Discovery and Optimization of a Series of Vinyl Sulfoximine-Based Analogues as Potent Nrf2 Activators for the Treatment of Multiple Sclerosis.

Multiple sclerosis (MS) is an immune-mediated neurodegenerative disease of the central nervous system (CNS), which leads to demyelination, axonal loss, and neurodegeneration. Increased oxidative stress and neurodegeneration have been implicated in all stages of MS, making neuroprotective therapeutics a promising strategy for its treatment. We previously have reported vinyl sulfones with antioxidative and anti-inflammatory properties that activate nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor that induces the expression of cytoprotective genes against oxidative stress. In this study, we synthesized vinyl sulfoximine derivatives by modifying the core structure and determined therapeutic potential as Nrf2 activators. Among them, 10v effectively activated Nrf2 (EC50 = 83.5 nM) and exhibited favorable drug-like properties. 10v successfully induced expression of Nrf2-dependent antioxidant enzymes and suppressed lipopolysaccharide (LPS)-induced inflammatory responses in BV-2 microglial cells. We also confirmed that 10v effectively reversed disease progression and attenuated demyelination in an experimental autoimmune encephalitis (EAE) mouse model of MS.

Summer temperature and emergency room visits due to urinary tract infection in South Korea: a national time-stratified case-crossover study.

BACKGROUND: Although urinary tract infection (UTI) is a common and severe public health concern, and there are clear biological mechanisms between UTI and hot temperatures, few studies have addressed the association between hot temperatures and UTI. METHODS: We designed a time-stratified case-crossover study using a population-representative sample cohort based on the National Health Insurance System (NHIS) in South Korea. We obtained all NHIS-based hospital admissions through the emergency room (ER) due to UTI (using a primary diagnostic code) from 2006 to 2019. We assigned satellite-based reanalyzed daily summer (June to September) average temperatures as exposures, based on residential districts of beneficiaries (248 districts in South Korea). The conditional logistic regression was performed to evaluate the association between summer temperature and UTI outcome. RESULTS: A total of 4,436 ER visits due to UTI were observed during the summer between 2006 and 2019 among 1,131,714 NHIS beneficiaries. For 20% increase in summer temperatures (0-2 lag days), the odd ratio (OR) was 1.06 (95% CI: 1.02-1.10) in the total population, and the association was more prominent in the elderly (people aged 65 y or older; OR:1.11, 95% CI: 1.05-1.17), females (OR: 1.12, 95% CI: 1.05-1.19), and people with diabetes history (OR: 1.14, 95% CI: 1.07-1.23). The effect modification by household income was different in the total and elderly populations. Furthermore, the association between summer temperature and UTI increased during the study period in the total population. CONCLUSIONS: Our results are consistent with the hypothesis that higher summer temperatures increase the risk of severe UTIs, and the risk might be different by sub-populations.

Prediction of Bone Marrow Metastases Using Computed Tomography (CT) Radiomics in Patients with Gastric Cancer: Uncovering Invisible Metastases.

We investigated whether radiomics of computed tomography (CT) image data enables the differentiation of bone metastases not visible on CT from unaffected bone, using pathologically confirmed bone metastasis as the reference standard, in patients with gastric cancer. In this retrospective study, 96 patients (mean age, 58.4 ± 13.3 years; range, 28-85 years) with pathologically confirmed bone metastasis in iliac bones were included. The dataset was categorized into three feature sets: (1) mean and standard deviation values of attenuation in the region of interest (ROI), (2) radiomic features extracted from the same ROI, and (3) combined features of (1) and (2). Five machine learning models were developed and evaluated using these feature sets, and their predictive performance was assessed. The predictive performance of the best-performing model in the test set (based on the area under the curve [AUC] value) was validated in the external validation group. A Random Forest classifier applied to the combined radiomics and attenuation dataset achieved the highest performance in predicting bone marrow metastasis in patients with gastric cancer (AUC, 0.96), outperforming models using only radiomics or attenuation datasets. Even in the pathology-positive CT-negative group, the model demonstrated the best performance (AUC, 0.93). The model's performance was validated both internally and with an external validation cohort, consistently demonstrating excellent predictive accuracy. Radiomic features derived from CT images can serve as effective imaging biomarkers for predicting bone marrow metastasis in patients with gastric cancer. These findings indicate promising potential for their clinical utility in diagnosing and predicting bone marrow metastasis through routine evaluation of abdominopelvic CT images during follow-up.

Development of Indocyanine Green/Methyl-ß-cyclodextrin Complex-Loaded Liposomes for Enhanced Photothermal Cancer Therapy.

Photothermal therapy (PTT) is a promising cancer therapeutic approach due to its spatial selectivity and high potency. Indocyanine green (ICG) has been considered a biocompatible PTT agent. However, ICG has several challenges to hinder its clinical use including rapid blood clearance and instability to heat, light, and solvent, leading to a loss of photoactivation property and PTT efficacy. Herein, we leveraged stabilizing components, methyl-ß-cyclodextrin and liposomes, in one nanoplatform (ICD lipo) to enhance ICG stability and the photothermal therapeutic effect against cancer. Compared to ICG, ICD lipo displayed a 4.8-fold reduction in degradation in PBS solvent after 30 days and a 3.4-fold reduction in photobleaching after near-infrared laser irradiation. Moreover, in tumor-bearing mice, ICD lipo presented a 2.7-fold increase in tumor targetability and inhibited tumor growth 9.6 times more effectively than did ICG without any serious toxicity. We believe that ICD lipo could be a potential PTT agent for cancer therapeutics.

Patient-centered radiology reports with generative artificial intelligence: adding value to radiology reporting.

The purposes were to assess the efficacy of AI-generated radiology reports in terms of report summary, patient-friendliness, and recommendations and to evaluate the consistent performance of report quality and accuracy, contributing to the advancement of radiology workflow. Total 685 spine MRI reports were retrieved from our hospital database. AI-generated radiology reports were generated in three formats: (1) summary reports, (2) patient-friendly reports, and (3) recommendations. The occurrence of artificial hallucinations was evaluated in the AI-generated reports. Two radiologists conducted qualitative and quantitative assessments considering the original report as a standard reference. Two non-physician raters assessed their understanding of the content of original and patient-friendly reports using a 5-point Likert scale. The scoring of the AI-generated radiology reports were overall high average scores across all three formats. The average comprehension score for the original report was 2.71 ± 0.73, while the score for the patient-friendly reports significantly increased to 4.69 ± 0.48 (p < 0.001). There were 1.12% artificial hallucinations and 7.40% potentially harmful translations. In conclusion, the potential benefits of using generative AI assistants to generate these reports include improved report quality, greater efficiency in radiology workflow for producing summaries, patient-centered reports, and recommendations, and a move toward patient-centered radiology.

Systematic Selection of High-Affinity ssDNA Sequences to Carbon Nanotubes.

Single-walled carbon nanotubes (SWCNTs) have gained significant interest for their potential in biomedicine and nanoelectronics. The functionalization of SWCNTs with single-stranded DNA (ssDNA) enables the precise control of SWCNT alignment and the development of optical and electronic biosensors. This study addresses the current gaps in the field by employing high-throughput systematic selection, enriching high-affinity ssDNA sequences from a vast random library. Specific base compositions and patterns are identified that govern the binding affinity between ssDNA and SWCNTs. Molecular dynamics simulations validate the stability of ssDNA conformations on SWCNTs and reveal the pivotal role of hydrogen bonds in this interaction. Additionally, it is demonstrated that machine learning could accurately distinguish high-affinity ssDNA sequences, providing an accessible model on a dedicated webpage (http://service.k-medai.com/ssdna4cnt). These findings open new avenues for high-affinity ssDNA-SWCNT constructs for stable and sensitive molecular detection across diverse scientific disciplines.

Phloroglucinol Derivatives Exert Anti-Inflammatory Effects and Attenuate Cognitive Impairment in LPS-Induced Mouse Model.

Neuroinflammation is an inflammatory immune response that arises in the central nervous system. It is one of the primary causes of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. Phloroglucinol (PG) is a natural product contained in extracts of plant, algae and microbe and has been reported to have antioxidant and anti-inflammatory properties. In this study, we synthesized PG derivatives to enhance antioxidant and anti-inflammatory activity. Among PG derivatives, 6 a suppressed pro-oxidative and inflammatory molecule nitric oxide (NO) production more effectively than PG. Moreover, 6 a dose-dependently reduced the expression of proinflammatory cytokines such as IL-6, IL-1ß, TNF-α, and NO producing enzyme iNOS in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. Additionally, we confirmed that 6 a alleviated cognitive impairment and glial activation in mouse model of LPS-induced neuroinflammation. These findings suggest that novel PG derivative, 6 a, is a potential treatment for neurodegenerative diseases.

Oral Postoperative Antibiotic Prophylaxis for Outpatient Total Hip and Knee Arthroplasty: Describing Current Practices.

BACKGROUND: Despite an increase in outpatient total hip arthroplasty (THA) and total knee arthroplasty (TKA), large-scale data are lacking on current practice for antibiotic prophylaxis prescribing. We aimed to describe current oral antibiotic prophylaxis practices nationally for outpatient THA and TKA. METHODS: This nationwide retrospective cohort study included primary outpatient THA or TKA procedures in patients aged 18 to 64 years from 2018 to 2021 using a national claims database. Oral antibiotic prescriptions filled perioperatively (defined as 5 days before to 3 days after surgery) were extracted; these were categorized and assumed to represent postoperative prophylaxis. Multivariable logistic regression measured associations between patient and surgery characteristics and perioperative oral antibiotic prophylaxis. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) are reported. RESULTS: Oral antibiotic prescriptions were filled in 16.5% of 73,015 outpatient THA and TKA (18.4% of 24,857 THAs, 15.5% of 48,158 TKAs) procedures. Prescriptions were most often for cephalosporins (74.3%), with cephalexin (52.8%), and cefadroxil (19.1%) being the most common. Non-cephalosporin antibiotics prescribed were mainly clindamycin (6.8%), sulfamethoxazole-trimethoprim (6.7%), and doxycycline (6.2%). The odds of receiving oral antibiotic prophylaxis were higher for THA compared to TKA (OR 1.13, 95% CI 1.09 to 1.18, P < .001) and in the presence of obesity, diabetes, and autoimmune conditions (OR 1.08 to 1.13, P < .001 to .01). Ambulatory surgery center procedures also had significantly increased odds of prophylaxis compared to hospital-based outpatient surgeries (OR 2.62, 95% CI 2.51 to 2.73, P < .001). Additionally, regional and time-based variations were noted. CONCLUSIONS: Perioperative oral antibiotic prophylaxis prescriptions were filled in only 16.5% of outpatient THA and TKA cases, with variation in the type of antibiotic prescribed. The receipt of any prophylaxis and specific medications was associated with demographic, clinical, and procedure-related characteristics. Follow-up research will evaluate associations with infection risk reduction.

Halide Ion Mixing across Colloidal 2D Ruddlesden-Popper Perovskites: Implication of Spacer Ligand on Mixing Kinetics.

Halide ion exchange seen in metal halide perovskites provide a substantial opportunity to control their halide composition and corresponding optoelectronic properties. Halide ion mixing across colloidal 3D perovskite nanocrystals have been extensively studied while the mixing within colloidal 2D counterparts remain underexplored. In this study, the halide ion exchange kinetics across colloidally stable 2D Ruddlesden-Popper layered bromide (Br) and iodide (I) perovskites using two different spacer ligands such as aromatic phenethylammonium (PEA) versus linear butyammonium (BA) is demonstrated. The halide exchange kinetic rate constant (k), as determined by tracking time-dependent absorbance changes, indicates that Br/I halide mixing in 2D PEA-based perovskites (2.7 × 10-3 min-1 ) occurs at an order of magnitude slower than in 2D BA-based perovskites (3.3 × 10-2 min-1 ). Concentration (≈1 mM to 100 mM) and temperature-dependent (50 to 80 °C) kinetic studies further allow for the determination of activation barrier for halide ion mixing across the 2D layered perovskites with 75.2 ± 4.4 kJ mol-1 (2D PEA) and 57.8 ± 7.8 kJ mol-1 (2D BA), respectively. The activation energy reveals that the type of spacer cations plays a crucial role in controlling the halide ion mobility and halide stability due mainly to the internal ligand chemical interaction within 2D structures.