CAR-NK cell therapy: a potential antiviral platform.

Viral infections persist as a significant cause of morbidity and mortality worldwide. Conventional therapeutic approaches often fall short in fully eliminating viral infections, primarily due to the emergence of drug resistance. Natural killer (NK) cells, one of the important members of the innate immune system, possess potent immunosurveillance and cytotoxic functions, thereby playing a crucial role in the host's defense against viral infections.

A mini review of leveraging biobanking in the identification of novel biomarkers in neurological disorders: insights from a rapid single-cell sequencing pipeline.

Recent successes in the identification of biomarkers and therapeutic targets for diagnosing and managing neurological diseases underscore the critical need for cutting-edge biobanks in the conduct of high-caliber translational neuroscience research. Biobanks dedicated to neurological disorders are particularly timely, given the increasing prevalence of neurological disability among the rising aging population. Translational research focusing on disorders of the central nervous system (CNS) poses distinct challenges due to the limited accessibility of CNS tissue pre-mortem.

Policing Black autistic children: A qualitative approach to understanding Black caregivers' concerns.

In the United States, Black autistic youth face elevated risk of negative outcomes during police interactions. Although the outcomes of these interactions are well-documented, less is known about Black autistic youths' experiences during police encounters, as the current literature has largely examined the experiences of autistic adults, mostly White American samples, and/or autistic youth abroad. This study utilizes qualitative methods to examine the perceptions and concerns of 43 Black caregivers (N = 43; 98% parents; 2% legal guardians; 93% mothers) of Black autistic children (mean age: 16.

Tethered release of the pseudorabies virus deubiquitinase from the capsid promotes enzymatic activity.

Unlabelled: Herpesviruses carry an assortment of proteins in the interstitial space between the capsid and membrane envelope, collectively referred to as the tegument. Upon virion fusion with a cell, envelope integrity is disrupted, and many tegument constituents disperse into the cytosol to carry out individual effector functions, while others direct transport of the capsid to the nucleus. To gain insight into the tegument dynamics that occur with disruption of envelope integrity, we used a combination of single-particle fluorescence and biochemical approaches that leveraged the previously established use of n-ethylmaleimide to inhibit virion dynamics.

A PSMA-targeted Tri-specific Killer Engager enhances NK cell cytotoxicity against prostate cancer.

Natural killer (NK) cell tumor infiltration is associated with good prognosis in patients with metastatic castration-resistant prostate cancer (mCRPC). NK cells recognize and kill targets by a process called natural cytotoxicity. We hypothesized that promoting an antigen-specific synapse with co-activation may enhance NK cell function in mCRPC.

COVID-19 Prevention Practices and Vaccine Acceptability Among Hispanic and Non-Hispanic Households in an Agricultural Community-Washington, 2020.

Objective: To investigate COVID-19 disparities between Hispanic/Latino persons (H/L) and non-H/L persons in an agricultural community by examining behavioral and demographic differences.

Methods: In September 2020, we conducted Community Assessments for Public Health Emergency Response in Wenatchee and East Wenatchee, Washington, to evaluate differences between H/L and non-H/L populations in COVID-19 risk beliefs, prevention practices, household needs, and vaccine acceptability. We produced weighted sample frequencies.

Differential interactions of ethacrynic acid and diethyl maleate with glutathione S-transferases and their glutathione co-factor in the house fly.

Glutathione S-transferases (GSTs) are an important class of enzymes that facilitate the conjugation of reduced glutathione (GSH) with electrophilic substrates, including some insecticides. Two inhibitors of GSTs, ethacrynic acid (EA) and diethyl maleate (DEM), are often used as diagnostic tools to implicate GST involvement in insecticide resistance, but their modes of action against insect GSTs are largely assumed based on mammalian studies. In mammalian studies, there are two proposed mechanisms of inhibition of GST function by EA and DEM: 1) scavenging or "depleting" cytosolic GSH through non-enzymatic conjugation, and 2) inhibition of GST activity directly by the inhibitor-GSH conjugate (EA-SG and DEM-SG).

Metabolic programs drive function of therapeutic NK cells in hypoxic tumor environments.

Limited oxygen (hypoxia) in solid tumors poses a challenge to successful immunotherapy with natural killer (NK) cells. NK cells have impaired cytotoxicity when cultured in hypoxia (1% oxygen) but not physiologic (>5%) or atmospheric oxygen (20%). We found that changes to cytotoxicity were regulated at the transcriptional level and accompanied by metabolic dysregulation.

Adaptive behavior in primary agenesis of the corpus callosum.

Background And Aims: Primary agenesis of the corpus callosum (ACC) is a congenital neurological disorder characterized by the absence, either partial or complete, of the corpus callosum in individuals who do not have intellectual disability and are otherwise neurologically asymptomatic. While mild to moderate neurocognitive deficits have been observed in individuals with primary ACC using neuropsychological assessments, the impact of this syndrome on adaptive behavior remains insufficiently understood.

Methods: This study used self- and informant-ratings on the Adaptive Behavior Assessment System, Second Edition (ABAS-II) to evaluate adaptive behavior in 35 adults diagnosed with primary ACC.

Pharmacologic Hedgehog inhibition modulates the cytokine profile of osteolytic breast cancer cells.

The establishment and progression of bone metastatic breast cancer is supported by immunosuppressive myeloid populations that enable tumor growth by dampening the innate and adaptive immune response. Much work remains to understand how to target these tumor-myeloid interactions to improve treatment outcomes. Noncanonical Hedgehog signaling is an essential component of bone metastatic tumor progression, and prior literature suggests a potential role for Hedgehog signaling and its downstream effector Gli2 in modulating immune responses.

iPSC-derived NK cells expressing high-affinity IgG Fc receptor fusion CD64/16A to mediate flexible, multi-tumor antigen targeting for lymphoma.

Introduction: NK cells can mediate tumor cell killing by natural cytotoxicity and by antibody-dependent cell-mediated cytotoxicity (ADCC), an anti-tumor mechanism mediated through the IgG Fc receptor CD16A (FcγRIIIA). CD16A polymorphisms conferring increased affinity for IgG positively correlate with clinical outcomes during monoclonal antibody therapy for lymphoma, linking increased binding affinity with increased therapeutic potential via ADCC. We have previously reported on the FcγR fusion CD64/16A consisting of the extracellular region of CD64 (FcγRI), a high-affinity Fc receptor normally expressed by myeloid cells, and the transmembrane/cytoplasmic regions of CD16A, to create a highly potent and novel activating fusion receptor.

Measurement invariance of the PROMIS emotional distress and subjective well-being domains among autistic and General Population adolescents.

Purpose: Quality of life (QoL) is identified as a clinical and research priority by the autistic community. Researchers have the responsibility to ensure that instruments used to measure QoL do so reliably and accurately among autistic participants.

Methods: Our study evaluated measurement invariance of Emotional Distress (Depression, Anxiety, Anger, Psychological Stress) and Subjective Well-Being (Life Satisfaction, Positive Affect, and Meaning & Purpose) scales of the Patient-Reported Outcomes Measurement Information System (PROMIS) among groups of autistic (N=140, n per scale=132-140) and general population (N=1,224, n per scale=406-411) teenagers (14-17 years).

Enhanced IL-15-mediated NK cell activation and proliferation by an ADAM17 function-blocking antibody involves CD16A, CD137, and accessory cells.

Background: Natural killer (NK) cells are being extensively studied as a cell therapy for cancer. These cells are activated by recognition of ligands and antigens on tumor cells. Cytokine therapies, such as IL-15, are also broadly used to stimulate endogenous and adoptively transferred NK cells in patients with cancer.

JAK2/mTOR inhibition fails to prevent acute GVHD despite reduced Th1/Th17 cells: final phase 2 trial results.

Our phase 1 graft-versus-host disease (GVHD) prevention trial of JAK2 inhibitor, pacritinib (PAC; recommended phase 2 dose: 100 mg orally twice a day on day 0 to +70) plus sirolimus and tacrolimus (SIR/TAC) demonstrated the regimen was safe and free of pan-JAK myelosuppression after allogeneic hematopoietic cell transplantation (alloHCT). PAC inhibits interleukin 6 (IL-6) receptor activity and pathogenic T helper cell 1 (Th1)/Th17 differentiation in preclinical models and the phase 1 trial. Herein, we report on our completed phase 2 trial of PAC/SIR/TAC after 8/8 human leukocyte antigen matched alloHCT.

Missing Ethnicity and Language Information in Healthcare Records of Patients from the Asian Diaspora.

The electronic health record (EHR) should contain information to support culturally responsive care and research; however, the widely used default "Asian" demographic variable in most US social systems (including EHRs) lacks information to describe the diverse experience within the Asian diaspora (e.g., ethnicities, languages).

High-dimensional single-cell analysis of human natural killer cell heterogeneity.

Natural killer (NK) cells are innate lymphoid cells (ILCs) contributing to immune responses to microbes and tumors. Historically, their classification hinged on a limited array of surface protein markers. Here, we used single-cell RNA sequencing (scRNA-seq) and cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) to dissect the heterogeneity of NK cells.

Enhanced IL-15-mediated NK cell activation and proliferation by an ADAM17 function-blocking antibody involves CD16A, CD137, and accessory cells.

Background: NK cells are being extensively studied as a cell therapy for cancer. Their effector functions are induced by the recognition of ligands on tumor cells and by various cytokines. IL-15 is broadly used to stimulate endogenous and adoptively transferred NK cells in cancer patients.

Antibody-mediated cellular responses are dysregulated in Multisystem Inflammatory Syndrome in Children (MIS-C).

Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe complication of SARS-CoV-2 infection characterized by multi-organ involvement and inflammation. Testing of cellular function ex vivo to understand the aberrant immune response in MIS-C is limited. Despite strong antibody production in MIS-C, SARS-CoV-2 nucleic acid testing can remain positive for 4-6 weeks after infection.

Disparities in Epilepsy Diagnosis and Management in High-Income Countries: A Review of the Literature.

Purpose Of Review: Currently, an estimated 3.4 million people in the United States live with epilepsy. Previous studies have identified health disparities associated with race/ethnicity, socioeconomic status (SES), sex, insurance status, and age in this population.