remains unclear.

Clinically relevant gene signatures provide independent prognostic information in older breast cancer patients.

Background: The clinical utility of gene signatures in older breast cancer patients remains unclear. We aimed to determine signature prognostic capacity in this patient subgroup.

Methods: Research versions of the genomic grade index (GGI), 70-gene, recurrence score (RS), cell cycle score (CCS), PAM50 risk-of-recurrence proliferation (ROR-P), and PAM50 signatures were applied to 39 breast cancer datasets (N = 9583).

Disruption of nontuberculous mycobacteria biofilms induces a highly vulnerable to antibiotic killing phenotype.

Objectives: Structural or mucus hypersecretory pulmonary diseases such as cystic fibrosis (CF), wherein viscous mucus accumulates and clearance functions are impaired, predispose people to lung infection by inhaled bacteria that form biofilm aggregates. Nontuberculous mycobacteria (NTM), primarily and are the growing cause of these lung infections and are extremely challenging to treat due to antibiotic recalcitrance. Better therapeutic approaches are urgently needed.

Metabolomic profiling of preterm birth in pregnant women living with HIV.

Background: Preterm birth is a leading cause of death in children under the age of five. The risk of preterm birth is increased by maternal HIV infection as well as by certain antiretroviral regimens, leading to a disproportionate burden on low- and medium-income settings where HIV is most prevalent. Despite decades of research, the mechanisms underlying spontaneous preterm birth, particularly in resource limited areas with high HIV infection rates, are still poorly understood and accurate prediction and therapeutic intervention remain elusive.

Efficacy, Safety, and Tolerability of Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate Fixed-Dose Combination Tablets in Adolescents Living With HIV: Results Through Week 96 from IMPAACT 2014.

Background: IMPAACT 2014 study is a phase I/II, multicenter, open-label, nonrandomized study of doravirine (DOR) co-formulated with lamivudine (3TC) and tenofovir disoproxil fumarate (TDF) as fixed-dose combination (DOR FDC) in adolescents with HIV-1. We report the efficacy, safety, and tolerability of DOR FDC through 96 weeks.

Methods: Participants were adolescents aged 12 to <18 years who weighed at least 45 kg and who were either antiretroviral (ARV)-naïve or virologically suppressed without documented resistance mutations to DOR/3TC/TDF.

Clot embolization studies and computational framework for embolization in a canonical tube model.

Despite recent advances in the development of computational methods of modeling thrombosis, relatively little effort has been made in developing methods of modeling blood clot embolization. Such a model would provide substantially greater understanding of the mechanics of embolization, as in-vitro and in-vivo characterization of embolization is difficult. Here, a method of computationally simulating embolization is developed.

Longitudinal relationship between the gut microbiota variation and diversity and gut graft-versus-host disease (GVHD) following pediatric allogeneic hematopoietic cell transplantation (HCT) - Case series.

Allogeneic Hematopoietic Cell Transplantation (HCT) offers children with life-threatening diseases a chance at survival. Complications from graft-versus-host disease (GVHD, Stages 0-4) represent a significant cause of morbidity and mortality which has been recently associated with gut dysbiosis the adult HCT population. Here, our objective was to conduct a prospective, longitudinal cohort study in nine pediatric allogeneic HCT participants by collecting longitudinally post-HCT stool specimens up to 1 year.

HIV-1 remission and possible cure in a woman after haplo-cord blood transplant.

Previously, two men were cured of HIV-1 through CCR5Δ32 homozygous (CCR5Δ32/Δ32) allogeneic adult stem cell transplant. We report the first remission and possible HIV-1 cure in a mixed-race woman who received a CCR5Δ32/Δ32 haplo-cord transplant (cord blood cells combined with haploidentical stem cells from an adult) to treat acute myeloid leukemia (AML). Peripheral blood chimerism was 100% CCR5Δ32/Δ32 cord blood by week 14 post-transplant and persisted through 4.

Persistent memory despite rapid contraction of circulating T Cell responses to SARS-CoV-2 mRNA vaccination.

Introduction: While antibodies raised by SARS-CoV-2 mRNA vaccines have had compromised efficacy to prevent breakthrough infections due to both limited durability and spike sequence variation, the vaccines have remained highly protective against severe illness. This protection is mediated through cellular immunity, particularly CD8+ T cells, and lasts at least a few months. Although several studies have documented rapidly waning levels of vaccine-elicited antibodies, the kinetics of T cell responses have not been well defined.

Spinal Cord Infarction With Prolonged Femoral Venoarterial Extracorporeal Membrane Oxygenation.

Objectives: There have been sporadic reports of ischemic spinal cord injury (SCI) during venoarterial extracorporeal membrane oxygenation (VA-ECMO) support. The authors observed a troubling pattern of this catastrophic complication and evaluated the potential mechanisms of SCI related to ECMO.

Design: This study was a case series.

Examining the universality of the hemolysis power law model from simulations of the FDA nozzle using calibrated model coefficients.

Computational fluid dynamics (CFD) is widely used to predict mechanical hemolysis in medical devices. The most popular hemolysis model is the stress-based power law model that is based on an empirical correlation between hemoglobin release from red blood cells (RBCs) and the magnitude of flow-induced stress and exposure time. Empirical coefficients are traditionally calibrated using data from experiments in simplified Couette-type blood-shearing devices with uniform-shear laminar flow and well-defined exposure times.

Toward modeling thrombosis and thromboembolism in laminar and turbulent flow regimes.

Thrombosis and thromboembolism are deadly risk factors in blood-contacting biomedical devices, and in-silico models of thrombosis are attractive tools to understand the mechanics of these processes, though the simulation of thromboembolism remains underdeveloped. The purpose of this study is to modify an existing computational thrombosis model to allow for thromboembolism and to investigate the behavior of the modified model at a range of flow rates. The new and existing models are observed to lead to similar predictions of thrombosis in a canonical backward-facing step geometry across flow rates, and neither model predicts thrombosis in a turbulent flow.

Pharmacokinetics, Tolerability, and Safety of Doravirine and Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate Fixed-Dose Combination Tablets in Adolescents Living With HIV: Week 24 Results From IMPAACT 2014.

Background: We studied the pharmacokinetics (PK) and safety of 100-mg doravirine and doravirine/lamivudine/tenofovir disoproxil fumarate fixed-dose combination (100/300/300 mg DOR FDC) treatment in adolescents with HIV-1.

Methods: Adolescents ages 12 to younger than 18 years were enrolled in 2 sequential cohorts. Cohort 1 evaluated intensive PK and short-term safety of 100-mg single-dose doravirine in adolescents ≥35 kg.

Gut dysbiosis and inflammatory blood markers precede HIV with limited changes after early seroconversion.

Background: Alterations in the gut microbiome have been associated with HIV infection, but the relative impact of HIV versus other factors on the gut microbiome has been difficult to determine in cross-sectional studies.

Methods: To address this, we examined the gut microbiome, serum metabolome, and cytokines longitudinally within 27 individuals before and during acute HIV using samples collected from several ongoing cohort studies. Matched control participants (n=28) from the same cohort studies without HIV but at similar behavioral risk were used for comparison.

Longitudinal Evaluation of Antibody Persistence in Mother-Infant Dyads After Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Pregnancy.

Background: There are limited data on how coronavirus disease 2019 (COVID-19) severity, timing of infection, and subsequent vaccination impact transplacental transfer and persistence of maternal and infant antibodies.

Methods: In a longitudinal cohort of pregnant women with polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, maternal/infant sera were collected at enrollment, delivery/birth, and 6 months. Anti-SARS-CoV-2 spike immunoglobulin (Ig)G, IgM, and IgA were measured by enzyme-linked immunosorbent assay.