CD137 agonism enhances anti-PD1 induced activation of expanded CD8 T cell clones in a neoadjuvant pancreatic cancer clinical trial.

Successful pancreatic ductal adenocarcinoma (PDAC) immunotherapy requires therapeutic combinations that induce quality T cells. Tumor microenvironment (TME) analysis following therapeutic interventions can identify response mechanisms, informing design of effective combinations. We provide a reference single-cell dataset from tumor-infiltrating leukocytes (TILs) from a human neoadjuvant clinical trial comparing the granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting allogeneic PDAC vaccine GVAX alone, in combination with anti-PD1 or with both anti-PD1 and CD137 agonist.

Analytical expressions of specific yield for shallow groundwater estimation and modeling.

Specific yield (S) is an essential hydrogeological parameter in groundwater-related modeling and estimation. In this study, we proposed several new analytical expressions of S to characterize the nonlinear variations of S under shallow groundwater environments, encompassing S for three-layered soil, transition zone S, and flux-dependent S (in Boussinesq-type equation). The proposed S expression for three-layered soils expanded the applicability of previous expressions for homogeneous soil.

Diagnostic value of dual-layer spectral detector CT parameters for differentiating high- from low-grade bladder cancer.

Objectives: This study aimed to investigate the diagnostic value of spectral parameters of dual-layer spectral detector computed tomography (DLCT) in distinguishing between low- and high-grade bladder cancer (BCa).

Methods: This single-center retrospective study included pathologically confirmed BCa patients who underwent preoperative contrast-enhanced DLCT. Patients were divided into low- and high-grade groups based on pathology.

Exploring Immune-Mediated Brain Function Abnormalities in Systemic Lupus Erythematosus: Neuroimaging Evidence of the Impact of Anti-Ribosomal P Protein Antibodies.

Rationale And Objectives: Neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the most severe complications of systemic lupus erythematosus (SLE), and its early biomarkers and immune mechanisms remain unclear. This study utilizes Resting-State functional magnetic resonance imaging (rs-fMRI) to explore early neuroimaging biomarkers and potential immune mechanisms of brain injury in SLE, with a particular focus on anti-ribosomal P protein antibody (ARPA).

Materials And Methods: A total of 47 SLE patients and 33 healthy controls (HCs) underwent rs-fMRI.

Zinc cadmium sulphide-based photoreforming of biomass-based monosaccharides to lactic acid and efficient hydrogen production.

Approaches that add value to biomass through the use of photoreforming reactions offer great opportunities for the efficient use of renewable resources. Here, we constructed a novel zinc cadmium sulphide/molybdenum dioxide-molybdenum carbide-carbon (ZnCdS-y/MoO-MoC-C) heterojunction which was applied to photoreforming of biomass-based monosaccharides for hydrogen and lactic acid production. Bandgap engineering effectively modulated the redox capacity of ZnCdS-y and exposed more (101) crystalline surfaces, which improved the lactic acid selectivity.

Prolonged Venous Transit on Perfusion Imaging is Associated with Longer Lengths of Stay in Acute Large Vessel Occlusions.

Background And Purpose: Prolonged venous transit (PVT+) is a marker of venous outflow; it is defined as the presence or absence of time-to-maximum ≥10 seconds timing in either the superior sagittal sinus or torcula. This novel perfusion imaging-based metric has been associated with higher odds of mortality and lower odds of functional recovery. This study aims to assess the relationship between PVT on admission perfusion imaging and length of hospital stay in large vessel occlusion strokes successfully reperfused with mechanical thrombectomy.

Upregulated let-7 expression in the follicular fluid of patients with endometriomas leads to dysfunction of granulosa cells through targeting of IGF1R.

Study Question: What molecular mechanisms underlie the decline in ovarian reserve as the number and quality of oocytes decrease in patients with ovarian endometriomas (OEM)?

Summary Answer: Elevated expression of the let-7 micro(mi)RNAs in the follicular microenvironment of OEM-affected ovaries targets the expression of type 1 insulin-like growth factor receptor (IGF1R) in granulosa cell (GC) and disrupts their proliferation, steroid hormone secretion levels, adenosine triphosphate (ATP) energy metabolism, and reactive oxygen species (ROS) oxidative stress levels.

What Is Known Already: Patients with OEM exhibit diminished ovarian reserve, characterized by reduced oocyte quantity and quality. Fibrotic changes in the ovarian tissue surrounding the OEM create a disruptive microenvironment for follicular growth and development.

ANK Deficiency-Mediated Cytosolic Citrate Accumulation Promotes Aortic Aneurysm.

Background: Disturbed metabolism and transport of citrate play significant roles in various pathologies. However, vascular citrate regulation and its potential role in aortic aneurysm (AA) development remain poorly understood.

Methods: Untargeted metabolomics by mass spectrometry was applied to identify upregulated metabolites of the tricarboxylic acid cycle in AA tissues of mice.

Role of Hypoperfusion Intensity Ratio in Vessel Occlusions: A Review on Safety and Clinical Outcomes.

The hypoperfusion intensity ratio (HIR) is a quantitative metric used in vascular occlusion imaging to evaluate the extent of brain tissue at risk due to hypoperfusion. Defined as the ratio of tissue volume with a time-to-maximum (Tmax) of >10 seconds to that of >6 seconds, HIR assists in differentiating between the salvageable penumbra and the irreversibly injured core infarct. This review explores the role of HIR in assessing clinical outcomes and guiding treatment strategies, including mechanical thrombectomy and thrombolytic therapy, for patients with large vessel occlusions (LVOs).

Preclinical Profile of the HIV-1 Maturation Inhibitor VH3739937.

The HIV-1 maturation inhibitor (MI) VH3739937 (VH-937) inhibits cleavage between capsid and spacer peptide 1 and exhibits an oral half-life in humans compatible with once-weekly dosing. Here, the antiviral properties of VH-937 are described. VH-937 exhibited potent antiviral activity against all HIV-1 laboratory strains, clinical isolates, and recombinant viruses examined, with half-maximal effective concentration (EC) values ≤ 5.

Promoting elemental mercury immobilization performance from smelting flue gas over a wide temperature range via cobalt-doped copper sulfide adsorbents.

Copper sulfide (CuS) sorbent exhibits great potential for gaseous elemental mercury (Hg) decontamination, but it still suffers from a narrow operating temperature. Therefore, designing advanced CuS sorbents that have a high activity level for capturing Hg and thermal stability at a high temperature range is challenging. Herein, we propose a metal doping strategy to fabricate a bimetallic sulfide adsorbent.

Diagnostic Utility of a 90-Gene Expression Assay (Canhelp-Origin) for Patients with Metastatic Cancer with an Unclear or Unknown Diagnosis.

Background: Metastatic cancers with unclear or unknown origins pose significant challenges in diagnosis and management, frequently leading to suboptimal outcomes. Studies have demonstrated that a 90-gene expression assay is effective in predicting the primary origin and guiding the site-specific therapy to improve prognosis. This study aimed to evaluate the clinical effectiveness of a 90-gene expression assay in patients with unclear or unknown diagnoses.

Sacubitril/Valsartan in Pediatric Heart Failure (PANORAMA-HF): A Randomized, Multicenter, Double-Blind Trial.

Background: Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), is an established treatment for heart failure (HF) with reduced left ventricular ejection fraction. It has not been rigorously compared with angiotensin-converting enzyme inhibitors in children. PANORAMA-HF (Prospective Trial to Assess the Angiotensin Receptor Blocker Neprilysin Inhibitor LCZ696 Versus Angiotensin-Converting Enzyme Inhibitor for the Medical Treatment of Pediatric HF) is a randomized, double-blind trial that evaluated the pharmacokinetics and pharmacodynamics (PK/PD), safety, and efficacy of sacubitril/valsartan versus enalapril in children 1 month to <18 years of age with HF attributable to systemic left ventricular systolic dysfunction (LVSD).

Conditional survival and changing risk profile in patients with gliosarcoma.

Background: Conditional survival (CS) considers the duration since the initial diagnosis and can provide supplementary informative insights. Our objective was to evaluate CS among gliosarcoma (GSM) patients and develop a CS-incorporated nomogram to predict the conditional probability of survival.

Methods: This retrospective study using the Surveillance, Epidemiology, and End Results (SEER) database included patients with GSM between 2000 and 2017.

The Alzheimer's Association Global Biomarker Standardization Consortium (GBSC) plasma phospho-tau Round Robin study.

Background: Phosphorylated tau (p-tau) is a specific blood biomarker for Alzheimer's disease (AD) pathology. Multiple p-tau biomarkers on several analytical platforms are poised for clinical use. The Alzheimer's Association Global Biomarker Standardisation Consortium plasma phospho-tau Round Robin study engaged assay developers in a blinded case-control study on plasma p-tau, aiming to learn which assays provide the largest fold-changes in AD compared to non-AD, have the strongest relationship between plasma and cerebrospinal fluid (CSF), and show the most consistent relationships between methods (commutability) in measuring both patient samples and candidate reference materials (CRM).

Ultra-Wide Interlayered WMoS Alloy Electrode Patterning through High-Precision Controllable Photonic-Synthesis.

Ultra-thin 2D materials have great potential as electrodes for micro-supercapacitors (MSCs) because of their facile ion transport channels. Here, a high-precision controllable photonic-synthesis strategy that provided 1 inch wafer-scale ultra-thin film arrays of alloyed WMoS with sulfur vacancies and expanded interlayer (13.2 Å, twice of 2H MoS) is reported.

Lysozyme 1 Inflamed CCR2 Macrophages Promote Obesity-Induced Cardiac Dysfunction.

Background: Macrophages are key players in obesity-associated cardiovascular diseases, which are marked by inflammatory and immune alterations. However, the pathophysiological mechanisms underlying macrophage's role in obesity-induced cardiac inflammation are incompletely understood. Our study aimed to identify the key macrophage population involved in obesity-induced cardiac dysfunction and investigate the molecular mechanism that contributes to the inflammatory response.

Effect of Activated Charcoal on Mavacamten Pharmacokinetics in Healthy Participants.

Objective: To assess the effect of activated charcoal on the single-dose pharmacokinetics of mavacamten when administered 2 h or 6 h after mavacamten dosing.

Methods: In this open-label, randomized, parallel-group study, healthy adults were randomized into three groups to receive mavacamten 15 mg alone or mavacamten 15 mg plus activated charcoal 50 g administered either 2 h or 6 h after mavacamten dosing. Pharmacokinetic parameters were derived from plasma concentration-time data using noncompartmental methods.

Protocol for performing deep learning-based fundus fluorescein angiography image analysis with classification and segmentation tasks.

Fundus fluorescein angiography (FFA) examinations are widely used in the evaluation of fundus disease conditions to facilitate further treatment suggestions. Here, we present a protocol for performing deep learning-based FFA image analytics with classification and segmentation tasks. We describe steps for data preparation, model implementation, statistical analysis, and heatmap visualization.

Multi-dimensional cell-free DNA-based liquid biopsy for sensitive early detection of gastric cancer.

Background: Gastric cancer is the fifth most common cancer type. Most patients are diagnosed at advanced stages with poor prognosis. A non-invasive assay for the detection of early-stage gastric cancer is highly desirable for reducing associated mortality.

Comparing Outcomes of Thrombectomy Versus Intravenous Thrombolysis Based on Middle Cerebral Artery M2 Occlusion Features.

Background: Current evidence provides limited support for the superiority of endovascular thrombectomy (EVT) in patients with M2 segment middle cerebral artery occlusion. We aim to investigate whether imaging features of M2 segment occlusion impact the effectiveness of EVT.

Methods: We conducted a retrospective cohort study from January 2017 to January 2022, drawing data from the CASE II registry (Computer-Based Online Database of Acute Stroke Patients for Stroke Management Quality Evaluation), which specifically documented patients with acute ischemic stroke presenting with M2 segment occlusion undergoing reperfusion therapy.

Ultrapotent Broadly Neutralizing Human-llama Bispecific Antibodies against HIV-1.

Broadly neutralizing antibodies are proposed as therapeutic and prophylactic agents against HIV-1, but their potency and breadth are less than optimal. This study describes the immunization of a llama with the prefusion-stabilized HIV-1 envelope (Env) trimer, BG505 DS-SOSIP, and the identification and improvement of potent neutralizing nanobodies recognizing the CD4-binding site (CD4bs) of vulnerability. Two of the vaccine-elicited CD4bs-targeting nanobodies, G36 and R27, when engineered into a triple tandem format with llama IgG2a-hinge region and human IgG1-constant region (G36×3-IgG2a and R27×3-IgG2a), neutralized 96% of a multiclade 208-strain panel at geometric mean ICs of 0.