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Wen-Lin Hsu,1,* Hung-Yi Chen,2,* Fung-Wei Chang,3–5 Ren-Jun Hsu6,71Department of Radiation Oncology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan; 2Divisions of Urology, Department of Surgery, Chang Gung Memorial Hospital, Keelung, Taiwan; 3Department of Obstetrics & Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 4Tri-Service General Hospital Penghu Branch, National Defense Medical Center, Penghu Branch, Taipei, Taiwan; 5Department of Health Promotion and Health Education, National Taiwan Normal University, Taipei, Taiwan; 6Cancer Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan; 7College of Medicine, Tzu Chi University, Hualien, TaiwanCorrespondence: Ren-Jun HsuCancer Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 707, Sec. 3, Chung-Yang Road, Hualien 970, TaiwanTel +886 3 856 1825Fax +886 3 856 1825#15620Email hsurnai@gmail.comFung-Wei ChangDepartment of Obstetrics & Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei, TaiwanEmail doc30666@gmail.com*These authors contributed equally to this workPurpose: Chronic obstructive pulmonary disease (COPD) is a major pulmonary disease. However, few studies have investigated the relationship between COPD and prostate cancer (PCa). This study aimed to investigate the association between COPD severity and PCa risk.Patients and methods: We conducted a nationwide population-based cohort study utilizing data from 2001 to 2013 from the National Health Insurance Research Database of Taiwan. Cox proportional hazards models with 1:1 propensity score-matched analysis were used to investigate the association between COPD and PCa risk. We further divided the COPD group according to severe complications (including acute respiratory failure, cardiopulmonary arrest, pneumonia, and acute exacerbation) to test for the relationship between COPD severity and PCa risk.Results: This study included 47,634 patients (23,817 COPD patients and 23,817 matched non-COPD controls). Among them, 756 (1.59%) were diagnosed with PCa during a mean follow-up period of 7.05±4.13 years; 387 (1.62%) were from the COPD group and 369 (1.55%) were from the control group. Compared with the patients without COPD, the adjusted hazard ratio (HR) for PCa in the COPD patients was 1.10 (95% confidence interval [CI] 0.95–1.27), while that in the COPD patients with complications was 2.46 (95% CI 1.96–3.61).Conclusions: An increased risk for PCa was found among the COPD patients with complications. COPD complications included acute respiratory failure, cardiopulmonary arrest, pneumonia, and acute exacerbation. These findings may help physicians in treating COPD with complications and in remaining alert to the potential development of PCa.Keywords: National Health Insurance Research Database, prostate cancer, chronic obstructive pulmonary disease

Li-Jen Liao,1 Wu-Chia Lo,1 Wan-Lun Hsu,2 Po-Wen Cheng,1 Cheng-Ping Wang3 1Department of Otolaryngology, Far Eastern Memorial Hospital, 2Genomics Research Center, Academia Sinica, 3Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan, Republic of China Objective: The aim of this study was to evaluate pain scores and specimen adequacy for ultrasound-guided fine-needle aspiration biopsy (US-FNAB) of thyroid nodules without and with local anesthesia (LA). Materials and methods: The US-FNAB procedure was performed on 183 patients with and without LA. One puncture was made for solid nodules, and if patients could tolerate it, a two-puncture technique was used for nodules with a cystic change. Four-point verbal rating scores were assessed by a nursing assistant after completion of US-FNAB. To be an adequate specimen, at least six groups of follicular cells are required, and each group should contain at least 10 cells.Results: Immediately after US-FNAB, 92% of patients with LA and 80% without LA reported no or mild pain (p=0.01). Most patients tolerated the procedure well, with no pain (82.5%) reported 5 minutes after the procedure. In univariate logistic regression, irregular boundary (odds ratio [OR]: 2.52, 95% confidence interval [CI]: 1.04–6.06, p=0.04), calcification (OR: 2.86, 95% CI: 1.06–7.76, p=0.04), and LA (OR: 0.35, 95% CI: 0.15–0.86, p=0.02) were significantly associated with immediate moderate or severe pain. Specimen adequacy was significantly associated with age (OR: 0.95, 95% CI: 0.92–0.97, p

Ethnopharmacological Relevance: The dried fruit of Ligustrum lucidum Ait. (FLL), known as Nuzhenzi, is traditionally recognized for its anti-aging properties in Chinese medicine. Nuezhenide, a water-soluble secoiridoid present in FLL, has demonstrated various pharmacological activities including neuroprotection, enhancement of learning and memory, antiosteoporotic, and antiviral activities. These therapeutic benefits align with the anti-aging effects attributed to ghrelin, particularly in the modulation of growth hormone secretagogue receptor type 1a (GHSR-1a) signaling., Aim of the Work: This study aimed to investigate the potential of FLL extracts, particularly its major compound nuezhenide, as agonists of GHSR-1a, a receptor implicated in anti-aging mechanisms, utilizing a stable GHSR-1a-expressing cell line., Materials and Methods: HEK293T cells expressing GHSR-1a-mCherry were used to assess the effects of FLL extract and its major compound, nuezhenide, on cell viability and ERK1/2 signaling. Molecular docking simulations predicted the interaction between nuezhenide and the GHSR-1a binding pocket. The impact of nuezhenide on ERK1/2 phosphorylation was evaluated, along with the involvement of phospholipase C and calcium signaling in this process., Results: Molecular docking simulations indicated that nuezhenide could interact with the GHSR-1a receptor, similar to teaghrelin, another known ghrelin analog. Experimental data showed that FLL extracts and nuezhenide enhanced cell viability and ERK1/2 activation in GHSR1a-mCherry HEK293T cells. The effect was specifically mediated by GHSR-1a, as confirmed by SP-analog treatment. Further analysis revealed that nuezhenide-induced ERK1/2 activation is likely mediated through a phospholipase C-dependent pathway involving intracellular calcium release., Conclusion: This study demonstrated for the first time that nuezhenide acts as a putative GHSR-1a agonist, promoting cell proliferation and activating ERK1/2 signaling via phospholipase C and calcium pathways. These findings support the traditional use of FLL as an anti-aging herbal remedy and suggest that nuezhenide could be developed as a therapeutic agent targeting GHSR-1a-mediated pathways., 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. ☒ The author is an Editorial Board Member/Editor-in-Chief/Associate Editor/Guest Editor for [Journal name] and was not involved in the editorial review or the decision to publish this article., (Copyright © 2024. Published by Elsevier B.V.)

Ambient fine particulate matter (PM 2.5 ), a vital environmental toxicant, not only adversely affects the cardiovascular and respiratory systems but also potentially exhibits an association with intestinal inflammation and colorectal cancer (CRC). The underlying molecular mechanisms of PM2.5 impacts on CRC are still unclear. In this study, we utilized collected ambient PM 2.5 and standard reference material SRM2786 to investigate the toxic effects on the colon through in vivo chronic exposure mouse and in vitro cell culture models. We employed a chronic mouse exposure model to clarify the colonic injury and gut microbiome biomarkers. Prolonged exposure to PM 2.5 via oropharyngeal aspiration led to a significant rise in colonic epithelial proliferation and reduced colon length in mice. It triggered characteristics indicative of gut microbiota dysbiosis linked to inflammatory bowel disease. The gut microbiome alternations may serve as a biomarker indicating the colonic health impacts of PM 2.5 exposure. PM 2.5 and SRM2786-induced cytotoxicity manifested as autophagy dysregulation-mediated abnormal proliferation, IL-8 production, p62/SQSTM1 accumulation, and lysosomal membrane damage in human colon cells WiDr and Caco-2. Both PM 2.5 and SRM2786 exposures led to the accumulation of p62/SQSTM1 and compromised lysosomal membrane integrity, showing impaired autophagic flux in WiDr and Caco-2 cells. Finally, we examined the correlations between atmospheric PM 2.5 data and biomarkers of colonic inflammation in human population. The serum level of IL-8 was significantly correlated with regional anthropogenic pollutants. In conclusion, our findings elucidate that ambient PM 2.5 exhibits adverse effects on colon health manifested as inflammation, aberrant proliferation, and gut dysbiosis, potentially mediated through autophagy dysregulation, thereby highlighting the importance of further research on the impact of environmental pollutants on gastrointestinal health., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yueh-Hsia Luo's report was supported by the National Science and Technology Council and the NCU-Landseed joint research grant of Taiwan. Pinpin Lin's report was funded by the National Health Research Institutes of Taiwan. Any additional authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Study Objectives: We investigated the therapeutic effects of exercise in patients with obstructive sleep apnea, aiming to identify the subgroups that benefit the most and determine the optimal exercise protocol., Methods: Major databases were searched for randomized controlled trials involving patients with obstructive sleep apnea performing aerobic exercise and/or resistance training. The investigated outcomes included apnea-hypopnea index (AHI), Epworth Sleepiness Scale, body mass index, and peak oxygen consumption during exercise (VO 2 peak). The pre- and postintervention unstandardized mean difference (USMD) of these parameters was compared between the exercise and control groups., Results: Twelve studies involving 526 patients were included. Exercise training significantly reduced AHI (USMD = -7.08 events/h, 95% confidence interval: -9.98 to -4.17, P < .00001), Epworth Sleepiness Scale (USMD = -2.37, 95% confidence interval: -3.21 to -1.54, P < .00001), and body mass index (USMD = -0.72 kg/m 2 , 95% confidence interval: -1.22 to -0.22, P = .005) and enhanced VO 2 peak (USMD = 3.46 ml·kg -1 ·min -1 , 95% confidence interval: 1.20 to 5.71, P = .003). Subgroup analyses revealed that in continuous positive airway pressure-adherent patients, exercise significantly improved VO 2 peak but did not reduce AHI and Epworth Sleepiness Scale. A trend was observed that combining resistance training with aerobic exercise resulted in greater AHI reduction and VO 2 peak enhancement. Notably, exercise improved AHI, Epworth Sleepiness Scale, body mass index, and VO 2 peak regardless of the baseline AHI or body mass index., Conclusions: Exercise, including resistance and aerobic training, should be part of treatment for patients with obstructive sleep apnea of all severities, regardless of obesity status, and even for those who are already under continuous positive airway pressure., Citation: Lin C-F, Ho N-H, Hsu W-L, Lin C-H, Wang Y-H, Wang Y-P. Effects of aerobic exercise and resistance training on obstructive sleep apnea: a systematic review and meta-analysis. J Clin Sleep Med. 2024;20(11):1839-1849., (© 2024 American Academy of Sleep Medicine.)

Nasopharyngeal carcinoma (NPC) risk prediction models based on Epstein-Barr virus (EBV)-antibody testing have shown potential for screening of NPC; however, the long-term stability is unclear. Here, we investigated the kinetics of two EBV-antibody NPC risk scores within the Taiwan NPC Multiplex Family Study. Among 545 participants with multiple blood samples, we evaluated the stability of a 2-marker enzyme-linked immunosorbent assay score and 13-marker multiplex serology score using the intra-class correlation coefficient (ICC) by fitting a linear mixed model that accounted for the clustering effect of multiple measurements per subject and age. We also estimated the clustering of positive tests using Fleiss's kappa statistic. Over an average 20-year follow-up, the 2-marker score showed high stability over time, whereas the 13-marker score was more variable (p < .05). Case-control status is associated with the kinetics of the antibody response, with higher ICCs among cases. Positive tests were more likely to cluster within the same individual for the 2-marker score than the 13-marker score (p < .05). The 2-marker score had an increase in specificity from ~90% for single measurement to ~96% with repeat testing. The 13-marker score had a specificity of ~73% for a single measurement that increased to ~92% with repeat testing. Among individuals who developed NPC, none experienced score reversion. Our findings suggest that repeated testing could improve the specificity of NPC screening in high-risk NPC multiplex families. Further studies are required to determine the impact on sensitivity, establish optimal screening intervals, and generalize these findings to general population settings in high-risk regions., (© 2024 UICC.)

Background: Repetitive motion can alter joint angles and subsequently affect the control of the center of mass (CoM). While the CoM has been studied as a fatigue indicator in various sports, the control of the whole-body CoM during repetitive pitching in baseball pitchers has not been examined. This study aimed to investigate changes in lower-extremity joint angles and CoM control in collegiate baseball pitchers after repetitive pitching., Hypothesis: Baseball pitchers would exhibit significant increase in lower-extremity flexion angles, CoM position, and CoM variability after repetitive pitching., Study Design: Descriptive laboratory study., Level of Evidence: Level 3., Methods: A total of 23 pitchers from the Collegiate Baseball League were recruited. A motion analysis system was employed to assess lower-extremity joint angles and CoM position during the simulated game, while pitching accuracy and velocity were also recorded., Results: The results revealed a significant forward and downward shift in CoM position ( P < 0.05), along with increased CoM variability in all directions ( P < 0.05) after the simulated game. Furthermore, there was a significant increase in flexion angles of the knee and hip ( P < 0.05); however, pitching velocity and accuracy did not demonstrate significant changes., Conclusion: Repetitive pitching leads to kinematic changes that should be monitored to prevent sports injuries., Clinical Relevance: Baseball pitchers have the ability to modify the control of their CoM and angles of their lower-extremity joints to sustain their pitching performance. It is crucial to monitor compensatory strategies closely to avoid shoulder and elbow injuries among these pitchers., Competing Interests: The authors report no potential conflicts of interest in the development and publication of this article.This work was supported by the National Science and Technology Council, Ministry of Science and Technology, Taiwan, (NSTC 112-2425-H-028-002).

Elevated levels of Epstein-Barr virus (EBV) gp350 and gH/gL antibodies have been associated with a lower risk of developing nasopharyngeal carcinoma (NPC), although the evidence remains inconclusive and unexplained. We conducted a longitudinal study within a high-risk Taiwanese cohort, analyzing total immunoglobulin against EBV-gp350 and -gH/gL in blood and EBV DNA shedding in saliva. Contrary to our hypothesis-that elevated levels of antibodies previously shown to be associated with a lower NPC risk should result in a decrease in EBV shedding in saliva-higher anti-gp350 antibodies at baseline were significantly associated with detectable EBV DNA in saliva at follow-up (odds ratio [OR], 1.99 [95% confidence interval {CI}, 1.03-3.97]; P = .04). Higher anti-EBV-gH/gL antibodies at baseline were not significantly associated with risk of detectable EBV DNA at follow-up (OR, 0.69 [95% CI, .35-1.32]; P = .26). These findings underscore the complexity of virus-host interactions and emphasize the need for further investigations into their role in EBV-associated diseases., Competing Interests: Potential conflicts of interest. Z. L. is currently an employee at Merck & Co, Inc, Rahway, New Jersey. The views and opinions expressed in this article do not represent the views and opinions of any public or private entity (e.g. agency, government, organization, institution, or company). All other authors report no conflicts of interest., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Osteoarthritis (OA) is a leading cause of pain and disability worldwide in elderly people. There is a critical need to develop novel therapeutic strategies that can effectively manage pain and disability to improve the quality of life for older people. Mesenchymal stem cells (MSCs) have emerged as a promising cell-based therapy for age-related disorders due to their multilineage differentiation and strong paracrine effects. Notably, MSC-derived exosomes (MSC-Exos) have gained significant attention because they can recapitulate MSCs into therapeutic benefits without causing any associated risks compared with direct cell transplantation. These exosomes help in the transport of bioactive molecules such as proteins, lipids, and nucleic acids, which can influence various cellular processes related to tissue repair, regeneration, and immune regulation. In this review, we have provided an overview of MSC-Exos as a considerable treatment option for osteoarthritis. This review will go over the underlying mechanisms by which MSC-Exos may alleviate the pathological hallmarks of OA, such as cartilage degradation, synovial inflammation, and subchondral bone changes. Furthermore, we have summarized the current preclinical evidence and highlighted promising results from in vitro and in vivo studies, as well as progress in clinical trials using MSC-Exos to treat OA.

Objective: The coronavirus disease 2019 (COVID-19) pandemic has caused significant transformations in healthcare. Many countries began the rapid development and adoption of telemedicine to avoid the spread of the pandemic and created an innovative model for healthcare delivery. This study identified the critical antecedents that affected the considered healthcare outcomes via teleophthalmology in Eastern Taiwan during the COVID-19 pandemic., Methods: This study's participants included residents of five towns in Taitung County who had experience with teleophthalmology. This study analyzed the structured questionnaires completed by the participants to validate the proposed research framework. Statistical methods were used to verify the research models, including descriptive statistical analysis, confirmatory factor analysis, and structural equation modeling. The date of this study was from 1 October 2020 to 31 July 2023., Results: The results of this study reveal that the average monthly use of teleophthalmology by individuals in rural areas increased annually. Females tended to utilize teleophthalmology services more than males. There were no significant differences across any of the constructs with respect to age or educational level. Additionally, the patients' awareness of healthcare accessibility via and the communication quality of teleophthalmology simultaneously affected teleophthalmology's adoption and service quality, which in turn jointly affected health outcomes. Both healthcare accessibility and communication quality were the antecedents of the healthcare outcomes. The health outcomes refer to the impact of teleophthalmology on the quality of the patients' health and well-being. Additionally, teleophthalmology's adoption and service quality acted as mediators., Conclusions: This study's findings are expected to increase attention to the healthcare outcomes and antecedents of teleophthalmology to promote better telemedicine practices and services for rural residents.

Objective: Verbal instruction is one of the most commonly used methods that therapists use to correct walking pattern for people with Parkinson disease. This study aimed to compare the long-term training effects of two different verbal instructions that either asked the participants to "take big steps" or "strike the ground with the heel" on walking ability in individuals with Parkinson disease., Design: Forty-five participants with Parkinson disease were randomized into the big-step or heel strike group. The participants underwent 12 sessions of treadmill and overground gait training. Throughout the interventions, the big-step group received an instruction to "take big steps," while the heel strike group received an instruction to "strike the ground with your heel." The primary outcome was gait performance, including velocity, stride length, cadence, and heel strike angle. The participants were assessed before, immediately after, and 1 mo after training., Results: Both groups showed significant improvements in gait performance after training. The heel strike group showed continuous improvements in velocity and stride length during the follow-up period; however, the big-step group showed slightly decreased performance., Conclusions: A verbal instruction emphasizing heel strike can facilitate long-term retention of walking performance in people with Parkinson disease., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Thyroid cancer incidence has increased globally in recent decades, especially in females, although its trends in Taiwan have not been studied extensively. This study aimed to investigate changes in female incidence and possible causes of thyroid cancer in Taiwan., Methods: Using the Taiwan Cancer Registry (TCR) Database, age-standardized incidence rates, age-specific incidence rates and birth cohorts were calculated. Correlation between female thyroid cancer incidence and cohort fertility rates were examined., Results: Thyroid cancer incidence increased in Taiwanese female, with age-adjusted rates per 100,000 people increasing from 7.37 during 1995-1999 to 20.53 during 2015-2019; the annual percentage change (APC) was 5.9% (95% CI, 5.3-6.5). Age-specific incidence rates increased with age, with peak rates occurring at younger ages. The APCs in the 50-54 age group were the highest (6.8%, 95% CI, 6.1-7.5). Incidence rates also increased with later birth cohorts. We observed a significant negative correlation between thyroid cancer incidence and fertility rates in the same birth cohort., Conclusions: We hypothesize that overdiagnosis may be a main reason for the rapidly increasing thyroid cancer incidence in Taiwanese females. Notably, we observed a strong negative correlation between fertility and thyroid cancer incidence. However, our study is limited by the absence of individual-level cancer data in the TCR database. These associations with fertility will be an important subject for future thyroid cancer research.

Introduction: Degenerative lumbar disease (DLD) is a prevalent disorder that predominantly affects the elderly population, especially female. Extensive research has demonstrated that overweight individuals (categorized by body fat distribution) have a higher susceptibility to developing DLD and an increased risk of falling. However, there is limited research available on the standing balance and functional performance of overweight females with DLD. Aims: To determine the impact of body fat distribution on standing balance and functional performance in overweight females with DLD. Methods: This cross-sectional study evaluated thirty females with DLD were categorized into three types of body fat distribution based on body mass index (BMI) and waist-hip ratio, specifically as android-type, gynoid-type, and normal weight groups. In addition, a control group of ten age-matched females with normal weight was recruited. The Visual Analogue Scale, Roland Morris Disability Questionnaire, Cobb angle (Determined using x-ray), and body composition (Determined using the InBody S10), were conducted only on the DLD groups. All participants were assessed standing balance in the anteroposterior and mediolateral directions. The functional assessments included timed-up-and-go and 5-times-sit-to-stand tests. Results: There were 10 people in each group. Android-type (Age = 65.00 ± 6.34 years; BMI = 26.87 ± 2.05 kg/m 2 ), Gynoid-type (Age = 65.60 ± 4.99 years; BMI = 26.60 ± 1.75 kg/m 2 ), Normal weight (Age = 65.70 ± 5.92 years; BMI = 22.35 ± 1.26 kg/m 2 ), and Control (Age = 65.00 ± 5.23 years; BMI = 22.60 ± 1.12 kg/m 2 ). The android-type group had higher body fat, visceral fat, and lower muscle mass ( p < 0.05), along with an increased Cobb angle ( p < 0.05). They showed greater ellipse area, total excursion, and mean distance in the anteroposterior direction ( p < 0.05). During the functional performance assessments, the android-type group had longer durations in both the 5-times-sit-to-stand and timed-up-and-go tasks ( p < 0.05). Conclusion: Our study found that android-type overweight individuals showed postural instability, reduced functional performance, and insufficient lower limb muscle strength and mass. These findings might help physical therapists in planning interventions, as they imply that patients with DLD may require specific types of standing balance training and lower extremities muscle-strengthening based on their body fat distribution. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT05375201., 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 Chen, Chen, Kantha, Tsai, Lai and Hsu.)

Long-term memory formation requires de novo RNA and protein synthesis. Using differential display PCR, we found that the NCoR1 cDNA fragment is differentially expressed between fast learners and slow learners, with fast learners showing a lower expression level than slow learners in the water maze learning task. Fast learners also show lower NCoR1 mRNA and protein expression levels. In addition, spatial training decreases both NCoR1 mRNA and protein expression, whereas NCoR1 conditional knockout (cKO) mice show enhanced spatial memory. In studying the molecular mechanism, we found that spatial training decreases the association between NCoR1 and DEC2. Both NCoR1 and DEC2 suppress the expression of BDNF, integrin α3 and SGK1 through C/EBPα binding to their DNA promoters, but overexpression of DEC2 in NCoR1 cKO mice rescues the decreased expression of these proteins compared with NCoR1 loxP mice overexpressing DEC2. Further, spatial training decreases DEC2 expression. Spatial training also enhances C/EBPα binding to Bdnf, Itga3 and Sgk1 promoters, an effect also observed in fast learners, and both NCoR1 and DEC2 control C/EBPα activity. Whereas knockdown of BDNF, integrin α3 or SGK1 expression impairs spatial learning and memory, it does not affect Y-maze performance, suggesting that BDNF, integrin α3 and SGK1 are involved in long-term memory formation, but not short-term memory formation. Moreover, NCoR1 expression is regulated by the JNK/c-Jun signaling pathway. Collectively, our findings identify DEC2 as a novel interacting protein of NCoR1 and elucidate the novel roles and mechanisms of NCoR1 and DEC2 in negative regulation of spatial memory formation., (© 2024. The Author(s).)

Nanofluidic channels in a membrane represent a promising avenue for harnessing blue energy from salinity gradients, relying on permselectivity as a pivotal characteristic crucial for inducing electricity through diffusive ion transport. Surface charge emerges as a central player in the osmotic energy conversion process, emphasizing the critical significance of a judicious selection of membrane materials to achieve optimal ion permeability and selectivity within specific channel dimensions. Alternatively, here we report a field-effect approach for in situ manipulation of the ion selectivity in a nanopore. Application of voltage to a surround-gate electrode allows precise adjustment of the surface charge density at the pore wall. Leveraging the gating control, we demonstrate permselectivity turnover to enhanced cation selective transport in multipore membranes, resulting in a 6-fold increase in the energy conversion efficiency with a power density of 15 W/m 2 under a salinity gradient. These findings not only advance our fundamental understanding of ion transport in nanochannels but also provide a scalable and efficient strategy for nanoporous membrane osmotic power generation.

Background: Central metatarsal pressure is increased in patients with hallux valgus, but the pedographic outcomes after hallux valgus (HV) correction are inconclusive. No known literature has reported the pedographic outcomes after HV correction with Minimally Invasive Chevron and Akin Osteotomy (MICA)., Methods: A prospective cohort of 31 feet from 25 patients with moderate-to-severe symptomatic HV but without metatarsalgia underwent MICA and was evaluated using radiographic parameters and pedographic measurements (Footscan ® , RSscan International, Olen, Belgium). Data were collected preoperatively and 3 months after surgery., Results: The radiographic parameters of the hallux valgus angle, intermetatarsal angle, distal metatarsal articular angle, first metatarsal head lateral shape, and lateral sesamoid grade significantly improved after MICA. The corrected first metatarsal length was significantly shortened by 2.3 mm, with consistent second metatarsal protrusion distance, lateral Meary's angle, and calcaneal pitch angle. Max force, max pressure, cumulative force, and cumulative pressure on the central metatarsals did not show significant changes between pre- and post-operative measurements, while these parameters significantly decreased in the hallux and first metatarsal area., Conclusion: MICA effectively corrects radiographic parameters but does not reduce central metatarsal loading in patients with moderate-to-severe HV without metatarsalgia.

High-entropy materials emerged as a field of research in 2004, when the first research on high-entropy alloys was published. The scope was soon expanded from high-entropy alloys to medium-entropy alloys, as well as to ceramics, polymers and composite materials. A fundamental understanding on high-entropy materials was proposed in 2006 by the 'four core effects' - high-entropy, severe-lattice-distortion, sluggish-diffusion and cocktail effects - which are often used to describe and explain the mechanisms of various peculiar phenomena associated with high-entropy materials. Throughout the years, the effects have been examined rigorously, and their validity has been affirmed. This Perspective discusses the fundamental understanding of the four core effects in high-entropy materials and gives further insights to strengthen the understanding for these effects. All these clarifications are believed to be helpful in understanding low-to-high-entropy materials as well as to aid the design of materials when studying new compositions or pursuing their use in applications., (© 2024. Springer Nature Limited.)

The leopard cat (Prionailurus bengalensis) is an endangered wildlife that is protected under Taiwan's regulations. The body of a road-killed leopard cat was found to contain sequences of feline calicivirus (FCV), designated W109-1443. Analysis of the complete genomic sequence revealed that it shared approximately 81% similarity with a Chinese strain of FCV found in a domestic cat. Phylogenetic analysis of the VP1 gene indicated that the W109-1443 isolate belonged to genogroup II. Recombination analysis revealed that the W109-1443 isolate may have resulted from recombination between two FCV strains. Given the potential impact of FCV on the health and survival of wild felids, further investigation is necessary to assess its pathogenicity in the leopard cat population.

Background: Individuals with diabetes have a significantly higher risk of developing various forms of cancer, and the potential biological links between these two diseases are not completely understood., Methods: This was a longitudinal retrospective nationwide cohort study, a study design that allows us to examine the natural course of cancer development over an extended period of time with a large sample size. Initially, 3,111,975 and 22,208,395 eligible patients aged ≥ 20 years with and without diabetes, respectively, were matched by age, sex, and the Charlson comorbidity index. Ultimately, 1,751,457 patients were selected from each group. Stratified populations for diabetic retinopathy (DR) (n = 380,822) and without DR (n = 380,822) as well as proliferative DR (PDR) (n = 141,150) and non-proliferative DR (NPDR) (n = 141,150) were analyzed in this study. The main outcome measure was the first-time diagnosis of cancer during the follow-up period., Results: We observed a 20% higher risk of total cancer incidence [hazard ratios (HR), 1.20; p < 0.001] in the diabetes cohort compared to the non-diabetes cohort. The highest HR was observed for liver and pancreas cancers. Moderately increased risks were observed for oral, colon, gallbladder, reproductive (female), kidney, and brain cancer. Furthermore, there was a borderline significantly increased risk of stomach, skin, soft tissue, female breast, and urinary tract (except kidney) cancers and lymphatic and hematopoietic malignancies. The stratified analysis revealed that the total cancer incidence was significantly higher in the DR cohort compared to the non-DR cohort (HR, 1.31; p < 0.001), and there was a borderline increased risk in the PDR cohort compared to the NPDR cohort (HR, 1.13; p = 0.001)., Conclusions: This study provides large-scale, nationwide, population-based evidence that diabetes is independently associated with an increased risk of subsequent development of total cancer and cancer at specific sites. Notably, this risk may further increase when DR develops., (© 2024. The Author(s).)

Background: This study validates real-time biofeedback for lumbopelvic control training in baseball. The lumbopelvic region is crucial for generating kinetic energy in pitching. Real-time biofeedback enhances training effectiveness and reduces injury risk. The validity and reliability of this system were examined., Purpose: This study was to investigate the validity and reliability of the real-time biofeedback system for lumbopelvic control training., Methods: Twelve baseball players participated in this study, with data collected in two sessions separated by a week. All participants needed to do the lateral slide exercise and single-leg squat exercise in each session. Pelvic angles detected by the real-time biofeedback system were compared to the three-dimensional motion capture system (VICON) during training sessions. Additionally, pelvic angles measured by the biofeedback system were compared between the two training sessions., Results: The real-time biofeedback system exhibited moderate to strong correlations with VICON in both exercises: lateral slide exercise ( r = 0.66-0.88, p < 0.05) and single-leg squat exercise ( r = 0.70-0.85, p < 0.05). Good to excellent reliability was observed between the first and second sessions for both exercises: lateral slide exercise (ICC = 0.76-0.97) and single-leg squat exercise (ICC = 0.79-0.90)., Conclusions: The real-time biofeedback system for lumbopelvic control training, accurately providing the correct pelvic angle during training, could enhance training effectiveness.

Background: Degenerative lumbar spine disease (DLD) is a prevalent condition in middle-aged and elderly individuals. DLD frequently results in pain, muscle weakness, and motor impairment, which affect postural stability and functional performance in daily activities. Simulated skateboarding training could enable patients with DLD to engage in exercise with less pain and focus on single-leg weight-bearing. The purpose of this study was to investigate the effects of virtual reality (VR) skateboarding training on balance and functional performance in patients with DLD., Methods: Fourteen patients with DLD and 21 age-matched healthy individuals completed a 6-week program of VR skateboarding training. The motion capture and force platform systems were synchronized to collect data during a single-leg stance test (SLST). Musculoskeletal simulation was utilized to calculate muscle force based on the data. Four functional performance tests were conducted to evaluate the improvement after the training. A Visual Analogue Scale (VAS) was also employed for pain assessment., Results: After the training, pain intensity significantly decreased in patients with DLD (p = 0.024). Before the training, patients with DLD took longer than healthy individuals on the five times sit-to-stand test (p = 0.024). After the training, no significant between-group differences were observed in any of the functional performance tests (p > 0.05). In balance, patients with DLD were similar to healthy individuals after the training, except that the mean frequency (p = 0.014) was higher. Patients with DLD initially had higher biceps femoris force demands (p = 0.028) but shifted to increased gluteus maximus demand after the training (p = 0.037). Gluteus medius strength significantly improved in patients with DLD (p = 0.039), while healthy individuals showed consistent muscle force (p > 0.05)., Conclusion: This is the first study to apply the novel VR skateboarding training to patients with DLD. VR skateboarding training enabled patients with DLD to achieve the training effects in a posture that relieves lumbar spine pressure. The results also emphasized the significant benefits to patients with DLD, such as reduced pain, enhanced balance, and improved muscle performance., (© 2024. The Author(s).)

Introduction: Angiotensin-converting enzyme 2 (ACE2) played an important role in the renin-angiotensin-aldosterone system (RAAS) and it was proved to be renoprotective in renal disease. Urinary angiotensin-converting enzyme 2 (uACE2) has been shown to reflect renal injury in human and experimental studies, but its role in feline kidney disease remains unknown., Aims: Our objectives involve comparing uACE2 concentrations and activities in cats across CKD stages with healthy controls, investigating the relationship between uACE2 concentrations, activities, and clinicopathological data in feline CKD patients, and assessing the predictive abilities of both for CKD progression., Methods: A retrospective, case-control study. The concentration and activity of uACE2 were measured by commercial ELISA and fluorometric assay kits, respectively. The concentration was adjusted to give uACE2 concentration-to-creatinine ratios (UACCRs)., Results: In total, 67 cats consisting of 24 control and 43 chronic kidney disease (CKD), including 24 early-stage CKD and 19 late-stage CKD, were enrolled in this study. UACCR values were significantly higher in both early-stage (2.100 [1.142-4.242] x 10 -6 ) and late-stage feline CKD (4.343 [2.992-5.0.71] x 10 -6 ) compared to healthy controls (0.894 [0.610-1.076] x 10 -6 ; p  < 0.001), and there was also significant difference between-early stage group and late-stage group ( p = 0.026). Urinary ACE2 activity (UAA) was significantly lower in CKD cats (1.338 [0.644-2.755] x pmol/min/ml) compared to the healthy cats (7.989 [3.711-15.903] x pmol/min/ml; p  < 0.001). UACCR demonstrated an independent, positive correlation with BUN ( p  < 0.001), and UAA exhibited an independent, negative correlation with plasma creatinine ( p  < 0.001). Both UACCR and UAA did not yield significant results in predicting CKD progression based on the ROC curve analysis., Conclusion and Clinical Importance: uACE2 concentration and activity exhibit varying changes as renal function declines, particularly in advanced CKD cats., 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 Kuo, Hsu, Wu, Jan, Tsai and Lee.)

Nonlocal effects originating from interactions between neighboring meta-atoms introduce additional degrees of freedom for peculiar characteristics of metadevices, such as enhancement, selectivity, and spatial modulation. However, they are generally difficult to manipulate because of the collective responses of multiple meta-atoms. Here, we experimentally demonstrate the nonlocal metasurface to realize the spatial modulation of dark-field emission. Plasmonic asymmetric split rings (ASRs) are designed to simultaneously excite local dipole resonance and nonlocal quasi-bound states in the continuum and spatially extended modes. With one type of unit, nonlocal effects are tailored by varying array periods. ASRs at the metasurface's edge lack sufficient interactions, resulting in stronger dark-field scattering and thus edge emission properties of the metasurface. Pixel-level spatial control is demonstrated by simply erasing some units, providing more flexibility than conventional local metasurfaces. This work paves the way for manipulating nonlocal effects and facilitates applications in optical trapping and sorting at the nanoscale.

Severe fever with thrombocytopenia syndrome virus (SFTSV) causes the highly fatal disease in humans. To facilitate diagnosis, the native form of subunit glycoprotein (Gn), a prime target for potential vaccines and therapies, was produced in Nicotiana benthamiana using a Bamboo mosaic virus-based vector system. By fusion with secretory signal tags, SS Ext , derived from the extension protein, and the (SP) 10 motif, the yield of the recombinant Gn (rGn) was remarkably increased to approximately 7 mg/kg infiltrated leaves. Ultimately, an rGn-based ELISA was successfully established for the detection of SFTSV-specific antibodies in serum samples from naturally infected monkeys. As validated with the reference method, the specificity and sensitivity of rGn-ELISA were 94% and 96%, respectively. In conclusion, utilizing well-suited fusion tags facilitates rGn production and purification in substantial quantities while preserving its antigenic properties. The rGn-ELISA, characterized by its commendable sensitivity and specificity could serve as a viable alternative diagnostic method for assessing SFTSV seroprevalence. KEY POINTS: • SFTSV Gn, fused with secretory signal tags, was expressed by the BaMV-based vector. • The plant fusion tags increased expression levels and eased the purification of rGn. • The rGn-ELISA was established and validated; its specificity and sensitivity > 94%., (© 2024. The Author(s).)

Natural language processing (NLP) has become an essential technique in various fields, offering a wide range of possibilities for analyzing data and developing diverse NLP tasks. In the biomedical domain, understanding the complex relationships between compounds and proteins is critical, especially in the context of signal transduction and biochemical pathways. Among these relationships, protein-protein interactions (PPIs) are of particular interest, given their potential to trigger a variety of biological reactions. To improve the ability to predict PPI events, we propose the protein event detection dataset (PEDD), which comprises 6823 abstracts, 39 488 sentences and 182 937 gene pairs. Our PEDD dataset has been utilized in the AI CUP Biomedical Paper Analysis competition, where systems are challenged to predict 12 different relation types. In this paper, we review the state-of-the-art relation extraction research and provide an overview of the PEDD's compilation process. Furthermore, we present the results of the PPI extraction competition and evaluate several language models' performances on the PEDD. This paper's outcomes will provide a valuable roadmap for future studies on protein event detection in NLP. By addressing this critical challenge, we hope to enable breakthroughs in drug discovery and enhance our understanding of the molecular mechanisms underlying various diseases., (© The Author(s) 2024. Published by Oxford University Press.)

In this paper, we present the design, optimization, and implementation of a sub-wavelength grating (SWG) multi-mode interference coupler (MMI) on the silicon nitride photonic integrated circuit (PIC) platform with a significantly enhanced bandwidth compared to the conventional MMI. We extend the SWG MMI theory, previously presented for the silicon-on-insulator platform, to the Si 3 N 4 /SiO 2 platform. Our approach involves an initial parameter optimization for a non-paired design, followed by a shift to a paired design that offers a smaller footprint and a broader bandwidth. The optimized SWG MMI exhibits a 1 dB bandwidth of 300 nm for both the insertion loss and power imbalance, making it a significant addition to silicon nitride photonics.

Flavivirus virus-like particles (VLPs) exhibit a striking structural resemblance to viral particles, making them highly adaptable for various applications, including vaccines and diagnostics. Consequently, increasing VLPs production is important and can be achieved by optimizing expression plasmids and cell culture conditions. While attempting to express genotype III (GIII) Japanese encephalitis virus (JEV) VLPs containing the G104H mutation in the envelope (E) protein, we failed to generate VLPs in COS-1 cells. However, VLPs production was restored by cultivating plasmid-transfected cells at a lower temperature, specifically 28 °C. Furthermore, we observed that the enhancement in JEV VLPs production was independent of amino acid mutations in the E protein. The optimal condition for JEV VLPs production in plasmid-transfected COS-1 cells consisted of an initial culture at 37 °C for 6 h, followed by a shift to 28 °C (37/28 °C) for cultivation. Under 37/28 °C cultivation conditions, flavivirus VLPs production significantly increased in various mammalian cell lines regardless of whether its expression was transiently transfected or clonally selected cells. Remarkably, clonally selected cell lines expressing flavivirus VLPs consistently achieved yields exceeding 1 μg/ml. Binding affinity analyses using monoclonal antibodies revealed similar binding patterns for VLPs of genotype I (GI) JEV, GIII JEV, West Nile virus (WNV), and dengue virus serotype 2 (DENV-2) produced under both 37 °C or 37/28 °C cultivation conditions. In summary, our study demonstrated that the production of flavivirus VLPs can be significantly improved under 37/28 °C cultivation conditions without affecting the conformational structure of the E protein. KEYPOINTS: • Low-temperature culture (37/28 °C) enhances production of flavivirus VLPs. • Flavivirus VLPs consistently achieved yields exceeding 1 μg/ml. • 37/28 °C cultivation did not alter the structure of flavivirus VLPs., (© 2024. The Author(s).)

Diazepam and zolpidem are the most widely used medications for managing insomnia. However, significant concerns regarding the potential risks of misuse and abuse problems arose in many literatures. While urine analysis is a valuable diagnostic tool, a challenge arises from the fact that some parent drugs may remain undetectable in urine. This necessitates concurrent monitoring of their metabolites. Here, we described an innovative on-line sample preconcentration technique known as micelle to solvent stacking (MSS) for the analysis of diazepam, zolpidem, and their main metabolites in urine. Several key parameters warrant further discussion to optimize the MSS model, enhancing its performance in terms of sensitivity and resolution. After optimizing the conditions, we conducted a validation test, achieving high correlation coefficients (greater than 0.9977) for intra-day and inter-day regression lines. Additionally, both the relative standard deviation (RSD) and relative error (RE) remained below 6.10% and 12.55%, respectively. The limits of detection (LODs, S/N = 3) for all five analytes ranged from 2.0 to 56 ng/mL. Compared to the conventional capillary zone electrophoresis method, this new approach exhibited remarkable sensitivity enhancements, ranging from 123 to 235-fold. Upon applying this method to actual urine samples from patients, we successfully detected nordiazepam, zolpidem, and its metabolites. This simple and sensitive approach has promising applications in supporting patient medication safety and bolstering forensic investigations., 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 Elsevier B.V. All rights reserved.)

A pregnancy booster dose significantly reduces the risk and severity of COVID-19, and it is widely recommended. A prospective cohort study was conducted to compare the transplacental passage of maternal antibodies from vaccination or infection during three trimesters against both the vaccine-targeted Wuhan strain and the Omicron strain of SARS-CoV-2. Maternal-infant dyads from vaccinated mothers were collected between 6 June 2022 and 20 September 2022. We analyzed 38 maternal-infant dyads from mothers who had been infected with COVID-19 and 37 from mothers without any previous infection. Pregnant women who received their last COVID-19 vaccine dose in the third trimester exhibited the highest anti-spike protein antibody levels and neutralizing potency against both the Wuhan strain and Omicron BA.2 variant in their maternal and cord plasma. Both second- and third-trimester vaccination could lead to a higher level of neutralization against the Wuhan and Omicron strains. COVID-19 infection had a negative effect on the transplacental transfer ratio of SARS-CoV-2 antibodies. A booster dose during the second or third trimester is encouraged for the maximum transplacental transfer of humoral protection against COVID-19 for infants.

Macrophages play a pivotal role in the response to injury, contributing significantly to the repair and regrowth of damaged tissues. The external lateral line system in aquatic organisms offers a practical model for studying regeneration, featuring interneuromast cells connecting sensory neuromasts. Under normal conditions, these cells remain dormant, but their transformation into neuromasts occurs when overcoming inhibitory signals from Schwann cells and posterior lateral line nerves. The mechanism enabling interneuromast cells to evade inhibition by Schwann cells remains unclear. Previous observations suggest that macrophages physically interact with neuromasts, nerves, and Schwann cells during regeneration. This interaction leads to the regeneration of neuromasts in a subset of zebrafish with ablated neuromasts. To explore whether macrophages achieve this effect through secreted cytokines, we conducted experiments involving tail amputation in zebrafish larvae and tested the impact of cytokine inhibitors on neuromast regeneration. Most injured larvae remarkably regenerated a neuromast within 4 days post-amputation. Intriguingly, removal of macrophages and inhibition of the anti-inflammatory cytokine transforming growth factor-beta (TGF-β) significantly delayed neuromast regeneration. Conversely, inhibition of the pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) had minor effects on the regeneration process. This study provides insights into how macrophages activate interneuromast cells, elucidating the pathways underlying neuromast regeneration., (© 2024 Japanese Society of Developmental Biologists.)

Introduction: Patients with head and neck cancer may develop a second primary neoplasm (SPN) of the esophagus due to field cancerization. This study investigated the impacts of esophageal cancer screening using magnifying endoscopy with narrow-band imaging (ME-NBI) on the outcomes of hypopharyngeal cancer patients., Methods: Patients with hypopharyngeal cancer diagnosed from 2008 to 2021 in a tertiary hospital were reviewed retrospectively. Screening and surveillance using ME-NBI examination of the esophagus were divided into three patterns: (1) ME-NBI never performed or more than 6 months after diagnosis of index primary hypopharyngeal cancer, (2) ME-NBI within 6 months only, and (3) ME-NBI within 6 months and regular surveillance., Results: A total of 261 were reviewed and 21 (8%) patients were in stage I, 20 (8%) in stage II, 27 (10%) in stage III, 116 (44%) in stage IVA, 65 (25%) in stage IVB, and 12 (5%) in stage IVC. Sixty-seven (26%) patients had SPN (50 esophagus, 10 oral cavity, 3 oropharynx, 2 nasopharynx, 1 larynx and 1 lung). Among esophageal SPN, 35 (70%) and 15 (30%) patients developed synchronous and metachronous neoplasia, respectively. In multivariate Cox regression analysis, advanced stages III and IV (compared with stages I and II, HR: 1.86, 1.18-2.95, p=0.008), ME-NBI examination of the esophagus received within 6 months and regular surveillance (HR: 0.53, 0.36-0.78, p=0.001) were independent factors affecting the overall survival of patients with hypopharyngeal cancer., Discussion: Our findings demonstrated that screening and surveillance of esophageal SPN by ME-NBI improves the survival of patients with hypopharyngeal cancer., 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 Chung, Wu, Lin, Lo, Cheng, Hsu and Liao.)

Plants offer a promising platform for cost-effective production of biologically active therapeutic glycoproteins. In previous studies, we have developed a plant expression system based on Bamboo mosaic virus (BaMV) by incorporating secretory signals and an affinity tag, which resulted in notably enhanced yields of soluble and secreted fusion glycoproteins (FGs) in Nicotiana benthamiana . However, the presence of fusion tags on recombinant glycoproteins is undesirable for biomedical applications. This study aimed to develop a refined expression system that can efficiently produce tag-free glycoproteins in plants, with enhanced efficacy of mature interferon gamma (mIFNγ) against viruses. To accommodate the specific requirement of different target proteins, three enzymatically or chemically cleavable linkers were provided in this renovated BaMV-based expression system. We demonstrated that Tobacco etch virus (TEV) protease could process the specific cleavage site (L TEV ) of the fusion protein, designated as SS Ext His(SP) 10 L TEV -mIFNγ, with optimal efficiency under biocompatible conditions to generate tag-free mIFNγ glycoproteins. The TEV protease and secretory-affinity tag could be effectively removed from the target mIFNγ glycoproteins through Ni 2+ -NTA chromatography. In addition, the result of an antiviral assay showed that the tag-free mIFNγ glycoproteins exhibited enhanced biological properties against Sindbis viru s, with comparable antiviral activity of the commercialized HEK293-expressed hIFNγ. Thus, the improved BaMV-based expression system developed in this study may provide an alternative strategy for producing tag-free therapeutic glycoproteins intended for biomedical applications., 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 Jiang, Hsu, Tseng, Lin, Hsu and Hu.)

Artificial nanofluidic networks are emerging systems for blue energy conversion that leverages surface charge-derived permselectivity to induce voltage from diffusive ion transport under salinity difference. Here the pivotal significance of electrostatic inter-channel couplings in multi-nanopore membranes, which impose constraints on porosity and subsequently influence the generation of large osmotic power outputs, is illustrated. Constructive interference is observed between two 20 nm nanopores of 30 nm spacing that renders enhanced permselectivity to osmotic power output via the recovered electroneutrality. On contrary, the interference is revealed as destructive in two-dimensional arrays causing significant deteriorations of the ion selectivity even for the nanopores sparsely distributed at an order of magnitude larger spacing than the Dukhin length. Most importantly, a scaling law is provided for deducing the maximal membrane area and porosity to avoid the selectivity loss via the inter-pore electrostatic coupling. As the electric crosstalk is inevitable in any fluidic network, the present findings can be a useful guide to design nanoporous membranes for scalable osmotic power generations., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors. Exploration published by Henan University and John Wiley & Sons Australia, Ltd.)

An analysis of the optical response of a GaN-based metalens was conducted alongside the utilization of two sequential artificial intelligence (AI) models in addressing the occasional issues of blurriness and color cast in captured images. The optical loss of the metalens in the blue spectral range was found to have resulted in the color cast of images. Autoencoder and CodeFormer sequential models were employed in order to correct the color cast and reconstruct image details, respectively. Said sequential models successfully addressed the color cast and reconstructed details for all of the allocated face image categories. Subsequently, the CIE 1931 chromaticity diagrams and peak signal-to-noise ratio analysis provided numerical evidence of the AI models' effectiveness in image reconstruction. Furthermore, the AI models can still repair the image without blue information. Overall, the integration of metalens and artificial intelligence models marks a breakthrough in enhancing the performance of full-color metalens-based imaging systems.

Background: Head and neck cancer is highly prevalent in Taiwan. Its treatment mainly relies on clinical staging, usually diagnosed from images. A major part of the diagnosis is whether lymph nodes are involved in the tumor. We present an algorithm for analyzing clinical images that integrates a deep learning model with image processing and attempt to analyze the features it uses to classify lymph nodes., Methods: We retrospectively collected pretreatment computed tomography images and surgery pathological reports for 271 patients diagnosed with, and subsequently treated for, naïve oral cavity, oropharynx, hypopharynx, and larynx cancer between 2008 and 2018. We chose a 3D UNet model trained for semantic segmentation, which was evaluated for inference in a test dataset of 29 patients., Results: We annotated 2527 lymph nodes. The detection rate of all lymph nodes was 80%, and Dice score was 0.71. The model has a better detection rate at larger lymph nodes. For those identified lymph nodes, we found a trend where the shorter the short axis, the more negative the lymph nodes. This is consistent with clinical observations., Conclusions: The model showed a convincible lymph node detection on clinical images. We will evaluate and further improve the model in collaboration with clinical physicians.

Background: Integrase strand transfer inhibitor (INSTIs)-based combination antiretroviral treatment in people living with HIV (PLWH) has been reportedly correlated with several adverse effects, such as weight gain, fetal defects or psychiatric disorders., Methods: To comprehensively understand the adverse effect of INSTIs, our study utilized Caenorhabditis Elegans (C. elegans) as a model to investigate how dolutegravir (DTG) affected its life cycle, growth, reproduction and lifespan., Results: Our results indicated that DTG enhanced body growth at the early stage of treatment, but no change was detected for long-term treatment. The treatment also influenced the reproductive system, decreased egg-hatching but had no effect on egg-laying. Besides, DTG resulted in lifespan reduction, which is dependent on increased levels of reactive oxidative species (ROS) accumulation. Treatment with N-acetyl-cysteine (NAC) in worms restrained intracellular ROS accumulation and improved DTG-induced lifespan reduction., Conclusions: Our study demonstrates for the first time the effect of DTG treatment on life cycle. DTG-induced adverse effects are potentially associated with intracellular ROS accumulation. Quenching ROS accumulation might provide a novel strategy for dealing with the adverse effects of INSTIs., (© 2023. The Author(s).)

Severe Fever with Thrombocytopenia Syndrome (SFTS), caused by the SFTS Virus (SFTSV), is a global health threat. SFTSV in Taiwan has only been reported in ruminants and wild animals. Thus, we aimed to investigate the infection statuses of dogs and cats, the animals with closer human interactions. Overall, the SFTSV RNA prevalence was 23% (170/735), with dogs showing a 25.9% (111/429) prevalence and cats at 19.3% (59/306) prevalence. Noticeably, the prevalence in stray animals (39.8% 77/193) was significantly higher than in domesticated ones (17.2%, 93/542). Among the four categories analyzed, the highest SFTSV prevalence was found in the stray dogs at 53.9% (120/193), significantly higher than the 24.2% prevalence noted in stray cats. In contrast, domesticated animals exhibited similar prevalence rates, with 17.1% for dogs and 17.2% for cats. It is noteworthy that in the domesticated animal groups, a significantly elevated prevalence (45%, 9/20) was observed among cats exhibiting thrombocytopenia compared to those platelet counts in the reference range (4.8%, 1/21). The high infection rate in stray animals, especially stray dogs, indicated that exposure to various outdoor environments influences the prevalence of infections. Given the higher human interaction with dogs and cats, there is a need for proactive measures to reduce the risk associated with the infection of SFTSV in both animals and humans.

This study aimed to investigate the prevalence of lower urinary tract symptoms (LUTS) in older men ( N = 3056) with benign prostatic hyperplasia (BPH) and its effects on their sexual function and mental health. Descriptive, correlation, and regression analyses were used to explore the relationships between prostate and lower urinary tract health and psychological well-being. Better prostate and lower urinary tract health positively affected psychological well-being, and sexual function also had a positive influence. LUTS have an adverse impact on sexual function and mental health. Early intervention is crucial for mitigating the negative impact of LUTS on the quality of life in older men. Addressing prostate and lower urinary tract health issues through appropriate interventions may improve psychological well-being. Health care professionals must consider the adverse effects of BPH and LUTS on sexual function and mental health, and implement interventions to enhance the overall quality of life in older men., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

To understand the effects of a high-fat diet (HFD) on lung cancer progression and biomarkers, we here used an inducible mutant epidermal growth factor receptor (EGFR)-driven lung cancer transgenic mouse model fed a regular diet (RD) or HFD. The HFD lung cancer (LC-HFD) group exhibited significant tumor formation and deterioration, such as higher EGFR activity and proliferation marker expression, compared with the RD lung cancer (LC-RD) group. Transcriptomic analysis of the lung tissues revealed that the significantly changed genes in the LC-HFD group were highly enriched in immune-related signaling pathways, suggesting that an HFD alters the immune microenvironment to promote tumor growth. Cytokine and adipokine arrays combined with a comprehensive analysis using meta-database software indicated upregulation of C-reactive protein (CRP) in the LC-HFD group, which presented with increased lung cancer proliferation and metastasis; this was confirmed experimentally. Our results imply that an HFD can turn the tumor growth environment into an immune-related pro-tumorigenic microenvironment and demonstrate that CRP has a role in promoting lung cancer development in this microenvironment., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)

As human-robot interaction becomes more prevalent in industrial and clinical settings, detecting changes in human posture has become increasingly crucial. While recognizing human actions has been extensively studied, the transition between different postures or movements has been largely overlooked. This study explores using two deep-learning methods, the linear Feedforward Neural Network (FNN) and Long Short-Term Memory (LSTM), to detect changes in human posture among three different movements: standing, walking, and sitting. To explore the possibility of rapid posture-change detection upon human intention, the authors introduced transition stages as distinct features for the identification. During the experiment, the subject wore an inertial measurement unit (IMU) on their right leg to measure joint parameters. The measurement data were used to train the two machine learning networks, and their performances were tested. This study also examined the effect of the sampling rates on the LSTM network. The results indicate that both methods achieved high detection accuracies. Still, the LSTM model outperformed the FNN in terms of speed and accuracy, achieving 91% and 95% accuracy for data sampled at 25 Hz and 100 Hz, respectively. Additionally, the network trained for one test subject was able to detect posture changes in other subjects, demonstrating the feasibility of personalized or generalized deep learning models for detecting human intentions. The accuracies for posture transition time and identification at a sampling rate of 100 Hz were 0.17 s and 94.44%, respectively. In summary, this study achieved some good outcomes and laid a crucial foundation for the engineering application of digital twins, exoskeletons, and human intention control.

Purpose: Two Epstein-Barr virus (EBV)-based testing approaches have shown promise for early detection of nasopharyngeal carcinoma (NPC). Neither has been independently validated nor their performance compared. We compared their diagnostic performance in an independent population., Methods: We tested blood samples from 819 incident Taiwanese NPC cases (213 early-stage, American Joint Committee on Cancer version 7 stages I and II) diagnosed from 2010 to 2014 and from 1,768 controls from the same region, frequency matched to cases on age and sex. We compared an EBV antibody score using immunoglobulin A antibodies measured by enzyme-linked immunosorbent assay (EBV antibody score) and plasma EBV DNA load measured by real-time PCR followed by next-generation sequencing (NGS) among EBV DNA-positive individuals (EBV DNA algorithm)., Results: EBV antibodies and DNA load were measured for 2,522 (802 cases; 1,720 controls) and 2,542 (797 cases; 1,745 controls) individuals, respectively. Of the 898 individuals positive for plasma EBV DNA and therefore eligible for NGS, we selected 442 (49%) for NGS testing. The EBV antibody score had a sensitivity of 88.4% (95% CI, 86.1 to 90.6) and a specificity of 94.9% (95% CI, 93.8 to 96.0) for NPC. The EBV DNA algorithm yielded significantly higher sensitivity (93.2%; 95% CI, 91.3 to 94.9; P = 1.33 × 10 -4 ) and specificity (98.1%; 95% CI, 97.3 to 98.8; P = 3.53 × 10 -7 ). For early-stage NPC, the sensitivities were 87.1% (95% CI, 82.7 to 92.4) for the EBV antibody score and 87.0% (95% CI, 81.9 to 91.5) for the EBV DNA algorithm ( P = .514). For regions with a NPC incidence of 20-100/100,000 person-years (eg, residents in southern China and Hong Kong), these two approaches yielded similar numbers needed to screen (EBV antibody score: 5,656-1,131; EBV DNA algorithm: 5,365-1,073); positive predictive values ranged from 0.4% to 1.7% and 1.0% to 4.7%, respectively., Conclusion: We demonstrated high sensitivity and specificity of EBV antibody and plasma EBV DNA for NPC detection, with slightly inferior performance of the EBV antibody score. Cost-effectiveness studies are needed to guide screening implementation.

The steel rail and wheel in the railway system offer a high precision and smooth-running surface. Nevertheless, the point of contact between the rail and wheel presents a critical area that can give rise to rail corrugation. This phenomenon can potentially elevate sound and vibration levels in the vicinity considerably, necessitating advanced monitoring and assessment measures. Recently, many efforts have been directed towards utilizing in-service trains for evaluating rail corrugation, and the evaluation has primarily relied on axle-box acceleration (ABA). However, the ABA measurements require a higher threshold for vibration detection. This study introduces a novel approach to rail corrugation detection by carriage floor acceleration (CFA), aimed at lowering the detection threshold. The method capitalizes on the acceleration data sensed on the carriage floor, which is induced by the sound pressure (e.g., sound-field excitation) generated at the wheel-rail contact point. An exploration of the correlation between these datasets is undertaken by simultaneously measuring both ABA and CFA. Moreover, a pivotal aspect of this research is the development of the eigenfrequency rail corrugation index (E-RCI), a mechanism that culminates energy around specific eigenfrequencies by CFA. Through this index, a focused analysis of rail corrugation patterns is facilitated. The study further delves into the stability, repeatability, and sensitivity of the E-RCI via varied measurement scenarios. Ultimately, the CFA-based rail corrugation identification is verified, establishing its practical applicability and offering a distinct approach to detecting and characterizing rail corrugation phenomena. This study has introduced an innovative methodology for rail corrugation detection using CFA, with the principal objective of lowering the detection threshold. This approach offers an efficient measurement technique for identifying rail corrugation areas, thereby potentially reducing maintenance costs and enhancing efficiency within the railway industry.

The gait pattern of exoskeleton control conflicting with the human operator's (the pilot) intention may cause awkward maneuvering or even injury. Therefore, it has been the focus of many studies to help decide the proper gait operation. However, the timing for the recognization plays a crucial role in the operation. The delayed detection of the pilot's intent can be equally undesirable to the exoskeleton operation. Instead of recognizing the motion, this study examines the possibility of identifying the transition between gaits to achieve in-time detection. This study used the data from IMU sensors for future mobile applications. Furthermore, we tested using two machine learning networks: a linearfFeedforward neural network and a long short-term memory network. The gait data are from five subjects for training and testing. The study results show that: 1. The network can successfully separate the transition period from the motion periods. 2. The detection of gait change from walking to sitting can be as fast as 0.17 s, which is adequate for future control applications. However, detecting the transition from standing to walking can take as long as 1.2 s. 3. This study also find that the network trained for one person can also detect movement changes for different persons without deteriorating the performance.

Background: Taiwan has one of the highest incidences of upper tract urothelial cancer (UTUC) worldwide, especially in women; however, no nationwide, long-term follow-up study has evaluated this., Methods: We investigated the incidence of UTUC in Taiwan using data from the national population-based Taiwan Cancer Registry database (1985-2019). We divided the birth cohort into nine 5-year age groups and calculated the age-specific incidence for these groups according to the corresponding birth years., Results: The average annual percent change in the incidence of renal pelvis cancer from 1985 to 2019 showed sex-specific differences, with 3.5% and 5.3% increases in the incidences in men and women, respectively. The age-specific incidence rate for renal pelvis cancer among women showed a gradual increase in the group with older women as well as an increase over time in each age group. The results of a birth cohort analysis revealed that younger cohorts had higher incidence rates of renal pelvis cancer than older cohorts did., Conclusion: We demonstrated that the incidence of UTUC is unusually high among older Taiwanese women and that younger cohorts have a high risk of UTUC than older cohorts., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Pattern hair loss can occur in both men and women, and the underlying molecular mechanisms have been continuously studied in recent years. Male androgenetic alopecia (M-AGA), also termed male pattern hair loss, is the most common type of hair loss in men. M-AGA is considered an androgen-dependent trait with a background of genetic predisposition. The interplay between genetic and non-genetic factors leads to the phenotype of follicular miniaturization. Although this similar pattern of phenotypic miniaturization can also be found in female pattern hair loss (FPHL), the corresponding genetic factors in M-AGA do not account for the phenotype in FPHL, indicating that there are different genes contributing to FPHL. Therefore, the role of genetic factors in FPHL is still uncertain. Understanding the genetic mechanism that causes FPHL is crucial for the future development of personalized treatment strategies. This review aims to highlight the differences in the ethnic prevalence and genetic background of FPHL, as well as the current genetic research progress in nutrition, Wnt signaling, and sex hormones related to FPHL.

Pathogens of wild bees in Japan remain largely unknown. We examined viruses harbored by solitary wild Osmia bees, including Osmia cornifrons and Osmia taurus. Interestingly, the full-length genome of a novel virus (designated as "Osmia-associated bee chuvirus", OABV) was identified in three Osmia taurus bees collected in Fukushima prefecture. The sequences and genomic features are similar to those of Scaldis River bee virus. Phylogenetic analysis based on RNA-dependent RNA polymerase, glycoprotein, and nucleoprotein sequences showed that OABV formed a subcluster within ollusviruses and was closely related to strains identified in European countries. This study extends our knowledge of wild bee parasites in Japan., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)