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This study integrates agent-based modeling (ABM) and causal machine learning (ML) to assess the impact of clinicians’ adherence to antibiotic guidelines in older adults hospitalized with community-acquired pneumonia (CAP). Using a synthetic population and longitudinal data, we estimate individual treatment effects of vancomycin via the longitudinal modified treatment policy (LMTP) algorithm and simulate clinical decision-making and MRSA transmission dynamics in a NetLogo-based ABM. We evaluate how varying hospital-level propensities toward vancomycin prescribing influence 30-day mortality under different causal and behavioral scenarios. Results show high model repeatability and confirm increased mortality among mechanically ventilated patients treated empirically with vancomycin. Integrating causal inference within ABM supports evidence-based antibiotic stewardship and privacy-preserving simulation of clinical behaviors.

An investigation of the Hawaiian marine-derived fungus Fusarium sp. strain FM701 led to the isolation of two new pyridinium-containing fusaric acid dimers (1, 2), fusaric acid (3), and two known fusaric acid derivatives (4, 5), beauvericin (6), beauvericin J (7), and desferricrocin (8). Structures of 1 and 2 were elucidated by NMR spectroscopy, GIAO NMR calculations, HRESIMS, and electronic circular dichroism analyses. Genome mining revealed putative biosynthetic gene clusters for fusaric acid, beauvericin, and desferricrocin. Chemical synthesis of 9,10-dehydrofusaric acid (4) and racemic fusarinolic acid (5), combined with feeding experiments, supported their plausible biosynthetic relationship and potential roles as biosynthetic building blocks of dimeric metabolites 1 and 2. Compounds 1, 2, 6, and 7 exhibited potent antibacterial activity against Gram-positive bacteria, and all compounds (1–8) showed 2- to 4-fold enhanced activity when combined with a subinhibitory concentration of chloramphenicol. Beauvericin (6) also displayed strong antiproliferative activity against human breast (MCF-7) and prostate (DU145) cancer cell lines, with low micromolar IC50 values. Together, these findings expand the chemical diversity of fusaric acid metabolites and the biological potential of marine fungal metabolites.

We report the complete genome sequence of CGI, a strain of varicella-zoster virus (VZV) isolated from a 3-year-old immunocompetent patient with severe herpes zoster. The isolated strain exhibits an ORF62 genotype characteristic of vOka, in addition to a wild-type ORF0 gene and a novel methionine to valine substitution in ORF58.

Escherichia coli O157:H7 (O157) is a foodborne pathogen that causes disease in humans with symptoms ranging from watery/bloody diarrhea to kidney failure. Cattle are the main reservoirs of this human pathogen, where O157 tends to persist at the rectoanal junction (RAJ) of the bovine gastrointestinal tract. However, the exact mechanisms by which O157 adheres and persists at the bovine RAJ is not fully understood. Here, we identified that the O157 carbon starvation-inducible lipoprotein (Slp) allows O157 to attach to cells at the RAJ using polymeric immunoglobulin receptor (pIgR) protein as the Slp-receptor. Not only does this attachment of Slp to the cattle receptor allow O157 to colonize cattle, but the interaction could potentially interfere with intestinal immune responses, further promoting long-term O157 colonization of cattle. This makes Slp an attractive target for therapeutic interventions, such as vaccines that could interfere with O157 attachment to cattle intestinal cells.

Pathogenic microbes utilize virulence strategies to subvert host immune responses, highlighting a continuous race between the pathogen and the host. The emergence of multidrug- resistant and hypervirulent strains of Klebsiella pneumoniae (Kp) poses a critical threat to public health. This critical evaluation identifies key gaps in understanding the interplay between Kp and host innate immunity. This review provides a comprehensive overview of the mechanisms by which Kp triggers various forms of cell death. This review highlights that immunomodulatory approaches targeting cell death regulators or immune checkpoints may offer host-directed strategies against Kp-induced sepsis.

The aim was to evaluate the association between glucagon-like peptide-1 receptor agonist (GLP-1 RA) initiation and adverse gastrointestinal, renal, respiratory and psychiatric outcomes among individuals with opioid use disorder (OUD). This retrospective cohort study was conducted using the MarketScan Commercial Claims and Encounters database (2016–2023) following a target trial emulation framework.

Animal models provide a crucial scientific substrate for medical innovation, yet findings in these models do not always translate directly to humans. Although murine models are extensively employed to study skeletal muscle aging, the extent to which they diverge from the human aging process remains poorly understood. This study examined transcriptional changes with aging in mouse and human skeletal muscle. Hypoxia signaling, VEGFA, and inflammatory pathways showed concordant downregulation with aging in both species; however, angiogenesis, neurogenesis, and myogenesis demonstrated opposing or non-significant trends. These findings caution against direct extrapolation of murine aging transcriptomics to human skeletal muscle biology, though select conserved pathways may represent viable cross-species targets for future investigation.

Voltage-gated sodium channels are the primary target site for many insecticides and natural products, including natural pyrethrins and pyrethroids. Mutations in these channels can reduce insecticide sensitivity and contribute to resistance. Previous work has shown that a select class of compounds, lipid alkamides, are able to affect sodium channels via a distinct mechanism from pyrethroids. Due to these distinct characteristics, it is possible that lipid alkamides may synergize natural pyrethrins or other sodium channel-directed insecticides. This study evaluated the potential of lipid alkamides to synergize natural pyrethrins. We found they are capable of synergizing natural pyrethrins via target-site synergism; however, these effects are mitigated in at least some forms of kdr-resistance.

Tuberculosis (TB) remains a leading cause of morbidity and mortality among children, particularly those living with HIV in sub-Saharan Africa. Despite advances in integrating TB and HIV care in Ghana, long-term data on pediatric treatment outcomes across various age groups and nutritional statuses remain limited. This study aimed to determine TB treatment outcomes among children aged 0 to 14 years and assess the association of HIV co-infection and other factors on unsuccessful treatment outcomes. The pediatric TB treatment success rate at KATH still falls short of the WHO target of 90%. Older age and HIV co-infection significantly increase the risk of unsuccessful treatment, with underweight children facing a greater risk. Strengthening integrated pediatric TB/HIV services through improved age-related enhanced adherence and nutritional support for adequate weight gain is crucial for improving outcomes and reducing default and mortality rates among children with TB in Ghana.

Leishmaniasis is a disease caused by parasites and spread through the bites of infected sand flies, and it remains a health concern in southeastern Peru. However, we still do not fully understand how environmental conditions affect where these insects live in the region. In this study, we collected sand flies during the wet season from four types of habitats, including secondary forests, fruit-crops, bamboo-dominated areas, and around homes, to better understand where they are most common and how local microclimate influences their distribution.