Single-cell data-driven design of armed oncolytic virus to boost cooperative innate-adaptive immunity against cancer.

Oncolytic viruses have been considered promising cancer immunotherapies. However, oncovirotherapy agents impart durable responses in only a subset of cancer patients. Thus, exploring the cellular and molecular mechanisms underlying the heterogeneous responses in patients can provide guidance to develop more effective oncolytic virus therapies.

Neoadjuvant PARPi or chemotherapy in ovarian cancer informs targeting effector Treg cells for homologous-recombination-deficient tumors.

Homologous recombination deficiency (HRD) is prevalent in cancer, sensitizing tumor cells to poly (ADP-ribose) polymerase (PARP) inhibition. However, the impact of HRD and related therapies on the tumor microenvironment (TME) remains elusive. Our study generates single-cell gene expression and T cell receptor profiles, along with validatory multimodal datasets from >100 high-grade serous ovarian cancer (HGSOC) samples, primarily from a phase II clinical trial (NCT04507841).

Associations of Intrapancreatic Fat Deposition With Incident Diseases of the Exocrine and Endocrine Pancreas: A UK Biobank Prospective Cohort Study.

Introduction: To investigate whether increased intrapancreatic fat deposition (IPFD) heightens the risk of diseases of the exocrine and endocrine pancreas.

Methods: A prospective cohort study was conducted using data from the UK Biobank. IPFD was quantified using MRI and a deep learning-based framework called nnUNet.

Automated Determination of the H3 K27-Altered Status in Spinal Cord Diffuse Midline Glioma by Radiomics Based on T2-Weighted MR Images.

Background And Purpose: Conventional MR imaging is not sufficient to discern the H3 K27-altered status of spinal cord diffuse midline glioma. This study aimed to develop a radiomics-based model based on preoperative T2WI to determine the H3 K27-altered status of spinal cord diffuse midline glioma.

Materials And Methods: Ninety-seven patients with confirmed spinal cord diffuse midline gliomas were retrospectively recruited and randomly assigned to the training ( = 67) and test ( = 30) sets.

Thalidomide for Recurrent Bleeding Due to Small-Intestinal Angiodysplasia.

Background: Recurrent bleeding from the small intestine accounts for 5 to 10% of cases of gastrointestinal bleeding and remains a therapeutic challenge. Thalidomide has been evaluated for the treatment of recurrent bleeding due to small-intestinal angiodysplasia (SIA), but confirmatory trials are lacking.

Methods: We conducted a multicenter, double-blind, randomized, placebo-controlled trial to investigate the efficacy and safety of thalidomide for the treatment of recurrent bleeding due to SIA.

Automated Classification of Intramedullary Spinal Cord Tumors and Inflammatory Demyelinating Lesions Using Deep Learning.

Accurate differentiation of intramedullary spinal cord tumors and inflammatory demyelinating lesions and their subtypes are warranted because of their overlapping characteristics at MRI but with different treatments and prognosis. The authors aimed to develop a pipeline for spinal cord lesion segmentation and classification using two-dimensional MultiResUNet and DenseNet121 networks based on T2-weighted images. A retrospective cohort of 490 patients (118 patients with astrocytoma, 130 with ependymoma, 101 with multiple sclerosis [MS], and 141 with neuromyelitis optica spectrum disorders [NMOSD]) was used for model development, and a prospective cohort of 157 patients (34 patients with astrocytoma, 45 with ependymoma, 33 with MS, and 45 with NMOSD) was used for model testing.

Reduced Adenoma Miss Rate With 9-Minute vs 6-Minute Withdrawal Times for Screening Colonoscopy: A Multicenter Randomized Tandem Trial.

Introduction: Although the 9-minute mean withdrawal time (m-WT) is often reported to be associated with the optimal adenoma detection rate (ADR), no randomized trials of screening colonoscopy have confirmed the impact of a 9-minute m-WT on adenoma miss rate (AMR) and ADR.

Methods: A multicenter tandem trial was conducted in 11 centers. Seven hundred thirty-three asymptomatic participants were randomized to receive segmental tandem screening colonoscopy with a 9-minute withdrawal, followed by a 6-minute withdrawal (9-minute-first group, 9MF, n = 366) or vice versa (6-minute-first group, 6MF, n = 367).

Preparation of long single-strand DNA concatemers for high-level fluorescence in situ hybridization.

Fluorescence in situ hybridization (FISH) is a powerful tool to visualize transcripts in fixed cells and tissues. Despite the recent advances in FISH detection methods, it remains challenging to achieve high-level FISH imaging with a simple workflow. Here, we introduce a method to prepare long single-strand DNA concatemers (lssDNAc) through a controllable rolling-circle amplification (CRCA).

Contemporary Update of Retinoblastoma in China: Three-Decade Changes in Epidemiology, Clinical Features, Treatments, and Outcomes.

Purpose: To report three-decade changes of clinical characteristics, progress of treatments, and risk factors associated with mortality and enucleation in patients with retinoblastoma in China.

Design: Retrospective cohort study.

Methods: This multicenter study included 2552 patients diagnosed with retinoblastoma in 38 medical centers in 31 provinces in China from 1989 to 2017, with follow-up data.

RBD-homodimer, a COVID-19 subunit vaccine candidate, elicits immunogenicity and protection in rodents and nonhuman primates.

The pandemic of COVID-19 caused by SARS-CoV-2 has raised a new challenges to the scientific and industrious fields after over 1-year spread across different countries. The ultimate approach to end the pandemic is the timely application of vaccines to achieve herd immunity. Here, a novel SARS-CoV-2 receptor-binding domain (RBD) homodimer was developed as a SARS-CoV-2 vaccine candidate.

PKM1 Exerts Critical Roles in Cardiac Remodeling Under Pressure Overload in the Heart.

Background: Metabolic remodeling precedes most alterations during cardiac hypertrophic growth under hemodynamic stress. The elevation of glucose utilization has been recognized as a hallmark of metabolic remodeling. However, its role in cardiac hypertrophic growth and heart failure in response to pressure overload remains to be fully illustrated.

Targeting Mitochondria-Inflammation Circuit by β-Hydroxybutyrate Mitigates HFpEF.

Rationale: Over 50% of patients with heart failure have preserved ejection fraction (HFpEF), rather than reduced ejection fraction. Complexity of its pathophysiology and the lack of animal models hamper the development of effective therapy for HFpEF.

Objective: This study was designed to investigate the metabolic mechanisms of HFpEF and test therapeutic interventions using a novel animal model.

Aqp-1 Gene Knockout Attenuates Hypoxic Pulmonary Hypertension of Mice.

Objective- Hypoxic pulmonary hypertension (HPH) is characterized by proliferative vascular remodeling. Abnormal pulmonary artery smooth muscle cells proliferation and endothelial dysfunction are the primary cellular bases of vascular remodeling. AQP1 (aquaporin-1) is regulated by oxygen level and has been observed to play a role in the proliferation and migration of pulmonary artery smooth muscle cells.

Preoperative Pain Sensitization Is Associated With Postoperative Pillar Pain After Open Carpal Tunnel Release.

Background: Postoperative pillar pain (deep-seated wrist pain worsened by leaning on the heel of the hand) sometimes occurs after carpal tunnel release (CTR), leading to weakness in the hand and delayed return to work. Increased pain sensitivity has been found to be associated with worse symptoms and poorer treatment response in a number of chronic musculoskeletal conditions, but few studies have investigated the association of pain sensitization with pillar pain after CTR.

Questions/purposes: (1) Is preoperative pain sensitization in patients with carpal tunnel syndrome (CTS) associated with increased severity of pillar pain after open CTR? (2) What other demographic, electrophysiological, or preoperative clinical characteristics are associated with pillar pain after CTR?

Methods: Over a 35-month period, one surgeon performed 162 open carpal tunnel releases.

Patients With Limited Health Literacy Have Similar Preferences but Different Perceptions in Surgical Decision-making for Carpal Tunnel Release.

Background: Health literacy is the ability to obtain, process, and understand health information needed to make appropriate health decisions. The proper comprehension by patients regarding a given disease, its treatment, and the physician's instructions plays an important role in shared decision-making. Studies have disagreed over the degree to which differences in health literacy affect patients' preferences for shared decision-making; we therefore sought to evaluate this in the context of shared decision-making about carpal tunnel release.

Identification of metabolites of N-(5-benzoyl-2-(4-(2-methoxyphenyl)piperazin-1-yl)thiazol-4-yl)pivalamide including CYP3A4-mediated C-demethylation in human liver microsomes with high-resolution/high-accuracy tandem mass.

KRO-105714 [N-(5-benzoyl-2-(4-(2-methoxyphenyl)piperazin-1-yl)thiazol-4-yl)pivalamide] is a 2,4,5-trisubstituted 1,3-thiazole derivative that exerts anti-atopic dermatitis activity via robust suppression of the sphingosylphosphorylcholine receptor. This study used high-resolution/high-accuracy tandem mass spectroscopy (HRMS) and recombinant cDNA-expressed cytochrome P450 (P450) isoforms to identify the metabolic pathway and metabolites of KRO-105714 in human liver microsomes (HLMs) as therapeutic agents for inflammation. The incubation of KRO-105714 with pooled HLMs in the presence of NADPH generated four metabolites (M1-M4).