Effect of fezolinetant on patient-reported quality-of-life outcomes: Data from a phase 3b study (DAYLIGHT) of the treatment of moderate to severe vasomotor symptoms associated with menopause in women considered unsuitable for hormone therapy.

Objective: To report patient-reported quality-of-life (QOL) outcomes in the DAYLIGHT study.

Study Design: DAYLIGHT was a phase 3b, randomized, double-blind, 24-week, placebo-controlled study. Participants were women aged ≥40 to ≤65 years with moderate to severe vasomotor symptoms (VMS) considered unsuitable for hormone therapy (HT) (contraindications, caution, stoppers, or averse) randomized 1:1 to placebo or fezolinetant 45 mg once daily.

Prospective validation of ORACLE, a clonal expression biomarker associated with survival of patients with lung adenocarcinoma.

Human tumors are diverse in their natural history and response to treatment, which in part results from genetic and transcriptomic heterogeneity. In clinical practice, single-site needle biopsies are used to sample this diversity, but cancer biomarkers may be confounded by spatiogenomic heterogeneity within individual tumors. Here we investigate clonally expressed genes as a solution to the sampling bias problem by analyzing multiregion whole-exome and RNA sequencing data for 450 tumor regions from 184 patients with lung adenocarcinoma in the TRACERx study.

Facile synthesis of 2-sulfonylbenzothiazoles cascade SO-NCS addition and S-C(sp) coupling.

A new synthetic route to 2-sulfonylbenzothiazoles (BtsR) employing cascade SO-NCS nucleophilic addition and CuI-catalysed S-C(sp) coupling was developed. Structurally diverse BtsR molecules were readily afforded in high yields from the rapid and benign reaction of 2-iodoarylisothiocyanates with sodium sulfinates in DMSO, generally without the need for further column isolation.

Acute Myeloid Leukemia with Normal Cytogenetics and -Mutation: Impact of Mutation Topography on Outcomes.

: About half of adults with acute myeloid leukemia with normal cytogenetics (CN-AML) have mutations. There is controversy regarding their prognosis and best therapy. : We studied 150 subjects with these features using targeted regional sequencing.

Large-Scale Plasma Proteomics Improves Prediction of Peripheral Artery Disease in Individuals With Type 2 Diabetes: A Prospective Cohort Study.

Objective: Peripheral artery disease (PAD) is a significant complication of type 2 diabetes (T2D), yet the association between plasma proteomics and PAD in people with T2D remains unclear. We aimed to explore the relationship between plasma proteomics and PAD in individuals with T2D, and assess whether proteomics could refine PAD risk prediction.

Research Design And Methods: This cohort study included 1,859 individuals with T2D from the UK Biobank.

Development of L-Met functionalized cellulose nanofiber for an efficient removal of Pb from aqueous solution: Characterization, adsorption behavior, DFT calculations and physiochemical mechanism.

Lead-containing wastewater has been a significant challenge in the field of wastewater treatment. Cellulose surface has a large number of active sites, which is conducive to load modification. And amino acids have rich functional groups, which is a good choice for cellulose modification.

Dipeptidyl peptidase-4 inhibitor linagliptin reduces inflammatory response, ameliorates tissue edema formation, and improves survival in severe sepsis.

Background: Excessive inflammation in sepsis causes microvascular dysfunction associated with organ dysfunction and high mortality. The present studies aimed to examine the therapeutic potential of linagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor in a clinically relevant polymicrobial sepsis model in mice.

Methods: Sepsis was induced by cecal ligation and puncture (CLP).

Current State and New Horizons in Applications of Physiologically Based Biopharmaceutics Modeling (PBBM): A Workshop Report.

This report summarizes the proceedings for Day 3 of the workshop titled "". This day focused on the current and future drug product quality applications of PBBM from the innovator and generic industries as well as the regulatory agencies perspectives. The presentations, which included several case studies, covered the applications of PBBM in generic drug product development, applications of virtual bioequivalence trials to support formulation bridging and the utility of absorption modeling in clinical pharmacology assessments.

Bidirectional high-speed optical wireless communication with tunable large field of view assisted by liquid crystal metadevice.

Beam-steered infrared (IR) light communication has gained tremendous attention as one of the solutions of congested wireless communication traffic. High performance active beam-steering devices play a crucial role in data allocation and exchange. Conventional beam-steering devices such as spatial light modulator (SLM) and micro-electrical mechanical system (MEMS) mirror and the current emerging nonmechanical beam-steering metasurface-based devices are challenging to realize a large tunable steering angle beyond several degrees, which significantly hinders the spatial application of optical wireless communications (OWC).

A Clinical Prediction Model For Short-Term Prognosis In Patients With Non Acute Myocardial Infarction Related Cardiogenic Shock.

Background: While acute myocardial infarction (AMI) is widely recognized as the primary cause of Cardiogenic Shock (CS), Non-AMI related CS has been excluded from the majority of CS studies. Information on its prognostic factors remains largely understudied, and it is necessary to focus on these patients to identify the specific risk factors. In this study, we aimed to build and validate a predictive nomogram and risk classification system.

The QIBA Profile for Dynamic Susceptibility Contrast MRI Quantitative Imaging Biomarkers for Assessing Gliomas.

The dynamic susceptibility contrast (DSC) MRI measures of relative cerebral blood volume (rCBV) play a central role in monitoring therapeutic response and disease progression in patients with gliomas. Previous investigations have demonstrated promise of using rCBV in classifying tumor grade, elucidating tumor viability after therapy, and differentiating pseudoprogression and pseudoresponse. However, the quantification and reproducibility of rCBV measurements across patients, devices, and software remain a critical barrier to routine or clinical trial use of longitudinal DSC MRI in patients with gliomas.

Staggered immunization with mRNA vaccines encoding SARS-CoV-2 polymerase or spike antigens broadens the T cell epitope repertoire.

Combining a T cell-targeting mRNA vaccine encoding the conserved SARS-CoV-2 RNA-dependent RNA polymerase, RdRp, with a Spike-encoding mRNA vaccine may offer an additional pathway toward COVID-19 protection. Here, we show that a nucleoside-modified RdRp mRNA vaccine raises robust and durable CD8+ T cell responses in mice. Immunization drives a CD8+ T cell response enriched toward a specific RdRp epitope.

Multifunctional Ultrathin TiCT MXene@CuCoO /PE Separator for Ultra-High-Energy-Density and Large-Capacity Lithium-Sulfur Pouch Cells.

The shuttling of lithium polysulfides (LiPSs), sluggish reaction kinetics, and uncontrolled lithium deposition/stripping remain the main challenges in lithium-sulfur batteries (LSBs), which are aggravated under practical working conditions, i.e., high sulfur loading and lean electrolyte in large-capacity pouch cells.

Trem2/Tyrobp Signaling Protects Against Aortic Dissection and Rupture by Inhibiting Macrophage Activation in Mice.

Background: The development of aortic dissection (AD) is closely associated with inflammation. The Trem2 (triggering receptor expressed on myeloid cells 2)/Tyrobp (TYRO protein tyrosine kinase-binding protein) signaling pathway critically regulates innate immunity and has emerged as an important target in cardiovascular diseases; however, its role in AD remains unclear.

Methods: Transcriptome data from human and mouse ADs were used to perform differentially expressed gene-based protein-protein interaction network analyses.

Short-chain fatty acids in viral infection: the underlying mechanisms, opportunities, and challenges.

Viral infections can cause cellular pathway derangements, cell death, and immunopathological responses, leading to host inflammation. Short-chain fatty acids (SCFAs), produced by the microbiota, have emerged as a potential therapeutic for viral infections due to their ability to modulate these processes. However, SCFAs have been reported to have both beneficial and detrimental effects, necessitating a comprehensive understanding of the underlying mechanisms.

Shc1 cooperates with Frs2 and Shp2 to recruit Grb2 in FGF-induced lens development.

Fibroblast growth factor (FGF) signaling elicits multiple downstream pathways, most notably the Ras/MAPK cascade facilitated by the adaptor protein Grb2. However, the mechanism by which Grb2 is recruited to the FGF signaling complex remains unresolved. Here we showed that genetic ablation of FGF signaling prevented lens induction by disrupting transcriptional regulation and actin cytoskeletal arrangements, which could be reproduced by deleting the juxtamembrane region of the FGF receptor and rescued by Kras activation.

Delivery of therapeutic RNA by extracellular vesicles derived from Saccharomyces cerevisiae for medicine applications.

Employing small extracellular vesicles (EVs) as drug delivery vehicles presents a plethora of advantages over conventional drug delivery methods, including biological compatibility, engineering versatility for targeted delivery, and biodegradability. Therefore, strategies aimed at amplifying their therapeutic potential involve developing efficient, tissue-specific, and non-immunogenic delivery approaches. Despite rapid advancements in the realm of EVs as drug delivery systems in recent years, the availability of a high-yield, reproducible, and cost-effective source for EVs production and isolation remains a limiting factor for practical application.

Clustering-aided prediction of outcomes in patients with idiopathic pulmonary fibrosis.

Background: Blood biomarkers predictive of the progression of idiopathic pulmonary fibrosis (IPF) would be of value for research and clinical practice. We used data from the IPF-PRO Registry to investigate whether the addition of "omics" data to risk prediction models based on demographic and clinical characteristics improved prediction of the progression of IPF.

Methods: The IPF-PRO Registry enrolled patients with IPF at 46 sites across the US.

Overloading And unpacKing (OAK) - droplet-based combinatorial indexing for ultra-high throughput single-cell multiomic profiling.

Multiomic profiling of single cells by sequencing is a powerful technique for investigating cellular diversity. Existing droplet-based microfluidic methods produce many cell-free droplets, underutilizing bead barcodes and reagents. Combinatorial indexing on microplates is more efficient for barcoding but labor-intensive.

Cancer treatment monitoring using cell-free DNA fragmentomes.

Circulating cell-free DNA (cfDNA) assays for monitoring individuals with cancer typically rely on prior identification of tumor-specific mutations. Here, we develop a tumor-independent and mutation-independent approach (DELFI-tumor fraction, DELFI-TF) using low-coverage whole genome sequencing to determine the cfDNA tumor fraction and validate the method in two independent cohorts of patients with colorectal or lung cancer. DELFI-TF scores strongly correlate with circulating tumor DNA levels (ctDNA) (r = 0.

Histopathologic pattern and molecular risk stratification are associated with prognosis in patients with stage IB lung adenocarcinoma.

Background: The benefit of adjuvant therapy remains controversial in completely resected (R0) stage IB non-small cell lung cancer (NCLSC) patients. In this study, we aimed to explore potential prognostic factors in stage IB NSCLC patients.

Methods: This study included 215 patients with R0 stage IB lung adenocarcinoma (LUAD) (tumor size: 3-4 cm).