Innovative Cancer Immunotherapy with MAGE-A3 mRNA Cancer Vaccines.

Cancer causes over 10 million deaths annually worldwide and remains a significant global health challenge. This study investigated advanced immunotherapy strategies, focusing on mRNA vaccines that target tumor-specific antigens to activate the immune system. We developed a novel mRNA vaccine using O,O'-dimyristyl-N-lysyl aspartate (DMKD) to improve stability and phosphatidylserine (PS) to enhance antigen presentation to immune cells. This vaccine, containing melanoma-associated antigen A3 (MAGE-A3) mRNA encapsulated within lipid nanoparticles (LNPs), was evaluated for its therapeutic potential against colorectal cancer. Our findings demonstrated that MAGE-A3 mRNA-containing DMKD-PS LNPs significantly reduced tumor size and weight, effectively combating metastatic cancer. The vaccine elicited a robust immune response, increasing specific immunoglobulin and cytokine levels without causing histotoxicity in major organs. These results confirm that the DMKD-PS-based MAGE-A3 mRNA vaccine holds promise for cancer prevention and treatment.

Association of monocyte-lymphocyte ratio and myocardial infarction in the U.S. population with diabetes.

Background and objective: The monocyte-to-lymphocyte ratio (MLR) has emerged as a novel inflammatory biomarker; however, its relationship with myocardial infarction (MI) in diabetic populations remains unclear. This study aimed to elucidate the association between MLR and MI prevalence in this unique population. Methods: This cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES), 2015-2018. MLR was utilized as both a continuous and categorical factor to examine its correlation with MI in individuals diagnosed with DM. Subgroup and sensitivity analyses were also performed. Results: In this study, 1,295 individuals with DM were enrolled, among whom 148 (11.4%) were diagnosed with MI. Patients with MI showed a greater MLR. Using a smoothed curve-fitting analysis, a linear relationship was observed between MLR and MI (pfor non-linearity = 0.27). Multivariate logistic regression analysis showed that MLR * 10 was positively correlated with the risk of MI (OR = 1.14, 95% CI 1.01∼1.29, p = 0.041). Compared with the lowest quartile, the OR for Q2, Q3, and Q4 were 2.13 (95% CI: 1.01∼4.47), 2.95 (95% CI: 1.45∼6.00), and 2.74 (95% CI: 1.32∼5.69), respectively. Subgroup analyses showed no significant interaction for MLR in any subgroup (all P > 0.05). The receiver operating characteristic (ROC) curve indicated that the area under the curve (AUCs) of MLR for predicting MI was 0.661 (95% CI: 0.617-0.706; P < 0.05). Conclusions: Our study demonstrated that MLR is significantly correlated with MI in patients with DM.

In-house CAD/CAM fabricated repositioning guide in maxillary repositioning after Le Fort I osteotomy.

OBJECTIVE: This study aimed to compare the accuracy of two transferring methods, which are the intermediate splint made by computer-aided design (CAD)/computer-aided manufacturing (CAM) and the customized maxillary repositioning guide for orthognathic surgery. MATERIALS AND METHODS: Patient data regarding virtual surgical simulations were collected. For analyzing the accuracy, the postoperative cone-beam computed tomography and preoperative simulation data were superimposed. The x, y, and z coordinates were obtained at three landmarks in the maxillary dentition, and the linear and angular differences between the surgical simulation and the actual surgery were evaluated. RESULTS: Thirty-three patients were included in this study, 16 in the splint group and 17 in the guide group. One coordinate in the guide group and nine in the splint group showed errors of >2 mm, with a statistically significant difference. There was no significant difference between the two groups in the three-dimensional error distance at each reference point. In most measurements, the interquartile range of the guide group showed a narrower distribution than that of the splint group. CONCLUSION: It is more advantageous to use a customized maxillary repositioning guide than an intermediate splint made via CAD/CAM to obtain an accuracy within the 2 mm discrepancy range.

Evaluation of amylose content: Structural and functional properties, analytical techniques, and future prospects.

Amylose content (AC) is critical in evaluating starch properties, significantly influencing the food industry and human nutrition. Although amylose is not completely linear, its unique structure makes it a key research focus across various scientific fields. Understanding amylose's structural and functional properties is essential for its applications in medical, nutritional, and industrial sectors. Accurate determination of AC, from simple qualitative assessments to precise quantitative measurements, is vital for effectively processing and using starch-rich products. The choice of AC determination method depends on the specific application and the required accuracy and detail. This review summarizes amylose's structural and functional characteristics and recent advancements in qualitative and quantitative AC determination techniques. It also provides insights into future trends and prospects for these technologies, emphasizing the need for more rapid, convenient, accurate, and customizable methods. In conclusion, advancements in amylose determination should enhance accuracy, speed, and ease of use to improve quality control and applications across various sectors while expanding our understanding of amylose and its functionalities.

Caffeic Acid Phenethyl Ester Administration Reduces Enterotoxigenic Bacteroides fragilis-Induced Colitis and Tumorigenesis.

The human colonic commensal enterotoxigenic Bacteroides fragilis (ETBF) is associated with chronic colitis and colon cancer. ETBF colonization induces colitis via the Bacteroides fragilis toxin (BFT). BFT secreted by ETBF cause colon inflammation via E-cadherin cleavage/NF-κB signaling. ETBF promotes colon tumorigenesis via interleukin 17A (IL-17A)/CXCL-dependent inflammation, but its bioactive therapeutics in ETBF-promoted tumorigenesis remain unexplored. In the current study, we investigated the caffeic acid phenethyl ester (CAPE) in the murine model of ETBF colitis and tumorigenesis. In this study, we observed that CAPE treatment mitigated inflammation induced by ETBF in mice. Additionally, our findings indicate that CAPE treatment offers protective effects against ETBF-enhanced colon tumorigenesis in a mouse model of colitis-associated colon cancer induced by azoxymethane (AOM) and dextran sulfate sodium. Notably, the decrease in colon tumorigenesis following CAPE administration correlates with a reduction in the expression of IL-17A and CXCL1 in the gastrointestinal tract. The molecular mechanism for CAPE-induced protection against ETBF-mediated tumorigenesis is mediated by IL-17A/CXCL1, and by NF-κB activity in intestinal epithelial cells. Our findings indicate that CAPE may serve as a preventive agent against the development of ETBF-induced colitis and colorectal cancer (CRC).

Invasive strategies for rhythm control of atrial fibrillation: a narrative review.

Atrial fibrillation (AF) is the most common sustained tachyarrhythmia and its increasing prevalence has resulted in a growing healthcare burden. A recent landmark randomized trial, the EAST-AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial), highlighted the importance of early rhythm control in AF, which was previously underemphasized. Rhythm control therapy includes antiarrhythmic drugs, direct-current cardioversion, and catheter ablation. Currently, catheter ablation is indicated for patients with AF who are either refractory or intolerant to antiarrhythmic drugs or who exhibit decreased left ventricular systolic function. Catheter ablation can be categorized according to the energy source used, including radiofrequency ablation (RFA), cryoablation, laser ablation, and the recently emerging pulsed field ablation (PFA). Catheter ablation techniques can also be divided into the point-by-point ablation method, which ablates the pulmonary vein (PV) antrum one point at a time, and the single-shot technique, which uses a spherical catheter to ablate the PV antrum in a single application. PFA is known to be applicable to both point-by-point and single-shot techniques and is expected to be promising owing to its tissue specificity, resulting in less collateral damage than catheter ablation involving thermal energy, such as RFA and cryoablation. In this review, we aimed to outline catheter ablation for rhythm control in AF by reviewing previous studies.

Does mandible ramus height asymmetry affect postoperative skeletal stability in orthognathic surgery patients?

BACKGROUND: Relapses following orthognathic surgery have been reported to exceed 2% to 50%, depending on multiple factors. This study aimed to analyze the stability after orthognathic surgery in patients with mandibular ramus height asymmetry through 3D reconstruction using Cone-beam CT. METHODS: This retrospective cohort study investigated patients who underwent mandibular setback surgery using bilateral sagittal split ramus osteotomy. Three-dimensional CT scans were taken at three different time points. Evaluation of the postoperative stability involved measuring changes in the x, y, and z axes as well as roll and yaw rotations of the mandible at specific landmarks (B point, mental foramen) on 3D CT scans obtained immediately after surgery and 6-12 months postoperatively. They were categorized into four groups based on bilateral mandibular height asymmetry through Asymmetry index (AI). The one-way ANOVA was implemented to compare the intergroup differences and Tukey's post hoc test was employed. Additionally, the Pearson correlation coefficient was also calculated. RESULTS: A total of 24 patients were included in this study. The corresponding AI, representing the degree of asymmetry in both mandibles, were calculated as Group 1 was 1.25 ± 0.64%, Group 2 was 2.89 ± 0.47%, Group 3 was 5.03 ± 0.51%, and Group 4 was 9.40 ± 1.99%. The x-axis change in Group 4 was significantly larger at 1.71 mm compared to Group 1 at 0.64 mm. The mandibular roll, Group 4 showed a statistically significant increase at 1.33° compared to Group 1 at 0.35°. And there was a significant positive correlation observed between x-axis change and AI (p = 0.019), as well as between mandibular roll and AI (p = 0.025). CONCLUSION: After orthognathic surgery, stability was influenced by numerous factors, with the findings of this study suggesting that the degree of ramus height asymmetry in the mandible can be considered one contributing factor.

A single-nucleus transcriptomic atlas characterizes cell types and their molecular features in the ovary of adult Nile tilapia.

In fish species, there is limited analysis of signature transcriptome profiles at the single-cell level in gonadal cells. Here, the molecular signatures of distinct ovarian cell categories in adult Nile tilapia (Oreochromis niloticus) were analysed using single-nucleus RNA sequencing (snRNA-seq). We identified four cell types (oogonia, oocytes, granulosa cell, and thecal cell) based on their specifically expressed genes and biological functions. Similarly, we found some key pathways involved in ovarian development that may affect germline-somatic interactions. A cell-to-cell communication network between the distinct cell types was constructed. We found that the bidirectional communication is mandatory for the development of germ cells and somatic cells in fish ovaries, and the granulosa cells and thecal cells play a central regulating role in the cell network in fish ovary. Additionally, we identified some novel candidate marker genes for various types of ovarian cells and also validated them using in situ hybridization. Our work reveals an ovarian atlas at the cellular and molecular levels and contributes to providing insights into oogenesis and gonad development in fish.

Comparative analysis of the transcriptomes from regenerated plants and root explants of endangered Oplopanax elatus.

BACKGROUND: Oplopanax elatus is a plant of therapeutic significance in oriental medicine; however, its mass cultivation is limited owing to the difficulties in propagating it from seeds. METHODS: In this study, we investigated the transcriptome profiles and transcriptional regulatory factors expressed during plantlet regeneration from root tissues of the endangered O. elatus. RESULTS: The RNA-seq results for the control and regenerated plants cultured in liquid medium for 8 weeks showed that the clean length of the control group was 11,901,667,912 and that of the 8-week sample was 10,115,155,171, indicating a clean value of 97% for both samples. The number of mapped paired-end reads was 63,922,480 for the control group and 54,146,902 for the 8-week sample. The number of genes for which at least one clean data point was mapped was 43,177 in the control group and 42,970 in the 8-week sample. The results of the differentially expressed gene analysis indicate that the number of upregulated genes in the 8-week sample was 158, and the number of downregulated genes was 424. Gene Ontology (GO) analysis of the upregulated genes revealed that GO terms were classified into 14 categories, and genes expressed in the biological process category occurred most frequently. GO terms of the downregulated genes were evenly distributed into two categories: biological process and molecular function. From the upregulated genes, eight reference genes with significant differences in expression were selected and analyzed using real-time PCR. The Oe38836 gene (late embryogenesis abundant protein M17-like isoform X1) showed the highest expression rate that was more than tenfold that of the control. Oe40610 (auxin-responsive protein SAUR21-like) and Oe07114 (glucose-1-phosphate adenyl transferase-like protein) genes showed expression levels that were increased eightfold relative to the control. CONCLUSIONS: The RNA sequencing (RNA-seq) results from the plants regenerated through liquid culture of O. elatus root tissue were confirmed using real-time PCR, indicating their reliability.

Disease progression subtypes of Parkinson's disease based on milestone events.

BACKGROUND: Parkinson's disease (PD) demonstrates considerable heterogeneity in the manifestation of clinical symptoms and disease progression. Recently, six clinical milestones have been proposed to evaluate disease severity in PD. However, the identification of PD progression subtypes based on these milestone events has not yet been performed. METHODS: Latent class analysis (LCA) was employed to identify subtypes of PD progression based on the timing of the first occurrence of six milestones within a 6-year follow-up period in Parkinson's Progression Markers Initiative (PPMI) database. RESULTS: The study cohort consisted of 354 early PD patients, of whom 42.9% experienced at least one milestone within six years. LCA identified two distinct subtypes of PD progression: slow progression (83%) and rapid progression (17%). The total number of milestones over six years was significantly higher in the rapid progression subtype compared to the slow progression subtype (median: 3.00 vs. 0.00, p < 0.001). At baseline, the rapid progression subtype, compared to the slow progression subtype, was characterized by an older age at onset and more severe motor and non-motor symptoms. On biomarkers, the rapid progression subtype demonstrated elevated CSF p-tau and serum NFL, but decreased mean striatal DAT uptake. Five clinical variables (age, SDMT score, MDS-UPDRS I score, MDS-UPDRS II + III scores, and RBD) were selected to construct the predictive model. The original predictive model achieved an AUC of 0.82. In internal validation using bootstrap resampling, the model achieved an AUC of 0.82, with a 95%CI ranging from 0.76 to 0.87. The model's performance was acceptable regarding both calibration and clinical utility. CONCLUSION: Approximately 17% of early PD patients exhibited the rapid progression subtype, characterized by the occurrence of more and earlier-onset milestones. The nomogram predictive model, incorporating five baseline clinical variables (age, SDMT score, MDS-UPDRS I score, MDS-UPDRS II + III scores, RBD), serves as a valuable tool for prognostic counseling and patient selection in PD clinical trials.

Reconsidering Neurogenetic Indication in the Human Brain: Broad Expression of Doublecortin Transcript in the Hippocampal and Cortical Cell Populations.

INTRODUCTION: Neurogenesis in the adult brain may play an important role in memory and cognition; however, knowledge of neurogenic markers in the human brain remains limited. We compared the single-nucleus transcriptome of the hippocampus with that of other cortical regions to identify hippocampus-specific neurogenic markers. METHODS: We analyzed 26,189 nuclei from four human brains collected within 16 h of death. Clustering and annotation were performed to examine differential expression, gene ontology, and intercellular communication. DCX expression was validated by ddPCR. RESULTS: Immature markers such as DCX, CALB2, NES, SOX2, PAX6, DPYSL3, and TUBB3 were expressed in both hippocampus and prefrontal cortex, with higher levels in the prefrontal cortex. ddPCR confirmed higher expression of DCX in the prefrontal cortex. DCX was involved in both neurogenesis and neuroprotection pathways. CONCLUSION: Neurogenic markers are not definitive indicators of adult neurogenesis as their roles are more complex than previously understood.

Silibinin Mitigates Vanadium-induced Lung Injury via the TLR4/MAPK/NF-κB Pathway in Mice.

BACKGROUND/AIM: Silibinin, has been investigated for its potential benefits and mechanisms in addressing vanadium pentoxide (V2O5)-induced pulmonary inflammation. This study explored the anti-inflammatory activity of silibinin and elucidate the mechanisms by which it operates in a mouse model of vanadium-induced lung injury. MATERIALS AND METHODS: Eight-week-old male BALB/c mice were exposed to V2O5 to induce lung injury. Mice were pretreated with silibinin at doses of 50 mg/kg and 100 mg/kg. Histological analyses were performed to assess cell viability and infiltration of inflammatory cells. The expression of pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß) and activation of the MAPK and NF-[Formula: see text]B signaling pathways, as well as the NLRP3 inflammasome, were evaluated using real-time PCR, western blot analysis, and immunohistochemistry. Whole blood analysis was conducted to measure white blood cell counts. RESULTS: Silibinin treatment significantly improved cell viability, reduced inflammatory cell infiltration, and decreased the expression of pro-inflammatory cytokines in V2O5-induced lung injury. It also notably suppressed the activation of the MAPK and NF-[Formula: see text]B signaling pathways, along with a marked reduction in NLRP3 inflammasome expression levels in lung tissues. Additionally, silibinin-treated groups exhibited a significant decrease in white blood cell counts, including neutrophils, lymphocytes, and eosinophils. CONCLUSION: These findings underscore the potent anti-inflammatory effects of silibinin in mice with V2O5-induced lung inflammation, highlighting its therapeutic potential. The study not only confirms the efficacy of silibinin in mitigating inflammatory responses but also provides a foundational understanding of its role in modulating key inflammatory pathways, paving the way for future therapeutic strategies against pulmonary inflammation induced by environmental pollutants.

Nationwide Birth Prevalence of Crucial Congenital Heart Defects From 2014 to 2018 in Korea.

BACKGROUND AND OBJECTIVES: A comprehensive survey of congenital heart disease (CHD) prevalence has not yet been conducted in South Korea. This study aimed to investigate the prevalence of CHDs in Korean children and lay the foundation for national CHD epidemiology. METHODS: Target patients were infantile crucial CHDs, which include critical CHDs (requiring urgent procedures after birth with common hypoxemic defects) and diverse categorical defects excluding simple shunt defects. Data were obtained from the National Health Insurance Service over a 5-year period (2014-2018). Birth prevalence (new cases per 1,000 live births) of CHDs in Korea was analyzed and compared with that of other countries. RESULTS: The birth prevalences of right heart obstructive defects (pulmonary valve stenosis and pulmonary atresia), conus anomalies (tetralogy of Fallot and double outlet right ventricle), and total anomalous pulmonary venous return showed significant increases in the East Asian group (P < 0.001), whereas those of left heart obstructive defects (coarctation of aorta, aortic stenosis, and hypoplastic left heart syndrome), truncus anomalies (D-transposition of great artery and persistent truncus arteriosus), atrioventricular septal defect, and hypoplastic right heart syndrome were significantly decreased in the East Asian group (P < 0.001). CONCLUSIONS: The overall birth prevalence of crucial CHDs in Korea was similar to that of critical CHDs in previous studies from other countries. Some subtypes of right heart obstructive defects, left heart obstructive defects, and conotruncal anomalies showed significant differences between East Asian and Western populations. This study contributes to a foundation for national CHD epidemiology in Korean children.

Effects of antiarrhythmic drug responsiveness and diagnosis-to-ablation time on outcomes after catheter ablation for persistent atrial fibrillation.

Background: The impact of delaying atrial fibrillation catheter ablation (AFCA) for antiarrhythmic drug (AAD) management on the disease course remains unclear. This study investigated AFCA rhythm outcomes based on the diagnosis-to-ablation time (DAT) and AAD responsiveness in participants with persistent AF (PeAF). Methods: We included data from 1038 AAD-resistant PeAF participants, all of whom had a clear time point for AF diagnosis, especially PeAF at diagnosis time, and had undergone an AFCA for the first time. Participants who experienced recurrences of paroxysmal type on AAD therapy were analyzed as a cohort of AAD-partial responders; those maintaining PeAF on AAD were AAD-non-responders. We determined the DAT cutoff for best discriminating long-term rhythm outcomes using a maximum log-likelihood estimation method based on the Cox proportional hazard regression model. Results: Of the participants (79.8% male; median age 61), 806 (77.6%) were AAD-non-responders. AAD-non-responders had a higher body mass index and a larger left atrial diameter than AAD-partial-responders. They also had a higher incidence of AF recurrence after AFCA (adjusted hazard ratio 1.75, 95% confidence interval 1.33-2.30; log-rank p < .001) compared to AAD-partial-responders. The maximum log-likelihood estimation showed bimodal cutoffs at 22 and 40 months. The optimal DAT cutoff rhythm outcome was 22 months, which discriminated better in the AAD-partial-responders than in the AAD-non-responders. Conclusions: Both DAT and AAD responsiveness influenced AFCA rhythm outcomes. Delaying AFCA to a DAT of longer than 22 months was inadvisable, particularly in the participants in whom PeAF was changed to paroxysmal AF during AAD therapy.

Synthesis and Evaluation of Chloride-Substituted Ramalin Derivatives for Alzheimer's Disease Treatment.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by the accumulation of amyloid-beta plaques and hyperphosphorylated tau proteins, leading to cognitive decline and neuronal death. However, despite extensive research, there are still no effective treatments for this condition. In this study, a series of chloride-substituted Ramalin derivatives is synthesized to optimize their antioxidant, anti-inflammatory, and their potential to target key pathological features of Alzheimer's disease. The effect of the chloride position on these properties is investigated, specifically examining the potential of these derivatives to inhibit tau aggregation and beta-site amyloid precursor protein cleaving enzyme 1 (BACE-1) activity. Our findings demonstrate that several derivatives, particularly RA-3Cl, RA-4Cl, RA-26Cl, RA-34Cl, and RA-35Cl, significantly inhibit tau aggregation with inhibition rates of approximately 50%. For BACE-1 inhibition, Ramalin and RA-4Cl also significantly decrease BACE-1 expression in N2a cells by 40% and 38%, respectively, while RA-23Cl and RA-24Cl showed inhibition rates of 30% and 35% in SH-SY5Y cells. These results suggest that chloride-substituted Ramalin derivatives possess promising multifunctional properties for AD treatment, warranting further investigation and optimization for clinical applications.

Portable and miniature sensors in supply chain for food authentication: a review.

Food fraud, a pervasive issue in the global food industry, poses significant challenges to consumer health, trust, and economic stability, costing an estimated $10-15 billion annually. Therefore, there is a rising demand for developing portable and miniature sensors that facilitate food authentication throughout the supply chain. This review explores the recent advancements and applications of portable and miniature sensors, including portable/miniature near-infrared (NIR) spectroscopy, e-nose and colorimetric sensors based on nanozyme for food authentication within the supply chain. After briefly presenting the architecture and mechanism, this review discusses the application of these portable and miniature sensors in food authentication, addressing the challenges and opportunities in integrating and deploying these sensors to ensure authenticity. This review reveals the enhanced utility of portable/miniature NIR spectroscopy, e-nose, and nanozyme-based colorimetric sensors in ensuring food authenticity and enabling informed decision-making throughout the food supply chain.

Clinical Implications of Polypharmacy for Patients with New-Onset Atrial Fibrillation Based on Real-World Data: Observations from the Korea National Health Insurance Service Data.

Background: Polypharmacy is commonly observed in atrial fibrillation (AF) and is associated with poorer clinical outcomes. Our study aimed to elucidate the polypharmacy prevalence, its associated risk factors, and its relationship with adverse clinical outcomes using a 'real-world' database. Methods: This study included 451,368 subjects without prior history of AF (median age, 54 [interquartile range, 48.0-63.0] years; 207,748 [46.0%] female) from the Korea National Health Insurance Service-Health Screening (NHIS-HealS) database between 2002 and 2013. All concomitant medications prescribed were collected, and the intake of five or more concomitant drugs was defined as polypharmacy. During the follow-up, all-cause death, major bleeding events, transient ischemic attack (TIA) or ischemic stroke, and admission due to worsened heart failure were recorded. Results: Based on up to 7.7 (6.8-8.3) years of follow-up and 768,306 person-years, there were 12,241 cases of new-onset AF identified. Among patients with new-onset AF (40.0% females, median age 63.0 [54.0-70.0] years), the polypharmacy prevalence was 30.9% (3784). For newly diagnosed AF, factors, such as advanced age (with each increase of 10 years, odds ratios (OR) 1.32, 95% confidence interval (CI) 1.26-1.40), hypertension (OR 4.00, 95% CI 3.62-4.43), diabetes mellitus (OR 3.25, 95% CI 2.86-3.70), chronic obstructive pulmonary disease (COPD) (OR 3.00, 95% CI 2.51-3.57), TIA/ischemic stroke (OR 2.36, 95% CI 2.03-2.73), dementia history (OR 2.30, 95% CI 1.06-4.98), end-stage renal disease (ESRD) or chronic kidney disease (CKD) (OR 1.97, 95% CI 1.38-2.82), and heart failure (OR 1.95, 95% CI 1.69-2.26), were found to be independently correlated with the incidence of polypharmacy. Polypharmacy significantly increased the incidence and risk of major bleeding (adjusted hazard ratio (aHR) 1.26, 95% CI 1.12-1.41). The study observed a statistically significant increase in the incidence of all-cause mortality, however, the risk for all-cause mortality elevated but did not show significance (aHR 1.11, 95% CI 0.99-1.24). The risk of stroke and admission for heart failure did not change with polypharmacy. Conclusions: In our investigation using data from a nationwide database, polypharmacy was widespread in new-onset AF population and was related to major bleeding events. However, polypharmacy does not serve as an independent risk factor for adverse outcomes, with exception of major bleeding event. For AF patients, ensuring tailored medication for comorbidities as well as reducing polypharmacy are essential considerations.

Cortical volumetric changes after cochlear implantation in postlingually deaf adults: correlation with speech perception abilities.

This study aims to analyse the volumetric changes in brain MRI after cochlear implantation (CI), focusing on the speech perception in postlingually deaf adults. We conducted a prospective cohort study with 16 patients who had bilateral hearing loss and received unilateral CI. Based on the surgical side, patients were categorized into left and right CI groups. Volumetric T1-weighted brain MRI were obtained before and one year after the surgery. To overcome the artifact caused by the internal device in post-CI scan, image reconstruction method was newly devised and applied using the contralateral hemisphere of the pre-CI MRI data, to run FreeSurfer. We conducted within-subject template estimation for unbiased longitudinal image analysis, based on the linear mixed effect models. When analyzing the contralateral cerebral hemisphere before and after CI, a substantial increase in superior frontal gyrus and superior temporal gyrus (STG) volumes was observed in the left CI group. A positive correlation was observed in the STG and post-CI word recognition score in both groups. As far as we know, this is the first study attempting longitudinal brain volumetry based on post-CI MRI scans. We demonstrate that better auditory performance after CI is associated with structural restoration in central auditory structures.

Transcriptome Analysis of the Striatum of Electroacupuncture-treated Naïve and Ischemic Stroke Mice.

Objectives: Electroacupuncture (EA) has been demonstrated to aid stroke recovery. However, few investigations have focused on identifying the potent molecular targets of EA by comparing EA stimulation between naïve and disease models. Therefore, this study was undertaken to identify the potent molecular therapeutic mechanisms underlying EA stimulation in ischemic stroke through a comparison of mRNA sequencing data obtained from EA-treated naïve control and ischemic stroke mouse models. Methods: Using both naïve control and middle cerebral artery occlusion (MCAO) mouse models, EA stimulation was administered at two acupoints, Baihui (GV20) and Dazhui (GV14), at a frequency of 2 Hz. Comprehensive assessments were conducted, including behavioral evaluations, RNA sequencing to identify differentially expressed genes (DEGs), functional enrichment analysis, protein-protein interaction (PPI) network analysis, and quantitative real-time PCR. Results: EA stimulation ameliorated the ischemic insult-induced motor dysfunction in mice with ischemic stroke. Comparative analysis between control vs. MCAO, control vs. control + EA, and MCAO vs. MCAO + EA revealed 4,407, 101, and 82 DEGs, respectively. Of these, 30, 7, and 1 were common across the respective groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed upregulated DEGs associated with the regulation of inflammatory immune response in the MCAO vs. MCAO + EA comparison. Conversely, downregulated DEGs in the control vs. control + EA comparison were linked to neuronal development. PPI analysis revealed major clustering related to the regulation of cytokines, such as Cxcl9, Pcp2, Ccl11, and Cxcl13, in the common DEGs of MCAO vs. MCAO + EA, with Esp8l1 identified as the only common downregulated DEG in both EA-treated naïve and ischemic models. Conclusion: These findings underscore the diverse potent mechanisms of EA stimulation between naïve and ischemic stroke mice, albeit with few overlaps. However, the potent mechanisms underlying EA treatment in ischemic stroke models were associated with the regulation of inflammatory processes involving cytokines.