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Background: Due to the lack of a comprehensive pharmacology test set, evaluating the potential and value of large language models (LLMs) in pharmacology is complex and challenging.

Aims: This study aims to provide a test set reference for assessing the application potential of both general-purpose and specialized LLMs in pharmacology.

Methods: We constructed a pharmacology test set consisting of three tasks: drug information retrieval, lead compound structure optimization, and research trend summarization and analysis. Subsequently, we compared the performance of general-purpose LLMs GPT-3.5 and GPT-4 on this test set.

Results: The results indicate that GPT-3.5 and GPT-4 can better understand instructions for information retrieval, scheme optimization, and trend summarization in pharmacology, showing significant potential in basic pharmacology tasks, especially in areas such as drug pharmacological properties, pharmacokinetics, mode of action, and toxicity prediction. These general LLMs also effectively summarize the current challenges and future trends in this field, proving their valuable resource for interdisciplinary pharmacology researchers. However, the limitations of ChatGPT become evident when handling tasks such as drug identification queries, drug interaction information retrieval, and drug structure simulation optimization. It struggles to provide accurate interaction information for individual or specific drugs and cannot optimize specific drugs. This lack of depth in knowledge integration and analysis limits its application in scientific research and clinical exploration.

Conclusion: Therefore, exploring retrieval-augmented generation (RAG) or integrating proprietary knowledge bases and knowledge graphs into pharmacology-oriented ChatGPT systems would yield favorable results. This integration will further optimize the potential of LLMs in pharmacology.

The Gram-positive cocci Staphylococcus aureus, Streptococcus spp., and Enterococcus spp. are the most frequent causative organisms of bloodstream infections and infective endocarditis. "Complicated bacteremia" is a term used in S. aureus bloodstream infections and originally implied the presence of metastatic infectious foci (i.e. complications of S. aureus bacteremia). These complications demand longer antimicrobial treatment durations and, frequently, interventional source control. Several risk factors for the incidence of bacteremia complications have been identified and are often used for the definition of complicated bacteremia. Here, we discuss management and diagnostic approaches and treatment options for patients with complicated bacteremia, with particular focus on infective endocarditis. We also summarize the available evidence regarding imaging modalities and the choice of antimicrobial mono- or combination therapy according to resistance patterns for these pathogens as well as treatment durations and optimized application routes. Finally, we synopsize current and future areas of research in complicated bacteremia and infective endocarditis.

Lysosomal storage disorders (LSDs) are rare inherited metabolic disorders characterized by defects in the function of specific enzymes responsible for breaking down substrates within cellular organelles (lysosomes) essential for the processing of macromolecules. Undigested substrate accumulates within lysosomes, leading to cellular dysfunction, tissue damage, and clinical manifestations. Clinical features vary depending on the degree and type of enzyme deficiency, the type and extent of substrate accumulated, and the tissues affected. The heterogeneous nature of LSDs results in a variety of treatment approaches, which must be tailored to patient presentation and characteristics. The treatment landscape for LSDs is rapidly evolving. An up-to-date discussion of current evidence is required to provide clinicians with an appropriate overview of treatment options. Therefore, we aimed to review current and ongoing trials pertaining to the treatment of common LSDs.

Inavolisib (Itovebi^™) is an orally administered, phosphatidylinositol-3-kinase alpha (PI3Kα) inhibitor being developed by Genentech, a member of the Roche group, for the treatment of solid tumours. On 10 October 2024, inavolisib received its first approval in the USA in combination with palbociclib and fulvestrant for the treatment of adults with endocrine-resistant, PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor 2 (HER2)-negative, locally advanced or metastatic breast cancer, as detected by an FDA-approved test, following recurrence on or after completing adjuvant endocrine therapy. In the EU and other countries worldwide, regulatory review of inavolisib is currently underway. This article summarises the milestones in the development of inavolisib leading to this first approval for endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative, locally advanced or metastatic breast cancer.

The human microbiome exerts profound influence over various biological processes within the body. Unlike many host determinants, it represents a readily accessible target for manipulation to promote health benefits. However, existing commercial microbiome-directed products often exhibit low efficacy. Advancements in technology are paving the way for the development of novel microbiome therapeutics, across a wide range of indications. In this narrative review, we provide an overview of state-of-the-art technologies in late-stage development, examining their advantages and limitations. By covering a spectrum, from fecal-derived products to live biotherapeutics, phage therapy, and synthetic biology, we illuminate the path toward the future of microbiome therapeutics.

Tuberculosis (TB) is the leading cause of death from a single infectious agent. The burden is highest in some low- and middle-income countries. One-quarter of the world's population is estimated to have been infected with TB, which is the seedbed for progressing from TB infection to the deadly and contagious disease itself. Although some individuals may clear their infections through innate and acquired immunity, many do not. People living with HIV, TB-exposed household contacts, other individuals recently infected, and immunosuppressed individuals are at especially high risk of progressing to TB disease. There have been major advances in recent years to support the programmatic management of TB infection. New tests of infection, including those that predict progression to TB disease, have become available. Numerous World Health Organization-recommended TB preventive treatment (TPT) regimens are available for all ages and for both drug-susceptible and drug-resistant TB infection. All regimens are generally safe, efficacious, and cost effective and have a low risk of generating resistance. TPT is recommended for pregnant women who are at risk for developing TB, but some regimens are associated with an increased likelihood of poor obstetric and fetal outcomes, and newer regimens have not yet been tested in pregnancy. New formulations of rifapentine-based TPT have been developed, and the cost has been radically reduced. Innovative models of delivery to support the scale up of TPT have been developed. Modeling suggests that scaling up TPT, especially regimens with optimal target product profile characteristics, can contribute substantially to ending the TB epidemic. The global uptake of TPT has increased substantially, especially for people living with HIV. Implementation gaps remain, particularly for children, pregnant women, and other household contacts. Further innovation is required to support the continued scale up of TPT and to contribute to ending the TB epidemic.

Marstacimab (marstacimab-hncq; HYMPAVZI™) is a subcutaneously administered human monoclonal immunoglobulin G1 antibody against tissue factor pathway inhibitor (TFPI) that is being developed by Pfizer for the treatment of hemophilia A and B. Marstacimab received its first approval on 11 October 2024 in the USA. It was approved for use as routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients 12 years of age and older with hemophilia A without factor VIII inhibitors or hemophilia B without factor IX inhibitors. Marstacimab has since been approved on 18 Nov in the EU for the treatment of adults and adolescents with severe hemophilia A or B without inhibitors. This article summarizes the milestones in the development of marstacimab leading to this first approval for hemophilia.

Buprenorphine is an agonist at the mu opioid receptor (MOR) and antagonist at the kappa (KOR) and delta (DOR) receptors and a nociceptin receptor (NOR) ligand. Buprenorphine has a relatively low intrinsic efficacy for G-proteins and a long brain and MOR dwell time. Buprenorphine ceiling on respiratory depression has theoretically been related multiple factors such as low intrinsic efficacy at MOR, binding to six-transmembrane MOR and interactions in MOR/NOR heterodimers. Buprenorphine reduces analgesic tolerance by acting as a delta opioid receptor (DOR) antagonist. As a kappa opioid receptor (KOR) antagonist, buprenorphine reduces craving associated with addiction. Buprenorphine is a model opioid for the ordinal bifunctional analogs BU10038, BU08028 which have been shown to be potent analgesics in non-human primates without reinforcing effects and little to no respiratory depression.