Hydrophobic, ultraviolet radiation-shielding, and antioxidant functionalities of TEMPO-oxidized cellulose nanofibril film coated with modified lignin nanoparticles.

In this study, lignin nanoparticles (LN) and octadecylamine-modified LN (LN-ODA) were utilized as coating materials to enhance the hydrophobic, antioxidant, and ultraviolet radiation-shielding (UV-shielding) properties of a TEMPO-oxidized nanocellulose film (TOCNF). The water contact angle (WCA) of the TOCNF was approximately 53° and remained stable for 1 min, while the modified LN-ODA-coated TOCNF reached over 130° and maintained approximately 85° for an hour. Pure TOCNF exhibited low antioxidant properties (4.7 %), which were significantly enhanced in TOCNF-LN (81.6 %) and modified LN-ODA (10.3 % to 27.5 %). Modified LN-ODA-coated TOCNF exhibited antioxidant properties two to six times higher than those of pure TOCNF. Modified LN-ODA exhibited thermal degradation max (Tmax) at 421 °C, while pure LN showed the main degradation temperature at approximately Tmax 330 °C. The thermal stability of TOCNF-LN-ODA-coated materials remained consistent with that of pure TOCNF, while the crystallinity index of the sample showed a slight decrease due to the amorphous nature of the lignin structure. The tensile strength of TOCNF was approximately 114.1 MPa and decreased to 80.1, 51.3, and 30.3 MPa for LN-ODA coating at 5, 10, and 15 g/m2, respectively.

Highly Conductive and Stretchable Hydrogel Nanocomposite Using Whiskered Gold Nanosheets for Soft Bioelectronics.

The low electrical conductivity of conductive hydrogels limits their applications as soft conductors in bioelectronics. This low conductivity originates from the high water content of hydrogels, which impedes facile carrier transport between conductive fillers. This study presents a highly conductive and stretchable hydrogel nanocomposite comprising whiskered gold nanosheets. A dry network of whiskered gold nanosheets is fabricated and then incorporated into the wet hydrogel matrices. The whiskered gold nanosheets preserve their tight interconnection in hydrogels despite the high water content, providing a high-quality percolation network even under stretched states. Regardless of the type of hydrogel matrix, the gold-hydrogel nanocomposites exhibit a conductivity of ≈520 S cm-1 and a stretchability of ≈300% without requiring a dehydration process. The conductivity reaches a maximum of ≈3304 S cm-1 when the density of the dry gold network is controlled. A gold-adhesive hydrogel nanocomposite, which can achieve conformal adhesion to moving organ surfaces, is fabricated for bioelectronics demonstrations. The adhesive hydrogel electrode outperforms elastomer-based electrodes in in vivo epicardial electrogram recording, epicardial pacing, and sciatic nerve stimulation.

A randomized study to evaluate the safety and immunogenicity of a pentavalent meningococcal vaccine.

A randomized, active-controlled, double-blind, first-in-human, phase 1 study was conducted in healthy Korean adults to evaluate the safety, tolerability, and immunogenicity of EuNmCV-5, a new pentavalent meningococcal vaccine targeting serogroups A, C, W, X, and Y. Sixty participants randomly received a single dose of either EuNmCV-5 or MenACWY-CRM, a quadrivalent vaccine containing serogroups A, C, W, and Y. Safety was assessed through monitoring anaphylactic reactions, adverse events for 28 days, and serious adverse events over 180 days. Immunogenicity was assessed via rabbit complement-dependent serum bactericidal antibody (rSBA) assay. EuNmCV-5 was safe, well-tolerated, and elicited a substantial antibody titer increase. The seroprotection rates exceeded 96.7%, and the seroconversion rates were over 85% for all the targeted serogroups. It showed higher seroconversion rates against serogroups A and C (p = 0.0016 and 0.0237, respectively) and elicited a substantial increase in GMT for all targeted serogroups compared to the MenACWY-CRM.ClinicalTrials.gov identifier: NCT05739292.

Efficacy and Safety of Lurasidone vs. Quetiapine XR in Acutely Psychotic Patients With Schizophrenia in Korea: A Randomized, Double-Blind, Active-Controlled Trial.

OBJECTIVE: This study was performed to evaluate the efficacy and safety of lurasidone (160 mg/day) compared to quetiapine XR (QXR; 600 mg/day) in the treatment of acutely psychotic patients with schizophrenia. METHODS: Patients were randomly assigned to 6 weeks of double-blind treatment with lurasidone 160 mg/day (n=105) or QXR 600 mg/day (n=105). Primary efficacy measure was the change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions severity (CGI-S) score. Adverse events, body measurements, and laboratory parameters were assessed. RESULTS: Lurasidone demonstrated non-inferiority to QXR on the PANSS total score. Adjusted mean±standard error change at week 6 on the PANSS total score was -26.42±2.02 and -27.33±2.01 in the lurasidone and QXR group, respectively. The mean difference score was -0.91 (95% confidence interval -6.35-4.53). The lurasidone group showed a greater reduction in PANSS total and negative subscale on week 1 and a greater reduction in end-point CGI-S score compared to the QXR group. Body weight, body mass index, and waist circumference in the lurasidone group were reduced, with significantly lower mean change compared to QXR. Endpoint changes in glucose, cholesterol, triglycerides, and low-density lipoprotein levels were also significantly lower. The most common adverse drug reactions with lurasidone were akathisia and nausea. CONCLUSION: Lurasidone 160 mg/day was found to be non-inferior to QXR 600 mg/day in the treatment of schizophrenia with comparable efficacy and tolerability. Adverse effects of lurasidone were generally tolerable, and beneficial effects on metabolic parameters can be expected.

Exercise improves load bearing bone structural properties in female secreted protein acidic and rich in cysteine (SPARC) null mice but not in males.

Secreted protein acidic and rich in cysteine (SPARC) is the most abundant glycoprotein in bone and is thought to play a critical role in bone remodeling and homeostasis. However, the effect of SPARC in relation to gender and exercise on bone quality is not well understood. The purpose of this study was to quantify differences in the structural and biomechanical properties between calvarial and femoral bone from male and female wild-type (WT) and SPARC null (SPARC(-/-)) mice as well as the ability of exercise to rescue bone health. Male and female WT and transgenic SPARC(-/-) mice were given either a fixed or rotating running wheel for exercise. Bone structural, biomechanical, and morphological parameters were quantified using micro computed tomography, push out testing for the calvaria, three-point flexural testing for the femurs, histological and immunofluorescent staining. Similar reductions in structural and biomechanical strength were observed in both male and female SPARC(-/-) calvaria, most of which were not significantly affected by exercise. In femurs, SPARC(-/-) had a significant effect on structural parameters in both sexes, but was more pronounced in females with some properties being rescued with running. Interestingly, the effect of SPARC(-/-) on bone mineral density was only detected in female SPARC(-/-) mice, not males, and was subsequently rescued with exercise. This study emphasizes the differences between sexes in WT and SPARC(-/-) mice in regard to structural parameters and biomechanical properties. Research into gender differences can help inform and personalize treatment options to more accurately meet patient needs.

Evaluation of resazurin phenoxazine dye as a highly sensitive cell viability potency assay for natural killer cell-derived extracellular vesicle-based cancer biotherapeutics.

Natural killer cell-derived extracellular vesicles (NK-EVs) are candidate biotherapeutics against various cancers. However, standardised potency assays are necessary for a reliable assessment of NK-EVs' cytotoxicity. This study aims to thoroughly evaluate a highly sensitive resazurin phenoxazine-based cell viability potency assay (measurement of the cellular redox metabolism) for quantifying the cytotoxicity of NK-EVs against leukaemia K562 cells (suspension model) and breast cancer MDA-MB-231 cells (adherent model) in vitro. The assay was evaluated based on common analytical parameters setforth by regulatory guidelines, including specificity, selectivity,accuracy, precision, linearity, range and stability. Our results revealed that this resazurin-based cell viability potency assay reliably and reproducibly measured a dose-response of NK-EVs' cytotoxic activity against both cancer models. The assay showed precision with 5% and 20% variation for intra-run and inter-run variability. The assay signal showed specificity and selectivity of NK-EVs against cancer target cells, as evidenced by the diminished viability of cancer cells following a 5-hour treatment with NK-EVs, without any detectable interference or background. The linearity analysis of target cancer cells revealed strong linearity for densities of 5000 K562 and 1000 MDA-MB-231 cells per test with a consistent range. Importantly, NK-EVs' dose-response for cytotoxicity showed a strong correlation (|ρ| ∼ 0.8) with the levels of known cytotoxic factors associated with the NK-EVs' corona (FasL, GNLY, GzmB, PFN and IFN-γ), thereby validating the accuracy of the assay. The assay also distinguished cytotoxicity changes in degraded NK-EVs, indicating the ability of the assay to detect the potential loss of sample integrity. Compared to other commonly reported bioassays (i.e., flow cytometry, cell counting, lactate dehydrogenase release assay, DNA-binding reporter assay and confluence assay), our results support this highly sensitive resazurin-based viability potency assay as a high-throughput and quantitative method for assessing NK-EVs' cytotoxicity against both suspension and adherent cancer models for evaluating NK-EVs' biotherapeutics.

Pharmacokinetic drug-drug interactions of JBPOS0101 mediated by cytochrome P450 3A4 and UDP-glucuronosyltransferases.

JBPOS0101 is a new antiepileptic drug and is a substrate of UDP-glucuronosyltransferases (UGTs) in in vitro test. In vitro experiments showed different results regarding whether JBPOS0101 induces (EC50 136 µM) or inhibits (IC50 95.4-386.5 µM) cytochrome P450 (CYP) 3A4. As co-medication of JBPOS0101 and carbamazepine (CBZ) is expected in clinical settings, drug-drug interactions (DDIs) between them should be determined. This study aimed to investigate pharmacokinetic (PK) interactions of JBPOS0101 influenced by CYP3A4 and UGTs using midazolam (MDZ) and CBZ. A two-cohort, open-label, fixed-sequence study was conducted in healthy Koreans. In cohort A, subjects received MDZ IV alone, and then JBPOS0101 were co-administered with MDZ after oral doses of JBPOS0101 for 7 days. In cohort B, multiple doses of JBPOS0101 and CBZ were administered respectively, and subjects received both together for 7 days. Serial blood samples were collected for PK analysis. When MDZ and JBPOS0101 were co-administered, the systemic exposure of MDZ decreased by 30%. Meanwhile, JBPOS0101 did not significantly changed the PK of CBZ. CBZ decreased the systemic exposure of JBPOS0101 at steady state by 40%, respectively. With IV administration of MDZ, JBPOS0101 acted as a weak inducer of hepatic CYP3A4 and decreased systemic exposure of MDZ. The ability of JBPOS0101 to similarly modulate gut CYP3A4 activity will require further evaluation. Co-administration of multiple doses of JBPOS0101 and CBZ did not significantly alter CBZ pharmacokinetics, but the clinical impact of decreased systemic exposure of JBPOS0101 by CBZ should be further considered.

Transcranial Electrical Stimulation: Clinical Implication and Practice for Treatment of Psychiatric Illness.

Brain electrical stimulation, particularly non-invasive brain stimulation (NIBS) techniques such as transcranial electrical stimulation (tES), have emerged as a promising treatment for various psychiatric disorders, including depression, anxiety, and post-traumatic stress disorder. tES techniques, such as transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), and transcranial random noise stimulation (tRNS), are cost-effective and safe interventions that are designed to affect neuronal circuits in the brain using various modalities. Although tES has shown effectiveness in the treatment of psychiatric disorders, there is a lack of comprehensive papers that consider its clinical implications. Therefore, this review aims to evaluate the clinical implications of tES and provide practical guidance for the treatment of psychiatric illnesses. Moreover, this review provides an overview of tES techniques and their mechanisms of action and summarizes recent clinical studies that have examined the use of tES for psychiatric disorders.

Diabetic Ketoacidosis as an Effect of Sodium-Glucose Cotransporter 2 Inhibitor: Real World Insights.

One of the notable adverse effects of sodium-glucose cotransporter 2 (SGLT2) inhibitor is diabetic ketoacidosis (DKA) often characterized by euglycemia. In this retrospective review of patients with DKA from 2015 to 2023, 21 cases of SGLT2 inhibitorassociated DKA were identified. Twelve (57.1%) exhibited euglycemic DKA (euDKA) while nine (42.9%) had hyperglycemic DKA (hyDKA). More than 90% of these cases were patients with type 2 diabetes mellitus. Despite similar age, sex, body mass index, and diabetes duration, individuals with hyDKA showed poorer glycemic control and lower C-peptide levels compared with euDKA. Renal impairment and acidosis were worse in the hyDKA group, requiring hemodialysis in two patients. Approximately one-half of hyDKA patients had concurrent hyperosmolar hyperglycemic state. Common symptoms included nausea, vomiting, general weakness, and dyspnea. Seizure was the initial manifestation of DKA in two cases. Infection and volume depletion were major contributors, while carbohydrate restriction and inadequate insulin treatment also contributed to SGLT2 inhibitor-associated DKA. Despite their beneficial effects, clinicians should be vigilant for SGLT2 inhibitor risk associated with DKA.

Real-time analysis and prediction method of ion concentration using the effect of O-H stretching bands in aqueous solutions based on ATR-FTIR spectroscopy.

Analyzing the concentration of ions in aqueous solutions in real-time plays an important role in the fields of chemistry and biology. Traditional methods for measuring ion concentrations, such as concentration analysis by measuring electrical conductivity, inductively coupled plasma mass spectrometry, and ion chromatography, have been used in many research fields. However, these methods are limited in determining ion concentrations instantaneously. Fourier-transform infrared-attenuated total reflectance (ATR-FTIR) spectroscopy provides a new approach for determining ion concentrations in aqueous solutions. This allows for fast analysis without pretreatment and is scalable for real-time measurements. In this study, we present a method for measuring ion concentrations by examining ion-water interactions in the O-H stretching band of aqueous solutions using ATR-FTIR spectroscopy. Five aqueous solutions, namely LiCl + HCl, LiOH + HCl, LiOH, Li3PO4, and NaCl were used in the experiments and prepared at concentrations between 0.5-2 M. The ion concentrations in the prepared aqueous solutions were measured using ATR-FTIR spectroscopy. We observed that the difference in absorbance increased and decreased linearly with changes in concentration. The concentration of ions in the aqueous solution could be measured by validating the designed linear regression analysis function model. In this study, we proposed five linear regression analysis function models, all of which showed high coefficients of determination above 0.9, with the highest coefficient of determination reaching 0.9969. These results show that ATR-FTIR spectroscopy has the potential to be applied as a rapid and simple concentration analysis system.

Ultrastable 3D Heterogeneous Integration via N-Heterocyclic Carbene Self-Assembled Nanolayers.

The commercialization of 3D heterogeneous integration through hybrid bonding has accelerated, and accordingly, Cu-polymer bonding has gained significant attention as a means of overcoming the limitations of conventional Cu-SiO2 hybrid bonding, offering high compatibility with other fabrication processes. Polymers offer robust bonding strength and a low dielectric constant, enabling high-speed signal transmission with high reliability, but suffer from low thermomechanical stability. Thermomechanical stability of polymers was not achieved previously because of thermal degradation and unstable anchoring. To overcome these limitations, wafer-scale Cu-polymer bonding via N-heterocyclic carbene (NHC) nanolayers was presented for 3D heterogeneous integration, affording ultrastable packing density, crystallinity, and thermal properties. NHC nanolayers were deposited on copper electrodes via electrochemical deposition, and wafer-scale 3D heterogeneous integration was achieved by adhesive bonding at 170 °C for 1 min. Ultrastable conductivity and thermomechanical properties were observed by the spatial mapping of conductivity, work function, and force-distance curves. With regard to the characterization of NHC nanolayers, low-temperature bonding, robust corrosion inhibition, enhanced electrical conductivity, back-end-of-line process compatibility, and fabrication process reduction, NHC Cu/polymer bonding provides versatile advances in 3D heterogeneous integration, indicating that NHC Cu/polymer bonding can be utilized as a platform for future 3D vertical chip architectures.

Molecular phylogeny reveals Varroa mites are not a separate family but a subfamily of Laelapidae.

Varroa mites, notorious for parasitizing honeybees, are generally classified as Varroidae. Their extremely modified morphologies and behaviors have led to debates regarding their phylogenetic position and classification as an independent family. In this study, two different datasets were employed to reconstruct the phylogenies of Varroa mites and related Laelapidae species: (1) 9257 bp from the whole 13 mitochondrial protein-coding genes of 24 taxa, (2) 3158 bp from 113 taxa using Sanger sequencing of four nuclear loci. Both mitochondrial and nuclear analyses consistently place Varroa mites within the Laelapidae. Here we propose to place Varroa mites in the subfamily Varroinae stat. nov., which represents a highly morphologically adapted group within the Laelapidae. Ancestral state reconstructions reveal that bee-associated lifestyles evolved independently at least three times within Laelapidae, with most phoretic traits originating from free-living ancestors. Our revised classification and evolutionary analyses will provide new insight into understanding the Varroa mites.

Comparative analysis of resting-state EEG-based multiscale entropy between schizophrenia and bipolar disorder.

BACKGROUND: Studies that use nonlinear methods to identify abnormal brain dynamics in patients with psychiatric disorders are limited. This study investigated brain dynamics based on EEG using multiscale entropy (MSE) analysis in patients with schizophrenia (SZ) and bipolar disorder (BD). METHODS: The eyes-closed resting-state EEG data were collected from 51 patients with SZ, 51 patients with BD, and 51 healthy controls (HCs). Patients with BD were further categorized into type I (n = 23) and type II (n = 16), and then compared with patients with SZ. A sample entropy-based MSE was evaluated from the bilateral frontal, central, and parieto-occipital regions using 30-s artifact-free EEG data for each individual. Correlation analyses of MSE values and psychiatric symptoms were performed. RESULTS: For patients with SZ, higher MSE values were observed at higher-scale factors (i.e., 41-70) across all regions compared with both HCs and patients with BD. Furthermore, there were positive correlations between the MSE values in the left frontal and parieto-occipital regions and PANSS scores. For patients with BD, higher MSE values were observed at middle-scale factors (i.e., 13-40) in the bilateral frontal and central regions compared with HCs. Patients with BD type I exhibited higher MSE values at higher-scale factors across all regions compared with those with BD type II. In BD type I, positive correlations were found between MSE values in all left regions and YMRS scores. CONCLUSIONS: Patients with psychiatric disorders exhibited group-dependent MSE characteristics. These results suggest that MSE features may be useful biomarkers that reflect pathophysiological characteristics.

Clinical, cognitive, and functional characteristics of recent-onset psychosis with autistic features: A 2-year longitudinal study.

Though categorized as separate illnesses, schizophrenia and autism are known to exhibit shared characteristics. This study explored the distinctions in clinical, cognitive, and functional characteristics among individuals with recent-onset psychosis, considering the severity of their autistic symptoms, involving longitudinal examinations. We analyzed 671 patients with recent-onset psychosis from Korean Early Psychosis Cohort Study (KEPS), and used the PANSS Autism Severity Score (PAUSS) to categorize patient into 'autistic', 'moderate', and 'non-autistic' groups. The autistic group had the highest rate of schizophrenia diagnosis, and the lowest incidence of comorbid psychiatric disorders. Schizophrenia diagnosis predicted membership of the autistic group. More severe autistic symptoms correlated with worse overall symptoms and functional outcomes, which significantly predicted membership of the autistic group. Cognitive impairments and emotional recognition difficulties increased with the severity of autistic symptoms. 2-year longitudinal assessments demonstrated that group differences in autistic features and overall symptoms, and functional outcomes remained consistent, and membership of the autistic group significantly predicted symptomatic remission and functional recovery. In conclusion, the presence of autistic symptoms has a significant impact on the overall symptomatology and functional capabilities. They are enduring attributes rather than temporary state variables, and serve as a significant predictor for both symptomatic and functional recovery.

Quantitative Comparison of the Hydration Capacity of Surface-Bound Dextran and Polyethylene Glycol.

We have quantified and compared the hydration capacity (i.e., capability to incorporate water molecules) of the two surface-bound hydrophilic polymer chains, dextran (dex) and poly(ethylene glycol) (PEG), in the form of poly(l-lysine)-graft-dextran (PLL-g-dex) and poly(l-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG), respectively. The copolymers were attached to a negatively charged silica-titania surface through the electrostatic interaction between the PLL backbone and the surface in neutral aqueous media. While the molecular weights of PLL and PEG were fixed, that of dex and the grafting density of PEG or dex on the PLL were varied. The hydration capacity of the polymer chains was quantified through the combined experimental approach of optical waveguide lightmode spectroscopy (OWLS) and quartz crystal microbalance with dissipation monitoring (QCM-D) to yield a value for areal solvation (Ψ), i.e., mass of associated solvent molecules within the polymer chains per unit substrate area. For the two series of copolymers with comparable stretched chain lengths of hydrophilic polymers, namely, PLL(20)-g-PEG(5) and PLL(20)-g-dex(10), the Ψ values gradually increased as the initial grafting density on the PLL backbone increased or as g decreased. However, the rate of increase in Ψ was higher for PEG than dextran chains, which was attributed to higher stiffness of the dextran chains. More importantly, the number of water molecules per hydrophilic group was clearly higher for PEG chains. Given that the -CH2CH2O- units that make up the PEG chains form a cage-like structure with 2-3 water molecules, these "strongly bound" water molecules can account for the slightly more favorable behavior of PEG compared to dextran in both aqueous lubrication and antifouling behavior of the copolymers.

Effects of statin use on serum creatinine phosphokinase levels in normal thyroid function.

BACKGROUND/AIMS: Statins are common lipid-lowering agents used in dyslipidemia. However, they increase serum creatinine phosphokinase (CPK) levels. Currently, there are no studies on the effect of thyroid-stimulating hormone (TSH) levels on CPK levels after statin administration. Therefore, this study aimed to investigate CPK level alterations after statin administration according to TSH quartiles in participants with euthyroidism. METHODS: This retrospective analysis included 25,047 patients with euthyroidism. CPK levels were measured before and 6 months after statin administration. Normal TSH levels were divided into four quartiles, and the CPK levels and proportions of patients with normal CPK levels after statin administration for each TSH quartile were evaluated. RESULTS: The baseline CPK level was significantly higher in the lowest TSH quartile (Q1) compared to the other quartiles but decreased after statin administration. Thus, the difference between the CPK levels and the other quartile groups was not significant. The proportion of patients with normal CPK levels was also significantly lowest in Q1 before statin administration; however, no significant difference was noted in the ratio among each group after statin administration. These findings were consistent with the findings of the analysis according to statin intensity. CONCLUSION: In patients in the lowest TSH quartile of the normal TSH range, the CPK level decreased, and the proportion of normal CPK levels increased significantly after statin administration. However, similar changes were not observed in other TSH quartiles. Therefore, further studies are required to mechanistically confirm these conclusions.

Pioglitazone-induced alterations of purine metabolism in healthy male subjects.

Pioglitazone is class of thiazolidinediones that activates peroxisome proliferator-activated receptors (PPARs) in adipocytes to improve glucose metabolism and insulin sensitivity and has been used as a treatment for type 2 diabetes. However, the underlying mechanisms of associated pioglitazone-induced effects remain unclear. Our study aimed to investigate endogenous metabolite alterations associated with pioglitazone administration in healthy male subjects using an untargeted metabolomics approach. All subjects received 30 mg of pioglitazone once daily in the assigned sequence and period. Urine samples were collected before pioglitazone administration and for 24 h after 7 days of administration. A total of 1465 compounds were detected and filtered using a coefficient of variance below 30% and 108 metabolites were significantly altered upon pioglitazone administration via multivariate statistical analysis. Fourteen significant metabolites were identified using authentic standards and public libraries. Additionally, pathway analysis revealed that metabolites from purine and beta-alanine metabolisms were significantly altered after pioglitazone administration. Further analysis of quantification of metabolites from purine metabolism, revealed that the xanthine/hypoxanthine and uric acid/xanthine ratios were significantly decreased at post-dose. Pioglitazone-dependent endogenous metabolites and metabolic ratio indicated the potential effect of pioglitazone on the activation of PPAR and fatty acid synthesis. Additional studies involving patients are required to validate these findings.

Real-world efficacy and safety of capecitabine with oxaliplatin in patients with advanced adenocarcinoma of the ampulla of Vater.

BACKGROUND: Adenocarcinoma of the ampulla of Vater (AoV) is one of the rare periampullary cancers, and due to its anatomical location, it is categorized into various histologic subtypes. Its rarity and diversity pose challenges in treatment decision-making for patients with advanced AoV carcinoma. This study investigated the efficacy and safety of the combined regimen of capecitabine and oxaliplatin (CAPOX) in a real-world clinical setting. METHODS: This investigation encompassed patients with advanced AoV carcinoma who underwent CAPOX treatment. Histologic phenotypes were identified through a combination of histopathological analysis and protein expression markers, including MUC1, CDX2, CK20, and MUC2. The correlation between histopathological determinants and survival outcomes was explored, in addition to an evaluation of the safety profile of CAPOX therapy. RESULTS: From January 2010 to June 2023, 42 patients received CAPOX. Of these, 14 patients (33.3%) had not received any prior palliative chemotherapy, while 28 patients (66.7%) had undergone one prior line of chemotherapy. At a median follow up of 9.0 months, the median progression-free survival (PFS) was 4.38 months (95% CI, 2.78-5.69) and the median overall survival (OS) was 9.57 months (95% CI 7.56-11.6). The objective response and disease control rates were 38.1% and 61.9%, respectively. Patients who received CAPOX as a second-line treatment had poorer PFS (HR = 2.62; 95% CI, 1.49-4.90, p = 0.003) and OS (HR = 2.82, 95% CI, 1.47-5.38, p = 0.001) compared to those who received CAPOX as a first-line chemotherapy. There were no statistically significant differences in PFS (p = 0.185) and OS (p = 0.097) between groups based on histologic subtypes. Neutropenia (14.3%) emerged as the predominant grade 3-4 toxicity. Notably, treatment cessation occurred in select instances owing to grade 3 fatigue (9.5%) and peripheral neuropathy (9.5%). CONCLUSIONS: This study confirmed the therapeutic efficacy and safety of CAPOX in a real-world setting, consistent with prior phase II trial results. While CAPOX proved feasible for advanced AoV carcinoma regardless of histologic subtype, its reduced effectiveness in second-line settings necessitates further research to determine its optimal palliative use.

Pharmacokinetic interactions between fexuprazan, a potassium-competitive acid blocker, and nonsteroidal anti-inflammatory drugs in healthy males.

Fexuprazan, a novel potassium-competitive acid blocker, is expected to be used for the prevention of nonsteroidal anti-inflammatory drugs (NSAIDs) induced ulcer. This study aimed to evaluate pharmacokinetic (PK) interactions between fexuprazan and NSAIDs in healthy subjects. A randomized, open-label, multicenter, six-sequence, one-way crossover study was conducted in healthy male subjects. Subjects randomly received one of the study drugs (fexuprazan 40 mg BID, celecoxib 200 mg BID, naproxen 500 mg BID, or meloxicam 15 mg QD) for 5 or 7 days in the first period followed by the combination of fexuprazan and one of NSAIDs for the same days and the perpetrator additionally administered for 1-2 days in the second period. Serial blood samples for PK analysis were collected until 48- or 72-h post-dose at steady state. PK parameters including maximum plasma concentration at steady state (Cmax,ss) and area under plasma concentration-time curve over dosing interval at steady state (AUCτ,ss) were compared between monotherapy and combination therapy. The PKs of NSAIDs were not significantly altered by fexuprazan. For fexuprazan, differences in PK parameters (22% in Cmax, 19% in AUCτ,ss) were observed when co-administered with naproxen, but not clinically significant. The geometric mean ratio (90% confidence interval) of combination therapy to monotherapy for Cmax,ss and AUCτ,ss was 1.22 (1.02-1.46) and 1.19 (1.00-1.43), respectively. There were no significant changes in the systemic exposure of fexuprazan by celecoxib and meloxicam. Fexuprazan and NSAIDs did not show clinically meaningful PK interactions.