Molecular dynamics at immune synapse lipid rafts influence the cytolytic behavior of CAR T cells.

Chimeric antigen receptor T cells (CART) targeting CD19 through CD28.ζ signaling induce rapid lysis of leukemic blasts, contrasting with persistent tumor control exhibited by 4-1BB.ζ-CART.

The association of vaping and electronic cigarette use with postoperative hypoxemia and respiratory complications: a retrospective cohort analysis.

Purpose: Initially introduced as a safer alternative to smoking, electronic cigarettes (e-cigarettes) and vaping have since been associated with lung injury. Nevertheless, there is limited perioperative data on their potential contribution to the harmful effects of mechanical ventilation on the lungs. We hypothesized that, in adults undergoing noncardiothoracic surgeries, preoperative vaping/e-cigarette use is associated with hypoxemia during the first postoperative hour, and with an increased incidence of intraoperative and postoperative pulmonary complications.

PostFocus: automated selective post-acquisition high-throughput focus restoration using diffusion model for label-free time-lapse microscopy.

Motivation: High-throughput time-lapse imaging is a fundamental tool for efficient living cell profiling at single-cell resolution. Label-free phase-contrast video microscopy enables noninvasive, nontoxic, and long-term imaging. The tradeoff between speed and throughput, however, implies that despite the state-of-the-art autofocusing algorithms, out-of-focus cells are unavoidable due to the migratory nature of immune cells (velocities >10 μm/min).

CD28 Costimulation Augments CAR Signaling in NK Cells via the LCK/CD3ζ/ZAP70 Signaling Axis.

Multiple factors in the design of a chimeric antigen receptor (CAR) influence CAR T-cell activity, with costimulatory signals being a key component. Yet, the impact of costimulatory domains on the downstream signaling and subsequent functionality of CAR-engineered natural killer (NK) cells remains largely unexplored. Here, we evaluated the impact of various costimulatory domains on CAR-NK cell activity, using a CD70-targeting CAR.

Identification of a clinically efficacious CAR T cell subset in diffuse large B cell lymphoma by dynamic multidimensional single-cell profiling.

Chimeric antigen receptor (CAR) T cells used for the treatment of B cell malignancies can identify T cell subsets with superior clinical activity. Here, using infusion products of individuals with large B cell lymphoma, we integrated functional profiling using timelapse imaging microscopy in nanowell grids with subcellular profiling and single-cell RNA sequencing to identify a signature of multifunctional CD8 T cells (CD8-fit T cells). CD8-fit T cells are capable of migration and serial killing and harbor balanced mitochondrial and lysosomal volumes.

Relationship between sociodemographic, clinical, and laboratory characteristics and severity of COVID-19 in pediatric patients.

COVID-19 affects children less seriously than adults; however, severe cases and deaths are documented. This study objective is to determine socio-demographic, clinical and laboratory indicators associated with severe pediatric COVID-19 and mortality at hospital entrance. A multicenter, retrospective, cross-sectional study was performed in 13 tertiary hospitals in Bolivia.

Paraneoplastic/autoimmune myelopathies.

Paraneoplastic myelopathies are a rare but important category of myelopathy. They usually present with an insidious or subacute progressive neurologic syndrome. Risk factors include tobacco use and family history of cancer.

Decoding the mechanisms of chimeric antigen receptor (CAR) T cell-mediated killing of tumors: insights from granzyme and Fas inhibition.

Chimeric antigen receptor (CAR) T cell show promise in cancer treatments, but their mechanism of action is not well understood. Decoding the mechanisms used by individual T cells can help improve the efficacy of T cells while also identifying mechanisms of T cell failure leading to tumor escape. Here, we used a suite of assays including dynamic single-cell imaging of cell-cell interactions, dynamic imaging of fluorescent reporters to directly track cytotoxin activity in tumor cells, and scRNA-seq on patient infusion products to investigate the cytotoxic mechanisms used by individual CAR T cells in killing tumor cells.

Receiver operating characteristic (ROC) to determine cut-off points of clinical and biomolecular markers to discriminate mortality in severe COVID-19 living at high altitude.

Background: In 2020, Ecuador had one of the highest death rates because of COVID-19. The role of clinical and biomolecular markers in COVID disease prognosis, is still not well supported by available data. In order for these markers to have practical application in clinical decision-making regarding patient treatment and prognosis, it is necessary to know an optimal cut-off point, taking into consideration ethnic differences and geographic conditions.

Progressive multifocal leukoencephalopathy without overt immunosuppression.

Progressive multifocal leukoencephalopathy (PML) is a central nervous system disease caused by the human polyomavirus 2 that usually occurs in a setting of immunodeficiency. PML without overt immunosuppression is considered a rare occurrence but has been described in multiple previous case reports and series. Its prevalence, overall frequency, and prognosis are largely unknown.

Generalizability of nociception level as a measure of intraoperative nociceptive stimulation: A retrospective analysis.

Background: Nociception-guided intraoperative opioid administration might help reduce postoperative pain. A commonly used and validated nociception monitor system is nociception level (NOL), which provides the nociception index, ranging from 0 to 100, with 0 representing no nociception and 100 representing extreme nociception. We tested the hypothesis that NOL responses are similar in men and women given remifentanil and fentanyl, across various types of anesthesia, as a function of American Society of Anesthesiologists physical status designations, and over a range of ages and body morphologies.

Identifying signatures of EV secretion in metastatic breast cancer through functional single-cell profiling.

Extracellular vesicles (EVs) regulate the tumor microenvironment by facilitating transport of biomolecules. Despite extensive investigation, heterogeneity in EV secretion among cancer cells and the mechanisms that support EV secretion are not well characterized. We developed an integrated method to identify individual cells with differences in EV secretion and performed linked single-cell RNA-sequencing on cloned single cells from the metastatic breast cancer cells.

Nociception Level Index-Guided Intraoperative Analgesia for Improved Postoperative Recovery: A Randomized Trial.

Background: Nociception is the physiological response to nociceptive stimuli, normally experienced as pain. During general anesthesia, patients experience and respond to nociceptive stimuli by increasing blood pressure and heart rate if not controlled by preemptive analgesia. The PMD-200 system from Medasense (Ramat Gan, Israel) evaluates the balance between nociceptive stimuli and analgesia during general anesthesia and generates the nociception level (NOL) index from a single finger probe.

Cerebral Cortical Encephalitis in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.

Cerebral cortical encephalitis (CCE) is a recently described myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) phenotype. In this observational retrospective study, we characterized 19 CCE patients (6.7% of our MOGAD cohort).

Acute symptomatic seizures secondary to myelin oligodendrocyte glycoprotein antibody-associated disease.

Objective: To report the clinical presentations and outcomes of patients with seizure and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).

Methods: We retrospectively reviewed the electronic medical records for clinical and paraclinical features among patients with seizures and MOG-IgG (immunoglobulin G) seropositivity.

Results: We identified 213 patients with MOG-IgG seropositivity who fulfilled criteria for MOGAD.

Septin-5 and -7-IgGs: Neurologic, Serologic, and Pathophysiologic Characteristics.

Background And Objectives: We sought to determine clinical significance of neuronal septin autoimmunity and evaluate for potential IgG effects.

Methods: Septin-IgGs were detected by indirect immunofluorescence assays (IFAs; mouse tissue and cell based) or Western blot. IgG binding to (and internalization of) extracellular septin epitopes were evaluated for by live rat hippocampal neuron assay.

Disseminated paracoccidioidomycosis associated with lymph node tuberculosis in a non immunocompromised child.

The association of paracoccidioidomycosis (PCM) and tuberculosis (TB) produces an uncommon hyperinflammatory syndrome, causing multiorgan dysfunction. TB associated PCM is a rare condition, but it is fatal if not treated. Herein, we present a immunocompetent child who is admitted for fever and painful lymphadenopathy, with evidence of acid-alcohol-resistant bacillus (AARB) in cervical lymph node biopsy, antituberculous treatment was started with partial clinical improvement and is given discharge from hospital.