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Wei-Hung Chan,1,2 Yu-Juei Hsu,3 Chiao-Pei Cheng,1 Kuan-Nien Chou,2,4 Chin-Li Chen,5 Shih-Ming Huang,6 Wei-Chih Kan,7,8,* Yi-Lin Chiu6,* 1Department of Anesthesiology, Tri-Service General Hospital, National Defense Medical Center, Taipei City, Taiwan, Republic of China; 2Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei City, Taiwan, Republic of China; 3Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei City, Taiwan, Republic of China; 4Department of Neurosurgery, Tri-Service General Hospital, National Defense Medical Center, Taipei City, Taiwan, Republic of China; 5Division of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei City, Taiwan, Republic of China; 6Department of Biochemistry, National Defense Medical Center, Taipei City, Taiwan, Republic of China; 7Department of Nephrology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan City, Taiwan, Republic of China; 8Department of Biological Science and Technology, Chung Hwa University of Medical Technology, Tainan City, Taiwan, Republic of China*These authors contributed equally to this workCorrespondence: Yi-Lin Chiu, Department of Biochemistry, National Defense Medical Center, Rm. 7323, 7F, No. 161, Sec. 6, Minquan E. Road, Neihu Dist, Taipei City, 114201, Taiwan, Republic of China, Tel +886 02 87923100#18828, Fax +886 02 87910776, Email yilin1107@mail.ndmctsgh.edu.twPurpose: In this study, we use animal models combined with bioinformatics strategies to investigate the potential changes in overall renal transcriptional expression after traumatic brain injury.Methods: Microarray analysis was performed after kidney acquisition using unilateral controlled cortical impact as the primary mouse TBI model. Multi-oriented gene set enrichment analysis was performed for differentially expressed genes.Results: The results showed that TBI affected the gene set associated with mitochondria function in kidney cells, and a negative enrichment of gene sets associated with immune cell migration and epidermal development was also observed. Analysis of the disease phenotype gene set revealed that differential expression of mitochondria-related genes was associated with lactate metabolism. Alternatively, activation and adhesion of immune cells associated with the complement system may promote autoinflammation in kidney tissue. The simulated immune cell infiltration analysis showed an increase in the proportion of activated memory CD4 T cells and a decrease in the proportion of resting memory CD4 T cells, suggesting that activated memory CD4 T cell infiltration may be involved in the inflammation of renal tissue and cause damage to renal cells, such as principal cells, mesangial cells and loops of Henle cells.Conclusion: This study is the first to reveal the effects of brain trauma on the kidney. TBI may affect the expression of mitochondria function-related gene sets in renal cells by increasing lactate. It may also affect renal mesangial cells by inducing increased infiltration of immune cells through mechanisms related to complement system activation or autoimmune antibodies.Keywords: traumatic brain injury, nephropathy, complement system, lactate metabolism, immune cell infiltration

Yen-Ling Chiu,1– 3 Mao-Jhen Jhou,4 Tian-Shyug Lee,4,5 Chi-Jie Lu,4– 6 Ming-Shu Chen7 1Graduate Institue of Medicine and Graduate School of Biomedical Informatics, Yuan Ze University, Taoyuan, 32003, Taiwan, Republic of China; 2Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, 10002, Taiwan, Republic of China; 3Department of Medical Research, Department of Medicine,Far Eastern Memorial Hospital, New Taipei, 22056, Taiwan, Republic of China; 4Graduate Institute of Business Administration, Fu Jen Catholic University, New Taipei, 242062, Taiwan, Republic of China; 5Artificial Intelligence Development Center, Fu Jen Catholic University, New Taipei City, 242062, Taiwan, Republic of China; 6Department of Information Management, Fu Jen Catholic University, New Taipei City, 242062, Taiwan, Republic of China; 7Department of Healthcare Administration,College of Healthcare and Management, Asia Eastern University of Science and Technology, New Taipei, 22061, Taiwan, Republic of ChinaCorrespondence: Chi-Jie Lu Fu Jen Catholic University, New Taipei 242062, Taiwan Email 059099@mail.fju.edu.twMing-Shu Chen Asia Eastern University of Science and Technology, TaiwanAsia Eastern University of Science and Technology, No.58, Sec. 2, Sichuan Rd, Pan-Chiao Dist., New Taipei, 22061, TaiwanEmail tree1013@gmail.comPurpose: As global aging progresses, the health management of chronic diseases has become an important issue of concern to governments. Influenced by the aging of its population and improvements in the medical system and healthcare in general, Taiwan’s population of patients with chronic kidney disease (CKD) has tended to grow year by year, including the incidence of high-risk cases that pose major health hazards to the elderly and middle-aged populations.Methods: This study analyzed the annual health screening data for 65,394 people from 2010 to 2015 sourced from the MJ Group – a major health screening center in Taiwan – including data for 18 risk indicators. We used five prediction model analysis methods, namely, logistic regression (LR) analysis, C5.0 decision tree (C5.0) analysis, stochastic gradient boosting (SGB) analysis, multivariate adaptive regression splines (MARS), and eXtreme gradient boosting (XGboost), with estimated glomerular filtration rate (e-GFR) data to determine G3a, G3b & G4 stage CKD risk factors.Results: The LR analysis (AUC=0.848), SGB analysis (AUC=0.855), and XGboost (AUC=0.858) generated similar classification performance levels and all outperformed the C5.0 and MARS methods. The study results showed that in terms of CKD risk factors, blood urea nitrogen (BUN) and uric acid (UA) were identified as the first and second most important indicators in the models of all five analysis methods, and they were also clinically recognized as the major risk factors. The results for systolic blood pressure (SBP), SGPT, SGOT, and LDL were similar to those of a related study. Interestingly, however, socioeconomic status-related education was found to be the third important indicator in all three of the better performing analysis methods, indicating that it is more important than the other risk indicators of this study, which had different levels of importance according to the different methods.Conclusion: The five prediction model methods can provide high and similar classification performance in this study. Based on the results of this study, it is recommended that education as the socioeconomic status should be an important factor for CKD, as high educational level showed a negative and highly significant correlation with CKD. The findings of this study should also be of value for further discussions and follow-up research.Keywords: chronic kidney disease, health screening, machine learning algorithms, risk indicators assessment, education

Yuan-Yuei Chen,1– 3 Tung-Wei Kao,3 Yi-Lin Chiu,4 Tao-Chun Peng,3 Hui-Fang Yang,3 Wei-Liang Chen3,4 1Department of Pathology, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China; 2Department of Pathology, Tri-Service General Hospital Songshan Branch, School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China; 3Division of Geriatric Medicine, Department of Family and Community Medicine, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China; 4Department of Biochemistry, National Defense Medical Center, Taiwan, Republic of ChinaCorrespondence: Wei-Liang ChenDivision of Geriatric Medicine, Department of Family Medicine, Tri-Service General Hospital, National Defense Medical Center, Number 325, Section 2, Chang-Gong Road, Nei-Hu District, Taipei, 114, TaiwanTel +886-2-87923311 ext. 16567Fax +886-2-87927057Email weiliang0508@gmail.comBackground: Emerging studies have proposed that cytokines secreted following macrophage polarization may contribute to skeletal muscle aging. The current study primarily aimed to determine whether these cytokines have an impact on the progression of sarcopenia in an elderly population.Methods: In total, 120 elderly adults aged 65 years and older who underwent health examinations from 2015 to 2019 were included in this retrospective study. Sarcopenia was based on the criteria proposed by the European Working Group on Sarcopenia in Older People in 2019. Macrophages and cytokines datasets were obtained from Gene Expression Omnibus (GEO) database. Comprehensive assessments were performed for muscle strength, muscle mass, gait speed, tumor growth factor-β (TGF-β), and interleukin-12 (IL-12). Thereafter, the association between sarcopenia and cytokines was analyzed using regression models.Results: Low muscle strength and low-speed gait were negatively associated with IL-12 [β: − 8.96 (95% CI: − 14.12, − 3.79) and − 7.16 (95% CI: − 12.54, − 1.78), respectively]. Participants with more sarcopenia components and more severe sarcopenia had lower IL-12 (P for trend < 0.001). Conversely, more amount of sarcopenia components were associated with increased TGF-β (P for trend < 0.05). A definite diagnosis of sarcopenia was associated with decreased IL-12 and increased TGF-β with β of − 8.96 (95% CI: − 14.12, − 3.79) and 147.75 (95% CI: 36.27, 259.23). Furthermore, increased IL-12 levels were significantly associated with reduced occurrence of sarcopenia with and odd ratio (OR) of 0.36 (95% CI: 0.15– 0.834).Conclusion: Our findings on the relationship between cytokines and age-related muscle loss showed that IL-12 may be an early diagnosis indicator for sarcopenia in the elderly population.Keywords: gender, sarcopenia, IL-12, TGF-β, macrophage

Hsuan-Wei Chen,1 Jung-Chun Lin,1 Ying-Hsuen Wu,2,3,* Yi-Lin Chiu4,* 1Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 2Department of Ophthalmology, China Medical University Hospital, China Medical University, Taichung City, Taiwan; 3School of Medicine, College of Medicine, China Medical University, Taichung City, Taiwan; 4Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan*These authors contributed equally to this workCorrespondence: Yi-Lin ChiuDepartment of Biochemistry, National Defense Medical Center, Taipei, TaiwanEmail yc566@georgetown.eduYing-Hsuen WuDepartment of Ophthalmology, China Medical University Hospital, China Medical University Email amywu0414@gmail.comBackground: Xanthelasma palpebrarum (XP) is a sign of hyperlipidemia and is closely linked to atherosclerosis. Since fatty liver shares similar risk factors with atherosclerosis, we hypothesized that patients with XP are also at risk of non-alcoholic fatty liver disease (NAFLD).Methods: In this retrospective cohort study, 37 patients with XP were compared with sex- and age-matched controls undergoing general health examination. Moreover, demographic information and lipid profiles were compared. The risk of NAFLD was evaluated using the hepatic steatosis and ZJU indices. In addition, we analyzed publicly available RNA sequencing data from the GSE48452 and GSE61260 datasets in the Gene Expression Omnibus database.Findings: Patients with XP had higher scores of hepatic steatosis index (37 ± 1.13 vs 32 ± 0.82, p=0.0006) and ZJU index (38.77 ± 1.0 vs 33.88 ± 0.74, p=0.0002). In addition, they had higher levels of lipid parameters, including total cholesterol, low-density lipoprotein (LDL), and fasting glucose. Among patients with fatty liver, individuals presenting with XP showed higher serum levels of total cholesterol (216 ± 10.4 vs 188.9 ± 7.6, p=0.04), fasting glucose (117.1 ± 6.4 vs 98.3 ± 2.4, p=0.002), and low-density lipoprotein (145.1 ± 8.7 vs 115.6 ± 6.4, p=0.009) than those without XP. In gene expression analysis, individuals presenting with non-alcoholic steatohepatitis showed higher Z scores of xanthelasma than those without non-alcoholic steatohepatitis.Conclusion: Our results suggest that individuals with XP have a higher risk of progression to NAFLD and develop a more severe dyslipidemia.Keywords: xanthelasma, xanthoma, fatty liver, NASH, NAFLD

Hsuan-Wei Chen,1 Yi-Lin Chiu,2 Tsai-Yuan Hsieh,1 Peng-Jen Chen,1 Tien-Yu Huang,1 Hsuan-Hwai Lin,1 Yu-Lueng Shih,1 Jung-Chun Lin1 1Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 2Department of Biochemistry, National Defense Medical Center, Taipei, TaiwanCorrespondence: Jung-Chun LinDivision of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, 325, Sec 2, Cheng-Kung Road, Neihu 114, Taipei, TaiwanTel +886-2- 87927409Fax +886-2- 87927139Email doc10506@gmail.comBackground: Vitamin D contributes to bone health and extra-skeletal effects. The mechanisms underlying vitamin D metabolism have not been extensively evaluated. The relationships between vitamin D and inflammatory cytokines are debated. Our objective was to investigate whether supplemental interferons are associated with longitudinal change of vitamin D status in humans.Methods: A total of 48 patients with 24 or 48 weeks of pegylated interferon-α plus ribavirin therapy were examined for serum 25-hydroxyvitamin D (25[OH]D) level before treatment, at the end of treatment, and 24 weeks after treatment. In addition, we analyzed publicly available RNA sequencing data from accession GSE42697 and GSE7123 in the Gene Expression Omnibus.Findings: The overall sustained virologic response (SVR) rate was 62.5%. There was no statistically significant association between baseline 25(OH)D concentrations and liver fibrosis. In patients with SVR, serum 25(OH)D increased markedly at end-of-treatment and decreased markedly by the end of the 24-week follow-up period. In the non-SVR group, this treatment-dependent change was lost. In gene expression analysis, the vitamin D biosynthesis process was activated in subjects with SVR, but not in patients without SVR. Furthermore, vitamin D receptor (VDR) signaling in peripheral blood mononuclear cells (PBMCs) was triggered in marked responders but not in poor responders.Conclusion: In the aggregate, these data suggest that interferons have a regulatory influence on vitamin D status that can contribute to VDR signaling in PBMCs.Keywords: cytokines, interferon-α, PBMCs, VDR signaling, vitamin D

Ana C Krieger,1 Heekoung Youn,2 Frank Modersitzki,2 Ya-Lin Chiu,1 Linda M Gerber,1 Elizabeth Weinshel,2 Christine R Fielding21Weill Cornell Medical College and New York Presbyterian Hospital, 2New York University School of Medicine and NYU Langone Medical Center, New York, NYBackground: Obstructive sleep apnea is commonly associated with metabolic changes and obesity, and changes in body weight by either medical or surgical approaches have been considered to affect the severity of sleep apnea and appetite-controlling hormones. This prospective study evaluated the effect of weight loss induced by laparoscopic adjustable gastric banding (LAGB) surgery on respiratory disturbance during sleep, oxygen saturation levels, sleep architecture, and leptin and ghrelin levels.Methods: Participants were patients at a university-based medical center surgical weight loss program. All participants with a body mass index > 30 kg/m2 undergoing LAGB surgery for weight reduction were offered the opportunity to participate in the study. Procedures included overnight polysomnography followed by fasting hormone levels at baseline and 12 months postoperatively.Results: Thirty subjects (10 men, 20 women) of mean age 44.0 ± 12.5 years were recruited. At 12 months postoperatively, mean excess weight loss was 44.4% ± 14%. The apnea-hypopnea index decreased from 34.2 ± 35 to 19.0 ± 21.7 events per hour (P < 0.0001), while leptin levels decreased from 24.5 ± 17.42 pg/mL to 11.6 ± 10.6 pg/mL (P = 0.02). Ghrelin levels did not change substantially. Nadir oxygen saturation levels increased from 81% to 84% at 12 months (P = 0.03). Mean oxygen saturation improved and was positively correlated with ghrelin levels at both time points (r = 0.39, P = 0.07, and r = 0.60, P = 0.01).Conclusion: LAGB surgery was associated with 44.4% excess weight loss at 12 months, accompanied by a 33.7% improvement in apnea-hypopnea index as well as a reduction in leptin levels by 31.7% in this group. An association between ghrelin and mean oxygen saturation was seen and deserves further investigation.Keywords: sleep apnea, obesity, bariatric surgery, weight loss, metabolism, leptin, ghrelin, sleep

AIMS: To examine the association between type 2 diabetes and serious psychological distress (SPD) and to assess if SPD was an independent risk factor for health risk behaviors and diabetes care among adults with diabetes. METHODS: Cross-sectional analysis was performed using the 2007 California Health Interview Survey with adults in California. Multiple logistic models were used to examine the associations between the multiple risk and outcome factors. RESULTS: Of the participants, 6.9% of adults had diagnoses of type 2 diabetes. SPD was present in 7.0% of adults with diabetes but only in 3.5% of adults without diabetes. Multiple logistic regression analysis revealed that participants with diabetes were significantly more likely than those without diabetes to experience SPD (OR=1.81; 95% CI=[1.3-2.5], p=0.0002), adjusting for other factors. In addition, participants with diabetes and SPD were more likely to report insufficient physical activity and more current cigarette smoking than participants without SPD. SPD among participants with diabetes, however, did not significantly affect good diabetes care. CONCLUSIONS: The findings suggest that adults with diabetes are more likely to experience SPD than adults without diabetes. Further research is needed to explore the underlying mechanisms for this association among adults with both diabetes and SPD. [ABSTRACT FROM AUTHOR]

BACKGROUND: The ability to administer the contents of an encapsulated-dose formulation in liquids or soft foods without compromising drug bioavailability is highly desirable for patients who are unable to swallow or have difficulty swallowing. OBJECTIVE: The purpose of this study was to compare the bioavailability of lansoprazole granules administered in 2 types of juice and a soft food with that of the intact capsule administered with water. METHODS: Healthy adult volunteers were eligible for this single-center, Phase I, single-dose, randomized, open-label, 4-period crossover study. Subjects received the enteric-coated granular contents of a 30-mg lansoprazole capsule in 3 test regimens (in 180 mL of orange juice, 180 mL of tomato juice, or 1 tablespoon of strained pears, each followed by 180 mL of water) and 1 reference regimen (the 30-mg intact capsule with 180 mL of water). The regimens were rotated at > or = 6-day intervals so that each subject received all 4 regimens. Blood samples for pharmacokinetic analyses were obtained during the 12 hours after each regimen. RESULTS: Twenty healthy adult volunteers (10 men, 10 women; mean age, 36 years [range, 19-53 years]) completed this study. Bioavailability of the 3 test regimens was assessed using the two 1-sided tests procedure for mean maximum plasma concentration and area under the plasma concentration-time curve (AUC) from time 0 through the last measurable concentration and AUC from time 0 to infinity. These results were compared with that of the intact capsule. This comparison indicated that the 90% CIs for all 3 test regimens were within the acceptable bioequivalence range of 0.80 to 1.25. Lansoprazole was well tolerated, with most of the adverse events being mild. Headache was the most frequently reported adverse event. CONCLUSION: The results of this study indicate that the bioavailability of lansoprazole granules, when administered in orange juice, tomato juice, or a small amount of strained pears, was similar to that of the intact capsule in these healthy adult volunteers. [ABSTRACT FROM AUTHOR]

This study assesses the first statewide program to provide simulation training conducted via videoconference to all new caseworkers. The simulation training in Illinois was conducted at a mock house. A mock family played by standardized clients is physically present, and trainees participate remotely. The program evaluation team implemented a survey that asks trainees to rate their confidence in different skills at multiple timepoints, to appraise the quality of feedback and debriefing of the training team, and to write text responses to the questions regarding their learning experience. Analysis of quantitative data over the course of the training showed statistically significant linear increases in trainees' confidence for all the 14 skills. Their text responses indicated that they received feedback they appreciated and felt they gained ability on a range of different skills. The simulation training makes a valued and effective contribution to the certification training.

Purpose: Clinical shadowing(CS) offers preclinical medical students the opportunity to observe certified physicians in practice. Analyzing the content of students' reflective writings(RWs) to understand core competencies they perceived during CS, as well as stages of their reflections, can offer valuable insights for course design and instructor guidance. This study aimed to address this matter by employing a thematic analysis of students' RWs to explore the learning outcomes derived from CS., Materials and Methods: The dataset of the thematic analysis comprised de-identified RWs from preclinical medical students who participated in the clinical shadowing program during the first semester of the 2019 academic year at National Taiwan University College of Medicine. Two researchers independently extracted and categorized pertinent content from the texts of RWs, aligning them with the six core competencies of ACGME and mapping them to the stages of Kolb's learning cycle. Additionally, correlation with shadowing specialties and fields was investigated., Results: In total, 155 RWs were analyzed. Patient care emerged as the most frequently reflected competency(30%), followed by systems-based practice(23%), and medical knowledge(21%). The shadowing specialties and fields had an impact on the core competencies students perceived. In terms of Kolb's learning stages, concrete experience(66%) predominated in RWs, while abstract conceptualization(19%) and reflective observation(14%) were less prevalent. For each competency, concrete experience was the prevailing stage, with active experimentation being the least dominant one. Students exhibited varying proportions of reflections at different stages for each core competency., Conclusions: Clinical shadowing experiences enable preclinical medical students to explore required clinical core competencies, with emphases depending on the shadowing specialties and fields. Currently, most reflections are concentrated at Kolb's concrete experience stage. This study offers valuable insights for designing future CS programs and improving faculty development, aimed at helping students achieve deeper and more comprehensive reflective learning in relation to core competencies, and even professional identity.

Background: The circulatory peripheral immune system is the most convenient approach for determining an individual's immune status. Due to various reasons, while previous studies have addressed the critical impact of age, most individual studies did not analyze immunosenescence in a systemic manner, which complicates the possibility of building a reference range for age-dependent immune profiles for effective immune monitoring. To address this gap, this study analyzed a group of healthy individuals to establish age-specific reference ranges of the healthy circulatory immune profile, and a systematic review and meta-analysis were conducted to validate the findings and create generalizable immune cell reference ranges., Results: Our study recruited a total of 363 healthy Taiwanese adults (median age 42 years [IQR 30, 62], age range 21 to 87 years, 43.3% male), including 158 under 40 years old, 127 between 40-64 years old, and 78 over 64 years old. Significant age-related alterations were observed in both adaptive and innate immune cell subsets. CD8 + T cells decreased and CD4/CD8 ratio increased, with notable increases in NK cells. CD4 + T cells were less impacted by aging, while CD8 + T cells significantly lost CD28 and increased CD31 expression with age. A clear reverse trend in naïve and memory subsets of CD4 + and CD8 + T cells was observed. Detailed reference ranges for immune cell subsets in healthy Taiwanese adults were established. A systematic review included 7,425 adults and a meta-analysis of 12 eligible studies confirmed our findings in Taiwan, enhancing generalizability., Conclusions: Combined with previous studies and original data through a systematic review and meta-analysis, we highlighted and quantified significant immune profile differences between older and younger individuals. The sex and age-specific reference ranges for peripheral immune cell subsets can serve as a basis for effective immune monitoring of various aging-related illnesses., (© 2024. The Author(s).)

Background: Collaborative learning is an essential pedagogy in medical education, within which small group learning constitutes an integral component. Online small group teaching has been widely applied and blended with in-person sessions in the aftermath of the Covid-19 pandemic. This study examined whether group metacognition was associated with teamwork satisfaction in an online small group teaching curriculum for medical students., Methods: We enrolled medical students of the 2nd and 4th years during the 2021 fall semester after they participated in 3 consecutive sessions of online small group tutorials (SGTs), which have been implemented in our medical school for more than 20 years. The students completed a group metacognitive scale (GMS) and a teamwork satisfaction scale (TSS) after the sessions. We analyzed whether group metacognition in 4 dimensions (knowledge of cognition, planning, evaluating, and monitoring) could be connected with medical students' teamwork satisfaction using partial least squares-structural equation modeling (PLS-SEM)., Results: A total of 263 medical students participated in this study. Both GMS and TSS exhibited good reliability and validity. Three of the 4 dimensions of group metacognition (cognition, planning, and evaluating) positively correlated with teamwork satisfaction (path coefficients 0.311, 0.279, and 0.21; p = 0.002, 0.002, and 0.043, respectively) following the online SGT curriculum, whereas the monitoring dimension did not (path coefficient 0.087; p = 0.357). The model achieved an adjusted R square of 0.683., Conclusion: We discovered that group metacognition correlated positively with better teamwork satisfaction, supporting the importance of group metacognitive competency for online collaborative learning., (© 2024. The Author(s).)

Introduction: Research has shown that speech analysis demonstrates sensitivity in detecting early Alzheimer's disease (AD), but the relation between linguistic features and cognitive tests or biomarkers remains unclear. This study aimed to investigate how linguistic features help identify cognitive impairments in patients in the early stages of AD., Method: This study analyzed connected speech from 80 participants and categorized the participants into early-AD and normal control (NC) groups. The participants underwent amyloid- β positron emission tomography scans, brain magnetic resonance imaging, and comprehensive neuropsychological testing. Participants' speech data from a picture description task were examined. A total of 15 linguistic features were analyzed to classify groups and predict cognitive performance., Results: We found notable linguistic differences between the early-AD and NC groups in lexical diversity, syntactic complexity, and language disfluency. Using machine learning classifiers (SVM, KNN, and RF), we achieved up to 88% accuracy in distinguishing early-AD patients from normal controls, with mean length of utterance (MLU) and long pauses ratio (LPR) serving as core linguistic indicators. Moreover, the integration of linguistic indicators with biomarkers significantly improved predictive accuracy for AD. Regression analysis also highlighted crucial linguistic features, such as MLU, LPR, Type-to-Token ratio (TTR), and passive construction ratio (PCR), which were sensitive to changes in cognitive function., Conclusion: Findings support the efficacy of linguistic analysis as a screening tool for the early detection of AD and the assessment of subtle cognitive decline. Integrating linguistic features with biomarkers significantly improved diagnostic accuracy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chou, Chang, Chang, Lee, Chuang, Chiu, Liang, Fan and Liu.)

A sex change phenomenon was reported in some free-living, non-sessile coral species of the Family Fungiidae. However, there are no reports describing sex change in sessile colonial species. Timing and cellular processes of sex change are also unclear in corals. Here, we report sex change of the colonial coral, Fimbriaphyllia ancora, and its cellular process. Of 26 colonies monitored at Nanwan Bay, southern Taiwan, about 70% changed their sex every year after annual spawning for least 3-4 consecutive years, i.e., colonies that were male two years ago became female last year, and male again this year. The remaining 30% were permanently male or female. Sex-change and non-sex-change colonies grew in close proximity or even side-by-side. No significant differences were found in colony size between sex-change and non-sex-change colonies. Histological analysis showed that, in female-to-male sex change, small oocytes were present up to 3 months in some gonads after spawning and disappeared by 5 months. This suggests that sex change occurred 4-5 months after spawning. In contrast, in male-to-female sex change, oocytes appeared weeks after sperm release and in most gonads by 3 months, suggesting that male-to-female sex change occurred 0-3 months after sperm release., (© 2024. The Author(s).)

Objectives: Emergency medical services (EMS) provide health care in situations with limited time and resources. Challenges arise when introducing novel medications, treatments, or technologies or modifying existing practices in these settings. Effective implementation strategies are pivotal for their success. This study aims to identify and categorize potential facilitators and barriers in the implementation of prehospital EMS through a review of relevant research articles., Methods: We searched PubMed and EMbase to identify studies published before December 2023, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for our search strategy and scoping review. We included original articles written in English that report on the factors that influence the implementation in prehospital settings. We extracted and categorized the factors into different themes., Results: Out of the 371 retrieved papers, we selected 19 (5%) for inclusion in this review. We extracted 46 influencing factors from the selected articles and categorized them into ten themes: (1) Outer system, (2) Inner system, (3) Practitioner characteristics, (4) Resources, (5) Communication and collaboration, (6) Patient factors, (7) Intervention characteristics, (8) De-implementation of prior practices, (9) Logistical issues, and (10) Quality improvement., Conclusions: This study examined the literature on EMS implementation factors and proposed a 10-theme EMS model framework. Key factors include training/education, equipment/tools, communication with hospitals, and practitioners' attitudes.

Background: Lytic Epstein-Barr virus (EBV) infection plays a major role in the pathogenesis of nasopharyngeal carcinoma (NPC). For patients with recurrent or metastatic NPC and resistant to conventional therapies, adoptive cell therapy using EBV-specific cytotoxic T cells (EBV-CTLs) is a promising option. However, the long production period (around 3 to 4 weeks) and low EBV-CTL purity (approximately 40% of total CD8 T cells) in the cell product limits the application of EBV-CTLs in clinics. Thus, this study aimed to establish a protocol for the rapid production of EBV-CTLs., Methods: By culturing peripheral blood mononuclear cells (PBMCs) from EBV-seropositive donors with EBV-specific peptides and interleukin (IL)-2, IL-15, and interferon α (IFN-α) for 9 days, we identified that IL-15 can enhance IL-2-mediated CTL activation and significantly increase the yield of CTLs., Results: When IFN-α was used in IL-2/IL-15-mediated CTL production from days 0 to 6, the productivity of EBV-CTLs and EBV-specific cytotoxicity significantly were reinforced relative to EBV-CTLs from IL-2/IL-15 treatment. Additionally, IFN-α-induced production improvement of virus-specific CTLs was not only the case for EBV-CTLs but also for cytomegalovirus-specific CTLs., Conclusion: We established a novel protocol to rapidly expand highly pure EBV-CTLs from PBMCs, which can produce EBV-CTLs in 9 days and does not require feeder cells during cultivation., (© 2024. The Author(s).)

Background: Air pollution is recognized as a modifiable risk factor for dementia, and recent evidence suggests that improving air quality could attenuate cognitive decline and reduce dementia risk. However, studies have yet to explore the effects of improved air quality on brain structures. This study aims to investigate the impact of air pollution reduction on cognitive functions and structural brain differences among cognitively normal older adults., Methods: Four hundred and thirty-one cognitively normal older adults were from the Epidemiology of Mild Cognitive Impairment study in Taiwan (EMCIT), a community-based cohort of adults aged 60 and older, between year 2017- 2021. Annual concentrations of PM 2.5 , NO 2 , O 3 , and PM 10 at participants' residential addresses during the 10 years before enrollment were estimated using ensemble mixed spatial models. The yearly rate of change (slope) in air pollutants was estimated for each participant. Cognitive functions and structural brain images were collected during enrollment. The relationships between the rate of air pollution change and cognitive functions were examined using linear regression models. For air pollutants with significant findings in relation to cognitive function, we further explored the association with brain structure., Results: Overall, all pollutant concentrations, except O 3 , decreased over the 10-year period. The yearly rates of change (slopes) in PM 2.5 and NO 2 were correlated with better attention (PM 2.5 : r = -0.1, p = 0.047; NO 2 : r = -0.1, p = 0.03) and higher white matter integrity in several brain regions. These regions included anterior thalamic radiation, superior longitudinal fasciculus, inferior longitudinal fasciculus, corticospinal tract, and inferior fronto-occipital fasciculus., Conclusions: Greater rate of reduction in air pollution was associated with better attention and attention-related white matter integrity. These results provide insight into the mechanism underlying the relationship between air pollution, brain health, and cognitive aging among older adults., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Mild cognitive impairment (MCI) is recognized as the prodromal phase of dementia, a condition that can be either maintained or reversed through timely medical interventions to prevent cognitive decline. Considerable studies using functional magnetic resonance imaging (fMRI) have indicated that altered activity in the medial prefrontal cortex (mPFC) serves as an indicator of various cognitive stages of aging. However, the impacts of intrinsic functional connectivity in the mPFC as a mediator on cognitive performance in individuals with and without MCI have not been fully understood. In this study, we recruited 42 MCI patients and 57 healthy controls, assessing their cognitive abilities and functional brain connectivity patterns through neuropsychological evaluations and resting-state fMRI, respectively. The MCI patients exhibited poorer performance on multiple neuropsychological tests compared to the healthy controls. At the neural level, functional connectivity between the mPFC and the anterior cingulate cortex (ACC) was significantly weaker in the MCI group and correlated with multiple neuropsychological test scores. The result of the mediation analysis further demonstrated that functional connectivity between the mPFC and ACC notably mediated the relationship between the MCI and semantic fluency performance. These findings suggest that altered mPFC-ACC connectivity may have a plausible causal influence on cognitive decline and provide implications for early identifications of neurodegenerative diseases and precise monitoring of disease progression., (© 2024. The Author(s).)

Coral polyps are composed of four tissues; however, their characteristics are largely unexplored. Here we report biological characteristics of tentacles (Te), mesenterial filaments (Me), body wall (Bo), and mouth with pharynx (MP), using comparative genomic, morpho-histological, and transcriptomic analyses of the large-polyp coral, Fimbriaphyllia ancora. A draft F. ancora genome assembly of 434 Mbp was created. Morpho-histological and transcriptomic characterization of the four tissues showed that they have distinct differences in structure, primary cellular composition, and transcriptional profiles. Tissue-specific, highly expressed genes (HEGs) of Te are related to biological defense, predation, and coral-algal symbiosis. Me expresses multiple digestive enzymes, whereas Bo expresses innate immunity and biomineralization-related molecules. Many receptors for neuropeptides and neurotransmitters are expressed in MP. This dataset and new insights into tissue functions will facilitate a deeper understanding of symbiotic biology, immunology, biomineralization, digestive biology, and neurobiology in corals., (© 2024. The Author(s).)

Boron neutron capture therapy (BNCT) targets invasive, radioresistant cancers but requires a selective and high B-10 loading boron drug. This manuscript investigates boron-rich poly(ethylene glycol)- block -(poly(4-vinylphenyl boronate ester)) polymer micelles synthesized via atom transfer radical polymerization for their potential application in BNCT. Transmission electron microscopy (TEM) revealed spherical micelles with a uniform size of 43 ± 10 nm, ideal for drug delivery. Additionally, probe sonication proved effective in maintaining the micelles' size and morphology postlyophilization and reconstitution. In vitro studies with B16-F10 melanoma cells demonstrated a 38-fold increase in boron accumulation compared to the borophenylalanine drug for BNCT. In vivo studies in a B16-F10 tumor-bearing mouse model confirmed enhanced tumor selectivity and accumulation, with a tumor-to-blood (T/B) ratio of 2.5, surpassing BPA's T/B ratio of 1.8. As a result, mice treated with these micelles experienced a significant delay in tumor growth, highlighting their potential for BNCT and warranting further research.

Malignant cancers, known for their pronounced heterogeneity, pose substantial challenges to monotherapeutic strategies and contribute to the risk of metastasis. Addressing this, our study explores the synergistic potential of combining boron neutron capture therapy (BNCT) with immune checkpoint blockade to enhance cancer treatment efficacy. We synthesized boron-rich block copolymer micelles as a novel boron drug for BNCT. Characterization was conducted using nuclear magnetic resonance, gel-permeation chromatography, transmission electron microscopy, and dynamic light scattering. These micelles, with an optimal size of 91.3 nm and a polydispersity index of 0.18, are suitable for drug delivery applications. In vitro assessments on B16-F10 melanoma cells showed a 13-fold increase in boron uptake with the micelles compared to borophenyl alanine (BPA), the conventional boron drug for BNCT. This resulted in a substantial increase in BNCT efficacy, reducing cell viability to 77% post-irradiation in micelle-treated cells, in contrast to 90% in BPA-treated cells. In vivo, melanoma-bearing mice treated with these micelles exhibited an 8-fold increase in boron accumulation in tumor tissues versus those treated with BPA, leading to prolonged tumor growth delay (5.4 days with micelles versus 3.3 days with BPA). Moreover, combining BNCT with anti-PD-L1 immunotherapy further extended the tumor growth delay to 6.6 days, and enhanced T-cell infiltration and activation at tumor sites, thereby indicating a boosted immune response. This combination demonstrates a promising approach by enhancing cytotoxic T-cell priming and mitigating the immunosuppressive effects of melanoma tumors., Competing Interests: Competing interes ts: The authors declare that they have no competing interests., (Copyright © 2024 Yi-Lin Chiu et al.)

Background : A person's cultural background shapes how they interpret and navigate problems. Given that large numbers of international researchers work and train in the U.S. we sought to better understand how researchers use the decision-making strategy of seeking help to navigate ethical and professional challenges. Methods : Participants ( N  = 300) were researchers working or training in the U.S. who were born in East Asia (EA) or born in the U.S. They completed a screening survey; then a subset completed think-aloud interviews ( n  = 66) focused on how they would respond to three hypothetical research scenarios. Results : Thematic analysis of the transcripts showed that seeking help was a commonly endorsed strategy, with some nuances between groups. Themes included seeking help in the form of getting advice, seeking someone to help solve the problem, and gathering information. Endorsement of the seeking help strategy frequently depended on participants' relationships; desiring to seek help from people they trusted. Notably, EA participants tended to prefer seeking help in ways that avoided reputational harm to others. Conclusion : A better understanding of how researchers from different cultural backgrounds use decision-making strategies can inform how to make educational programs more inclusive and comprehensive to more effectively develop researchers' ethical and professional decision-making skills.

Background: The prevalence of end-stage renal disease (ESRD) in Taiwan is among the highest in the world. Although kidney transplant is the most effective treatment for ESRD, the willingness of patients with ESRD to undergo kidney transplantation is low in Taiwan. The factors associated with willingness to accept kidney transplantation remain unclear, and studies on kidney transplant willingness and associated factors among Taiwanese patients with ESRD are scarce., Purpose: The aim of this study was to assess willingness to undergo a kidney transplant and related factors among patients with ESRD in Taiwan., Methods: A cross-sectional design was employed. Two hundred fourteen participants from a single medical center in Taiwan were recruited, and 209 valid questionnaires were collected (valid response rate: 97.7%). The study instruments included a kidney transplant knowledge scale, a kidney transplant attitude scale, and a kidney transplant willingness scale. Data were analyzed using Pearson's product-moment correlations, t tests, one-way analyses of variance, and multiple regressions., Results: The mean kidney transplant willingness in the sample was 13.23 (out of 20). Being male, younger, married, or employed; having a college education or above; and having a shorter dialysis duration were all associated with higher kidney transplant willingness. Sociodemographics, dialysis duration, knowledge, and attitudes explained 45.4% of the variance in kidney transplant willingness, with two of these, kidney transplant attitudes (β = .61, p < .001) and dialysis duration (β = -.11, p = .041), identified as significant., Conclusions/implications for Practice: The findings support the important role of cultivating positive attitudes in patients with ESRD to increasing willingness to undergo kidney transplantation interventions., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc.)

In patients with nasopharyngeal carcinoma (NPC), the alteration of immune responses in peripheral blood remains unclear. In this study, we established an immune cell profile for patients with NPC and used flow cytometry and machine learning (ML) to identify the characteristics of this profile. After isolation of circulating leukocytes, the proportions of 104 immune cell subsets were compared between NPC group and the healthy control group (HC). Data obtained from the immune cell profile were subjected to ML training to differentiate between the immune cell profiles of the NPC and HC groups. We observed that subjects in the NPC group presented higher proportions of T cells, memory B cells, short-lived plasma cells, IgG-positive B cells, regulatory T cells, MHC II + T cells, CTLA4 + T cells and PD-1 + T cells than subjects in the HC group, indicating weaker and compromised cellular and humoral immune responses. ML revealed that monocytes, PD-1 + CD4 T cells, memory B cells, CTLA4 + CD4 T reg cells and PD-1 + CD8 T cells were strongly contributed to the difference in immune cell profiles between the NPC and HC groups. This alteration can be fundamental in developing novel immunotherapies for NPC., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Fixed-dose combination (FDC) therapies can enhance patient convenience and adherence to prescribed treatment regimens. Elagolix is a novel oral gonadotropin-releasing hormone receptor antagonist approved for management of moderate to severe pain associated with endometriosis and heavy menstrual bleeding associated with uterine fibroids. Hormonal add-back therapy can attenuate the reversible hypoestrogenic effects of elagolix. An FDC formulation containing elagolix/estradiol (E2)/norethindrone acetate (NETA) 300/1/0.5 mg as the morning dose and an elagolix 300 mg capsule as the evening dose, were evaluated in 2 bioequivalence studies including the effects of food. Study 1 in premenopausal women assessed the bioavailability of the elagolix 300-mg capsule relative to the commercially available elagolix 300-mg tablet. Study 2 in postmenopausal women, elagolix/E2/NETA (300 mg/1 mg/0.5 mg) FDC capsule was assessed relative to the elagolix 300-mg tablet coadministered with E2/NETA 1-mg/0.5-mg tablet, the regimen that was studied in Phase 3 uterine fibroid studies. Under fasting conditions, the test elagolix 300-mg capsule was bioequivalent to the reference elagolix 300-mg tablet. Under fasting conditions, the elagolix/E2/NETA FDC capsule was bioequivalent to the coadministered elagolix 300-mg tablet and E2/NETA 1/0.5-mg tablet. Following administration of elagolix/E2/NETA FDC capsule after a high-fat breakfast, elagolix mean maximum concentration (C max ) and area under the plasma concentration-time curve (AUC) were 38% and 28% lower, relative to fasting conditions. NETA mean C max was 51% lower and AUC from time 0 to infinity was 20% higher, while baseline-adjusted total estrone mean C max and AUC were 46% and 14% lower, respectively. No safety concerns were identified. These results enabled bridging the elagolix/E2/NETA FDC capsule., (© 2024 AbbVie Inc. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)