Functional genomics pipeline identifies CRL4 inhibition for the treatment of ovarian cancer.

Background: The goal of precision oncology is to find effective therapeutics for every patient. Through the inclusion of emerging therapeutics in a high-throughput drug screening platform, our functional genomics pipeline inverts the common paradigm to identify patient populations that are likely to benefit from novel therapeutic strategies.

Approach: Utilizing drug screening data across a panel of 46 cancer cell lines from 11 tumor lineages, we identified an ovarian cancer-specific sensitivity to the first-in-class CRL4 inhibitors KH-4-43 and 33-11.

Defining proteoform-specific interactions for drug targeting in a native cell signalling environment.

Understanding the dynamics of membrane protein-ligand interactions within a native lipid bilayer is a major goal for drug discovery. Typically, cell-based assays are used, however, they are often blind to the effects of protein modifications. In this study, using the archetypal G protein-coupled receptor rhodopsin, we found that the receptor and its effectors can be released directly from retina rod disc membranes using infrared irradiation in a mass spectrometer.

Development and Validation of an AI-Based Multimodal Model for Pathological Staging of Gastric Cancer Using CT and Endoscopic Images.

Rationale And Objectives: Accurate preoperative pathological staging of gastric cancer is crucial for optimal treatment selection and improved patient outcomes. Traditional imaging methods such as CT and endoscopy have limitations in staging accuracy.

Methods: This retrospective study included 691 gastric cancer patients treated from March 2017 to March 2024.

A bibliometric analysis of research trends and hotspots of pilocytic astrocytoma from 2004 to 2023.

Pilocytic astrocytoma (PA) is a WHO grade I neoplasm with a favorable prognosis. It is the most common pediatric benign tumor. Recently, PA has attracted more and more attention and discussion from scholars.

Comparative Efficacy of Non-contrast vs. Contrast-enhanced CT Radiomics in Predicting Coronary Artery Plaques Among Patients with Low Agatston Scores.

Rationale And Objectives: Patients with a low Agatston score often present with clinical signs and symptoms suggestive of coronary artery disease, despite having minimal calcium deposits. This study aimed to compare the efficacy of low-dose non-contrast cardiac CT with coronary computed tomography angiography (CCTA) in pericoronary adipose tissue (PCAT) radiomics for predicting coronary artery plaques, using CCTA as the reference standard.

Materials And Methods: This retrospective study analyzed 459 patients with suspected coronary artery disease and a coronary artery calcium score < 100 Agatston units, who were treated between June 2021 and December 2023 at a tertiary hospital.

Retinal Degeneration Associated With Biallelic RDH12 Variants: Longitudinal Evaluation of Retinal Structure and Visual Function in Pediatric Patients.

Purpose: The purpose of this study was to determine the natural history of the photoreceptor disease in a large group of pediatric patients with RHD12-associated Leber congenital amaurosis (RDH12-LCA), to estimate the changes expected over the duration of a clinical trial, and to define the relationship between the photoreceptor loss and visual dysfunction.

Methods: Forty-six patients representing 36 families were included. The great majority of patients were under the age of 18 years.

Multicenter Analysis of the Relationship Between Operative Team Familiarity and Safety and Efficiency Outcomes in Cardiac Surgery.

Background: Safety in cardiac surgical procedures is predicated on effective team dynamics. This study associated operative team familiarity (ie, the extent of clinical collaboration among surgical team members) with procedural efficiency and Society of Thoracic Surgeons (STS) adjudicated patient outcomes.

Methods: Institutional STS adult cardiac surgery registry and electronic health record data from 2014 to 2021 were evaluated across 3 quaternary hospitals.

Evaluating the Value of Eye-Tracking Augmented Debriefing in Medical Simulation-A Pilot Randomized Controlled Trial.

Introduction: Debriefing after simulation facilitates reflective thinking and learning. Eye-tracking augmented debriefing (ETAD) may provide advantages over traditional debriefing (TD) by leveraging video replay with first-person perspective. This multisite randomized controlled trial compared the impact of ETAD with TD (without eye-tracking and without video) after simulation on 4 outcomes: (1) resident metacognitive awareness (the primary outcome), (2) cognitive load (CL) of residents and debriefers, (3) alignment of resident self-assessment and debriefer assessment scores, and (4) resident and debriefer perceptions of the debriefing experience.

Multiomics profiling of mouse polycystic kidney disease progression at a single-cell resolution.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and causes significant morbidity, ultimately leading to kidney failure. PKD pathogenesis is characterized by complex and dynamic alterations in multiple cell types during disease progression, hampering a deeper understanding of disease mechanism and the development of therapeutic approaches. Here, we generate a single-nucleus multimodal atlas of an orthologous mouse PKD model at early, mid, and late timepoints, consisting of 125,434 single-nucleus transcriptomic and epigenetic multiomes.

A new theoretical model for high-order harmonics of SH mode ultrasonic guided waves based on magnetostrictive mechanism.

In recent years, it was found that magnetostrictive ultrasonic guided wave transducers experimentally excited nonlinear harmonic components under a certain combination of dynamic and static magnetic fields. However, a satisfactory model for the relevant excitation mechanisms is not available. In this study, a new magnetostrictive guided wave excitation model was established and the causes for harmonics generation were analyzed.

Ziresovir in Hospitalized Infants with Respiratory Syncytial Virus Infection.

Background: Respiratory syncytial virus (RSV) is a leading cause of severe illness in infants, with no effective treatment. Results of a phase 2 trial suggested that ziresovir may have efficacy in the treatment of infants hospitalized with RSV infection.

Methods: In a phase 3, multicenter, double-blind, randomized, placebo-controlled trial conducted in China, we enrolled participants 1 to 24 months of age who were hospitalized with RSV infection.

Actively Targeting Redox-Responsive Multifunctional Micelles for Synergistic Chemotherapy of Cancer.

Stimuli-responsive polymeric micelles decorated with cancer biomarkers represent an optimal choice for drug delivery applications due to their ability to enhance therapeutic efficacy while mitigating adverse side effects. Accordingly, we synthesized a digoxin-modified novel multifunctional redox-responsive disulfide-linked poly(ethylene glycol--poly(lactic--glycolic acid) copolymer (Bi(Dig-PEG-PLGA)-S) for the targeted and controlled release of doxorubicin (DOX) in cancer cells. Within the micellar aggregate, the disulfide bond confers redox responsiveness, while the presence of the digoxin moiety acts as a targeting agent and chemosensitizer for DOX.

Nonlinear dynamics of multi-omics profiles during human aging.

Aging is a complex process associated with nearly all diseases. Understanding the molecular changes underlying aging and identifying therapeutic targets for aging-related diseases are crucial for increasing healthspan. Although many studies have explored linear changes during aging, the prevalence of aging-related diseases and mortality risk accelerates after specific time points, indicating the importance of studying nonlinear molecular changes.

Combinations of Clinical Factors, CT Signs, and Radiomics for Differentiating High-Density Areas after Mechanical Thrombectomy in Patients with Acute Ischemic Stroke.

Background And Purpose: Clinically, hemorrhagic transformation (HT) after mechanical thrombectomy (MT) is a common complication. This study aimed to investigate the value of clinical factors, CT signs, and radiomics in the differential diagnosis of high-density areas (HDAs) in the brain after MT in patients with acute ischemic stroke with large-vessel occlusion (AIS-LVO).

Materials And Methods: A total of 156 eligible patients with AIS-LVO in Center I from December 2015 to June 2023 were retrospectively enrolled and randomly divided into training ( = 109) and internal validation ( = 47) sets at a ratio of 7:3.

Discordant High Remnant Cholesterol With LDL-C Increases the Risk of Stroke: A Chinese Prospective Cohort Study.

Background: Previous studies focusing on assessing the effects of remnant cholesterol (RC) and low-density lipoprotein cholesterol (LDL-C) on stroke may not consider their mutual influence. We aimed to explore the associations of RC and discordant high RC with LDL-C with stroke, ischemic stroke (IS), and hemorrhagic stroke.

Methods: This prospective cohort study was conducted based on 3 cohorts of the China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) project.

Minimal residual disease monitoring via ctDNA: a case report of Lynch syndrome with synchronous colorectal cancer and review of literature.

Background: The investigation of circulating tumor DNA (ctDNA) as a substitute for minimal residual disease (MRD) has been a central focus in various clinical trials, with findings highlighting its effectiveness as a sensitive marker for detecting recurrence. In 2018, a joint review by the American Society of Clinical Oncology and the College of American Pathologists acknowledged a lack of current evidence guiding clinical decisions regarding ctDNA. Nevertheless, there are a multitude of ongoing studies exploring the future applications of ctDNA and its role in clinical decision making for select patient populations.

 (Boraginaceae), a new species from Xinjiang, China.

D.H.Liu & W.

Bispecific CAR-T cells targeting FAP and GPC3 have the potential to treat hepatocellular carcinoma.

Chimeric antigen receptor (CAR) T cell therapy has demonstrated robust efficacy against hematological malignancies, but there are still some challenges regarding treating solid tumors, including tumor heterogeneity, antigen escape, and an immunosuppressive microenvironment. Here, we found that SNU398, a hepatocellular carcinoma (HCC) cell line, exhibited high expression levels of fibroblast activation protein (FAP) and Glypican 3 (GPC3), which were negatively correlated with patient prognosis. The HepG2 HCC cell line highly expressed GPC3, while the SNU387 cell line exhibited high expression of FAP.

Multi-omics profiling of mouse polycystic kidney disease progression at a single cell resolution.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and causes significant morbidity, ultimately leading to end-stage kidney disease. PKD pathogenesis is characterized by complex and dynamic alterations in multiple cell types during disease progression, hampering a deeper understanding of disease mechanism and the development of therapeutic approaches. Here, we generate a single nucleus multimodal atlas of an orthologous mouse PKD model at early, mid and late timepoints, consisting of 125,434 single-nucleus transcriptomic and epigenetic multiomes.

A Highly Conductive -Type Conjugated Polymer Synthesized in Water.

Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) is a benchmark hole-transporting (-type) polymer that finds applications in diverse electronic devices. Most of its success is due to its facile synthesis in water, exceptional processability from aqueous solutions, and outstanding electrical performance in ambient. Applications in fields like (opto-)electronics, bioelectronics, and energy harvesting/storage devices often necessitate the complementary use of both -type and -type (electron-transporting) materials.

Generalizable transcriptome-based tumor malignant level evaluation and molecular subtyping towards precision oncology.

In cancer treatment, therapeutic strategies that integrate tumor-specific characteristics (i.e., precision oncology) are widely implemented to provide clinical benefits for cancer patients.