Survival outcomes, multidimensional prediction and subsequent therapy in patients with hormone receptor-positive advanced breast cancer receiving palbociclib: a real-world analysis.

Background: To date, the overall survival (OS) of hormone receptor-positive advanced breast cancer (ABC) treated with palbociclib has not been reported in Chinese patients. It still remains unclear what kind of patients may benefit in OS from palbociclib treatment and what the optimal sequential antineoplastic regimen is for those progressing on palbociclib. Therefore, we aimed to investigate the OS outcome of ABC patients receiving palbociclib, establish a predictive model to identify the potential candidates who may benefit from palbociclib and explore the ideal subsequent treatment strategy after palbociclib.

qPRF: A system to accelerate population receptive field modeling.

BOLD response can be fitted using the population receptive field (PRF) model to reveal how visual input is represented on the cortex (Dumoulin and Wandell, 2008). Fitting the PRF model costs considerable time, often requiring days to analyze BOLD signals for a small cohort of subjects. We introduce the qPRF ("quick PRF"), a system for accelerated PRF modeling that reduced the computation time by a factor >1,000 without losing goodness-of-fit when compared to another widely available PRF modeling package (Kay et al.

Development and validation of a prognostic and drug sensitivity model for gastric cancer utilizing telomere-related genes.

Background: Gastric cancer (GC) poses a major global health challenge because of its unfavorable prognosis. Elevated telomerase activity has been linked to the rapid growth and invasiveness of GC tumors. Investigating the expression profiles of telomerase could improve our understanding of the mechanisms underlying telomere-related GC advancement and its applicability as potential targets for diverse therapeutic strategies for GC.

Incremental Prognostic Value of Cardiac MRI Feature Tracking and T1 Mapping in Arrhythmogenic Right Ventricular Cardiomyopathy.

Purpose To explore the role of cardiac MRI feature tracking (FT) and T1 mapping in predicting sustained ventricular arrhythmias (VA) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and to investigate their possible incremental value beyond ARVC risk score. Materials and Methods The retrospective study analyzed 91 patients with ARVC (median age, 36 years [IQR, 27-50 years]; 60 male, 31 female) who underwent cardiac MRI examinations between November 2010 and March 2022. The primary end point was the first occurrence of sustained VA after cardiac MRI to first VA, with censoring of patients who were alive without VA at last follow-up.

Utilising an in silico model to predict outcomes in senescence-driven acute liver injury.

Currently liver transplantation is the only treatment option for liver disease, but organ availability cannot meet patient demand. Alternative regenerative therapies, including cell transplantation, aim to modulate the injured microenvironment from inflammation and scarring towards regeneration. The complexity of the liver injury response makes it challenging to identify suitable therapeutic targets when relying on experimental approaches alone.

Targeting the GTPase RAN by liposome delivery for tackling cancer stemness-emanated therapeutic resistance.

Cancer therapeutic resistance as a common hallmark of cancer is often responsible for treatment failure and poor patient survival. Cancer stem-like cells (CSCs) are one of the main contributors to therapeutic resistance, cancer relapse and metastasis. Through screening from our in-house library of natural products, we found polyphyllin II (PPII) as a potent anti-CSC compound for triple-negative breast cancer (TNBC).

qPRF: A system to accelerate population receptive field decoding.

Patterns of BOLD response can be decoded using the population receptive field (PRF) model to reveal how visual input is represented on the cortex (Dumoulin and Wandell, 2008). The time cost of evaluating the PRF model is high, often requiring days to decode BOLD signals for a small cohort of subjects. We introduce the qPRF, an efficient method for decoding that reduced the computation time by a factor of 1436 when compared to another widely available PRF decoder (Kay, Winawer, Mezer and Wandell, 2013) on a benchmark of data from the Human Connectome Project (HCP; Van Essen, Smith, Barch, Behrens, Yacoub and Ugurbil, 2013).

Exploiting in silico modelling to enhance translation of liver cell therapies from bench to bedside.

Cell therapies are emerging as promising treatments for a range of liver diseases but translational bottlenecks still remain including: securing and assessing the safe and effective delivery of cells to the disease site; ensuring successful cell engraftment and function; and preventing immunogenic responses. Here we highlight three therapies, each utilising a different cell type, at different stages in their clinical translation journey: transplantation of multipotent mesenchymal stromal/signalling cells, hepatocytes and macrophages. To overcome bottlenecks impeding clinical progression, we advocate for wider use of mechanistic in silico modelling approaches.

Remodeling ceramide homeostasis promotes functional maturation of human pluripotent stem cell-derived β cells.

Human pluripotent stem cell-derived β cells (hPSC-β cells) show the potential to restore euglycemia. However, the immature functionality of hPSC-β cells has limited their efficacy in application. Here, by deciphering the continuous maturation process of hPSC-β cells post transplantation via single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq), we show that functional maturation of hPSC-β cells is an orderly multistep process during which cells sequentially undergo metabolic adaption, removal of negative regulators of cell function, and establishment of a more specialized transcriptome and epigenome.

Heart Failure with Normal Natriuretic Peptide Levels and Preserved Ejection Fraction: A Prospective Clinical and Cardiac MRI Study.

Purpose To describe the clinical presentation, comprehensive cardiac MRI characteristics, and prognosis of individuals with predisposed heart failure with preserved ejection fraction (HFpEF). Materials and Methods This prospective cohort study (part of MISSION-HFpEF [Multimodality Imaging in the Screening, Diagnosis, and Risk Stratification of HFpEF]; NCT04603404) was conducted from January 1, 2019, to September 30, 2021, and included individuals with suspected HFpEF who underwent cardiac MRI. Participants who had primary cardiomyopathy and primary valvular heart disease were excluded.

Rectifying METTL4-Mediated N-Methyladenine Excess in Mitochondrial DNA Alleviates Heart Failure.

Background: Myocardial mitochondrial dysfunction underpins the pathogenesis of heart failure (HF), yet therapeutic options to restore myocardial mitochondrial function are scarce. Epigenetic modifications of mitochondrial DNA (mtDNA), such as methylation, play a pivotal role in modulating mitochondrial homeostasis. However, their involvement in HF remains unclear.

Identification of Circulating Plasma Proteins as a Mediator of Hypertension-Driven Cardiac Remodeling: A Mediation Mendelian Randomization Study.

Background: This study focused on circulating plasma protein profiles to identify mediators of hypertension-driven myocardial remodeling and heart failure.

Methods: A Mendelian randomization design was used to investigate the causal impact of systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure on 82 cardiac magnetic resonance traits and heart failure risk. Mediation analyses were also conducted to identify potential plasma proteins mediating these effects.

A potent and broad-spectrum neutralizing nanobody for SARS-CoV-2 viruses, including all major Omicron strains.

SARS-CoV-2 viruses are highly transmissible and immune evasive. It is critical to develop broad-spectrum prophylactic and therapeutic antibodies for potential future pandemics. Here, we used the phage display method to discover nanobodies (Nbs) for neutralizing SARS-CoV-2 viruses especially Omicron strains.

Vepafestinib is a pharmacologically advanced RET-selective inhibitor with high CNS penetration and inhibitory activity against RET solvent front mutations.

RET receptor tyrosine kinase is activated in various cancers (lung, thyroid, colon and pancreatic, among others) through oncogenic fusions or gain-of-function single-nucleotide variants. Small-molecule RET kinase inhibitors became standard-of-care therapy for advanced malignancies driven by RET. The therapeutic benefit of RET inhibitors is limited, however, by acquired mutations in the drug target as well as brain metastasis, presumably due to inadequate brain penetration.

Safety and Immunogenicity of the BNT162b2 Vaccine Coadministered with Seasonal Inactivated Influenza Vaccine in Adults.

Introduction: Vaccination is a critical tool for preventing coronavirus disease 2019 (COVID-19) and influenza illnesses. Coadministration of the COVID-19 vaccine, BNT162b2, with seasonal inactivated influenza vaccine (SIIV) can provide substantial benefits, including streamlining vaccine delivery.

Methods: In this phase 3 study, healthy 18- to 64-year-olds who had received three previous doses of BNT162b2 were randomized (1:1) to the coadministration group (month 0, BNT162b2 + SIIV; month 1, placebo) or the separate-administration group (month 0, placebo + SIIV; month 1, BNT162b2).

DNA-encoded chemical libraries yield non-covalent and non-peptidic SARS-CoV-2 main protease inhibitors.

The development of SARS-CoV-2 main protease (M) inhibitors for the treatment of COVID-19 has mostly benefitted from X-ray structures and preexisting knowledge of inhibitors; however, an efficient method to generate M inhibitors, which circumvents such information would be advantageous. As an alternative approach, we show here that DNA-encoded chemistry technology (DEC-Tec) can be used to discover inhibitors of M. An affinity selection of a 4-billion-membered DNA-encoded chemical library (DECL) using M as bait produces novel non-covalent and non-peptide-based small molecule inhibitors of M with low nanomolar K values.

Trichosanates A-G and cucurbitacins W-Y, anticomplement monoterpenoids and cucurbitane-type triterpenoids from the pericarps of Trichosanthes kirilowii.

The pericarps of Trichosanthes kirilowii are often used to treat cough in traditional Chinese medicine, and its ethanol extract exhibited effective therapeutic effects on acute lung injury (ALI) in vivo caused by H1N1. An anticomplement activity-guided fractionation on the extract resulted in the isolation of ten new terpenoids, including seven monoterpenoids, trichosanates A-G (1-7), and three cucurbitane-type triterpenoids, cucurbitacins W-Y (8-10), as well as eleven known terpenoids (11-21). The new terpenoids' structures were determined by spectroscopic analysis, X-ray crystallographic analysis (1), electronic circular dichroism (ECD) analysis and calculations (2-10).

Adenosine Triphosphate Stress Myocardial Strain in Ischemic Heart Disease: An Animal Study with Histological Validation.

Rationale And Objectives: It is still challenging for cardiac magnetic resonance (CMR) to detect ischemic heart disease (IHD) without the use of gadolinium contrast. We aimed to evaluate the potential value of adenosine triphosphate (ATP) stress myocardial strain derived from feature tracking (FT) as a novel method for detecting IHD in a swine model.

Materials And Methods: CMR cines, myocardial perfusion imaging at rest and during ATP stress, and late gadolinium enhancement were obtained in both control and IHD swine.

Discovery and characterization of potent pan-variant SARS-CoV-2 neutralizing antibodies from individuals with Omicron breakthrough infection.

The SARS-CoV-2 Omicron variant evades most currently approved neutralizing antibodies (nAbs) and caused drastic decrease of plasma neutralizing activity elicited by vaccination or prior infection, urging the need for the development of pan-variant antivirals. Breakthrough infection induces a hybrid immunological response with potentially broad, potent and durable protection against variants, therefore, convalescent plasma from breakthrough infection may provide a broadened repertoire for identifying elite nAbs. We performed single-cell RNA sequencing (scRNA-seq) and BCR sequencing (scBCR-seq) of B cells from BA.