Trehalose dimycolate inhibits phagosome maturation and promotes intracellular growth via noncanonical SNARE interaction.

Unlabelled: Mycobacterial cell envelopes are rich in unusual lipids and glycans that play key roles during infection and vaccination. The most abundant envelope glycolipid is trehalose dimycolate (TDM). TDM compromises the host response to mycobacterial species via multiple mechanisms, including inhibition of phagosome maturation.

Spatial distribution and isotopic signatures of N and C in mosses across Europe.

The accumulation of nitrogen (N) in moss tissue has proven to be a reliable marker of increasing N deposition. However, this measurement does not offer additional data about the origin of pollution. In this respect, the analysis of the N isotopic ratios might be a helpful tool in providing supplementary information about the nature of the nitrogenous species in biomonitoring surveys.

Impact of the Amount of Intravenous Glucose Administration on Hospitalization for Acute Gastroenteritis in a Pediatric Emergency Department.

Introduction: In case of failure of oral rehydration, children with acute gastroenteritis can be hydrated using intravenous (IV) solution. The choice of the intravenous solution itself (solutions containing dextrose versus crystalloids alone) and the glucose quantities to administer are not well established.

Objectives: The main objective of this study was to evaluate the association between the amount of intravenous glucose provided and hospitalization for children with acute gastroenteritis.

Spatial Architecture of Single-Cell and Vasculature in Tumor Microenvironment Predicts Clinical Outcomes in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited treatment options, which warrants the identification of novel therapeutic targets. Deciphering nuances in the tumor microenvironment (TME) may unveil insightful links between antitumor immunity and clinical outcomes; however, such connections remain underexplored. Here, we employed a data set derived from imaging mass cytometry of 71 TNBC patient specimens at single-cell resolution and performed in-depth quantifications with a suite of multiscale computational algorithms.

The Expression of Genes Related to Reverse Cholesterol Transport and Leptin Receptor Pathways in Peripheral Blood Mononuclear Cells Are Decreased in Morbid Obesity and Related to Liver Function.

Obesity is frequently accompanied by non-alcoholic fatty liver disease (NAFLD). These two diseases are associated with altered lipid metabolism, in which reverse cholesterol transport (LXRα/ABCA1/ABCG1) and leptin response (leptin receptor (Ob-Rb)/Sam68) are involved. The two pathways were evaluated in peripheral blood mononuclear cells (PBMCs) from 86 patients with morbid obesity (MO) before and six months after Roux-en-Y gastric bypass (RYGB) and 38 non-obese subjects.

Neratinib and ado-trastuzumab emtansine for pretreated and untreated human epidermal growth factor receptor 2 (HER2)-positive breast cancer brain metastases: Translational Breast Cancer Research Consortium trial 022.

Background: Treatment options for human epidermal growth factor receptor 2 (HER2)-positive breast cancer brain metastases (BCBMs) remain limited. We previously reported central nervous system (CNS) activity for neratinib and neratinib-capecitabine. Preclinical data suggest that neratinib may overcome resistance to ado-trastuzumab emtansine (T-DM1) when given in combination.

Virtual patient analysis identifies strategies to improve the performance of predictive biomarkers for PD-1 blockade.

Patients with metastatic triple-negative breast cancer (TNBC) show variable responses to PD-1 inhibition. Efficient patient selection by predictive biomarkers would be desirable, but is hindered by the limited performance of existing biomarkers. Here, we leveraged in-silico patient cohorts generated using a quantitative systems pharmacology model of metastatic TNBC, informed by transcriptomic and clinical data, to explore potential ways to improve patient selection.

Bi-level Graph Learning Unveils Prognosis-Relevant Tumor Microenvironment Patterns in Breast Multiplexed Digital Pathology.

The tumor microenvironment is widely recognized for its central role in driving cancer progression and influencing prognostic outcomes. There have been increasing efforts dedicated to characterizing this complex and heterogeneous environment, including developing potential prognostic tools by leveraging modern deep learning methods. However, the identification of generalizable data-driven biomarkers has been limited, in part due to the inability to interpret the complex, black-box predictions made by these models.

Analysis and prediction of long-term survival using a clinically applicable risk score based on the Electronic Health Record.

Background: The long-term survival of a population assigned to a hospital can be essential to anticipate, manage, and provide appropriate hospital healthcare resources or lead preventive actions for high-risk mortality individuals. In this study, we discriminate which electronic health record variables are most relevant to predict the long-term survival of a population, and apply the results to identify high-risk mortality groups.

Materials And Methods: A prospective cohort study was conducted on a population of 113,403 individuals alive on July 1st, 2018 from the General Hospital of Castellón (Spain).

Epithelial Expressed B7-H4 Drives Differential Immunotherapy Response in Murine and Human Breast Cancer.

Unlabelled: Combinations of immune checkpoint inhibitors (ICI, including anti-PD-1/PD-L1) and chemotherapy have been FDA approved for metastatic and early-stage triple-negative breast cancer (TNBC), but most patients do not benefit. B7-H4 is a B7 family ligand with proposed immunosuppressive functions being explored as a cancer immunotherapy target and may be associated with anti-PD-L1 resistance. However, little is known about its regulation and effect on immune cell function in breast cancers.

Mass, Spectroscopy, and Two-Neutron Decay of ^{16}Be.

The structure and decay of the most neutron-rich beryllium isotope, ^{16}Be, has been investigated following proton knockout from a high-energy ^{17}B beam. Two relatively narrow resonances were observed for the first time, with energies of 0.84(3) and 2.

Dendritic Cells as a Therapeutic Strategy in Acute Myeloid Leukemia: Vaccines.

Dendritic cells (DCs) serve as professional antigen-presenting cells (APC) bridging innate and adaptive immunity, playing an essential role in triggering specific cellular and humoral responses against tumor and infectious antigens. Consequently, various DC-based antitumor therapeutic strategies have been developed, particularly vaccines, and have been intensively investigated specifically in the context of acute myeloid leukemia (AML). This hematological malignancy mainly affects the elderly population (those aged over 65), which usually presents a high rate of therapeutic failure and an unfavorable prognosis.

Tissue-specific early and late activated lymphocytes immunophenotype in chronic rhinosinusitis with nasal polyps.

T-cell activation in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) is enriched by late cytotoxic T cells. The proportion of early and intermediate activated cytotoxic T cells decreases in nasal polyps of patients with CRSwNP. Our results identify late activated cytotoxic T cells as potential biomarkers or therapeutic targets for patients with CRSwNP.

Dendritic cells: the yin and yang in disease progression.

Dendritic cells (DCs) are antigen presenting cells that link innate and adaptive immunity. DCs have been historically considered as the most effective and potent cell population to capture, process and present antigens to activate naïve T cells and originate favorable immune responses in many diseases, such as cancer. However, in the last decades, it has been observed that DCs not only promote beneficial responses, but also drive the initiation and progression of some pathologies, including inflammatory bowel disease (IBD).

Atezolizumab in Combination With Carboplatin and Survival Outcomes in Patients With Metastatic Triple-Negative Breast Cancer: The TBCRC 043 Phase 2 Randomized Clinical Trial.

Importance: Agents targeting programmed death ligand 1 (PD-L1) have demonstrated efficacy in triple-negative breast cancer (TNBC) when combined with chemotherapy and are now the standard of care in patients with PD-L1-positive metastatic disease. In contrast to microtubule-targeting agents, the effect of combining platinum compounds with programmed cell death 1 (PD-1)/PD-L1 immunotherapy has not been extensively determined.

Objective: To evaluate the efficacy of atezolizumab with carboplatin in patients with metastatic TNBC.

Cryptic diversity and phylogeographic patterns of (Isopoda: Detonidae) in southern Africa.

Recent phylogeographic studies of poorly-dispersing coastal invertebrates in highly biodiverse regions have led to the discovery of high levels of cryptic diversity and complex phylogeographic patterns that suggest isolation, geological, and ecological processes have shaped their biodiversity. Studies of southern African coastal invertebrates have uncovered cryptic diversity for various taxa and phylogeographic patterns that, although sharing some similarities across taxa, do differ. These findings underscore the need for additional studies to better understand the biodiversity levels, distributional patterns, and processes responsible for producing coastal biodiversity in that region.

Strong Evidence for ^{9}N and the Limits of Existence of Atomic Nuclei.

The boundaries of the chart of nuclides contain exotic isotopes that possess extreme proton-to-neutron asymmetries. Here we report on strong evidence of ^{9}N, one of the most exotic proton-rich isotopes where more than one half of its constitute nucleons are unbound. With seven protons and two neutrons, this extremely proton-rich system would represent the first-known example of a ground-state five-proton emitter.

Coffee Colored Serum, Adverse Reaction of Eltrombopag.

Serum index and macroscopic characteristics of samples can give valuable information and should be interpreted as a result. Following centrifugation of the sample, on gross inspection it was observed that the serum had a brown color. After ruling out the main causes that can cause a brown coloration, such as intravascular hemolysis or high concentrations of methemoglobin, it was noted that the patient was receiving a high-dose of Eltrombopag therapy.