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Jin-Wei Lin,1– 3 Pei-Ying Lin,1,2 Tse-Yao Wang,1,2 Ying-Ju Chen,1,2 David Hung-Tsang Yen,1– 5 Hsien-Hao Huang1– 3 1Department of Emergency Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 2Emergency Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 3Institute of Emergency and Critical Care Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 4Department of Nursing, Yuanpei University of Medical Technology, Hsinchu, Taiwan; 5Chang Bing Show-Chwan Memorial Hospital, Changhua City, TaiwanCorrespondence: Hsien-Hao Huang, Department of Emergency Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Road, Beitou District, Taipei, 112201, Taiwan, Email hhhuang@vghtpe.gov.twBackground: Frailty epitomizes the most complex consequence of an aging population. This study aimed to evaluate the impact of frailty, measured using the Clinical Frailty Scale (CFS), on outcomes of older people in an emergency department (ED).Methods: We conducted a prospective observational study enrolling patients aged 65 years and older in a medical center of Taiwan between March 8, 2021, and November 30, 2021. The primary outcome was 90-day mortality rate. Individuals were categorized into three groups based on the CFS scores. Logistic regression was employed to examine the influence of frailty on clinical outcomes following covariate adjustment. Survival analysis was conducted using Kaplan–Meier curves and Log rank tests.Results: A total of 473 individuals were included in the study, with a mean age of 82.1 years, and 60.5% of them were males. The 90-day mortality rate was 10.6%. Among these groups, the CFS score 7– 9 group had the highest 90-day mortality rate (15.9%), followed by the CFS score 4– 6 group (8.0%) and the CFS score 1– 3 group (7.1%). The multiple logistic regression analyses demonstrated a significant impact of CFS score on prognosis, with adjusted odd ratios of 1.24 (95% CI 1.06– 1.47) for 90-day mortality, 1.18 (95% CI 1.06– 1.31) for hospitalization, and 1.30 (95% CI 1.12– 1.52) for 180-day mortality. The Kaplan–Meier curves revealed a significantly higher 90-day mortality rate for patients with high CFS scores (Log rank tests, p = 0.019).Conclusion: In the older ED population, the severity of frailty assessed by the CFS emerged as a significant and important prognostic factor for hospitalization, 90-day mortality, and 180-day mortality.Keywords: frailty, emergency service, hospital, triage, mortality

Jin-Wei Lin, Hsien-Hao Huang Department of Emergency Medicine, Taipei Veterans General Hospital, Taipei, TaiwanCorrespondence: Hsien-Hao Huang, Email hhhuang@vghtpe.gov.tw

Hung-Hsiang Huang,1,* Chi-Jie Lu,2– 4,* Mao-Jhen Jhou,4 Tzu-Chi Liu,4 Chih-Te Yang,5 Shang-Ju Hsieh,1 Wen-Jen Yang,6 Hsiao-Chun Chang,1 Ming-Shu Chen7 1Department of Urology, Surgery, Far Eastern Memorial Hospital, New Taipei City, 220, Taiwan; 2Artificial Intelligence Development Center, Fu Jen Catholic University, New Taipei City, 242, Taiwan; 3Department of Information Management, Fu Jen Catholic University, New Taipei City, 242, Taiwan; 4Graduate Institute of Business Administration, Fu Jen Catholic University, New Taipei City, 242, Taiwan; 5Department of Business Administration, Tamkang University, New Taipei City, 251, Taiwan; 6Health Screening Center, Chi Hsin Clinic, Taipei City, 104, Taiwan; 7Department of Healthcare Administration, Asia Eastern University of Science and Technology, New Taipei City, 220, Taiwan*These authors contributed equally to this workCorrespondence: Ming-Shu Chen; Hsiao-Chun Chang, Email tree1013@mail.gmail.com; liberalcsc@gmail.comPurpose: Approximately 20% of couples face infertility challenges and struggle to conceive naturally. Despite advances in artificial reproduction, its success hinges on sperm quality. Our previous study used five machine learning (ML) algorithms, random forest, stochastic gradient boosting, least absolute shrinkage and selection operator regression, ridge regression, and extreme gradient boosting, to model health data from 1375 Taiwanese males and identified ten risk factors affecting sperm count.Methods: We employed the CART algorithm to generate decision trees using identified risk factors to predict healthy sperm counts. Four error metrics, SMAPE, RAE, RRSE, and RMSE, were used to evaluate the decision trees. We identified the top five decision trees based on their low errors and discussed in detail the tree with the least error.Results: The decision tree featuring the least error, comprising BMI, UA, ST, T-Cho/HDL-C ratio, and BUN, corroborated the negative impacts of metabolic syndrome, particularly high BMI, on sperm count, while emphasizing the link between good sleep and male fertility. Our study also sheds light on the potentially significant influence of high BUN on spermatogenesis. Two novel risk factors, T-Cho/HDL-C and UA, warrant further investigation.Conclusion: The ML algorithm established a predictive model for healthcare personnel to assess low sperm counts. Refinement of the model using additional data is crucial for improved precision. The risk factors identified offer avenues for future investigations.Keywords: sperm count, metabolic syndrome, sleep time, food metabolite, decision tree

Chung-Hwan Chen,1,2 Shyh Ming Kuo,3 Yin-Chun Tien,4,5 Po-Chih Shen,4 Yi-Wen Kuo,6 Han Hsiang Huang7 1Department of Orthopedics and Orthopedic Research Center, Kaohsiung Municipal Ta-Tung Hospital and Kaohsiung Medical University Hospital, College of Medicine, Kaohsiung Medical University, Kaohsiung City 80708, Taiwan; 2Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung City 80424, Taiwan; 3Department of Biomedical Engineering, I-Shou University, Kaohsiung City 82445, Taiwan; 4Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung City 80708, Taiwan; 5Department of Orthopedics, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; 6Orthopedic Research Center, Kaohsiung Medical University, Kaohsiung City 80708, Taiwan; 7Department of Veterinary Medicine, National Chiayi University, Chiayi City 60054, TaiwanCorrespondence: Han Hsiang Huang 580 Xinmin Road, Chiayi City 60054, TaiwanTel +886 5-2732952Fax +886-5-2732917Email hhuang@mail.ncyu.edu.twIntroduction: Rapamycin has been considered as a potential treatment for osteoarthritis (OA). Drug carriers fabricated from liposomes can prolong the effects of drugs and reduce side effects of drugs. Low-intensity pulsed ultrasound (LIPUS) has been found to possess anti-OA effects.Materials and Methods: The anti-osteoarthritic effects of liposome-encapsulated rapamycin (L-rapa) combined with LIPUS were examined by culture of normal and OA chondrocytes in alginate beads and further validated in OA prone Dunkin-Hartley guinea pigs.Results: L-rapa with LIPUS largely up-regulated aggrecan and type II collagen mRNA in human OA chondrocytes (HOACs). L-rapa with LIPUS caused significant enhancement in proteoglycan and type II collagen production in HOACs. Large decreases in both MMP-13 and IL-6 proteins were found in the HOACs exposed to L-rapa with LIPUS. Intra-articular injection of 40 μL L-rapa at both 5 μM and 50 μM twice a week combined with LIPUS thrice a week for 8 weeks significantly increased GAGs and type II collagen in the cartilage of knee. Results on OARSI score showed that intra-articular injection of 5 μM L-rapa with LIPUS displayed the greatest anti-OA effects. Immunohistochemistry revealed that L-rapa with or without LIPUS predominantly reduced MMP-13 in vivo. The values of complete blood count and serum biochemical examinations remained in the normal ranges after the injections with or without LIPUS. These data indicated that intra-articular injection of L-rapa collaborated with LIPUS is not only effective against OA but a safe OA therapy.Conclusion: Taken together, L-rapa combined with LIPUS possessed the most consistently and effectively anabolic and anti-catabolic effects in HOACs and the spontaneous OA guinea pigs. This study evidently revealed that liposome-encapsulation collaborated with LIPUS is able to reduce the effective dose and administration frequency of rapamycin and further stably reinforce its therapeutic actions against OA.Keywords: liposome-encapsulation, rapamycin, osteoarthritis, low-intensity pulsed ultrasound, OA prone Dunkin-Hartley guinea pigs

Heng Dong,1,* Na Zhou,1,* Hui Liu,1,* Haohao Huang,2 Guangwen Yang,1 Li Chen,1 Meng Ding,3 Yongbin Mou1 *These authors contributed equally to this work 1Department of Oral Implantology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing,Jiangsu, People’s Republic of China; 2Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, People’s Republic of China; 3Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, People’s Republic of ChinaBackground: The factors influencing satisfaction of the patients with implant treatments are still unclear. This study aims to evaluate the patients’ satisfaction and to identify influencing factors, which will improve the medical quality of oral implantology.Materials and methods: Patients who lost single teeth and received implant treatments were enrolled in Nanjing Stomatological Hospital between February 2016 and March 2018. A questionnaire survey was performed to assess patient satisfaction and data were collected at four time points. Information included gender, age, educational level, application of bone augmentation, type of prosthetic restoration, period of teeth loss, dentist qualification, and tooth position. Meanwhile, the satisfaction of the patients was evaluated by visual analog scale.Results: A total of 373 patients completed the questionnaires. The mean of overall satisfaction score was 69.05±7.10. Lower overall satisfaction score was found in patients who received bone augmentation (P

Chen CH, Kuo SM, Tien YC, Shen PC, Kuo YW, Huang HH. Int J Nanomedicine. 2020;15:3771–3790. The authors have advised due to an error at the time of figure assembly, Figure 2B on page 3778 is incorrect. The correct Figure 2 is shown below. The authors apologize for this error and advise it does not affect the results of the paper. Read the original article

Chia-Ming Chang,1–3 Ming-Shun Hsieh,1–4 Tsung-Chieh Yang,3,5 Vivian Chia-Rong Hsieh,6 Jen-Huai Chiang,7 Hsien-Hao Huang,1,3 Chorng-Kuang How,1,3 Sung-Yuan Hu,8 David Hung-Tsang Yen1,3 1Department of Emergency Medicine, Taipei Veterans General Hospital, 2Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, 3College of Medicine, National Yang-Ming University, Taipei, 4Department of Emergency Medicine, 5Division of Gastroenterology, Department of Internal Medicine, Taipei Veterans General Hospital, Taoyuan Branch, Taoyuan, 6Department of Health Services Administration, 7Management Office for Health Data, China Medical University, 8Department of Emergency Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China Background: This study aimed to investigate the association between the use of selective serotonin reuptake inhibitors (SSRIs) and the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection.Methods: We conducted a population-based cohort study by using claims data from the Taiwan National Health Insurance Research Database (NHIRD). The study cohort comprised 1380 newly diagnosed HBV-infected patients with SSRI use who were frequency matched by age, sex, liver cirrhosis, and index year with HBV-infected patients without SSRI use in the comparison cohort. Each patient case was followed from 2000 to 2012 to identify incident HCC cases. Cox proportional hazards regression was performed to evaluate the association between SSRI use and HCC risk. The further sensitivity analysis used case-control study design. A total of 9070 HCC subjects retrieved from NHIRD, and equal non-HCC subjects were analyzed after matching for age and sex.Results: We identified 9 and 24 HCC cases in the study and comparison cohorts during the follow-up period of 7056 and 6845 person-years, respectively. The incidence rate of HCC was 1.28 and 3.51 per 1000 person-years for SSRI and non-SSRI users, respectively. After adjusting for potential confounders, the adjusted hazard ratio (HR) for SSRI use was 0.28 (95% confidence interval [CI], 0.12–0.64; p = 0.0027). For SSRI users with a cumulative defined daily dose (cDDD) of 28–89, 90–364, and ≥365, the adjusted HRs were 0.51, 0.22, and 0.12, respectively, (95% CI, 0.21–1.25, 0.05–0.94, and 0.02–0.90, respectively) compared with non-SSRI users (

Hsien-Hao Huang,1,2 Liang-Yu Chen,3,4 Ming-Luen Doong,5 Shi-Chuan Chang,6,7 Chih-Yen Chen8–10 1Institute of Clinical Medicine, National Yang-Ming University of Medicine, 2Department of Emergency Medicine, Taipei Veterans General Hospital, 3Aging and Health Research Center, National Yang-Ming University, 4Center for Geriatrics and Gerontology, Taipei Veterans General Hospital, 5Institute of Physiology, National Yang-Ming University School of Medicine, 6Institute of Emergency and Critical Medicine, National Yang-Ming University School of Medicine, 7Department of Chest Medicine, Taipei Veterans General Hospital, 8Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, 9Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, 10Taiwan Association for the Study of Small Intestinal Diseases, Guishan, Taiwan Background: Acyl ghrelin-induced intake depends on hypothalamic neuropeptide Y and agouti-related protein (AgRP) neurotransmitters. Intracerebroventricular (ICV) injection of AgRP increases feeding through competitive antagonism at melanocortin receptors. ICV administration of α-melanocyte stimulating hormone (α-MSH), a natural antagonist of AgRP, may modulate the acyl ghrelin-induced orexigenic effect.Objective: This study aimed to investigate the modulating effect of α-MSH on the central acyl ghrelin-induced food intake, gastrointestinal motility, and colonic secretion in rats.Methods and procedures: We examined the effects of α-MSH and acyl ghrelin on food intake, gastric emptying, small intestinal transit, colonic motility, and secretion in conscious rats with a chronic implant of ICV catheters.Results: ICV injection of O-n-octanoylated ghrelin (0.1 nmol/rat) significantly increased the cumulative food intake up to 8 h (P

Han Hsiang Huang,1 Shyh Ming Kuo,2 Yi-Jhen Wu,2 Jui-Hsin Su3 1Department of Veterinary Medicine, National Chiayi University, Chiayi City, 2Department of Biomedical Engineering, I-Shou University, Kaohsiung City, 3National Museum of Marine Biology and Aquarium, Pingtung, Taiwan Abstract: The effects against tumors exerted by marine active compounds have been highlighted and investigated. Polymeric nanoparticles made from biodegradable and biocompatible molecules such as hyaluronan (HA) and chitosan (CHI) are able to aggregate the compounds to enhance their activities against tumor cells and reduce the toxicity on normal cells. Here, we extensively examined the antitumor activities and the mechanisms of HA/CHI nanoparticles-aggregated heteronemin (HET) extracted from the sponge Hippospongia sp. The half-maximal inhibitory concentration (IC50) of pure HET toward T24 bladder carcinoma cells is ~0.28 µg/mL. Pure HET from 0.2 to 0.8 µg/mL and HA nanoparticles-aggregated HET at 0.1 and 0.2 µg/mL significantly reduced T24 cell viability. Compared to pure HET, HA nanoparticles/HET aggregates showed much weaker viability-inhibitory effects on L929 normal fibroblasts. HET dose-dependently suppressed cancer cell migration as HA/CHI nanoparticles-aggregated HET displayed stronger migration-inhibitory effects than pure HET. Flow cytometric analysis showed that pure HET increased early/total apoptosis and JC-1 monomer fluorescence, while HA/CHI nanoparticles-aggregated HET induced higher apoptosis and JC-1 monomer rates than pure HET, suggesting that aggregation of HA nanoparticles offers HET stronger apoptosis-inducing capacity through mitochondrial depolarization. Western blot analysis showed that HA nanoparticles-aggregated HET further increased mitochondrial-associated, caspase-dependent and caspase-independent, as well as endoplasmic reticulum stress-related factors in comparison with pure HET. These data indicated that pure HET possesses cytotoxic, antimigratory, and apoptosis-inducing effects on bladder cancer cells in vitro, and its induction of apoptosis in bladder carcinoma cells is mainly caspase dependent. Moreover, HA nanoparticle aggregation reinforced the cytotoxic, antimigratory, and apoptosis-inducing activities against bladder carcinoma cells and attenuated the viability-inhibitory effects on normal fibroblasts. This aggregation reinforces antibladder carcinoma effects of HET via diverse routes, including mitochondrial-related/caspase-dependent, caspase-independent, and endoplasmic reticulum stress-related pathways. The current data also strongly suggested that HA/CHI nanoparticles-aggregated HET would be a potential treatment for urothelial cancer in vivo. Keywords: heteronemin, hyaluronan, chitosan, nanoparticle, bladder carcinoma cells

Segmentation of a fetal head from three-dimensional (3-D) ultrasound images is a critical step in the quantitative measurement of fetal craniofacial structure. However, two main issues complicate segmentation, including fuzzy boundaries and large variations in pose and shape among different ultrasound images. In this article, we propose a new registration-based method for automatically segmenting the fetal head from 3-D ultrasound images. The proposed method first detects the eyes based on Gabor features to identify the pose of the fetus image. Then, a reference model, which is constructed from a fetal phantom and contains prior knowledge of head shape, is aligned to the image via feature-based registration. Finally, 3-D snake deformation is utilized to improve the boundary fitness between the model and image. Four clinically useful parameters including inter-orbital diameter (IOD), bilateral orbital diameter (BOD), occipital frontal diameter (OFD) and bilateral parietal diameter (BPD) are measured based on the results of the eye detection and head segmentation. Ultrasound volumes from 11 subjects were used for validation of the method accuracy. Experimental results showed that the proposed method was able to overcome the aforementioned difficulties and achieve good agreement between automatic and manual measurements. [ABSTRACT FROM AUTHOR]

This study conducted a secondary analysis to objectively measure the effects of modified ride-on cars (MROCs) training in different postures on physical activity (PA) levels in children with motor delays. Data from 39 participants were analyzed in a randomized controlled trial. The participants included those using MROC in standing postures ( n  = 11, mean age = 22.87 months), MROC in sitting postures ( n  = 16, mean age = 19.53 months), and a control group that received conventional therapy ( n  = 12, mean age = 23.30 months). PA intensity was measured using an ActiGraph GT3X on the participants' wrists and right hip at weeks 1, 6, and 12 of the 12-week intervention period. This trial was registered at ClinicalTrials.gov (NCT02527356). The demographic data were similar across the groups. No significant differences were found in the interaction, group, or time effects for any of the positions ( p  > 0.05). The PA levels were consistent in at least light PA intensity range. MROC training may yield PA levels comparable to those of conventional therapy. Variations in activity and motor impairment severity could affect outcomes. Future studies should investigate factors such as task characteristics, motor delay severity, PA cutoff points, and training dosage that may influence PA intensity.

Background: While miRNAs are increasingly recognized for their role in tumorigenesis, their involvement in head and neck cancer (HNC) remains insufficiently explored. Additionally, the carcinogenic mechanisms of areca nut, a major habitual carcinogen in Southeast Asia, are not well understood., Methods and Results: This study adopts a systematic approach to identify miRNA profiles associated with areca nut-induced HNC. Using miRNA microarray analysis, we identified 292 miRNAs dysregulated in areca nut-treated HNC cells, with 136 upregulated and 156 downregulated. Bioinformatic analysis of the TCGA-HNSC dataset uncovered a set of 692 miRNAs relevant to HNC development, comprising 449 overexpressed and 243 underexpressed in tumor tissues. Integrating these datasets, we defined a signature of 84 miRNAs, including 39 oncogenic miRNAs (OncomiRs) and 45 tumor-suppressive miRNAs (TsmiRs), highlighting their pivotal role in areca nut-induced carcinogenesis. MultiMiR analysis identified 740 genes cross-regulated by eight hub TsmiRs, significantly impacting key cancer-related pathways (p53, PI3K-AKT, MAPK, and Ras) and critical oncogenic processes. Moreover, we validated miR-499a-5p as a vital regulator, demonstrating its ability to mitigate areca nut-induced cancer progression by reducing cell migration, invasion, and chemoresistance., Conclusions: Thus, this miRNA signature addresses a crucial gap in understanding the molecular underpinnings of areca nut-induced carcinogenesis and offers a promising platform for clinical applications in risk assessment, diagnosis, and prognosis of areca nut-associated malignancies.

Twelve compounds, including eleven bisabolane-type sesquiterpenoids ( 1  -  11 ), and one bacillibactin ( 12 ) were identified from marine-derived fungus Aspergillus sydowii SCSIO 41041 isolated from Creseis acicula . The chemical structures were elucidated by the basis of spectroscopic evidences, including HRESIMS, NMR and optical rotation. Biologically, all compounds were evaluated for their acetyl cholin-esterase (AChE) enzyme, pancreatic lipase (PL) enzyme, neuraminidase (NA) and phosphodiesterase 4 (PDE4) inhibitory activities. Compound 12 displayed significant inhibitory activity against neuraminidase (NA) with an IC 50 value of 24.0 μM, which was equivalent to the positive drug oseltamivir phosphate (IC 50 value of 20.0 μM). And the NA inhibitory activity was confirmed by molecular docking analysis.

Objectives: To investigate the roles of Ca 2+ influx-regulated circular RNAs (circRNAs) in T cells from patients with systemic lupus erythematosus (SLE)., Methods: The expression profile of circRNAs in Jurkat cells, co-cultured with and without ionomycin, was analyzed by next-generation sequencing and validated using real-time polymerase chain reaction. The identified Ca 2+ influx-regulated circRNAs were further examined in T cells from 42 patients with SLE and 23 healthy controls. The biological function of specific circRNA was investigated using transfection and RNA pull-down assay., Results: After validation, we confirmed that the expression levels of circ-ERCC4, circ-NFATC2, circ-MYH10, circ-CAMTA1, circ-ASH1L, circ-SOCS7, and circ-ASAP1 were consistently increased in Jurkat cells following Ca 2+ influx. The expression levels of circ-CAMTA1, circ-ASH1L, and circ-ASAP1 were significantly lower in T cells from patients with SLE, with even lower levels observed in those with higher disease activity. Interferon (IFN)-α was found to suppress the expression of circ-CAMTA1. Circ-CAMTA1 bound to pyruvate carboxylase and inhibited its biological activity. Overexpression of circ-CAMTA1, but not its linear form, significantly decreased extracellular glucose levels. Furthermore, increased expression of circ-CAMTA1, but not its linear form, decreased miR-181c-5p expression, resulting increased IL-2 secretion., Conclusion: Three Ca 2+ influx-regulated circ-RNAs-circ-CAMTA1, circ-ASH1L, and circ-ASAP1 -were significantly reduced in T cells from patients with SLE and associated with disease activity. IFN-α suppressed the expression of circ-CAMTA1, which interacted with pyruvate carboxylase, inhibited its activity, affected glucose metabolism, and increased IL-2 secretion. These findings suggest that circ-CAMTA1 regulated by Ca²⁺ influx modulated T cell function in patients with SLE., (© 2024. The Author(s).)

In this study, Phylloporia fontanesiae polysaccharide was successfully isolated through a sequential water extraction and alcohol precipitation process. Utilizing the Box-Behnken design, the extraction process was optimized based on single-factor experiments, considering variables such as the material-to-liquid ratio, extraction temperature, extraction time, and the number of extractions. The polysaccharide composition of P. fontanesiae is predominantly composed of mannose, glucuronic acid, glucose, and galactose, with a molar mass ratio of 4.31:4.10:36.83:1, along with minor amounts of aminoglucose and fucose. The polysaccharide fraction of P. fontanesiae comprises two distinct components, possessing relative molecular masses of 8.85 kDa and 134.03 kDa. Notably, the polysaccharide exhibited significant antioxidant activity. After undergoing simulated gastrointestinal digestion, no significant changes were observed in its antioxidant activity, molecular weight, or monosaccharide composition. This study not only enhanced the extraction efficiency of P. fontanesiae polysaccharide but also provided valuable insights into its composition, structure, and digestion characteristics. PRACTICAL APPLICATION: The optimum extraction process, stability, and antioxidant activity of Phylloporia fontanesiae polysaccharide during simulated digestion of gastrointestinal tract were studied. The results provide a theoretical basis for the development and application of this polysaccharide in the field of food and health products., (© 2024 Institute of Food Technologists.)

Optimizing prevention and early detection of cancer requires understanding the number, types and timing of driver mutations. To quantify this, we exploited the elevated cancer incidence and mutation rates in germline BRCA1 and BRCA2 (gBRCA1/2) carriers. Using novel statistical models, we identify genomic deletions as the likely rate-limiting mutational processes, with 1-3 deletions required to initiate breast and ovarian tumors. gBRCA1/2 -driven hereditary and sporadic tumors undergo convergent evolution to develop a similar set of driver deletions, and deletions explain the elevated cancer risk of gBRCA1/2 -carriers. Orthogonal mutation timing analysis identifies deletions of chromosome 17 and 13q as early, recurrent events. Single-cell analyses confirmed deletion rate differences in gBRCA1/2 vs. non-carrier tumors as well as cells engineered to harbor gBRCA1/2 . The centrality of deletion-associated chromosomal instability to tumorigenesis shapes interpretation of the somatic evolution of non-malignant tissue and guides strategies for precision prevention and early detection., Competing Interests: COMPETING FINANCIAL INTERESTS K.H. is a co-founder and board member of a not-for-profit organization, Open Box Science, where he does not receive any compensation. P.C.B. sits on the scientific advisory boards of BioSymetrics, Inc. and Intersect Diagnostics, Inc. and previously sat on that of Sage Bionetworks. All other authors declare no competing financial interests.

This prospective cohort study assessed the impact of intrinsic capacity on hospital admissions among older adults after an Emergency Department (ED) visit. Assessing 1132 patients according to WHO's Integrated Care for Older People guidelines between March 1 and August 30, 2022, we found that 784 (69.26%) were admitted. The admission group demonstrated significantly lower intrinsic capacity scores (mean ± SD, 2.92 ± 1.29) compared to the discharge group (3.44 ± 1.23; p < .001). Multivariable logistic regression showed that higher intrinsic capacity scores were associated with lower odds of admission (adjusted odds ratio [aOR] = 0.81; 95% CI: 0.71-0.92; p < .001). Notably, patients with malnutrition had significantly higher odds of admission (OR = 3.12; 95% CI: 2.16-4.50; p < .001). These findings underscore the importance of integrating the intrinsic capacity assessment with traditional clinical indicators in the emergency care of older adults., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Single nucleotide polymorphism (SNP) rs1347093 shows statistically significant association with lung cancer risk, but there is no further rs1347093 expression quantitative trait loci (eQTL) effect information. SNP rs1347093 is located in microRNA-216/-217 (miR-216/-217) locus. In addition, miR-216/-217 have pancreas-enriched expressions. In this study, we examined a potential miR-216/-217 promoter region, and investigated the effect of rs1347093-A allele on the miR-216/-217 promoter activity., Methods: Bioinformatics analysis, quantitative real-time PCR, luciferase reporter assay, Western blotting, and cell counting kit-8 (CCK-8) assay were performed., Results: The miR-216/-217 expressions are down-regulated in pancreatic cancer. In pancreatic cancer patients carrying the rs1347093-A allele, miR-216/-217 expressions were more largely suppressed. We identified a potential promoter region in miR-216/-217 locus and further showed that rs1347093-A allele resulted in significantly reduced promoter activity in pancreatic cancer cells, which could be mediated by MEF2C activities. In terms of mechanism in the pathogenesis of pancreatic cancer, miR-216b-5p expression was down-regulated, thereby preventing it from interacting with beclin-1 mRNA while promoting the survival of pancreatic cancer cells., Conclusions: This study may reveal the biological relevance underlying rs1347093-A allele with an increase in pancreatic cancer risk. SNP rs1347093 could be meaningful as a novel biomarker for pancreatic cancer risk., 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. Published by Elsevier B.V.)

Background: Inhibitory control function and proinflammatory cytokines play a role in the pathomechanisms underlying major affective disorders and suicidal behavior. However, the distinct or interactive effects of major affective disorders and suicidal symptom severity on inhibitory control function and proinflammatory cytokines remain unclear., Methods: This study included 287 patients with bipolar disorder, 344 with major depressive disorder, and 169 healthy controls. We categorized the participants into 3 groups based on Montgomery-Åsberg Depression Rating Scale (MADRS) item 10 (suicidal symptoms) score: 0, 2 or 3, and ≥4. The participants completed the go/no-go task and the measurements for C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α) levels., Results: Errors in the go/no-go task were associated with suicidality (P = .040), regardless of the severity of suicidal symptoms and diagnosis. An elevated CRP level was especially associated with a Montgomery-Åsberg Depression Rating Scale item 10 score ≥4 (P = .001). An increased TNF-α level could distinguish bipolar disorder from major depressive disorder (P < .001)., Discussion: Our study indicated the distinct effects of major affective disorder diagnosis and suicide symptom severity on inhibitory control function and CRP and TNF-α levels. Importantly, individuals with the poorest inhibitory control function and highest CRP levels had more severe suicidal symptoms., (© The Author(s) 2024. Published by Oxford University Press on behalf of CINP.)

Introduction: The histological transformation (HT) of follicular lymphoma (FL) is a crucial biological event. The study aimed to evaluate the incidence, clinicial characteristics, prognosis and impact of HT time on survival of FL transforming to diffuse large B-cell lymphoma in population-based large-scale cohorts., Methods: A retrospective cohort study of FL with HT was performed in the Surveillance, Epidemiology, and End Results database. The Hematological Malignancy Research Network FL cohort and Aristotle study FL cohort were used to assess the external validity., Results: Among 44,127 FL cases from the Surveillance, Epidemiology, and End Results database, 1311 cases were pathology-proven recorded to transform to diffuse large B-cell lymphoma. The cumulative rates of HT at 5, 10, and 15 years after FL diagnosis were estimated to be 1.19%, 2.93%, and 5.01%, respectively. Significantly worse overall survival and cancer-specific survival were exhibited in patients with HT than those without HT. Early HT (transformation of FL within 48 months after FL diagnosis [TOD48]) was an independent predictor for adverse overall survival of HT patients, regardless of treatment modalities before transformation. The adverse prognostic effect of TOD48 was validated in the Hematological Malignancy Research Network cohort and Aristotle study cohort. Older age (>75 years) and B symptoms within FL at diagnosis were the independent risk factors of TOD48. Furthermore, a novel prognostic model combining TOD48 with Follicular Lymphoma International Prognostic Index (TOD48-FLIPI) was constructed and validated for risk stratification., Conclusion: TOD48 was a risk indicator of HT, and the novel prognostic model "TOD48-FLIPI" for HT patients was proposed., (© 2024 American Cancer Society.)

Background: Sarcopenia, a group of muscle-related disorders, leads to the gradual decline and weakening of skeletal muscle over time. Recognizing the pivotal role of gastrointestinal conditions in maintaining metabolic homeostasis within skeletal muscle, we hypothesize that the effectiveness of the myogenic programme is influenced by the levels of gastrointestinal hormones in the bloodstream, and this connection is associated with the onset of sarcopenia., Methods: We first categorized 145 individuals from the Emergency Room of Taipei Veterans General Hospital into sarcopenia and non-sarcopenia groups, following the criteria established by the Asian Working Group for Sarcopenia. A thorough examination of specific gastrointestinal hormone levels in plasma was conducted to identify the one most closely associated with sarcopenia. Techniques, including immunofluorescence, western blotting, glucose uptake assays, seahorse real-time cell metabolic analysis, flow cytometry analysis, kinesin-1 activity assays and qPCR analysis, were applied to investigate its impacts and mechanisms on myogenic differentiation., Results: Individuals in the sarcopenia group exhibited elevated plasma levels of glucagon-like peptide 1 (GLP-1) at 1021.5 ± 313.5 pg/mL, in contrast to non-sarcopenic individuals with levels at 351.1 ± 39.0 pg/mL (P < 0.05). Although it is typical for GLP-1 levels to rise post-meal and subsequently drop naturally, detecting higher GLP-1 levels in starving individuals with sarcopenia raised the possibility of GLP-1 influencing myogenic differentiation in skeletal muscle. Further investigation using a cell model revealed that GLP-1 (1, 10 and 100 ng/mL) dose-dependently suppressed the expression of the myogenic marker, impeding myocyte fusion and the formation of polarized myotubes during differentiation. GLP-1 significantly inhibited the activity of the microtubule motor kinesin-1, interfering with the translocation of glucose transporter 4 (GLUT4) to the cell membrane and the dispersion of mitochondria. These impairments subsequently led to a reduction in glucose uptake to 0.81 ± 0.04 fold (P < 0.01) and mitochondrial adenosine triphosphate (ATP) production from 25.24 ± 1.57 pmol/min to 18.83 ± 1.11 pmol/min (P < 0.05). Continuous exposure to GLP-1, even under insulin induction, attenuated the elevated glucose uptake., Conclusions: The elevated GLP-1 levels observed in individuals with sarcopenia are associated with a reduction in myogenic differentiation. The impact of GLP-1 on both the membrane translocation of GLUT4 and the dispersion of mitochondria significantly hinders glucose uptake and the production of mitochondrial ATP necessary for the myogenic programme. These findings point us towards strategies to establish the muscle-gut axis, particularly in the context of sarcopenia. Additionally, these results present the potential of identifying relevant diagnostic biomarkers., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Background: Most breast cancer-related deaths are caused by distant metastases and drug resistance. It is important to find appropriate biomarkers to monitor the disease and to predict patient responses after treatment early and accurately. Many studies have found that clustered circulating tumor cells, with more correlations with metastatic cancer and poor survival of patients than individual ones, are promising biomarkers., Methods: Eighty samples from eleven patients with breast cancer during follow-up visits were examined. By using a microfluidic chip and imaging system, the number of circulating tumor cells and microemboli (CTC/CTM) were counted to assess the distribution in stratified patients and the potential in predicting the disease condition of patients after treatments during follow-up visits. Specific components and subtypes of CTM were also preliminarily investigated., Results: Compared to CTC, CTM displayed a distinguishable distribution in stratified patients, having a better AUC value, in predicting the disease progression of breast cancer patients during follow-up visits in this study. Four subtypes were categorized from the identified CTM by considering different components. In combination with CEA and CA153, enumerated CTC and CTM from individual patients were applied to monitor the disease condition and patient response to the therapy during follow-up visits., Conclusions: The CTM and its subtypes are promising biomarkers and valuable tools for studying cancer metastasis and longitudinally monitoring cancer patients during follow-up visits.

A cooperative Rh(II)/Pd(0) dual-catalysis strategy that enabled divergent reactions of α-diazo 1,3-dicarbonyl compounds with allylic carbonates involving ketene versus carbene intermediates is described. The efficient synthesis of α-quaternary allylated β-keto-esters was accomplished by the Rh(II)/Pd(0) dual-catalysis allylic alkylation of α-diazo 1,3-dicarbonyl compounds. Alternatively, an unprecedented (1+4) annulation of α-diazo 1,3-dicarbonyl compounds with 2-(hydroxymethyl)allyl carbonates via Rh(II)/Pd(0) dual catalysis was also successfully developed, affording a wide variety of α-quaternary tetrahydrofurans in good to high yields.

Traditional photosensitizers (PS) in photodynamic therapy (PDT) have restricted tissue penetrability of light and a lack of selectivity for tumor cells, which diminishes the efficiency of PDT. Our aim is to effectively screen porphyrin-based PS medication through computational simulations of large-scale design and screening of PDT candidates via a precise description of the state of the light-stimulated PS molecule. Perylene-diimide (PDI) shows an absorption band in the near-infrared region (NIR) and a great photostability. Meanwhile, the insertion of metal can enhance tumor targeting. Therefore, on the basis of the original porphyrin PS segments, a series of metalloporphyrin combined with PDI and additional allosteric Zn-porphyrin-PDI systems were designed and investigated. Geometrical structures, frontier molecular orbitals, ultraviolet-visible (UV-vis) absorption spectra, adiabatic electron affinities (AEA), especially the triplet excited states and spin-orbit coupling matrix elements (SOCME) of these expanded D-A porphyrin were studied in detail using the density functional theory (DFT) and time-dependent density functional theory (TDDFT) methods. PS candidates, conforming type I or II mechanism for PDT, have been researched carefully by molecular docking which targeted Factor-related apoptosis (Fas)/Fas ligand (Fasl) mediated signaling pathway. It was found that porphyrin-PDI, Fe 2 -porphyrin-PDI, Zn-porphyrin-PDI, Mg-porphyrin-PDI, Zn-porphyrin combined with PDI through single bond (compound 1), and two acetylenic bonds (compound 2) in this work would be proposed as potential PS candidates for PDT process. This study was expected to provide PS candidates for the development of novel medicines in PDT., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Introduction: This study comprehensively investigates the changes in healthcare utilization among chronic patients with regular outpatient visits to hospitals after the occurrence of Covid-19. The research examines whether patients altered their originally regular medical attendance frequencies due to the pandemic and explores potential negative impacts on the health conditions of those irregular attendees post-pandemic., Methods: Data for this study were sourced from a database at a medical center in Taiwan. The subjects were chronic patients with regular hospital outpatient visits before the Covid-19 outbreak. The study tracked medical utilization patterns from 2017 to 2022 for different patient characteristics and outpatient behaviors, employing statistical methods such as Repeated Measures ANOVA and Generalized Estimating Equation to analyze changes in healthcare utilization and health status during the post-pandemic period., Results: The results reveal that, compared to the regular group, chronic patients with irregular outpatient visits during the post-pandemic period exhibited a decrease of 5.85 annual outpatient visits, a reduction of NT$20,290.1 in annual medical expenses, and a significantly higher abnormality rate in average biochemical test results by 0.9%., Conclusions: The findings contribute to understanding the impact of the Covid-19 pandemic on healthcare utilization and health conditions among outpatient chronic disease populations. In response to the new medical landscape in the post-pandemic era, proactive suggestions are made, including providing telemedicine outpatient services and referral-based medical care to meet the needs of the target population, ensuring a continuous and reassuring healthcare model for chronic patients, and mitigating the operational impacts of public health emergencies on hospitals., (© 2024. The Author(s).)

To better understand the migration behavior of plastic fragments in the environment, development of rapid non-destructive methods for in-situ identification and characterization of plastic fragments is necessary. However, most of the studies had focused only on colored plastic fragments, ignoring colorless plastic fragments and the effects of different environmental media (backgrounds), thus underestimating their abundance. To address this issue, the present study used near-infrared spectroscopy to compare the identification of colored and colorless plastic fragments based on partial least squares-discriminant analysis (PLS-DA), extreme gradient boost, support vector machine and random forest classifier. The effects of polymer color, type, thickness, and background on the plastic fragments classification were evaluated. PLS-DA presented the best and most stable outcome, with higher robustness and lower misclassification rate. All models frequently misinterpreted colorless plastic fragments and its background when the fragment thickness was less than 0.1mm. A two-stage modeling method, which first distinguishes the plastic types and then identifies colorless plastic fragments that had been misclassified as background, was proposed. The method presented an accuracy higher than 99% in different backgrounds. In summary, this study developed a novel method for rapid and synchronous identification of colored and colorless plastic fragments under complex environmental backgrounds., 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 © 2023. Published by Elsevier B.V.)

Introduction: Repetitive transcranial magnetic stimulation (rTMS) is used for treatment-resistant major depressive disorder (MDD) and obsessive-compulsive disorder (OCD), but there are few studies on patient outcomes in Southeast Asia. In this study, we describe the clinical profile and outcome of patients with MDD and OCD treated with rTMS in Singapore., Method: A naturalistic retrospective study of 71 patients (inpatient and outpatient) who received rTMS treatment between June 2018 and April 2023 was conducted. The depressive and obsessive outcome rating scales used were clinician-rated Montgomery-Åsberg Depression Rating Scale (MADRS), Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Clinical Global Impressions-Severity (CGI-S) and self-rated Depression Anxiety and Stress Scale-21 (DASS-21)., Results: Clinician-rated and self-rated mood and general condition improved significantly. MADRS mean score improved from 28.1 (standard deviation [SD] 7.3) to 20.7 (SD 10.1) ( P <0.0001) (20.8% response rate/17% remission rate). CGI-S mean 4.6 (SD 0.8) improved to 3.3 (SD 1.2) ( P <0.0001). DASS-21 total mean improved from 67.3 (SD 24.6) to 49.6 (SD 28.0) ( P <0.0001). Y-BOCS mean score displayed a trend towards improvement from 30.1 (SD 7.5) to 27.2 (SD 6.9) ( P =0.799). However, 44.4% of patients with OCD responded with a minimal 20% reduction in baseline Y-BOCS. Moreover, the subgroup of 35.8% of patients with less than 30 rTMS sessions had contributed disproportionately to nonresponse (85.7%). Patients who received rTMS treatment (>30 sessions) had a trend of larger improvement of MADRS score when compared to patients with (≤30 sessions) (9.4 [SD 9.7] versus 3.8 [SD 12.3] [ P =0.078])., Conclusion: Response and remission rates for MDD and OCD suggest patients have a good response to rTMS treatment. Dosing longer rTMS sessions after an acute course helps to maximise effectiveness. Further research to determine predictors of outcome and characterise clinical features of late responders to target treatment more effectively is recommended.

Background: This study conducted in-depth interviews to explore the factors that influence the adoption of fall detection technology among older adults and their families, providing a valuable evaluation framework for healthcare providers in the field of fall detection, with the ultimate goal of assisting older adults immediately and effectively when falls occur., Methods: The method employed a qualitative approach, utilizing semi-structured interviews with 30 older adults and 29 families, focusing on their perspectives and expectations of fall detection technology. Purposive sampling ensured representation from older adults with conditions such as Parkinson's, dementia, and stroke., Results: The results reveal key considerations influencing the adoption of fall-detection devices, including health factors, reliance on human care, personal comfort, awareness of market alternatives, attitude towards technology, financial concerns, and expectations for fall detection technology., Conclusions: This study identifies seven key factors influencing the adoption of fall detection technology among older adults and their families. The conclusion highlights the need to address these factors to encourage adoption, advocating for user-centered, safe, and affordable technology. This research provides valuable insights for the development of fall detection technology, aiming to enhance the safety of older adults and reduce the caregiving burden., (© 2024. The Author(s).)

Objectives: Evidence on the link between long-term ambient particulate matter (PM) exposures and childhood sleep disorders were scarce. We examined the associations between long-term exposures to PM 2.5 and PM 1 (PM with an aerodynamic equivalent diameter <2.5 μm and <1 μm, respectively) with sleep disorders in children., Methods: We performed a population-based cross-sectional survey in 177,263 children aged 6 to 18 years in 14 Chinese cities during 2012-2018. A satellite-based spatiotemporal model was employed to estimate four-year annual average PM 2.5 and PM 1 exposures at residential and school addresses. Parents or guardians completed a checklist using the Sleep Disturbance Scale for Children. We estimated the associations using generalized linear mixed models with adjustment for characteristics of children, parents, and indoor environments., Results: Long-term PM 2.5 and PM 1 exposures were positively associated with odds of sleep disorders for almost all domains. For example, increments in PM 2.5 and PM 1 per 10 μg/m 3 were associated with odds ratios of global sleep disorder of 1.24 (95 % confidence interval [CI]: 1.14, 1.35) and 1.31 (95 %CI: 1.18, 1.46), respectively. Similar results were observed for subtypes of sleep disorder. These associations were heterogeneous regionally, with stronger associations among children residing in southeast region than in northeast and northwest regions. Moreover, larger estimates of PM 1 were found than that of PM 2.5 in southeast region., Conclusion: Long-term PM 2.5 and PM 1 exposures are independently associated with higher risks of childhood sleep disorders, and these associations vary by geographical region., 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.)