The impact of imprecise case definitions in electronic health record research: a melanoma case-study from the Million Veteran Program.

Cases for a disease can be defined broadly using diagnostic codes, or narrowly using gold-standard confirmation that often is not available in large administrative datasets. These different definitions can have significant impacts on the results and conclusions of studies. We conducted this study to assess how using melanoma phecodes versus histologic confirmation for invasive or in situ melanoma impacts the results of a genome-wide association study (GWAS) using the Million Veteran Program.

Immunogenic dying cells elicit potent anti-tumor T cell immunity against lung metastasis and tumorigenesis.

Purpose: Immune checkpoint blockades (ICBs) are promising, however they do not fit all types of tumor, such as those lack of tumor antigens. Induction of potent anti-tumor T cell immunity is critical for cancer therapy. In this study, we investigated the efficacy of immunotherapy via the immunogenic cell death (ICD) dying tumor cells in mouse models of lung metastasis and tumorigenesis.

Durvalumab and tremelimumab in patients with advanced rare cancer: a multi-centre, non-blinded, open-label phase II basket trial.

Background: Dual inhibition of cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and programmed death ligand 1 (PD-L1) has been shown to be an effective treatment strategy in many cancers. We sought to determine the objective response rate of combination durvalumab (D) plus tremelimumab (TM) in parallel cohorts of patients with carefully selected rare cancer types in which these agents had not previously been evaluated in phase II trials and for which there was clinical or biological rationale for dual immune checkpoint inhibitor therapy to be active.

Methods: We designed a multi-centre, non-blinded, open-label phase II basket trial with each of the following 8 rare cancers considered a separate phase II trial: salivary carcinoma, carcinoma of unknown primary (CUP) with tumour infiltrating lymphocytes and/or expressing PD-L1, mucosal melanoma, acral melanoma, osteosarcoma, undifferentiated pleomorphic sarcoma, clear cell carcinoma of the ovary (CCCO) or squamous cell carcinoma of the anal canal (SCCA).

The burden and long-term trends of breast cancer by different menopausal status in China.

Background: The burden of breast cancer in women of different menopausal status has not been assessed in China previously. We aim to evaluate and project the burden of breast cancer in different menopausal status in China.

Methods: The incidence and mortality of breast cancer were estimated using the data of 554 cancer registries in 2017 and the trends of incidence and mortality of 112 cancer registries from 2010 to 2017.

Islet-derived exosomal miR-204 accelerates insulin resistance in skeletal muscle by suppressing sirtuin 1: An in vivo study in a mouse model of high-fat diet-induced obesity.

Aims: The interaction between pancreatic islets and skeletal muscle plays a pivotal role in the development of insulin resistance. The present study aimed to elucidate the impact of non-hormonal molecules from islets on the insulin sensitivity of skeletal muscle cells.

Materials And Methods: We developed a mouse model of obesity through a high-fat diet, assessing glucose tolerance and conducting miRNA sequencing on skeletal muscle samples.

Aggregate Science: from Molecules, beyond Molecules.

Over the past centuries, molecular science has played a dominant role in the advancement of physical science by exploring the structure-property relationships at a single molecular level. However, when molecules form aggregates, a dilemma arises as the structures and properties often differ significantly from those of molecular constituents. To address this, the concept of aggregate science emphasizes a holistic approach to understanding the structures-properties relationship of substances.

Polygenic risk for alcohol use disorder affects cellular responses to ethanol exposure in a human microglial cell model.

Polygenic risk scores (PRSs) assess genetic susceptibility to alcohol use disorder (AUD), yet their molecular implications remain underexplored. Neuroimmune interactions, particularly in microglia, are recognized as notable contributors to AUD pathophysiology. We investigated the interplay between AUD PRS and ethanol in human microglia derived from iPSCs from individuals with AUD high-PRS (diagnosed with AUD) or low-PRS (unaffected).

Methylene Blue: An FDA-Approved NIR-II Fluorogenic Probe with Extremely Low pH Responsibility for Hyperchlorhydria Imaging.

Methylene blue (MB) is an FDA (Food and Drug Administration)-approved contrast agent with donor-acceptor (D-A) structure integrated with carbonyl-containing nitrogen-heterocycles. MB can be converted into MBH (protonated MB) by protonation, which not only induces the fluorescence emission red-shifted from the first near-infrared window (NIR-I, 650-950 nm) to the second near-infrared window (NIR-II, 1000-1700 nm) but also achieves ACQ-to-AIE conversion. MB has been successfully demonstrated in hyperacidemia imaging with an extremely low pH value (<1).

No Increased Risk of Major Adverse Cardiovascular Events following Nicotinamide Exposure.

Importance: Nicotinamide metabolites have recently been implicated in increased risk of major cardiovascular events (MACE). Supportive data about clinical risk of MACE for nicotinamide users is lacking.

Objective: To determine whether nicotinamide use results in an increase of MACE.

EIF4A3 is stabilized by the long noncoding RNA BC200 to regulate gene expression during Epstein-Barr virus infection.

Epstein‒Barr virus (EBV) regulates the expression of host genes involved in functional pathways for viral infection and pathogenicity. Long noncoding RNAs (lncRNAs) have been found to be important regulators of cellular biology. However, how EBV affects host biological processes via lncRNAs remains elusive.

Advances of conductive hydrogel designed for flexible electronics: A review.

In recent years, there has been considerable attention devoted to flexible electronic devices within the realm of biomedical engineering. These devices demonstrate the capability to accurately capture human physiological signals, thereby facilitating efficient human-computer interaction, and providing a novel approach of flexible electronics for monitoring and treating related diseases. A notable contribution to this domain is the emergence of conductive hydrogels as a novel flexible electronic material.

Phosphorylation of the transcription factor SlBIML1 by SlBIN2 kinases delays flowering in tomato.

Brassinosteroids (BRs) are well known for their important role in the regulation of plant growth and development. Plants with deficiency in BR signaling show delayed plant development and exhibit late flowering phenotypes. However, the precise mechanisms involved in this process require investigation.

Scaled and efficient derivation of loss-of-function alleles in risk genes for neurodevelopmental and psychiatric disorders in human iPSCs.

Translating genetic findings for neurodevelopmental and psychiatric disorders (NPDs) into actionable disease biology would benefit from large-scale and unbiased functional studies of NPD genes. Leveraging the cytosine base editing (CBE) system, we developed a pipeline for clonal loss-of-function (LoF) allele mutagenesis in human induced pluripotent stem cells (hiPSCs) by introducing premature stop codons (iSTOP) that lead to mRNA nonsense-mediated decay (NMD) or protein truncation. We tested the pipeline for 23 NPD genes on 3 hiPSC lines and achieved highly reproducible, efficient iSTOP editing in 22 genes.

Incidence, mortality, and disability-adjusted life years of female breast cancer in China, 2022.

Background: Breast cancer is ranked among the most prevalent malignancies in the Chinese female population. However, comprehensive reports detailing the latest epidemiological data and attributable disease burden have not been extensively documented.

Methods: In 2018, high-quality cancer surveillance data were recorded in 700 population-based cancer registries in China.

Large Language Models Improve the Identification of Emergency Department Visits for Symptomatic Kidney Stones.

Background: Recent advancements of large language models (LLMs) like Generative Pre-trained Transformer 4 (GPT-4) have generated significant interest among the scientific community. Yet, the potential of these models to be utilized in clinical settings remains largely unexplored. This study investigated the abilities of multiple LLMs and traditional machine learning models to analyze emergency department (ED) reports and determine if the corresponding visits were caused by symptomatic kidney stones.

BET degrader exhibits lower antiproliferative activity than its inhibitor via EGR1 recruiting septins to promote E2F1-3 transcription in triple-negative breast cancer.

The bromodomain and extraterminal domain (BET) family proteins serve as primary readers of acetylated lysine residues and play crucial roles in cell proliferation and differentiation. Dysregulation of BET proteins has been implicated in tumorigenesis, making them important therapeutic targets. BET-bromodomain (BD) inhibitors and BET-targeting degraders have been developed to inhibit BET proteins.

Alzheimer's disease protective allele of modulates neuronal excitability through lipid-droplet-mediated neuron-glia communication.

Genome-wide association studies (GWAS) of Alzheimer's disease (AD) have identified a plethora of risk loci. However, the disease variants/genes and the underlying mechanisms remain largely unknown. For a strong AD-associated locus near (), we tied an AD protective allele to a role of neuronal CLU in promoting neuron excitability through lipid-mediated neuron-glia communication.

LncRNA BC200 promotes the development of EBV-associated nasopharyngeal carcinoma by competitively binding to miR-6834-5p to upregulate TYMS expression.

Nasopharyngeal carcinoma (NPC) is closely related to Epstein-Barr virus (EBV) infection. Long noncoding RNAs (lncRNAs) play important roles in cancers. However, the molecular mechanism underlying the roles of lncRNAs in EBV-associated NPC remains largely unclear.

Probing action potentials of single beating cardiomyocytes using atomic force microscopy.

This paper presents a method for using atomic force microscopy to probe action potentials of single beating cardiomyocytes at the nanoscale. In this work, the conductive tip of an atomic force microscope (AFM) was used as a nanoelectrode to record the action potentials of self-beating cardiomyocytes in both the non-constant force contact mode and the constant force contact mode. An electrical model of a tip-cell interface was developed and the indentation force effect on the seal of an AFM conductive tip-cell membrane was theoretically analyzed.