Enhancing pharmacogenomic data accessibility and drug safety with large language models: a case study with Llama3.1.

Pharmacogenomics (PGx) holds the promise of personalizing medical treatments based on individual genetic profiles, thereby enhancing drug efficacy and safety. However, the current landscape of PGx research is hindered by fragmented data sources, time-consuming manual data extraction processes, and the need for comprehensive and up-to-date information. This study aims to address these challenges by evaluating the ability of Large Language Models (LLMs), specifically Llama3.

The incorporation of MALDI mass spectrometry imaging in studies to identify markers of toxicity following opioid exposures in mouse fetuses.

Introduction: In 2015, the FDA released a Drug Safety Communication regarding a possible link between opioid exposure during early pregnancy and an increased risk of fetal neural tube defects (NTDs). At the time, the indications for opioid use during pregnancy were not changed due to incomplete maternal toxicity data and limitations in human and animal studies. To assess these knowledge gaps, largescale animal studies are ongoing; however, state-of-the-art technologies have emerged as promising tools to assess otherwise non-standard endpoints.

State of the science on assessing developmental neurotoxicity using new approach methods.

The workshop titled State of the Science on Assessing Developmental Neurotoxicity Using New Approach Methods was co-organized by University of Maryland's Joint Institute for Food Safety and Applied Nutrition (JIFSAN) and the U.S. Food and Drug Administration's (FDA) Center for Food Safety and Applied Nutrition (CFSAN; now called the Human Foods Program), and was hosted by FDA in College Park, MD on November 14-15, 2023.

Causes, patterns, and epidemiology of tattoo-associated infections since 1820.

Despite increased awareness and public health initiatives, the incidence of microbial infections related to tattoos has increased since 2000. Building on the first paper in this two-part Series, which detailed the microbiological aspects of tattoo-related infections over the past two centuries from 1820 to 2023, this second paper describes the patterns, causes, and other related epidemiological factors of these infections. Since 2000, bacterial outbreaks, particularly those caused by non-tuberculous mycobacteria, have increased, prompting a re-evaluation of tattoos as a serious public health risk.

Microbiology of tattoo-associated infections since 1820.

The increasing popularity of tattoos parallels the rise in microbial infections associated with tattooing. This two-part Series provides a comprehensive overview of microbial infections linked to tattoos dating back to 1820. This first paper in the Series particularly emphasises the changing landscape of infections since 2000, a period marked by enhanced public health regulations and growing awareness.

Untargeted metabolomics and lipidomics in COVID-19 patient plasma reveals disease severity biomarkers.

Introduction: Coronavirus disease 2019 (COVID-19) has widely varying clinical severity. Currently, no single marker or panel of markers is considered standard of care for prediction of COVID-19 disease progression. The goal of this study is to gain mechanistic insights at the molecular level and to discover predictive biomarkers of severity of infection and outcomes among COVID-19 patients.

Enhancing Bias Assessment for Complex Term Groups in Language Embedding Models: Quantitative Comparison of Methods.

Background: Artificial intelligence (AI) is rapidly being adopted to build products and aid in the decision-making process across industries. However, AI systems have been shown to exhibit and even amplify biases, causing a growing concern among people worldwide. Thus, investigating methods of measuring and mitigating bias within these AI-powered tools is necessary.

An efficient enzymatic system for studying structure-carcinogenicity relationships: metabolism of pyrrolizidine alkaloids by human liver microsomes in the presence of calf thymus DNA, resulting in the formation of DNA adducts.

Pyrrolizidine alkaloids (PAs) form a family of toxic and carcinogenic phytochemicals found in plants worldwide. The metabolism of toxic PAs, both and , generates four (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5-pyrrolizine (DHP)-derived DNA adducts, namely, DHP-dG-3, DHP-dG-4, DHP-dA-3, and DHP-dA-4, as documented in previous research. We have proposed that these DHP-DNA adducts play a pivotal role in the induction of liver tumor by PAs in rats and mice, serving as potential common biological biomarkers for PA exposure and carcinogenesis.

Dietary soy protein reverses obesity-induced liver steatosis and alters fecal microbial composition independent of isoflavone level.

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major public health concern that is exacerbated by the obesity pandemic. Dietary interventions have the potential to alleviate obesity-associated MASLD through variable mechanisms, including optimizing the gut microbiota. Previously, we reported that soy protein concentrate (SPC) with low or high levels of isoflavone (LIF or HIF) protected young obese Zucker rats from developing liver steatosis.

Salmonella enterica virulence databases and bioinformatic analysis tools development.

Salmonella enterica, a prominent foodborne pathogen, contributes significantly to global foodborne illnesses annually. This species exhibits significant genetic diversity, potentially impacting its infectivity, disease severity, and antimicrobial resistance. Whole genome sequencing (WGS) offers comprehensive genetic insights that can be utilized for virulence assessment.

Mutagenicity and genotoxicity evaluation of 15 nitrosamine drug substance-related impurities in human TK6 cells.

Nitrosamine drug substance-related impurities (NDSRIs) are a sub-category of N-nitrosamine drug impurities that share structural similarity to the corresponding active pharmaceutical ingredient. The mutagenicity of NDSRIs is poorly understood. We previously tested a series of NDSRIs using the Enhanced Ames Test (EAT).

Physiological liver microtissue 384-well microplate system for preclinical hepatotoxicity assessment of therapeutic small molecule drugs.

Hepatotoxicity can lead to the discontinuation of approved or investigational drugs. The evaluation of the potential hepatoxicity of drugs in development is challenging because current models assessing this adverse effect are not always predictive of the outcome in human beings. Cell lines are routinely used for early hepatotoxicity screening, but to improve the detection of potential hepatotoxicity, in vitro models that better reflect liver morphology and function are needed.

Clonal expansion of cancer driver gene mutants investigated using advanced sequencing technologies.

Advanced sequencing technologies (ASTs) have revolutionized the quantitation of cancer driver mutations (CDMs) as rare events, which has utility in clinical oncology, cancer research, and cancer risk assessment. This review focuses on studies that have used ASTs to characterize clonal expansion (CE) of cells carrying CDMs and to explicate the selective pressures that shape CE. Importantly, high-sensitivity ASTs have made possible the characterization of mutant clones and CE in histologically normal tissue samples, providing the means to investigate nascent tumor development.

Development of a comprehensive open access "molecules with androgenic activity resource (MAAR)" to facilitate risk assessment of chemicals.

The increasing prevalence of endocrine-disrupting chemicals (EDCs) and their potential adverse effects on human health underscore the necessity for robust tools to assess and manage associated risks. The androgen receptor (AR) is a critical component of the endocrine system, playing a pivotal role in mediating the biological effects of androgens, which are male sex hormones. Exposure to androgen-disrupting chemicals during critical periods of development, such as fetal development or puberty, may result in adverse effects on reproductive health, including altered sexual differentiation, impaired fertility, and an increased risk of reproductive disorders.

Optimizing the detection of N-nitrosamine mutagenicity in the Ames test.

Accurately determining the mutagenicity of small-molecule N-nitrosamine drug impurities and nitrosamine drug substance-related impurities (NDSRIs) is critical to identifying mutagenic and cancer hazards. In the current study we have evaluated several approaches for enhancing assay sensitivity for evaluating the mutagenicity of N-nitrosamines in the bacterial reverse mutagenicity (Ames) test. Preincubation assays were conducted using five activation conditions: no exogenous metabolic activation and metabolic activation mixes employing both 10% and 30% liver S9 from hamsters and rats pretreated with inducers of enzymatic activity.

Comprehensive Genomic Analysis of Uropathogenic : Virulence Factors, Antimicrobial Resistance, and Mobile Genetic Elements.

Our whole-genome sequencing analysis of sixteen uropathogenic isolates revealed a concerning picture of multidrug resistance and potentially virulent bacteria. All isolates belonged to four distinct clonal groups, with the highly prevalent ST131 lineage being associated with extensive antibiotic resistance and virulence factors. Notably, all isolates exhibited multidrug resistance, with some resistant to as many as 12 antibiotics.

Coupling antitoxins and blue/white screening with /resolvase mutation as a strategy for spp. plasmid curing.

Unlabelled: Despite the dissemination of multidrug resistance plasmids, including those carrying virulence genes in spp., efficient plasmid curing tools are lacking. Plasmid partitioning and multimer resolution systems are attractive targets for plasmid cure.

Biodistribution and toxic potential of silver nanoparticles when introduced to the female rat reproductive tract.

The prevalence of ionic silver and silver nanomaterials in hygiene products has been increasing due to their antimicrobial activity. While numerous studies have examined the effects of nanosilver in laboratory settings, there is a limited understanding of its impact on reproductive tissues, as well as its biodistribution and toxicity upon intra-vaginal exposure. If ionic or nanosilver enters adjacent and internal tissues via intra-vaginal exposure, the overuse of hygiene products containing silver may potentially threaten woman's health.

Complete genome sequence of cephalosporin and tetracycline-resistant CF51 isolate from a patient with urinary tract infection.

We report here the complete genome sequence of cephalosporin (cefazolin and cephalotin) and tetracycline-resistant strain CF51, isolated from a patient with a urinary tract infection. The genome comprises a 5.0-Mb chromosome, along with an 87.

The acquired gene cluster in mediates resistance to copper.

The pervasive environmental metal contamination has led to selection of heavy-metal resistance genes in bacteria. The and clusters are located on a mobile genetic element and linked to heavy-metal resistance. These clusters have been found in serovars isolated from human clinical cases and foods of animal origin.

Complete genome sequence of strain FW102 with β-galactosidase activity in drinking fountain water.

is a ubiquitous environmental microbe in nature, particularly abundant in soil and water sources. Recently, has been considered to be a potential opportunistic pathogen in humans. We report the 5,9540,064-bp genome sequence of strain FW102 isolated from drinking fountain water and predicted to have multiple copies of β-galactosidase genes.