Clinical and CSF single-cell profiling of post-COVID-19 cognitive impairment.

Natural history and mechanisms for persistent cognitive symptoms ("brain fog") following acute and often mild COVID-19 are unknown. In a large prospective cohort of people who underwent testing a median of 9 months after acute COVID-19 in the New York City/New Jersey area, we found that cognitive dysfunction is common; is not influenced by mood, fatigue, or sleepiness; and is correlated with MRI changes in very few people. In a subgroup that underwent cerebrospinal fluid analysis, there are no changes related to Alzheimer's disease or neurodegeneration.

A paracrine circuit of IL-1β/IL-1R1 between myeloid and tumor cells drives genotype-dependent glioblastoma progression.

Monocytes and monocyte-derived macrophages (MDMs) from blood circulation infiltrate glioblastoma (GBM) and promote growth. Here, we show that PDGFB-driven GBM cells induce the expression of the potent proinflammatory cytokine IL-1β in MDM, which engages IL-1R1 in tumor cells, activates the NF-κB pathway, and subsequently leads to induction of monocyte chemoattractant proteins (MCPs). Thus, a feedforward paracrine circuit of IL-1β/IL-1R1 between tumors and MDM creates an interdependence driving PDGFB-driven GBM progression.

Charting the Next Road Map for CSF Biomarkers in Alzheimer's Disease and Related Dementias.

Clinical prediction of underlying pathologic substrates in people with Alzheimer's disease (AD) dementia or related dementia syndromes (ADRD) has limited accuracy. Etiologic biomarkers - including cerebrospinal fluid (CSF) levels of AD proteins and cerebral amyloid PET imaging - have greatly modernized disease-modifying clinical trials in AD, but their integration into medical practice has been slow. Beyond core CSF AD biomarkers (including beta-amyloid 1-42, total tau, and tau phosphorylated at threonine 181), novel biomarkers have been interrogated in single- and multi-centered studies with uneven rigor.

Melanoma Cell Intrinsic GABA Receptor Enhancement Potentiates Radiation and Immune Checkpoint Inhibitor Response by Promoting Direct and T Cell-Mediated Antitumor Activity.

Purpose: Most patients with metastatic melanoma show variable responses to radiation therapy and do not benefit from immune checkpoint inhibitors. Improved strategies for combination therapy that leverage potential benefits from radiation therapy and immune checkpoint inhibitors are critical.

Methods And Materials: We analyzed metastatic melanoma tumors in the TCGA cohort for expression of genes coding for subunits of type A γ-aminobutyric acid (GABA) receptor (GABAR), a chloride ion channel and major inhibitory neurotransmitter receptor.

A Chimeric Signal Peptide-Galectin-3 Conjugate Induces Glycosylation-Dependent Cancer Cell-Specific Apoptosis.

Purpose: Exploitation of altered glycosylation in cancer is a major goal for the design of new cancer therapy. Here, we designed a novel secreted chimeric signal peptide-Galectin-3 conjugate (sGal-3) and investigated its ability to induce cancer-specific cell death by targeting aberrantly glycosylated cell surface receptors on cancer cells.

Experimental Design: sGal-3 was genetically engineered from Gal-3 by extending its N-terminus with a noncleavable signal peptide from tissue plasminogen activator.