Investigating the Influence of Covariates on Axicabtagene Ciloleucel (axi-cel) Kinetics in Patients with Non-Hodgkin's Lymphoma.

Background And Objective: Axicabtagene ciloleucel (axi-cel, Yescarta) is an autologous, anti-CD19, chimeric antigen receptor (CAR) T-cell therapy approved for patients with relapsed and refractory non-Hodgkin's lymphoma. Substantial inter-individual variability in cellular kinetics has been observed with CAR-T therapies and factors impacting CAR-T cellular kinetics remain poorly understood. This work reports a population cellular kinetic model of axi-cel in relapsed and patients with refractory non-Hodgkin's lymphoma and investigated the impact of covariates on early and late kinetic phases of CAR-T exposure.

The plant terpenes DMNT and TMTT function as signaling compounds that attract Asian corn borer (Ostrinia furnacalis) to maize plants.

During their co-evolution with herbivorous insects, plants have developed multiple defense strategies that resist pests, such as releasing a blend of herbivory-induced plant volatiles (HIPVs) that repel pests or recruit their natural enemies. However, the responses of insects to HIPVs in maize (Zea mays L.) are not well understood.

Serum high-density lipoprotein cholesterol levels predict early recurrence and prognosis of intrahepatic cholangiocarcinoma after surgical resection.

Introduction: Dysregulation in lipid metabolism contributes to the occurrence and development of various cancers. The connection between changes in lipid metabolism and the development of intrahepatic cholangiocarcinoma remains uncertain. Our objective was to investigate the significance of blood lipid levels in patients with intrahepatic cholangiocarcinoma who have undergone surgery.

4D Flow MRI of Portal Vein Hemodynamics in Healthy Volunteers and Patients with Chronic Liver Disease.

Aim: To identify age-matched healthy volunteers, non-cirrhotic chronic liver disease (CLD) and cirrhotic patients based on portal hemodynamic parameters using 4D flow MRI.

Methods: A total of 10 age-matched healthy volunteers and 69 CLD patients were enrolled and underwent 4D flow MRI prospectively. 4D flow MR images were processed by an MD in biomedical engineering working on the GTFlow platform.

Polydatin improves vascular endothelial function by maintaining mitochondrial homeostasis under high glucose conditions.

Previous studies have shown that polydatin (Poly) confer cardioprotective effects. However, its underlying mechanisms remain elusive. This study showed that Poly (10 µM) treatment reversed the high glucose (HG)-induced decrease in acetylcholine-elicited vasodilation in aortas.

Predicting Breast Cancer Subtypes Using Magnetic Resonance Imaging Based Radiomics With Automatic Segmentation.

Objective: The aim of the study is to demonstrate whether radiomics based on an automatic segmentation method is feasible for predicting molecular subtypes.

Methods: This retrospective study included 516 patients with confirmed breast cancer. An automatic segmentation-3-dimensional UNet-based Convolutional Neural Networks, trained on our in-house data set-was applied to segment the regions of interest.

Parallel Proteomic Comparison of Mutants With Altered Carbon Metabolism Reveals Hik8 Regulation of P Phosphorylation and Glycogen Accumulation in a Cyanobacterium.

Carbon metabolism is central to photosynthetic organisms and involves the coordinated operation and regulation of numerous proteins. In cyanobacteria, proteins involved in carbon metabolism are regulated by multiple regulators including the RNA polymerase sigma factor SigE, the histidine kinases Hik8, Hik31 and its plasmid-borne paralog Slr6041, and the response regulator Rre37. To understand the specificity and the cross-talk of such regulations, we simultaneously and quantitatively compared the proteomes of the gene knockout mutants for the regulators.

Computed tomography-based COVID-19 triage through a deep neural network using mask-weighted global average pooling.

Background: There is an urgent need to find an effective and accurate method for triaging coronavirus disease 2019 (COVID-19) patients from millions or billions of people. Therefore, this study aimed to develop a novel deep-learning approach for COVID-19 triage based on chest computed tomography (CT) images, including normal, pneumonia, and COVID-19 cases.

Methods: A total of 2,809 chest CT scans (1,105 COVID-19, 854 normal, and 850 non-3COVID-19 pneumonia cases) were acquired for this study and classified into the training set (n = 2,329) and test set (n = 480).

Spatial Proteome Reorganization of a Photosynthetic Model Cyanobacterium in Response to Abiotic Stresses.

Spatial proteome reorganization in response to a changing environment represents a different layer of adaptation mechanism in addition to differential expression of a subset of stress responsive genes in photosynthetic organisms. Profiling such reorganization events is critically important to extend our understanding how photosynthetic organisms adapt to adverse environments. Thus, we treated a unicellular photosynthetic model cyanobacterium, sp.

Five-year follow-up of ZUMA-1 supports the curative potential of axicabtagene ciloleucel in refractory large B-cell lymphoma.

In phase 2 of ZUMA-1, a single-arm, multicenter, registrational trial, axicabtagene ciloleucel (axi-cel) autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy demonstrated durable responses at 2 years in patients with refractory large B-cell lymphoma (LBCL). Here, we assessed outcomes in ZUMA-1 after 5 years of follow-up. Eligible adults received lymphodepleting chemotherapy followed by axi-cel (2 × 106 cells per kg).

Two-year follow-up of KTE-X19 in patients with relapsed or refractory adult B-cell acute lymphoblastic leukemia in ZUMA-3 and its contextualization with SCHOLAR-3, an external historical control study.

Background: Brexucabtagene autoleucel (KTE-X19) is an autologous anti-CD19 CAR T-cell therapy approved in the USA to treat adult patients with relapsed or refractory B-precursor acute lymphoblastic leukemia (R/R B-ALL) based on ZUMA-3 study results. We report updated ZUMA-3 outcomes with longer follow-up and an extended data set along with contextualization of outcomes to historical standard of care.

Methods: Adults with R/R B-ALL received a single infusion of KTE-X19 (1 × 10 CAR T cells/kg).

Efficacy and Safety of TKI Plus PD-1 Inhibitors in Elderly uHCC Patients: A Retrospective Study.

Purpose: To explore the efficacy and safety of sorafenib- or lenvatinib-based combination therapy with PD-1 inhibitors in elderly patients aged ≥75 years with unresectable hepatocellular carcinoma (uHCC).

Patients And Methods: Systemic therapy-naïve uHCC patients who received first-line sorafenib- or lenvatinib-based combination therapy with PD-1 inhibitors were continually reviewed. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) in accordance with the Response Evaluation Criteria in Solid Tumors version 1.

Proximity Labeling Facilitates Defining the Proteome Neighborhood of Photosystem II Oxygen Evolution Complex in a Model Cyanobacterium.

Ascorbate peroxidase (APEX)-based proximity labeling coupled with mass spectrometry has a great potential for spatiotemporal identification of proteins proximal to a protein complex of interest. Using this approach is feasible to define the proteome neighborhood of important protein complexes in a popular photosynthetic model cyanobacterium Synechocystis sp. PCC6803 (hereafter named as Synechocystis).

Deep learning-based automatic segmentation for size and volumetric measurement of breast cancer on magnetic resonance imaging.

Purpose: In clinical work, accurately measuring the volume and the size of breast cancer is significant to develop a treatment plan. However, it is time-consuming, and inter- and intra-observer variations among radiologists exist. The purpose of this study was to assess the performance of a Res-UNet convolutional neural network based on automatic segmentation for size and volumetric measurement of mass enhancement breast cancer on magnetic resonance imaging (MRI).

Limited diagnostic value of liver stiffness for clinically significant portal hypertension in HBV-related cirrhosis.

Purpose: Hepatic venous pressure gradient (HVPG) is the gold standard for portal pressure in cirrhosis, but most previous studies focused on the diagnostic value of clinically significant portal hypertension (CSPH) based on the correlation between liver stiffness (LS) and HVPG in hepatitis C virus (HCV) patients and alcoholic liver. Therefore, it is necessary to clarify the diagnostic value of LS for CSPH and the correlation with HVPG in hepatitis B virus (HBV) patients.

Methods: A total of 137 patients from the Fifth Medical Center of PLA General Hospital were divided into HBV group and non-HBV group according to etiology.

Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial.

High-risk large B-cell lymphoma (LBCL) has poor outcomes with standard first-line chemoimmunotherapy. In the phase 2, multicenter, single-arm ZUMA-12 study (ClinicalTrials.gov NCT03761056) we evaluated axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, as part of first-line treatment in 40 patients with high-risk LBCL.

Human mesenchymal stem cells treatment for severe COVID-19: 1-year follow-up results of a randomized, double-blind, placebo-controlled trial.

Background: The long-term consequences of human umbilical cord-derived mesenchymal stem cell (UC-MSC) treatment for COVID-19 patients are yet to be reported. This study assessed the 1-year outcomes in patients with severe COVID-19, who were recruited in our previous UC-MSC clinical trial.

Methods: In this prospective, longitudinal, cohort study, 100 patients enrolled in our phase 2 trial were prospectively followed up at 3-month intervals for 1 year to evaluate the long-term safety and effectiveness of UC-MSC treatment.

A Systematic Survey of the Light/Dark-dependent Protein Degradation Events in a Model Cyanobacterium.

Light is essential for photosynthetic organisms and is involved in the regulation of protein synthesis and degradation. The significance of light-regulated protein degradation is exemplified by the well-established light-induced degradation and repair of the photosystem II reaction center D1 protein in higher plants and cyanobacteria. However, systematic studies of light-regulated protein degradation events in photosynthetic organisms are lacking.

Earlier corticosteroid use for adverse event management in patients receiving axicabtagene ciloleucel for large B-cell lymphoma.

Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed or refractory large B-cell lymphoma (R/R LBCL). To reduce axi-cel-related toxicity, several exploratory safety management cohorts were added to ZUMA-1 (NCT02348216), the pivotal phase 1/2 study of axi-cel in refractory LBCL. Cohort 4 evaluated the rates and severity of cytokine release syndrome (CRS) and neurologic events (NEs) with earlier corticosteroid and tocilizumab use.

Berberine Reverses Nitroglycerin Tolerance through Suppressing Protein Kinase C Alpha Activity in Vascular Smooth Muscle Cells.

Purpose: The aim of this study was to evaluate the effects of berberine on nitroglycerin (NTG) tolerance and explore the underlying mechanism involved.

Methods: NTG tolerance was induced by pre-exposure of Sprague-Dawley rat aortas to NTG in vitro or by pretreating Sprague-Dawley rats with an NTG patch in vivo. The aortas were pre-treated with berberine or PKC inhibitors for different durations of time before induction of NTG tolerance.