CDK4 selective inhibition improves preclinical anti-tumor efficacy and safety.

CDK4/6 inhibitors have revolutionized treatment of hormone receptor positive (HR+), HER2 non-amplified (HER2-) breast cancer. Yet, all "dual" CDK4/6 inhibitors show common dose-limiting hematologic toxicities, foremost neutropenia. This poses challenges to provide these agents at concentrations necessary to extinguish cell cycling in tumors.

A Polygenic Risk Score for Late Bladder Toxicity Following Radiotherapy for Non-Metastatic Prostate Cancer.

Background: Late bladder toxicity is a concern for patients receiving prostate cancer radiotherapy and negatively impacts survivors. Few risk factors are known beyond the radiation dose and volume of bladder exposed. A polygenic risk score (PRS) could identify susceptible patients.

Intestinal Microbiota Contributes to the Development of Cardiovascular Inflammation and Vasculitis in Mice.

Background: Alterations in the intestinal microbiota contribute to the pathogenesis of various cardiovascular disorders, but how they affect the development of Kawasaki disease, an acute pediatric vasculitis, remains unclear. Here, using a murine model mimicking Kawasaki disease vasculitis, we assessed the contribution of the intestinal microbiota to the development of vascular inflammation.

Methods And Results: We report that depleting the gut microbiota reduces the development of cardiovascular inflammation in a murine model mimicking Kawasaki disease vasculitis.

Comparison of triglyceride glucose index and modified triglyceride glucose indices in predicting cardiovascular diseases incidence among populations with cardiovascular-kidney-metabolic syndrome stages 0-3: a nationwide prospective cohort study.

Background: Cardiovascular-kidney-metabolic (CKM) syndrome has been recently proposed by American Heart Association recently. The triglyceride glucose (TyG) index and TyG-related indices combined with obesity indicators have proven to be associated with the incidence of cardiovascular diseases (CVD). However, there are few studies to explore whether these associations exist among people with CKM syndrome stages 0-3.

Long-Term Outcomes of Transarterial Chemoembolization plus Ablation versus Surgical Resection in Patients with Large BCLC Stage A/B HCC.

Rationale And Objectives: Large hepatocellular carcinoma (HCC) exhibits heterogeneous morphologies and varied responses to treatment. We evaluated outcomes of patients with different large HCC classifications receiving surgical resection (SR) or transarterial chemoembolization plus ablation (TA).

Materials And Methods: Patients with HCC ≥ 5 cm receiving SR or TA between May 2016 and December 2020 at one center were analyzed retrospectively and with propensity score matching (PSM).

Glucagon-Like Peptide-1 Receptor Agonists and Risk for Depression in Older Adults With Type 2 Diabetes : A Target Trial Emulation Study.

Background: Although glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown potential antidepressant effects, population studies yield inconsistent results.

Objective: To compare the risk for depression in older adults with type 2 diabetes (T2D) initiating treatment with GLP-1RAs versus sodium-glucose cotransporter-2 inhibitors (SGLT2is) or dipeptidyl peptidase-4 inhibitors (DPP4is).

Design: Target trial emulation study.

Predicting Late Adverse Events in Uncomplicated Stanford Type B Aortic Dissection: Results From the ROADMAP Validation Study.

Background: Risk stratification is highly desirable in patients with uncomplicated Stanford type B aortic dissection but inadequately supported by evidence. We sought to validate externally a published prediction model for late adverse events (LAEs), consisting of 1 clinical (connective tissue disease) and 4 imaging variables: maximum aortic diameter, false lumen circumferential angle, false lumen outflow, and number of identifiable intercostal arteries.

Methods: We assembled a retrospective multicenter cohort (ROADMAP [Registry of Aortic Diseases to Model Adverse Events and Progression]) of 401 patients with uncomplicated Stanford type B aortic dissection presenting to 1 of 8 aortic centers between 2001 and 2013, followed until 2020.

Understanding the adult and adolescent patient experience with cyclic vomiting syndrome: a concept elicitation study.

Background: Cyclic vomiting syndrome (CVS) is a phasic disorder of gut-brain interaction characterized by episodes of severe nausea and vomiting. In-depth qualitative research on phase-specific CVS symptoms and impacts is lacking. The study objectives were to explore the experience of patients with CVS in the United States and to identify CVS symptoms and impacts on adults, adolescents, and caregivers.

Predicting cell properties with AI from 3D imaging flow cytometer data.

Predicting the properties of tissues or organisms from the genomics data is widely accepted by the medical community. Here we ask a question: can we predict the properties of each individual cell? Single-cell genomics does not work because the RNA sequencing process destroys the cell, not allowing us to verify our predictions. To test the hypothesis, we investigate the approach of using AI to analyze single-cell images obtained from a 3D imaging flow cytometer.

Evaluating the prognostic significance of tumor deposits in gastric cancer and strategies for their integration into the TNM staging system: a single-center retrospective study.

Purpose: To propose a new optimal strategy for incorporating tumor deposit (TD) into TNM staging.

Methods: Totally, 2730 consecutive gastric cancer (GC) patients were included according to the presence and count of TDs between January 2011 and December 2014. Overall survival (OS) was analyzed using Cox regression and propensity score matching (PSM).

Chiral-Unit-Oriented Design of Non-π-Conjugated Noncentrosymmetric Phosphates with Short Absorption Edges.

Deep ultraviolet (UV) nonlinear optical (NLO) crystals are important optoelectronic materials in high-tech applications. How to effectively design a noncentrosymmetric (NCS) structure, which is the rigorous prerequisite for second-order NLO crystals, remains a great challenge. Introducing chiral methylpiperazine into phosphates achieved two polar phosphates, - and -(CHN)(HPO)·HO.

Pan-gastrointestinal adenocarcinoma analysis uncovers the prognostic and immune correlates of ferroptosis-related genes.

Background: Gastrointestinal adenocarcinomas (GIACs) are common malignant tumors with poor prognosis in the world. Ferroptosis, characterized by the accumulation of intracellular iron and lipid reactive oxygen species, emerges as a pivotal process in tumorigenesis and cancer advancement. However, the implications of ferroptosis-related genes in GIAC remain to be elucidated.

Intrinsic electrical activity drives small-cell lung cancer progression.

Elevated or ectopic expression of neuronal receptors promotes tumour progression in many cancer types; neuroendocrine (NE) transformation of adenocarcinomas has also been associated with increased aggressiveness. Whether the defining neuronal feature, namely electrical excitability, exists in cancer cells and impacts cancer progression remains mostly unexplored. Small-cell lung cancer (SCLC) is an archetypal example of a highly aggressive NE cancer and comprises two major distinct subpopulations: NE cells and non-NE cells.

A double-confined strategy for enhancing the pseudocapacitance performance of nickel-based sulfides-unveiling aqueous pseudocapacitive energy storage mechanism.

Lower voltage window and limited pseudocapacitive active sites are identified as critical impediments hindering the advancement of nickel-based supercapacitors. Herein, a double-confined strategy involving nanosizing and heterointerfaces is proposed to construct nickel-based sulfide composite (PMO@NiS/NiS@C) with abundant oxygen vacancies (O), sulfur vacancies (S), and heterostructures. The composite was prepared using liquid-phase in situ self-assembly and low-temperature in situ induction techniques.

A sex-disaggregated analysis of the prognostic value of lean type 2 diabetes mellitus in the adult population with acute myocardial infarction.

Background: Emerging evidence has demonstrated the unfavourable cardiovascular risk of individuals with lean type 2 diabetes mellitus (T2DM). Our study aims to investigate the prognostic value of lean T2DM in patients with acute myocardial infarction (AMI), stratified by sex.

Methods: The study cohort examines the clinical characteristics and long-term outcomes of individuals with AMI, stratified by four phenotypes based on T2DM and lean body category-lean T2DM, non-lean T2DM, lean non-T2DM and non-lean non-T2DM.

The synergistic effect of the triglyceride-glucose index and a body shape index on cardiovascular mortality: the construction of a novel cardiovascular risk marker.

Background: Insulin resistance, represented by increased triglyceride-glucose (TyG) index levels, shows interplay with visceral obesity and together promotes cardiovascular diseases and mortality. However, significant controversies exist regarding whether modified TyG indices, such as TyG-BMI, TyG-WC, and TyG-WHtR, outperform the TyG index in predicting cardiovascular outcomes. We aimed to explore whether there was a synergistic effect of a body shape index (ABSI), a better parameter reflecting visceral obesity, and the TyG index on cardiovascular mortality.

Machine learning-based plasma metabolomics for improved cirrhosis risk stratification.

Background: Cirrhosis is a leading cause of mortality in patients with chronic liver disease (CLD). The rapid development of metabolomic technologies has enabled the capture of metabolic changes related to the progression of cirrhosis.

Methods: This study used proton nuclear magnetic resonance (1 H-NMR) serum metabolomics data from the UK Biobank (UKB) and employed elastic net-regularized Cox proportional hazards models to explore the role of metabolomics in cirrhosis risk stratification in patients with CLD.

Synthetic lethality of mRNA quality control complexes in cancer.

Synthetic lethality exploits the genetic vulnerabilities of cancer cells to enable a targeted, precision approach to treat cancer. Over the past 15 years, synthetic lethal cancer target discovery approaches have led to clinical successes of PARP inhibitors and ushered several next-generation therapeutic targets such as WRN, USP1, PKMYT1, POLQ and PRMT5 into the clinic. Here we identify, in human cancer, a novel synthetic lethal interaction between the PELO-HBS1L and SKI complexes of the mRNA quality control pathway.

Downregulated PSME3 Contributes to Severe Preeclampsia by Promoting Trophoblast Cell Apoptosis.

Background: Severe preeclampsia (sPE) is a serious condition posing risks to both maternal and fetal health. Based on mass spectrometry analysis, we identified a key protein, PSME3 (proteasome activator subunit 3), an 11S proteasome activator, whose protein level was significantly downregulated in sPE placentas and whose function in sPE remains unknown.

Methods: PSME3 protein levels in human placental tissue were detected using Western blot, and PSME3 concentration in serum was detected by ELISA assay.

Lunar and Martian gravity alter immune cell interactions with endothelia in parabolic flight.

Returning to the moon and traveling to Mars represent the main targets of human space exploration missions within the upcoming decades. Comparable to microgravity, partial gravity in these destinations is assumed to dysregulate immune functions, thereby threatening astronauts´ health. To investigate the impact of partial gravity on immune cell attachment to vessel endothelia, THP-1 cells and HUVEC cell layers were monitored in a flow chamber system during parabolic flight in lunar (0.

Multiscale deep learning radiomics for predicting recurrence-free survival in pancreatic cancer: A multicenter study.

Purpose: This multicenter study aimed to develop and validate a multiscale deep learning radiomics nomogram for predicting recurrence-free survival (RFS) in patients with pancreatic ductal adenocarcinoma (PDAC).

Materials And Methods: A total of 469 PDAC patients from four hospitals were divided into training and test sets. Handcrafted radiomics and deep learning (DL) features were extracted from optimal regions of interest, encompassing both intratumoral and peritumoral areas.

Novel Cellulosic Fiber Composites with Integrated Multi-Band Electromagnetic Interference Shielding and Energy Storage Functionalities.

In an era where technological advancement and sustainability converge, developing renewable materials with multifunctional integration is increasingly in demand. This study filled a crucial gap by integrating energy storage, multi-band electromagnetic interference (EMI) shielding, and structural design into bio-based materials. Specifically, conductive polymer layers were formed within the 2,2,6,6-tetramethylpiperidine-1-oxide (TEMPO)-oxidized cellulose fiber skeleton, where a mild TEMPO-mediated oxidation system was applied to endow it with abundant macropores that could be utilized as active sites (specific surface area of 105.

Advances in biotechnology and breeding innovations in China's marine aquaculture.

Biotechnology is the key driving force behind the sustainable development of aquaculture, as biological innovation would significantly improve the capabilities of aquatic breeding and achieve independent and controllable seeding sources to ensure food safety. In this article, we have analyzed the current status and existing problems of marine aquaculture in China. Based on these data, we have summarized the recent (especially the last 10 years) biotechnological innovation and breeding progress of marine aquaculture in China, including whole genome sequencing, sex-related marker screening, genomic selection, and genome editing, as well as progress of improved marine fish varieties in China.

Transient Ischemic Attack in Women: Real-World Hospitalization Incidence, Outcomes, and Risk of Hemorrhage and Stroke.

Background: Sex-specific differences in stroke risk factors, clinical presentation, and outcomes are well documented. However, little is known about real-world differences in transient ischemic attack (TIA) hospitalizations and outcomes between men and women.

Methods: This was a retrospective cohort study of the 2016 to 2021 Nationwide Readmissions Database in the United States.

Pharmacological characterization of the novel selective kappa opioid receptor agonists 10-Iodo-Akuammicine and 10-Bromo-akuammicine in mice.

Akuammicine (AKC), an indole alkaloid, is a kappa opioid receptor (KOR) full agonist with a moderate affinity. 10-Iodo-akuammicine (I-AKC) and 10-Bromo-akuammicine (Br-AKC) showed higher affinities for the KOR with K values of 2.4 and 5.