Multimodal nanoparticle-containing modified suberoylanilide hydroxamic acid polymer conjugates to mitigate immune dysfunction in severe inflammation.

Excessive immune activation and immunosuppression are opposing factors that contribute to the dysregulated innate and adaptive immune responses seen in severe inflammation and sepsis. Here, a novel analog of the histone deacetylase inhibitor (HDACi), suberoylanilide hydroxamic acid (SAHA-OH), was incorporated into immunomodulatory poly(lactic acid)-based nanoparticles (iNP-SAHA) by employing a prodrug approach through the covalent modification of poly(lactic-co-glycolic acid) (PLGA) with SAHA-OH. iNP-SAHA formulation allowed for controlled incorporation and delivery of SAHA-OH from iNP-SAHA and treatment led to multimodal biological responses including significant reductions in proinflammatory cytokine secretions and gene expression, while increasing the survival of primary macrophages under lipopolysaccharide (LPS) challenge.

Holistic processing and face expertise after pediatric resection of occipitotemporal cortex.

The nature and extent of hemispheric lateralization and its potential for reorganization continues to be debated, although there is general agreement that there is a right hemisphere (RH) advantage for face processing in human adults. Here, we examined face processing and its lateralization in individuals with a single preserved occipitotemporal cortex (OTC), either in the RH or left hemisphere (LH), following early childhood resection for the management of drug-resistant epilepsy. The matched controls and those with a lesion outside of OTC evinced the standard superiority in processing upright over inverted faces and the reverse sensitivity to a nonface category (bicycles).

Enhancing oral squamous cell carcinoma prediction: the prognostic power of the worst pattern of invasion and the limited impact of molecular resection margins.

Objective: Oral squamous cell carcinoma (OSCC) originates from the mucosal lining of the oral cavity. Almost half of newly diagnosed cases are classified as advanced stage IV disease, which makes resection difficult. In this study, we investigated the pathological features and mutation profiles of tumor margins in OSCC.

DeepFreeze 3D-biofabrication for Bioengineering and Storage of Stem Cells in Thick and Large-Scale Human Tissue Analogs.

3D bioprinting holds great promise for meeting the increasing need for transplantable tissues and organs. However, slow printing, interlayer mixing, and the extended exposure of cells to non-physiological conditions in thick structures still hinder clinical applications. Here the DeepFreeze-3D (DF-3D) procedure and bioink for creating multilayered human-scale tissue mimetics is presented for the first time.

Microneedle array delivery of recapitulates bubonic plague.

Fleas transmit directly within the dermis of mammals to cause bubonic plague. Syringe-mediated inoculation is widely used to recapitulate bubonic plague and study pathogenesis. However, intradermal needle inoculation is tedious, error prone, and poses a significant safety risk for laboratorians.

Cortical Thin Patch Fraction Reflects Disease Burden in MS: The Mosaic Approach.

Background And Purpose: GM pathology plays an essential role in MS disability progression, emphasizing the importance of neuroradiologic biomarkers to capture the heterogeneity of cortical disease burden. This study aimed to assess the validity of a patch-wise, individual interpretation of cortical thickness data to identify GM pathology, the "mosaic approach," which was previously suggested as a biomarker for assessing and localizing atrophy.

Materials And Methods: We investigated the mosaic approach in a cohort of 501 patients with MS with respect to 89 internal and 651 external controls.

The lived experiences of individuals with postpartum psychosis: A qualitative analysis.

Postpartum psychosis (PP) is a severe psychiatric illness that occurs in about 1 to 2 per 1000 people in the perinatal period. To date, qualitative research investigating PP has focused on specific topics, such as treatment experiences or the impact of the illness on patients' lives and families. These studies have included small samples of women with histories of PP, often limited to certain geographical areas or treatment centers.

Concomitant assessment of PD-1 and CD56 expression identifies subsets of resting cord blood Vδ2 T cells with disparate cytotoxic potential.

Vγ9Vδ2 T lymphocytes are programmed for broad antimicrobial responses with rapid production of Th1 cytokines even before birth, and thus thought to play key roles against pathogens in infants. The process regulating Vδ2 cell acquisition of cytotoxic potential shortly after birth remains understudied. We observed that perforin production in cord blood Vδ2 cells correlates with phenotypes defined by the concomitant assessment of PD-1 and CD56.

Association of neighborhood gentrification with prostate cancer and immune markers in African American and European American men.

Background: Prior studies showed that neighborhood deprivation increases the risk of lethal prostate cancer. However, the role of neighborhood gentrification in prostate cancer development and outcome remains poorly understood. We examined the relationships of gentrification with prostate cancer and serum proteome-defined inflammation and immune function in a diverse cohort.

Safety and efficacy of the oral TLR8 agonist selgantolimod in individuals with chronic hepatitis B under viral suppression.

Background & Aims: Selgantolimod (GS-9688) is a Toll-like receptor 8 (TLR8) agonist that suppresses HBV in vitro. In a phase II study, we evaluated the safety and efficacy of weekly selgantolimod treatment in virally suppressed individuals with chronic HBV taking oral antiviral treatment.

Methods: Forty-eight patients were randomized into two cohorts (hepatitis B e antigen [HBeAg]-positive and -negative [n = 24 each]) to receive oral selgantolimod 3 mg, 1.

Peripheral immunity changes are associated with neurodegeneration and worse clinical outcome in idiopathic normal pressure hydrocephalus.

Background And Purpose: Idiopathic normal pressure hydrocephalus (iNPH) pathogenesis is multifactorial. Systemic inflammation might have a role in gathering clinical-pathological trajectories. We aimed to shape the peripheral immune profile of iNPH and establish correlations with cerebrospinal fluid (CSF) markers, ventricular enlargement, and clinical outcomes.

Addressing the disparities: the approach to the African American patient with multiple myeloma.

There are significant disparities with regards to incidence, timely diagnosis, access to treatment, clinical trial participation and health care utilization that negatively impact outcomes for African American patients with multiple myeloma. Health care providers have a role in ameliorating these disparities with thoughtful consideration of historical, sociocultural, individual and disease characteristics that influence the care provided to African American patient population. This review by a group of experts committed to health disparity in multiple myeloma provides a snapshot of disparities at both biologic and non-biologic levels, barriers to clinical care, and best practices to ensure that African American patients receive the best care available.

Substance-dependent EEG during recovery from anesthesia and optimization of monitoring.

The electroencephalographic (EEG) activity during anesthesia emergence contains information about the risk for a patient to experience postoperative delirium, but the EEG dynamics during emergence challenge monitoring approaches. Substance-specific emergence characteristics may additionally limit the reliability of commonly used processed EEG indices during emergence. This study aims to analyze the dynamics of different EEG indices during anesthesia emergence that was maintained with different anesthetic regimens.

A single C-terminal residue controls SARS-CoV-2 spike trafficking and incorporation into VLPs.

The spike (S) protein of SARS-CoV-2 is delivered to the virion assembly site in the ER-Golgi Intermediate Compartment (ERGIC) from both the ER and cis-Golgi in infected cells. However, the relevance and modulatory mechanism of this bidirectional trafficking are unclear. Here, using structure-function analyses, we show that S incorporation into virus-like particles (VLP) and VLP fusogenicity are determined by coatomer-dependent S delivery from the cis-Golgi and restricted by S-coatomer dissociation.

Identification of CT-based non-invasive radiomic biomarkers for overall survival prediction in oral cavity squamous cell carcinoma.

This study addresses the limited non-invasive tools for Oral Cavity Squamous Cell Carcinoma (OSCC) survival prediction by identifying Computed Tomography (CT)-based biomarkers to improve prognosis prediction. A retrospective analysis was conducted on data from 149 OSCC patients, including CT radiomics and clinical information. An ensemble approach involving correlation analysis, score screening, and the Sparse-L1 algorithm was used to select functional features, which were then used to build Cox Proportional Hazards models (CPH).

Characterization of CYP2B6 and CYP2A6 Pharmacogenetic Variation in Sub-Saharan African Populations.

Genetic variation in CYP2B6 and CYP2A6 is known to impact interindividual response to antiretrovirals, nicotine, and bupropion, among other drugs. However, the full catalogue of clinically relevant pharmacogenetic variants in these genes is yet to be established, especially across African populations. This study therefore aimed to characterize the star allele (haplotype) distribution in CYP2B6 and CYP2A6 across diverse and understudied sub-Saharan African (SSA) populations.

Methods for studying mammalian aquaporin biology.

Aquaporins (AQPs), transmembrane water-conducting channels, have earned a great deal of scrutiny for their critical physiological roles in healthy and disease cell states, especially in the biomedical field. Numerous methods have been implemented to elucidate the involvement of AQP-mediated water transport and downstream signaling activation in eliciting whole cell, tissue, and organ functional responses. To modulate these responses, other methods have been employed to investigate AQP druggability.

Exposure to violence and associated factors among abortion-seeking women - A multicentre study in Sweden during the Covid-19 pandemic.

Unlabelled: This study aimed to investigate factors associated with exposure to violence over the past 12 months among women seeking abortion.

Materials And Methods: We conducted a cross-sectional study, nested within a multi-center questionnaire survey, involving 623 abortion-seeking women in Sweden from January to June 2021. Descriptive statistics, bivariate analyses, and multivariate regression analysis (using odds ratios [OR] and 95% confidence intervals [CI]) were employed.

Genomic profiling of tissue and blood predicts survival outcomes in patients with resected pleural mesothelioma.

Purpose: Pleural mesothelioma (PM) is an aggressive tumor still considered incurable, in part due to the lack of predictive biomarkers. Little is known about the clinical implications of molecular alterations in resectable PM tissues and blood. Here, we characterized genetic alterations to identify prognostic and predictive biomarkers in patients with resected PM.

In Vivo Evaluation of Safety and Efficacy of Ethyl Cellulose-Ethanol Tissue Ablation in a Swine Cervix Model.

Current therapies for treating cervical dysplasia are often inaccessible in low and middle-income countries (LMICs), highlighting the need for novel low-cost therapies that can be delivered at the point of care. Ethanol ablation is a low-cost therapy designed to treat locoregional cancers, which we augmented into an ethyl cellulose (EC)-ethanol gel formulation to enhance its efficacy. Here, we evaluated whether EC-ethanol ablation is able to safely achieve an ablation zone comparable to thermocoagulation, a commonly used therapy for cervical dysplasia.

Disparities in outcomes between Black and White patients in North America with thoracic malignancies and COVID-19 infection (TERAVOLT).

Background: Patients with thoracic malignancies who develop COVID-19 infection have a higher hospitalization rate compared to the general population and to those with other cancer types, but how this outcome differs by race and ethnicity is relatively understudied.

Methods: The TERAVOLT database is an international, multi-center repository of cross-sectional and longitudinal data studying the impact of COVID-19 on individuals with thoracic malignancies. Patients from North America with thoracic malignancies and confirmed COVID-19 infection were included for this analysis of racial and ethnic disparities.

Cell and biomaterial delivery strategies to induce immune tolerance.

The prevalence of immune-mediated disorders, including autoimmune conditions and allergies, is steadily increasing. However, current therapeutic approaches are often non-specific and do not address the underlying pathogenic condition, often resulting in impaired immunity and a state of generalized immunosuppression. The emergence of technologies capable of selectively inhibiting aberrant immune activation in a targeted, antigen (Ag)-specific manner by exploiting the body's intrinsic tolerance pathways, all without inducing adverse side effects, holds significant promise to enhance patient outcomes.