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Abstract Background Prior research has highlighted the synergistic impact of protein supplementation on muscle function post‐exercise in adults; however, evidence supporting the combined effects were less robust and inconsistent on those with protein insufficiency. This investigation aims to explore efficacy of protein‐enriched soup coupled with exercise on muscle health and metabolism in middle‐aged and older adults with suboptimal protein intake. Methods An open‐label, 12‐week, randomized controlled trial involving participants with insufficient protein intake (

Abstract Sleeve and double‐sleeve lobectomies are lung‐sparing techniques for treating central lung cancers. However, if the tumour extends to involve the bronchi and vessels, lung auto‐transplantation may be an alternative to pneumonectomy. Neoadjuvant therapy after surgery is the most common strategy for patients with extensive central lung cancer. Herein, we report a case of central lung cancer in a patient who underwent immunochemotherapy as neoadjuvant therapy following lung auto‐transplantation. A 68‐year‐old man with stage IIIA non‐small cell lung cancer and left upper lobe squamous cell carcinoma underwent neoadjuvant immunochemotherapy. Following partial regression, a multidisciplinary team decided on a back‐table procedure with auto‐lung transplantation after pneumonectomy to preserve pulmonary function. The patient had an uneventful recovery and was discharged after three weeks with no residual tumour or lymph node metastases. Lung auto‐transplantation can be successfully performed in non‐lung transplantation centres, potentially broadening treatment options for patients with central lung cancer.

Objectives: To develop an intrinsic capacity (IC) score and to investigate the association between IC transition with overall and cause-specific mortality, incident disability and healthcare utilization. Design: Retrospective cohort study Setting and participants: Data from 1852 respondents aged ≥ 65 years who completed the 1999 and 2003 surveys of the Taiwan Longitudinal Study on Aging were analyzed. Measurements: Transitions of IC score were categorized into three groups: (1) Improved IC (IC2003−1999 >0), (2) Stable IC (IC2003−1999 = 0), (3) Worsened IC (IC2003−1999

Background: The early diagnosis of acral lentiginous melanoma (ALM) contributes to clinical outcomes since ALM can be mistaken for acral melanocytic nevus (AMN). ALM occurrence is reported to correlate with stress-bearing areas, which may assist in differential diagnoses. Our objective is to evaluate the distribution patterns of ALMs and AMNs on the palms and soles among Taiwanese patients. Methods: A retrospective analysis was performed by reviewing the charts of 1400 patients diagnosed with benign and malignant pigmented lesions confirmed after excisional biopsy at our institution between 2000 and 2022 in Taiwan. Correlations between lesions and clinicopathological factors were analyzed. Results: 309 AMNs and 177 ALMs were included. Mechanical stress was significantly associated with plantar ALMs (weight-bearing area: 92.65 %, arch: 7.35 %, P

This retrospective cohort study enrolled 385 patients diagnosed with cutaneous melanoma from 1980 to 2021 in National Taiwan University Hospital (NTUH). The aim of this study was to investigate the relationship between thickness of primary melanoma lesions and disease outcome of melanoma patients, in particular, those diagnosed with acral lentiginous melanoma (ALM). The association between important clinicopathological characteristics other than tumor thickness and disease outcome was also analyzed. Survival analyses with the Kaplan-Meier method were utilized to investigate the prognoses of patients with different lesion thickness. The male-to-female ratio was 1.12:1. The median age at diagnosis was 63 years old (mean: 62.2 years). There were 283 cases (73.5%) of acral lentiginous melanoma (ALM) with a male-to-female ratio of 1.04:1. Between patients with primary ALM lesions 4.1 millimeters (mm) to 8.0 mm thick and those with lesions over 8.0 mm thick, significant differences in prognostic outcomes including incidence of second recurrences within 1 year (raw p = 0.003, Bonferroni corrected p = 0.009) and distant metastases within 1 year (raw p = 0.003, Bonferroni corrected p = 0.008), were observed. Significantly worse 1-year (raw p = 0.01, Bonferroni corrected p=0.03) and 2-year survival (raw p = 0.006, Bonferroni corrected p = 0.02) were found in ALM patients with lesions of over 8 mm thick than those with lesions 4.1 mm to 8.0 mm at diagnosis. Vigilant short-term follow-up is warranted in ALM patients with lesions of over 8.0 mm thick at diagnosis due to higher risks of adverse outcome.

Background: Risk factors of lymphatic and hematogenous metastasis in cutaneous melanoma remained unclear in Asian population. This study aimed to identify clinical and histopathological factors to predict metastatic pathways in cutaneous melanoma in Taiwan. Methods: A total of 247 patients diagnosed as stage I and II melanoma, followed at National Taiwan University Hospital were included in this retrospective study from 1980 to 2020. Kaplan–Meier curves and Cox proportional hazards regression were utilized to identify risk factors. Results: During a median follow-up of 143 months, 48 (19.4%) and 62 (25.1%) patients developed lymphatic and hematogenous metastasis respectively. In the univariate analysis, age> 70 years, greater Breslow thickness, ulceration, neurotropism, and NRAS mutation were significant risk factors for lymphatic metastasis in all subtypes of melanoma. Age >70 years, head and neck location, thickness, ulceration, higher mitotic rate, neurotropism, and NRAS mutation were significant predictors of hematogenous metastasis in all subtypes. In the multivariate analysis, greater thickness (HR for 2.0–4.0 mm, 4.5; p = .009 and HR for >4.0 mm, 5.7; p = .003) retained its significance as an independent risk factor for lymphatic metastasis in all subtypes of melanoma. Thickness (HR for >4.0 mm, 5.7; p

Abstract Hyoscine-N-butylbromide (HBB) is the most used antiperistaltic agent during esophagogastroduodenoscopy (EGD). However, almost half of the elderly have a contraindication to HBB. We aimed to evaluate l-menthol’s antiperistaltic effect and safety for EGD in the elderly with contraindication to HBB. This prospective, randomized, double-blind, placebo-controlled study screened 86 elderly patients (≥ 65 years old) scheduled to undergo EGD, and 52 of them with contraindication to HBB were enrolled. The participants were randomized to receive l-menthol (n = 26) or a placebo (n = 26), which was locally sprayed on the gastric antrum endoscopically. The proportion of patients with no or mild peristalsis after medication and at the end of EGD was significantly higher in the l-menthol group (76.9%) than in the placebo group (11.5%, p

Abstract Background Sarcopenic obesity aims to capture the risk of functional decline and cardiometabolic diseases, but its operational definition and associated clinical outcomes remain unclear. Using data from the Longitudinal Aging Study of Taipei, this study explored the roles of the muscle‐to‐fat ratio (MFR) with different definitions and its associations with clinical characteristics, functional performance, cardiometabolic risk and outcomes. Methods (1) Appendicular muscle mass divided by total body fat mass (aMFR), (2) total body muscle mass divided by total body fat mass (tMFR) and (3) relative appendicular skeletal muscle mass (RASM) were measured. Each measurement was categorized by the sex‐specific lowest quintiles for all study participants. Clinical outcomes included all‐cause mortality and fracture. Results Data from 1060 community‐dwelling older adults (mean age: 71.0 ± 4.8 years) were retrieved for the study. Overall, 196 (34.2% male participants) participants had low RASM, but none was sarcopenic. Compared with those with high aMFR, participants with low aMFR were older (72 ± 5.6 vs. 70.7 ± 4.6 years, P = 0.005); used more medications (2.9 ± 3.3 vs. 2.1 ± 2.5, P = 0.002); had a higher body fat percentage (38 ± 4.8% vs. 28 ± 6.4%, P

Abstract Background Few studies have made longitudinal comparisons between frailty phenotype (FP) and frailty index (FI) changes. We aimed to investigate frailty status changes defined by FP and FI concurrently, and to compare the associated factors and incident disability among different combination of FI and FP trajectory groups. Methods Data on respondents aged over 50 who completed the 1999, 2003 and 2007 Taiwan Longitudinal Study on Aging (TLSA) surveys (n = 2807) were excerpted. Changes of FI, FP and major time-dependent variables were constructed by group-based trajectory modeling. Logistic regression was used to investigate the associated factors and relationships with incident disability among different frailty trajectories. Results We identified four FP trajectories – stably robust, worsened frailty, improved frailty, and stably frail and three FI trajectories – stable FI, moderate increase FI and rapid increase FI. Lower self-rated health, mobility impairment, and depressed mood were associated with unfavorable FP and FI changes (all p

Abstract Background Expression of translocator protein (TSPO) on the outer mitochondrial membrane of activated microglia is strongly associated with neuroinflammation. The second-generation PET ligand [18F]FEPPA specifically binds TSPO to enable in vivo visualization and quantification of neuroinflammation. We optimized a fully automated radiosynthesis method and evaluated the utility of [18F]FEPPA, the second-generation PET ligand specifically binds TSPO, in a mouse model of systemic LPS challenge to detect TSPO-associated signals of central and peripheral inflammation. In vivo dynamic PET/MR imaging was performed in LPS-induced and control mice after [18F]FEPPA administration. The relationship between the [18F]FEPPA signal and the dose of LPS was assessed. The cytokine levels (i.e., TNF-α, Il-1β, Il-6) in LPS-induced mice were measured by RT-PCR. Standard uptake value (SUV), total volume of distribution (VT) and area under the curve (AUC) were determined based on the metabolite-uncorrected plasma input function. Western blotting and immunostaining were used to measure TSPO expression in the brain. Results The fully automated [18F]FEPPA radiosynthesis produced an uncorrected radiochemical yield of 30 ± 2% within 80 min, with a radiochemical purity greater than 99% and specific activity of 148.9‒216.8 GBq/µmol. Significant differences were observed in the brain after [18F]FEPPA administration: SUV, VT and AUC were 1.61 ± 0.1, 1.25 ± 0.12 and 1.58 ± 0.09-fold higher in LPS-injected mice than controls. TNF-α, Il-1β and Il-6 mRNA levels were also elevated in the brains of LPS-injected mice. Western blotting revealed TSPO (p

We present a facile low-cost method to produce nitrogen-doped holey graphene (N-HGE) and its application to supercapacitors. A composite of N-HGE and activated carbon (AC) was used as the electrode active material in organic-electrolyte supercapacitors, and the performances were evaluated. Melamine was mixed into graphite oxide (GO) as the N source, and an ultra-rapid heating method was used to create numerous holes during the reduction process of GO. X-ray photoelectron spectra confirmed the successful doping with 2.9–4.5 at.% of nitrogen on all samples. Scanning electron micrographs and Raman spectra revealed that a higher heating rate resulted in more holes and defects on the reduced graphene sheets. An extra annealing step at 1000 °C for 1 h was carried out to further eliminate residual oxygen functional groups, which are undesirable in the organic electrolyte system. Compared to the low-heating-rate counterpart (N-GE-15), N-HGE boosted the specific capacity of the supercapacitor by 42 and 22% at current densities of 0.5 and 20 A/g, respectively. The effects of annealing time (0.5, 1, and 2 h) at 1000 °C were also studied. Longer annealing time resulted in higher capacitance values at all current densities due to the minimized oxygen content. Volumetric specific capacitances of 49 and 24 F/cm3 were achieved at current densities of 0.5 and 20 A/g, respectively. For the high-power-density operation at 31,000 W/kg (or 10,000 W/L), an energy density as high as 11 Wh/kg (or 3.5 Wh/L) was achieved. The results indicated that N-HGE not only improved the conductivity of the composite supercapacitors but also accelerated ion transport by way of shortened diffusion paths through the numerous holes all over the graphene sheets.

Arsenic in drinking water has been recognized as carcinogenic to humans and can cause solid cancers of lung, urinary bladder, and skin. Positive associations have also been reported between arsenic ingestion and cancers of kidney, liver and prostate. Nevertheless, arsenic trioxide has been used successfully in the treatment of acute promyelocytic leukemia. Therefore, arsenic might play different roles in the carcinogenesis of solid cancers and hematologic malignancies. The relationship between arsenic in drinking water and the incidences of hematologic malignancies has not been fully investigated. We established a cohort of Taiwanese population and assorted 319 townships of Taiwan into two exposure categories using 0.05 mg/L as the cutoff. Then, we linked these data to the Taiwan Cancer Registry and computed standardized incidence ratios (SIRs) of lymphoma and leukemia by sex, exposure category and time period. The trend of changes in the SIRs over time was assessed, from 1981–1990 to 1991–2000 and then to 2001–2010. We found that in both lymphoma and leukemia, the higher exposure category was associated with lower SIRs in both men and women. In terms of time trends, the SIRs in both lymphoma and leukemia showed increasing trends in both sexes, while exposure to arsenic in drinking water decreased over time. The arsenic level in drinking water was negatively associated with the incidences of lymphoma and leukemia in both men and women. This study supports the dual effects of arsenic on carcinogenesis, with a potential protective effect against hematologic malignancies.

Abstract Background Frailty is the pre‐eminent exigency of aging. Although frailty‐related impairments are preventable, and multidomain interventions appear more effective than unimodal ones, the optimal components remain uncertain. Methods We devised multidomain interventions against physical and cognitive decline among prefrail/frail community‐dwelling ≥65‐year‐olds and evaluated these in complementary cluster‐randomized trials of efficacy and participant empowerment. The Efficacy Study compared ~3‐monthly telephone consultations vs. 16, 2 h sessions/year comprising communally partaken physical and cognitive training plus nutrition and disease education; the Empowerment Study compared the standard Efficacy Study multidomain intervention (Sessions 1–10) vs. an enhanced version redesigned to empower and motivate individual participants. Changes from baseline in physical, functional, and cognitive performance were measured after 6 and 12 months in the Efficacy Study and after 6 months in the Empowerment Study, with post‐intervention follow‐up at 9 months. Primary outcomes are as follows: Cardiovascular Health Study frailty score; gait speed; handgrip strength; and Montreal Cognitive Assessment (MoCA). Secondary outcomes are as follows: instrumental activities of daily living; metabolic equivalent of task (MET); depressed mood (Geriatric Depression Scale‐5 ≥2); and malnutrition (Mini‐Nutritional Assessment short‐form ≤11). Intervention effects were analyzed using a generalized linear mixed model. Results Efficacy Study participants (n = 1082, 40 clusters) were 75.1 ± 6.3 years old, 68.7% women, and 64.7% prefrail/frail; analytic clusters: 19 intervention (410/549 completed) vs. 21 control (375/533 completed). Empowerment Study participants (n = 440, 14 clusters) were 75.9 ± 7.1 years old, 83.6% women, and 56.7% prefrail/frail; analytic clusters: seven intervention (209/230 completed) vs. seven control (189/210 completed). The standard and enhanced multidomain interventions both reduced frailty and significantly improved aspects of physical, functional, and cognitive performance, especially among ≥75‐year‐olds. Standard multidomain intervention decreased depression [odds ratio 0.56, 95% confidence interval (CI) 0.32, 0.99] and malnutrition (odds ratio 0.45, 95% CI 0.26, 0.78) by 12 months and improved concentration at Months 6 (0.23, 95% CI 0.04, 0.42) and 12 (0.46, 95% CI 0.22, 0.70). Participant empowerment augmented activity (4.67 MET/h, 95% CI 1.64, 7.69) and gait speed (0.06 m/s, 95% CI 0.00, 0.11) at 6 months, with sustained improvements in delayed recall (0.63, 95% CI 0.20, 1.06) and MoCA performance (1.29, 95% CI 0.54, 2.03), and less prevalent malnutrition (odds ratio 0.39, 95% CI 0.18, 0.84), 3 months after the intervention ceased. Conclusions Pragmatic multidomain intervention can diminish physical frailty, malnutrition, and depression and enhance cognitive performance among community‐dwelling elders, especially ≥75‐year‐olds; this might supplement healthy aging policies, probably more effectively if participants are empowered.

Background: The outcome of open-heart surgery for patients with liver cirrhosis (LC) varies widely, indicating multifactorial influences on liver injury after cardiopulmonary bypass (CPB). Methods: This observational single center study evaluated adult LC patients receiving open heart surgery with CPB during 2007 and 2017. The primary endpoint was post-operative hypoxic hepatitis (POHH), defined by post-operative serum glutamate oxaloacetate transaminase and glutamate pyruvate transaminase more than 10 times the pre-operative value. Results: In total, 61 patients were included in the study, of whom 14 (18.7%) developed POHH. Hospital mortality of non-POHH group (4.3%) was similar to that estimated using Euroscore II (4.0%), but that of the POHH group (21.4%) was 2.7 times as that estimated using Euroscore II (8.0%). Model for End-Stage Liver Disease (MELD) score and CPB duration were found as independent risk factors for POHH by multivariate logistic regression. POHH incidence was 0.0% if MELD 20 regardless of CPB duration. For those with MELD between 5 and 20, POHH incidence increases as CPB duration increases. Conclusion: For LC patients undergoing cardiac surgery with CPB, the incidence of POHH is highly associated with MELD score and CPB duration. To prevent POHH, the CPB duration should be shortened for those with MELD score between 5 and 20, and CPB be avoid for those with MELD >20. Keywords: Liver cirrhosis, Open heart surgery, Cardiopulmonary bypass, MELD score, Post-operative hypoxic hepatitis

Abstract Background Myostatin is a negative regulator of muscle growth but the relationship between serum myostatin levels and muscle mass is unclear. This study investigated the association between serum myostatin levels and skeletal muscle mass among healthy older community residents in Taiwan, to evaluate the potential of serum myostatin as a biomarker for diagnosing sarcopenia and/or evaluating the effect of its treatment. Methods Study data were excerpted from a random subsample of the I‐Lan Longitudinal Aging Study population. Serum myostatin levels were determined and categorized into tertiles (low, medium, high). Relative appendicular skeletal muscle mass (RASM) was calculated as appendicular lean body mass by dual‐energy X‐ray absorptiometry divided by height squared (kg/m2). Low muscle mass was defined as recommended by the Asian Working Group for Sarcopenia. Results The analytic study sample comprised 463 adults (mean age: 69.1 years; 49.5% men). Compared with subjects with normal RASM, those with lower RASM were older and frailer, with significantly higher prevalence of malnutrition, lower serum dehydroepiandrosterone (DHEA) levels, and were more likely to have low serum myostatin status. Multivariable logistic regression analysis showed that male sex (OR 3.60, 95% CI 1.30–9.92), malnutrition (OR 4.39, 95% CI 1.56–12.36), DHEA (OR 0.99, 95% CI 0.99–1.00), and low myostatin (OR 3.23, 95% CI 1.49–7.01) were all independent risk factors for low RASM (all P

Hydrogen/oxygen-generating biomaterials, a new trend in regenerative medicine, generate and supply hydrogen/oxygen to increase the local levels of hydrogen/oxygen to support tissue healing and regeneration. In this study, we carefully defined a strategic plan to develop a gas-permeable layer suitable for use in sanitary products that is capable of supplying hydrogen or oxygen in situ using calcium hydroxides as chemical oxygen sources. In vitro physicochemical evaluations of hydrogen- and oxygen-generation efficiency were performed to determine the amount of hydrogen and oxygen produced. An in vivo permeation study was conducted to assess biological parameters, including blood oxygen (O2) and hydrogen (H+) levels. The stress hormone corticosterone and inflammation marker interleukin 6 (IL-6) were also quantified. The hydrogen/oxygen-generating patch (HOGP) continuously generated H+ or O2 for up to 12 h after activation by water. An in vivo evaluation showed blood H+ peaked at 2 h after application of the HOGP and then progressively decreased until the end of study (24 h), whereas oxygen content (O2(ct)) and oxygen saturation (SO2(SAT)) continuously increased up to 6 h. Hematological and electrolyte parameters did not significantly change compared to baseline. Wearing the stretch fabric used to secure the patch did not significantly increase serum corticosterone or interleukin 6 (IL-6) in the animals. This novel design of a hydrogen/oxygen-generating biomaterial for supplying topical H+/O2 may hold potential for increasing in situ or circulating H+/O2 levels to improve healthcare outcomes.

The Top-pressure Recovery Turbine (TRT) uses the blast furnace gas generated in the iron and steel manufacturing process to push the turbine which drives the generator to generate electricity, and the generated electric energy is supplied to in-plant equipment. In this paper, we investigate the aerodynamic force, centrifugal force, and maximum stress on the structure of the TRT rotor in rated working conditions and the positions of occurrence using the Finite Element Method (FEM), as well as discuss the dynamic characteristics of bladed disks during TRT operation through Campbell and SAFE diagrams. To confirm the effectiveness of the finite element models, the mode shapes and natural frequencies in the FEA-based modal analysis of the TRT rotor will be captured and compared with those of the practical structures through the Experimented Modal Analysis (EMA). To verify the agreement between the mode shapes of the finite element analysis and those of the actual structure, the Modal Assurance Criterion (MAC) is introduced here to confirm the reliability of the finite element model. The stress distribution on the structure in the rotation is obtained by centrifugal force analysis. The TRT rotor is driven as the blast furnace top pressure pushes the moving blade; when the rotor rotates, the moving blade bears centrifugal and periodic aerodynamic forces. The stress distribution is investigated on the structure when these forces act simultaneously using aerodynamic analysis. To discuss whether the bladed disks will resonate with the external force under the operating conditions, Campbell and SAFE diagrams are used for evaluation, and the modal parameters obtained from the EMA are used to estimate the strength and durability of the blades. According to the analysis results when the TRT rotor is in working conditions, the fatigue failure may occur at the maximum stress existing on the dovetail slot.

Corrosion prevention and infrared (IR) stealth are conflicting goals. While graphene nanosheets (GN) provide an excellent physical barrier against corrosive agent diffusion, thus lowering the permeability of anti-corrosion coatings, they have the side-effect of decreasing IR stealth. In this work, the anti-corrosion properties of 100-μm-thick composite epoxy coatings with various concentrations (0.01–1 wt.%) of GN fillers thermally reduced at different temperatures (300 °C, 700 °C, 1100 °C) are first compared. The performance was characterized by potentiodynamic polarization scanning, electrochemical impedance spectroscopy, water contact angle and salt spray tests. The corrosion resistance for coatings was found to be optimum at a very low filler concentration (0.05 wt.%). The corrosion current density was 4.57 × 10−11 A/cm2 for GN reduced at 1100 °C, showing no degradation after 500 h of salt-spray testing: a significant improvement over the anti-corrosion behavior of epoxy coatings. Further, to suppress the high IR thermal signature of GN and epoxy, Al was added to the optimized composite at different concentrations. The increased IR emissivity due to GN was not only eliminated but was in fact reduced relative to the pure epoxy. These optimized coatings of Al-GN-epoxy not only exhibited greatly reduced IR emissivity but also showed no sign of corrosion after 500 h of salt spray test.

Abstract Dysmobility syndrome is a newly proposed concept to comprehensively consider bone-muscle-adiposity as a whole to associate with mortality and other adverse outcomes in the older adults. Little was known in Asian populations since the body composition was highly related to ethnicity. The study aimed to evaluate the association between dysmobility syndrome and mortality and to explore the most optimal operational definition for dysmobility syndrome. The prevalence of dysmobility syndrome was 3.9–10.1% based on different operational definitions of adiposity and skeletal muscle index. Subjects with dysmobility syndrome were older, more often to be women, having higher adiposity, lower lean body mass and bone mineral density. Multivariate Cox proportional hazard model showed that dysmobility and pre-dysmobility syndrome had higher risk of mortality than the robust group (Hazard ratio (HR): 11.3, 95% confidence interval (CI): 1.2–109.1; and HR 8.7, 95% CI 1.1-67.3, respectively). Overall, the modified operational definition of dysmobility syndrome in Asian populations using FNIH-adjusted skeletal muscle mass and waist circumference-defined adiposity may be the most optimal model for mortality prediction. Taking the nexus of body composition as a whole to evaluate the mortality risk of older adults is an important improvement beyond sarcopenia and osteoporosis.

Abstract The pathogenesis of melanomas emerging in plantar surfaces remains unclear; however, mechanical stress has been reported to increase the formation of melanomas. In this study, we conducted a multicenter retrospective analysis of 153 acral melanomas diagnosed between 2000 and 2015 in Taiwan. The male-to-female ratio of the patients in question was 1:1.28, and the mean age at diagnosis was 68 years. We examined whether melanomas which developed in different areas of the patients’ soles differed in their associations with various clinicopathological characteristics and survival. Testing by goodness of fit indicated that stress-bearing areas were significantly more conducive to the generation of melanomas than non-stress-bearing areas (P

The conventional eigensystem realization algorithm with data correlation (ERA/DC) combines the impulse response or free response data of a structural system with the concept of correlation function to identify the modal parameter of the structural system. Previous studies have shown that the modal parameters of structural systems subjected to stationary white noise excitation can be estimated by ERA/DC from the ambient response without excitation data. This concept is extended in this paper for output-only modal identification for the structural system with complex modes under ambient excitation as a nonstationary process in the form of a product model. Numerical simulations and experimental verification are used to validate the effectiveness of the proposed method for response-only modal estimation, and the stabilization diagram is used with modal assurance criterion (MAC) to distinguish structural modes from fictitious modes.

BRAF and NRAS mutations have been described in melanomas among Caucasians and some Asian populations. However, few large-scale studies have investigated the status and clinical significance of BRAF and NRAS mutations in a Taiwanese population. Methods: Melanoma samples (n = 119) were analyzed for mutations in exons 11 and 15 of the BRAF gene, and in exons 1 and 2 of the NRAS gene. The samples were studied in genomic DNA, using polymerase chain reaction amplification and Sanger sequencing. Mutations of the BRAF and NRAS genes were then correlated with clinicopathological features and patients' prognosis. Results: The incidence of somatic mutations within the BRAF and NRAS genes was 14.3% (17/119 patients) and 10.1% (12/119 patients), respectively. Among the 17 patients with BRAF mutations, 15 (88.2%) had V600E mutations. BRAF mutation was frequently detected in younger patients (p = 0.0035), in thin melanomas (p = 0.0181), and in melanomas with less ulceration (p = 0.0089). NRAS mutation was more often seen in patients with lymph node metastasis (p = 0.0332). Both BRAF and NRAS mutations were not significantly correlated with overall survival and disease-free survival. Conclusion: As BRAF and NRAS mutations are rare in Taiwan, BRAF- or NRAS-targeted therapies may be effective only for selected Taiwanese melanoma patients.

We demonstrate a facile and effective method, which is low-cost and easy to scale up, to fabricate holey graphene nanosheets (HGNSs) via ultrafast heating during synthesis. Various heating temperatures are used to modify the material properties of HGNSs. First, we use HGNSs as the electrode active materials for electric double-layer capacitors (EDLCs). A synthesis temperature of 900 °C seems to be optimal, i.e., the conductivity and adhesion of HGNSs reach a compromise. The gravimetric capacitance of this HGNS sample (namely HGNS-900) is 56 F·g−1. However, the volumetric capacitance is low, which hinders its practical application. Secondly, we incorporate activated carbon (AC) into HGNS-900 to make a composite EDLC material. The effect of the AC:HGNS-900 ratio on the capacitance, high-rate performance, and cycling stability are systematically investigated. With a proper amount of HGNS-900, both the electrode gravimetric and volumetric capacitances at high rate charging/discharging are clearly higher than those of plain AC electrodes. The AC/HGNS-900 composite is a promising electrode material for nonaqueous EDLC applications.

Studies surveying melanomas associated with melanocytic nevi in Asia are rare. In this study, we examined whether nevus-associated melanomas differ from de novo melanomas in terms of their associations with clinical factors, histologic characteristics, and patient survival in Taiwan. Using data on cancer cases obtained from the Department of Pathology archives and the Cancer Registry of National Taiwan University Hospital, we conducted a retrospective analysis of 103 consecutive melanoma patients who were diagnosed between 2010 and 2015 and received follow-up through November 2016. Approximately 17.5% of the melanomas in question were associated with a nevus. In patients under 65 years of age, non-acral lentiginous melanomas were significantly associated with a higher percentage of nevus-associated melanomas. The superficial spreading subtype, younger patient age, thinner tumor, intermittent solar exposure, and early stage were significant predictors of a melanoma being histologically associated with a nevus. The appearance of a nevus associated with a melanoma predicted better recurrence-free survival compared with de novo melanomas. Although acral lentiginous melanomas (70.9%) constituted the most common histologic subtype, only 9.6% of the acral lentiginous melanomas were associated with a nevus. Furthermore, there was no statistically significant difference between the nevus-associated and de novo acral lentiginous melanomas with regard to clinicopathological factors and survival. In conclusion, nevus-associated melanomas were uncommon among acral lentiginous melanomas. Relatedly, because over half of all melanomas in Asians are acral lentiginous melanomas, Asians are less likely than Caucasians to have nevus-associated melanomas.

This paper presents a forecasting method for product different size production method, which is for the customers and company has different size requirement on single product design, based on multi-attribute decision making (MADM). Because of the forecast product production factor is complicated, so that first step will filter out the evaluation criteria of wheelset design through practical experiences of focus group, seven professional product designers. After filter out, the evaluation criteria are including maneuverability, manufacturability, style, creativity, and cost. We proposed to use grey number design evaluation to solve forecast product production problem, to set weights for evaluation criteria, and to takes wheelset series of product design for example to verify the method. Grey number design evaluation mainly uses grey numbers to represent the ideas of customers and designers, and then uses Grey relational analysis to find out which factor is most needed by customers and forecast needs extra production among series of product design proposal. The prediction results assisted designer to choose the best alternative from single product proposals and serialized proposals.

Insulin-like growth factor-II mRNA-binding protein 3 (IMP-3) is an RNA-binding protein expressed in multiple cancers, including melanomas. However, the expression of IMP-3 has not been investigated in acral lentiginous melanoma (ALM). This study sought to elucidate its prognostic value in ALMs. IMP-3 expression was studied in 93 patients diagnosed with ALM via immunohistochemistry. Univariate and multivariate analyses for survival were performed, according to clinical and histologic parameters, using the Cox proportional hazard model. Survival curves were graphed using the Kaplan-Meier method. IMP-3 was over-expressed in 70 out of 93 tumors (75.3%). IMP-3 expression correlated with thick and high-stage tumor and predicted poorer overall, melanoma-specific, recurrence-free and distant metastasis-free survivals (P = 0.002, 0.006, 0.008 and 0.012, respectively). Further analysis showed that patients with tumor thickness ≤ 4.0 mm and positive IMP-3 expression had a significantly worse melanoma-specific survival than those without IMP-3 expression (P = 0.048). IMP-3 (hazard ratio 3.67, 95% confidence intervals 1.35-9.97, P = 0.011) was confirmed to be an independent prognostic factor for melanoma-specific survival in multivariate survival analysis. Positive IMP-3 expression was an important prognostic factor for ALMs.

A multicenter study (NCT00449670) conducted across Taiwan, Singapore, Hong Kong and Thailand evaluated the safety and manufacturing consistency of four formulations of an AS03A-adjuvanted H5N1 vaccine in terms of immune response against the vaccine-homologous strain (A/Vietnam/1194/2004). This manuscript presents data from the Taiwanese population. Methods: A total of 400 individuals, aged 18–60 years, were randomized into six groups (2:2:2:2:1:1 ratio) to receive two doses (21 days apart) of one of the four adjuvanted formulations (H5N1-AS03A-groups) or one of the two nonadjuvanted formulations (H5N1-DIL-groups). Blood samples collected before vaccination (Day 0) and 21 days after each vaccine dose were analyzed using hemagglutination inhibition (HI) assay. Adverse events were recorded. Results: All four AS03A-adjuvanted formulations induced comparable immune responses against the A/Vietnam/1194/2004 strain; following the second dose, immune response in terms of HI antibodies was higher in the H5N1-AS03A-groups {seroprotection rate=91.6% [95% confidence interval (CI): 87.9–94.4]; geometric mean titer (GMT)=177.6 (95% CI: 153.2–206.0)} compared with the H5N1-DIL-groups [seroprotection rates=5.0% (95% CI: 1.4–12.3); GMT=6.3 (95% CI: 5.4–7.4)]. Immune response against the heterologous A/Indonesia/05/2005 strain was also stronger in the H5N1-AS03A-groups [seroprotection rate=45.6% (95% CI: 40.0–51.4); GMT=20.5 (95% CI: 17.8–23.7)] compared with the H5N1-DIL groups [seroprotection rate=0.0% (95% CI: 0.0–4.5); GMT=5.0 (95% CI: 5.0–5.0)]. The overall reactogenicity profile of the adjuvanted formulations was clinically acceptable. Conclusion: The AS03A-adjuvanted H5N1 influenza vaccine formulations induced stronger immune response against the vaccine-homologous and heterologous strains than the nonadjuvanted formulations. The AS03A-adjuvanted H5N1 vaccine demonstrated a good immunogenicity and an acceptable safety profile in the Taiwanese population.

Association of frailty with adverse clinical outcomes has been reported in Western countries, but data from the Asian population are scarce. This study aimed to evaluate the epidemiology of frailty among community-dwelling middle-aged and elderly population and to explore its association with musculoskeletal health in Taiwan.I-Lan Longitudinal Aging Study (ILAS) data were retrieved for this study. Frailty was defined by the Fried's criteria; a comparison of demographic characteristics, physical performance, and body composition, including skeletal muscle mass and bone mineral density (BMD), as well as recent falls, history of hip fractures and the functional status of subjects with different frailty statuses were accomplished.Overall, the data of 1,839 participants (mean age: 63.9±9.3 years, male 47.5%) were obtained for analysis. The prevalence of pre-frailty was 42.3% in men and 38.8% in women, whereas the prevalence of frailty was 6.9% and 6.7% in men and women, respectively. Frailty was significantly associated with older age, the male gender, larger waist circumference, lower skeletal muscle index, lower hip BMD, poorer physical function, poorer nutritional status, and poorer cognitive function. Also, frailty was significantly associated with osteoporosis (OR: 7.73, 95% CI: 5.01-11.90, p

PURPOSE: PEGylated liposomes are important drug carriers that can passively target tumor by enhanced permeability and retention (EPR) effect in neoplasm lesions. This study demonstrated that tumor burden determines the tumor uptake, and also the tumor response, in cancer treatment with PEGylated liposomal drugs in a C26/tk-luc colon carcinoma-bearing mouse model. METHODS: Empty PEGylated liposomes (NanoX) and those encapsulated with VNB (NanoVNB) were labeled with In-111 to obtain InNanoX and InVNBL in high labeling yield and radiochemical purity (all >90%). BALB/c mice bearing either small (58.4±8.0 mm(3)) or large (102.4±22.0 mm(3)) C26/tk-luc tumors in the right dorsal flank were intravenously administered with NanoVNB, InNanoX, InVNBL, or NanoX as a control, every 7 days for 3 times. The therapeutic efficacy was evaluated by body weight loss, tumor growth inhibition (using calipers and bioluminescence imaging) and survival fraction. The scintigraphic imaging of tumor mouse was performed during and after treatment. RESULTS: The biodistribution study of InVNBL revealed a clear inverse correlation (r (2) = 0.9336) between the tumor uptake and the tumor mass ranged from 27.6 to 623.9 mg. All three liposomal drugs showed better therapeutic efficacy in small-tumor mice than in large-tumor mice. Tumor-bearing mice treated with InVNBL (a combination drug) showed the highest tumor growth inhibition rate and survival fraction compared to those treated with NanoVNB (chemodrug only) and InNanoX (radionuclide only). Specific tumor targeting and significantly increased tumor uptake after periodical treatment with InVNBL were evidenced by scintigraphic imaging, especially in mice bearing small tumors. CONCLUSION: The significant differences in the outcomes of cancer treatment and molecular imaging between animals bearing small and large tumors revealed that tumor burden is a critical and discriminative factor in cancer therapy using PEGylated liposomal drugs.