XCal: model-based approach to X-ray CT spectral calibration.

Transmission X-ray computed tomography (CT) is widely used to quantitatively reconstruct 3D objects composed of multiple materials. However, accurate CT reconstruction requires the system to be calibrated to account for the effective X-ray spectrum. Unfortunately, measurement of the effective spectrum is ill-posed, and existing calibration methods require that the system be recalibrated when the system parameters are changed.

Disparities in clinical trial enrollment related to laser interstitial thermal therapy for central nervous system metastases.

Objective: Laser interstitial thermal therapy (LITT) is a minimally invasive option for the management of a variety of intracranial pathologies, including radiographically progressive tumor following stereotactic radiosurgery. Although LITT has been increasingly accepted in recent years, little is known regarding selection and outcomes for patients of diverse backgrounds, particularly at centers specializing in central nervous system (CNS) metastases.

Methods: Patients receiving their index LITT treatment for brain metastasis at a single center from 2015 to 2023 were retrospectively reviewed.

Age-associated differences in mucosal and systemic host responses to SARS-CoV-2 infection.

Age is among the strongest risk factors for severe outcomes from SARS-CoV-2 infection. Here we describe upper respiratory tract (URT) and peripheral blood transcriptomes of 202 participants (age range of 1 week to 83 years), including 137 non-hospitalized individuals with mild SARS-CoV-2 infection and 65 healthy individuals. Among healthy children and adolescents, younger age is associated with higher URT expression of innate and adaptive immune pathways.

Temporal Shift Module (TSM) Based Automatic Fall Detection with Bounding Box Grounding.

Fall detection is one of the important tenets of remote geriatric care operations. Fall is one of the main causes of injury in old individuals leading to fractures, concussions, and different issues that might lead to prompt demise. In a world increasingly making the elderly live in isolation, accurate and real-time detection of falls is very important to remote caregivers to be able to provide timely medical assistance.

Differential host responses within the upper respiratory tract and peripheral blood of children and adults with SARS-CoV-2 infection.

Unlabelled: Age is among the strongest risk factors for severe outcomes from SARS-CoV-2 infection. We sought to evaluate associations between age and both mucosal and systemic host responses to SARS-CoV-2 infection. We profiled the upper respiratory tract (URT) and peripheral blood transcriptomes of 201 participants (age range of 1 week to 83 years), including 137 non-hospitalized individuals with mild SARS-CoV-2 infection and 64 uninfected individuals.

CD8 T cells maintain killing of MHC-I-negative tumor cells through the NKG2D-NKG2DL axis.

The accepted paradigm for both cellular and anti-tumor immunity relies upon tumor cell killing by CD8 T cells recognizing cognate antigens presented in the context of target cell major histocompatibility complex (MHC) class I (MHC-I) molecules. Likewise, a classically described mechanism of tumor immune escape is tumor MHC-I downregulation. Here, we report that CD8 T cells maintain the capacity to kill tumor cells that are entirely devoid of MHC-I expression.

Interdependencies of the Neuronal, Immune and Tumor Microenvironment in Gliomas.

Gliomas are the most common primary brain malignancy and are universally fatal. Despite significant breakthrough in understanding tumor biology, treatment breakthroughs have been limited. There is a growing appreciation that major limitations on effective treatment are related to the unique and highly complex glioma tumor microenvironment (TME).

Dendritic cell vaccine trials in gliomas: Untangling the lines.

Glioblastoma is a deadly brain tumor without any significantly successful treatments to date. Tumor antigen-targeted immunotherapy platforms including peptide and dendritic cell (DC) vaccines, have extended survival in hematologic malignancies. The relatively "cold" tumor immune microenvironment and heterogenous nature of glioblastoma have proven to be major limitations to translational application and efficacy of DC vaccines.

Novel Immunotherapeutic Approaches for the Treatment of Glioblastoma.

Glioblastoma is highly aggressive and remains difficult to treat despite being the most common malignant primary brain tumor in adults. Current standard-of-care treatment calls for maximum resection of the tumor mass followed by concurrent chemotherapy and radiotherapy and further adjuvant chemotherapy if necessary. Despite this regimen, prognosis remains grim.

Age and Comorbidities Predict COVID-19 Outcome, Regardless of Innate Immune Response Severity: A Single Institutional Cohort Study.

Unlabelled: The COVID-19 pandemic has claimed over eight hundred thousand lives in the United States alone, with older individuals and those with comorbidities being at higher risk of severe disease and death. Although severe acute respiratory syndrome coronavirus 2-induced hyperinflammation is one of the mechanisms underlying the high mortality, the association between age and innate immune responses in COVID-19 mortality remains unclear.

Design: Flow cytometry of fresh blood and multiplexed inflammatory chemokine measurements of sera were performed on samples collected longitudinally from our cohort.

Multicenter randomized phase II trial of atezolizumab with or without cobimetinib in biliary tract cancers.

BACKGROUNDMEK inhibitors have limited activity in biliary tract cancers (BTCs) as monotherapy but are hypothesized to enhance responses to programmed death ligand 1 (PD-L1) inhibition.METHODSThis open-label phase II study randomized patients with BTC to atezolizumab (anti-PD-L1) as monotherapy or in combination with cobimetinib (MEK inhibitor). Eligible patients had unresectable BTC with 1 to 2 lines of prior therapy in the metastatic setting, measurable disease, and Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1.

For whom the T cells troll? Bispecific T-cell engagers in glioblastoma.

Glioblastoma is the the most common primary brain tumor in adults. Onset of disease is followed by a uniformly lethal prognosis and dismal overall survival. While immunotherapies have revolutionized treatment in other difficult-to-treat cancers, these have failed to demonstrate significant clinical benefit in patients with glioblastoma.

Enhancing T Cell Chemotaxis and Infiltration in Glioblastoma.

Glioblastoma is an immunologically 'cold' tumor, which are characterized by absent or minimal numbers of tumor-infiltrating lymphocytes (TILs). For those tumors that have been invaded by lymphocytes, they are profoundly exhausted and ineffective. While many immunotherapy approaches seek to reinvigorate immune cells at the tumor, this requires TILs to be present.

The safety and efficacy of dexamethasone in the perioperative management of glioma patients.

Objective: In this single-institution retrospective cohort study, the authors evaluated the effect of dexamethasone on postoperative complications and overall survival in patients with glioma undergoing resection.

Methods: A total of 435 patients who underwent resection of a primary glioma were included in this retrospective cohort study. The inclusion criterion was all patients who underwent resection of a primary glioma at a tertiary medical center between 2014 and 2019.

Mixture Model Framework for Traumatic Brain Injury Prognosis Using Heterogeneous Clinical and Outcome Data.

Prognoses of Traumatic Brain Injury (TBI) outcomes are neither easily nor accurately determined from clinical indicators. This is due in part to the heterogeneity of damage inflicted to the brain, ultimately resulting in diverse and complex outcomes. Using a data-driven approach on many distinct data elements may be necessary to describe this large set of outcomes and thereby robustly depict the nuanced differences among TBI patients' recovery.

Targeting Immunometabolism in Glioblastoma.

We have only recently begun to understand how cancer metabolism affects antitumor responses and immunotherapy outcomes. Certain immunometabolic targets have been actively pursued in other tumor types, however, glioblastoma research has been slow to exploit the therapeutic vulnerabilities of immunometabolism. In this review, we highlight the pathways that are most relevant to glioblastoma and focus on how these immunometabolic pathways influence tumor growth and immune suppression.

Development, Practice Patterns, and Early Clinical Outcomes of a Multidisciplinary Liver Cancer Clinic.

Multidisciplinary care has been associated with improved survival in patients with primary liver cancers. We report the practice patterns and real world clinical outcomes for patients presenting to the Johns Hopkins Hospital (JHH) multidisciplinary liver clinic (MDLC). We analyzed hepatocellular carcinoma (HCC, n = 100) and biliary tract cancer (BTC, n = 76) patients evaluated at the JHH MDLC in 2019.

Tumor and Systemic Immunomodulatory Effects of MEK Inhibition.

Purpose Of Review: Mitogen-activated protein kinase (MAPK) kinase (MEK) is an integral component of the RAS signaling pathway, one of the most frequently mutated pathways in cancer biology. MEK inhibitors were initially developed to directly target oncogenic signaling, but are recognized to have pleiotropic effects on both tumor cells and lymphocytes. Here, we review the preclinical and clinical evidence that MEK inhibition is immunomodulatory and discuss the potential rationale for combining MEK inhibitors with systemic immunotherapies.

MEK inhibition suppresses B regulatory cells and augments anti-tumor immunity.

Mitogen-activated protein kinase (MAPK) kinase (MEK) is an integral component of the RAS pathway and a therapeutic target in RAS-driven cancers. Although tumor responses to MEK inhibition are rarely durable, MEK inhibitors have shown substantial activity and durable tumor regressions when combined with systemic immunotherapies in preclinical models of RAS-driven tumors. MEK inhibitors have been shown to potentiate anti-tumor T cell immunity, but little is known about the effects of MEK inhibition on other immune subsets, including B cells.

Publisher Correction: Smac mimetics synergize with immune checkpoint inhibitors to promote tumour immunity against glioblastoma.

This corrects the article DOI: 10.1038/ncomms14278.