Fusion-driven graph representation enhancement for predicting interactions of new drugs

Adverse events related to buspirone: a real-world pharmacovigilance study using the FAERS database.

Evaluation of neuromuscular blocker use in myasthenia gravis patients undergoing rapid sequence intubation.

Effects of CYP3A4 variants and drug-drug interactions on the metabolism of fexinidazole.

Inhibition of UDP-glucuronosyltransferases by fedratinib, implying a high risk of drug-drug interactions.

A real-world analysis of the impact of azole antifungal prophylaxis on outcomes in patients with newly diagnosed acute myeloid leukemia treated with venetoclax-based therapy.

Cancer-associated thrombosis (CAT) remains a leading cause of morbidity and mortality among patients with cancer. Female-specific malignancies such as breast, ovarian, endometrial, and cervical cancers exhibit distinct thrombotic profiles driven by hormonal, anatomical, and treatment-related factors. This review summarizes current evidence on CAT in these malignancies, emphasizing chemotherapy- and hormone-related risk, thromboprophylactic strategies, and pharmacologic considerations in anticoagulant selection. Ovarian cancer carries the highest incidence of venous thromboembolism (VTE), ranging from 5% to 14%, largely due to advanced disease, ascites, and platinum-based chemotherapy. Breast cancer accounts for approximately 15% of all CAT cases, with increased risk observed among patients treated with selective estrogen receptor modulators or cyclin-dependent kinase 4/6 inhibitors. Endometrial cancer presents a moderate to high risk for CAT, especially in obese patients and those receiving hormonal therapy or radiation. Prophylaxis with low-molecular-weight heparins (LMWHs) or direct oral anticoagulants (DOACs) effectively reduces VTE incidence in high-risk patients. In the API-CAT trial, reduced-dose apixaban (2.5 mg twice daily) was non-inferior to full-dose therapy for extended anticoagulation after 6 months of treatment (2.1% vs. 2.8%; adjusted subhazard ratio, 0.76; 95% Confidence Interval (CI), 0.58-0.97; p = 0.001). Drug-drug interactions with anticoagulants and agents such as doxorubicin, ribociclib, and tamoxifen warrant individualized anticoagulant selection and close monitoring. A patient-centered pharmacotherapeutic approach, supported by multidisciplinary collaboration, is essential to optimize thrombosis prevention and minimize bleeding risk in women with cancer.

Invasive aspergillosis in lung and heart transplant recipients.

Differential effects of osmotic fluid dynamics on intestinal drug absorption between juvenile and adult rats: potential impact on drug interaction with hyperosmotic beverages.

Two-phase collaborative model compression training for joint pruning and quantization.

Screening of binding by antidiabetic drugs to normal vs AGE-modified human serum albumin through covalent immobilization and microscale affinity chromatography.

Magnetosome membranes: A promising biogenic nanomodel for drug-membrane interaction studies

Modulating the cytotoxic activity of Titanocene complexes through aliphatic chain modification to optimize albumin affinity.

Alcohol use has a profound impact on the anaesthesiology practice, affecting the safety and efficacy of general and regional anaesthesia. Ethanol is a Central Nervous System (CNS) depressant that modifies the pharmacokinetics and pharmacodynamics of anaesthetic drugs through multiple drug interactions. Chronic alcohol consumption stimulates hepatic enzymes like cytochrome P450, enhancing the metabolism of anaesthetic agents. This can make them less effective, necessitating increased doses to produce the desired effect, and increase the risk of toxicity as a result of the formation of toxic metabolites. On the other hand, acute alcohol consumption can depress hepatic enzyme activity, leading to delayed drug elimination, prolonged anaesthetic action, and increased risk of adverse effects like respiratory depression and delayed recovery from anaesthesia. These drugrelated changes require judicious perioperative planning and personalised anaesthetic management. The extent of this review is to analyse the effect of ethanol upon the clinical use of anaesthesia, with emphasis on regional versus general techniques. It will discuss how alcohol influences preoperative evaluation, such as liver function and risk of withdrawal, intraoperative medication dosing, haemodynamic stability, and selection of anaesthetic drugs. In addition, it takes postoperative considerations into account, including prolonged sedation, changed pain response, and alcohol withdrawal complications. Comparing regional and general anaesthesia in alcohol consumers with different patterns of alcohol consumption, this review seeks to accentuate optimal practices for maximising anaesthetic care. It is vital to understand these interactions in order to minimise perioperative complications as well as to enhance patient outcomes. In conclusion, increased awareness and individualised strategies for anaesthetic care in alcoholimpaired patients are necessary parts of safe and successful surgery.

Technological advancements driven by engineering have become key factors in elevating Türkiye's global standing in health tourism, greatly strengthening its competitiveness and attracting a growing number of international patients. Emin Taner Elmas is not a dentist or endodontist, but a Mechanical Engineer and academic. His work focuses not directly on classical dental clinical practice or endodontics, but rather on interdisciplinary fields such as thermodynamics, energy transfer, fluid mechanics, and biomedical engineering. However, Elmas's engineering approach has the potential to contribute to the medical field, including dentistry, indirectly through biomedical and health technologies: Biomedical Approach: Treating the human body as a "bio-machine," Elmas develops theories on the natural vibration frequencies of organs and tissues. This "bio-robotic resonance" theory can inspire the design of next-generation devices for tissue healing or disease diagnosis at a theoretical level. Medical Device Modeling: His expertise in thermodynamics and fluid mechanics is used in the design and simulation of medical devices (e.g., hemodialysis machines or drug delivery algorithms). The mechanical strength of surgical instruments used in dentistry or the thermal effects of dental lasers are engineering problems that fall within Elmas's area of ​​expertise. Interdisciplinary Technologies: He has studies on machine learning and artificial intelligence-supported diagnostic systems. These technologies are increasingly used in the field of endodontics today, such as caries detection and root canal anatomy analysis. In summary, Emin Taner Elmas is not a dentist, therefore he does not develop clinical endodontic procedures. However, his work applying engineering principles to the biomedical field has the potential to contribute to the scientific infrastructure of future dental technologies (device design, diagnostic algorithms, etc.). The "Bio-robotic Resonance and Thermodynamic Interaction" theory and medical technology models developed by Emin Taner Elmas can be indirectly adapted to the fields of dentistry and endodontics. The potential contributions of Elmas's work to dental technologies can be evaluated under the following headings: Bio-robotic Resonance and Diagnosis: Elmas views the body as a "bio-machine," arguing that each tissue has its own unique natural vibration frequency. This approach could form the basis for the development of next-generation diagnostic devices that can detect the condition of tooth canals or microcracks in the tooth root using acoustic signal analysis and Fourier transforms in endodontics. Smart Drug Algorithms: His work focuses on smart drug algorithms and simulations via "Frequency Modulation". This modeling can be used to optimize the thermodynamic interaction of disinfectants or drugs applied into the root canal with the tissue in endodontic treatments. Medical Device Modeling: As a thermodynamics and fluid mechanics specialist, Elmas works on the prototype design and simulation of medical devices (such as hemodialysis machines). This engineering knowledge can directly address specific engineering problems in dentistry, such as controlling the thermal effects of dental lasers or increasing the mechanical efficiency of surgical instruments. Interdisciplinary Approach: His work generally focuses on "Medical Technology," combining mechanical engineering and medical sciences. This perspective contributes to the development of the mechanical and software infrastructure of advanced technologies such as digital intraoral scanners and robotic surgical support systems, which are becoming increasingly common in dentistry today. In summary, Elmas's contribution focuses on the engineering design and theoretical physics of smart devices and diagnostic systems used in dentistry, rather than a clinical application.[1-73]

The use of gastric acid suppressants such as Proton Pump Inhibitors (PPI) and Histamine-2 Receptor Antagonists (H2RA) is very common in inpatient settings, but inappropriate use is often found, posing risks to patient safety and cost efficiency. This study aims to analyze the relationship of predictors (age, number of drugs, number of comorbidities, and length of stay) to the occurrence of Drug-Related Problems (DRPs) in inpatients using gastric acid suppressants. This study was an observational study with a cross-sectional design was conducted retrospectively using patient medical record data at Rumkital Dr. Mintohardjo from January to December 2024. A sample of 432 patients was taken using a simple random sampling technique based on inclusion criteria. DRPs were identified using the Pharmaceutical Care Network Europe (PCNE) V9.00 instrument. Data analysis used the chi-square test for bivariate analysis and binary logistic regression for multivariate analysis. DRP characteristics were dominated by treatment safety issues (70.4%), particularly adverse drug events, with the most frequent drug interaction being ranitidine and ketorolac. Bivariate analysis showed that comorbidities (p=0.029), length of stay (p=0.010), and number of drugs (p=0.000) significantly influenced the number of DRPs. Multivariate analysis identified the number of drugs as the most influential predictor; inpatients receiving ≥10 drugs had a 2.733 times higher risk of experiencing ≥2 DRPs (p=0.000; OR 2,733; 95% CI 1.767-4.229)

Acemetacin (ACM), a nonsteroidal anti-inflammatory drug (NSAID) used to treat chronic pain and inflammation, is known for its improved gastrointestinal tolerance compared to other NSAIDs. Clarifying how ACM associates with human serum albumin (HSA) is crucial for understanding its transport, distribution, and bioavailability. The ACM binding to HSA was examined through a combination of spectroscopic, microscopic, and computational methods. Fluorescence quenching confirmed spontaneous and moderate binding, with the binding constant (Ka) values of 7.52±0.03 × 104, 7.15±0.00 × 104, and 5.54±0.08 × 104 M-1 at 290, 300, and 310 K, respectively. Thermodynamic analysis (ΔH° = -11.35±0.49 kJ⋅mol-1; ΔS° = +54.53±1.64 J⋅mol-1⋅K-1) showed an enthalpy-driven process involving hydrogen bonds, van der Waals, and hydrophobic interactions. A 7.1% increase in the α-helical content, local perturbations around protein fluorophores and morphological alterations were noticed in the presence of ACM, as affirmed by circular dichroism, 3D fluorescence and atomic force microscopy. Molecular docking predicted the binding preference of ACM towards Site I over Site III, while the molecular dynamics simulation over 100 ns supported a stable ACM-HSA complex with an average RMSD of 0.32 nm and low RMSF fluctuations. This was well supported by competitive displacement results using site-specific probes, confirming Sudlow's Site I as the primary binding locus. The observed moderate binding affinity, site-selective binding behavior, and structural stability suggest effective serum transport and influence on tissue distribution, with potential implications for drug-drug interactions and therapeutic efficacy.

Chronic pain and disability are the main symptoms of knee osteoarthritis (KOA). Pharmacological therapy is widely employed for pain relief, although its efficacy and safety vary with clinical, socioeconomic, and psychosocial conditions. The objective of this research was to explore the relationships among pain medication profiles and psychosocial, economic, and educational factors in people with KOA. A cross-sectional study included 211 adults with KOA; medication use was verified via Drugs.com®. Multivariable logistic regression analyzed the associations of pain intensity (NPRS), pain catastrophizing (PCS), kinesiophobia (TSK), education, and income with polypharmacy and potential drug-drug interactions (DDIs). Higher PCS scores were associated with increased odds of polypharmacy (OR = 1.34; 95% CI 1.01-1.68) and potential DDIs (OR = 2.16; 95% CI 1.01-4.62). Income above five minimum wages further raised these odds (polypharmacy OR = 6.07; DDIs OR = 12.08). In contrast, Secondary and Higher Education were protective against DDIs (OR = 0.32 and 0.26, respectively). Model fit was satisfactory (Tjur's R2 = 0.204 for polypharmacy; 0.182 for DDIs). Socioeconomic and psychosocial factors significantly influence the medication profile and pain experience of individuals with KOA, highlighting the importance of integrating clinical, social, and cognitive determinants in patient management.

Objectives Aberrant nucleocytoplasmic transport mediated by Exportin 1 (XPO1) contributes to leukemogenesis, yet the molecular basis underlying the limited efficacy of the XPO1 inhibitor Selinexor in acute myeloid leukemia (AML) remains unclear. This study aimed to define the role of XPO1 in AML and elucidate the mechanism by which Selinexor regulates homologous recombination (HR). Methods Public AML datasets and patient samples were analyzed to assess XPO1 expression and clinical relevance. Functional assays evaluated the effects of XPO1 knockdown on AML cell proliferation, apoptosis, and cell cycle progression. Transcriptomic analysis, immunoprecipitation, subcellular fractionation, DNA damage assays, and direct HR functional assays were used to investigate Selinexor-mediated mechanisms. Drug interaction analyses assessed the combined effect of Selinexor and Mitoxantrone. Results XPO1 was significantly overexpressed in AML, particularly in relapsed cases, and high expression was associated with poor prognosis. XPO1 knockdown suppressed proliferation, induced apoptosis, and caused cell cycle arrest. High XPO1 expression correlated with activation of the HR pathway. Mechanistically, Selinexor disrupted the interaction between XPO1 and the transcriptional repressor E2F7, resulting in nuclear retention of E2F7 and downregulation of BRCA1 and RAD51. E2F7 silencing reversed Selinexor-induced HR suppression and DNA damage. In addition, Selinexor synergized with Mitoxantrone to enhance DNA damage and apoptosis in AML cells. Discussion E2F7-mediated HR inhibition is a key mechanism underlying Selinexor activity in AML. Conclusion The XPO1-E2F7-HR axis represents a potential therapeutic vulnerability, supporting the rational combination of Selinexor with DNA-damaging agents to improve AML treatment outcomes.

Background Multimorbidity (co-occurrence of ≥2 chronic conditions) in older adults is a global health challenge, often managed with polypharmacy that carries risks of adverse events and drug–drug interactions. As a pilot randomized controlled trial (RCT), this study first aims to assess the feasibility of low-frequency transcutaneous electrical nerve stimulation (Lo-TENS) delivery in older adults with multimorbidity and estimate effect sizes for a subsequent definitive trial. Second, we examine the efficacy of Lo-TENS as an adjunct to routine clinical management for improving blood pressure, glycemic control, and lipid profiles, and explore the underlying autonomic nervous system (ANS) modulation mechanisms through analysis of heart rate variability and key inflammatory/metabolic biomarkers, which are hypothesized to mediate Lo-TENS’s beneficial effects on clinical indicators. Methods A pilot single-center, single-blinded, sham-controlled RCT will enroll 50 older adults (≥60 years) with multimorbidity (≥2 of EH, T2DM, hyperlipidemia). Participants will be randomly allocated (1,1) to receive Lo-TENS (2 Hz, 30 min/day, 5 days/week for 4 weeks) plus routine care or sham Lo-TENS plus routine care. Co-primary outcomes are office systolic blood pressure (SBP), fasting blood glucose (FBG), and low-density lipoprotein cholesterol (LDL-C) at post-intervention. Secondary outcomes include 24-h ambulatory BP, heart rate variability (HRV), inflammatory/metabolic biomarkers, and quality of life. Mechanistic analyses will explore mediation by ANS and inflammatory markers. Follow-up assessments will be conducted 4 weeks post-intervention. Discussion This trial will provide evidence on the effectiveness of Lo-TENS on clinical outcomes in multimorbidity in older adults, and explore the underlying mechanisms through which Lo-TENS may alleviate the clinical indicators of multimorbidity, specifically by analyzing heart rate variability and key inflammatory and metabolic biomarkers. Trial registration www.chictr.org.cn , identifier ChiCTR2400093956.