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Abstract The Ou Backbone Range in the Tohoku Region of Japan is bounded on its both sides by two major active fault systems: the Western Fault Zone of Kitakami Lowland in the east and the Eastern Fault Zone of Yokote Basin in the west. Although these two systems are primary active fault systems in the region, information on their long-term activity characteristics is still quite limited. Therefore, we analyzed the normalized channel steepness indexes of river valleys trending perpendicular to the range front along both flanks of the Ou Backbone Range. Our results show that the eastern flank has gentler river valleys, whereas rivers along the northwestern flank are steeper. Our field investigation shows that knickpoints in this area are mostly related to local lithologic boundaries or are check dams along the valleys, thus the river systems are likely under steady-state conditions. Hence, the steeper river valleys in northwestern Ou Backbone Range indicate a higher uplift rate of the area. Because both fault systems are primarily dip-slip reverse faults and do not have significant variations in their subsurface geometry, the faster uplift suggests that the northern segment of the Eastern Fault Zone of Yokote Basin has a higher slip rate. This is consistent with results of previous studies, and the fact that the rupture of the 1896 Rikuu earthquake, the only historical surface-rupturing event in this region, was only limited along the northern segment of this fault system.

The mosquito microbiota is a critical determinant of mosquito life history. It is therefore a target for novel vector control strategies like paratransgenesis. However, the microbiota in Anopheles funestus, a major African malaria vector, is poorly characterized. Thus, the study aimed to investigate the overall bacterial landscape in the salivary glands, ovaries and midguts of three laboratory strains of An. funestus differing in insecticide-resistant phenotype by sequencing the V3–V4 hypervariable region of bacterial 16S rRNA genes. When examining alpha diversity, the salivary glands harbored significantly more bacteria in terms of species richness and evenness compared to ovaries and midguts. On the strain level, the insecticide-susceptible FANG strain had significantly lower bacterial diversity than the insecticide-resistant FUMOZ and FUMOZ-R strains. When looking at beta diversity, the compositions of microbiota between the three tissues as well as between the strains were statistically different. While there were common bacteria across all three tissues and strains of interest, each tissue and strain did exhibit differentially abundant bacterial genera. However, overall, the top five most abundant genera across all tissues and strains were Elizabethkingia, Acinetobacter, Aeromonas, Cedecea and Yersinia. The presence of shared microbiota suggests a core microbiota that could be exploited for paratransgenesis efforts.

Abstract Because of the cancer incidence increase and population aging in Taiwan, we aimed to assess the cancer prevalence, to summarize the comorbidities of older patients with the five most common cancers (i.e., breast, colorectal, liver, lung, and oral), and to develop a Taiwan cancer comorbidity index (TCCI) for studying their actual prognosis. The linkage of the Taiwan Cancer Registry, Cause of Death Database, and National Health Insurance Research Database was used. We followed the standard statistical learning steps to obtain a survival model with good discriminatory accuracy in predicting death due to noncancer causes, from which we obtained the TCCI and defined comorbidity levels. We reported the actual prognosis by age, stage, and comorbidity level. In Taiwan, cancer prevalence nearly doubled in 2004–2014, and comorbidities were common among older patients. Stage was the major predictor of patients' actual prognoses. For localized and regional breast, colorectal, and oral cancers, comorbidities correlated with noncancer-related deaths. Compared with the US, the chances of dying from comorbidities in Taiwan were lower and the chances of dying from cancer were higher for breast, colorectal, and male lung cancers. These actual prognoses could help clinicians and patients in treatment decision-making and help policymakers in resource planning.

BackgroundPredicting physical function upon discharge among hospitalized older adults is important. This study has aimed to develop a prediction model of physical function upon discharge through use of a machine learning algorithm using electronic health records (EHRs) and comprehensive geriatrics assessments (CGAs) among hospitalized older adults in Taiwan.MethodsData was retrieved from the clinical database of a tertiary medical center in central Taiwan. Older adults admitted to the acute geriatric unit during the period from January 2012 to December 2018 were included for analysis, while those with missing data were excluded. From data of the EHRs and CGAs, a total of 52 clinical features were input for model building. We used 3 different machine learning algorithms, XGBoost, random forest and logistic regression.ResultsIn total, 1,755 older adults were included in final analysis, with a mean age of 80.68 years. For linear models on physical function upon discharge, the accuracy of prediction was 87% for XGBoost, 85% for random forest, and 32% for logistic regression. For classification models on physical function upon discharge, the accuracy for random forest, logistic regression and XGBoost were 94, 92 and 92%, respectively. The auROC reached 98% for XGBoost and random forest, while logistic regression had an auROC of 97%. The top 3 features of importance were activity of daily living (ADL) at baseline, ADL during admission, and mini nutritional status (MNA) during admission.ConclusionThe results showed that physical function upon discharge among hospitalized older adults can be predicted accurately during admission through use of a machine learning model with data taken from EHRs and CGAs.

Recent technological advancements led to the development of various plasma-based technologies for post-packaging modifications. The purpose of the present preclinical in vivo study was to assess the safety and efficacy of a novel chairside nonthermal gas plasma treatment for enhancing osseointegration of titanium implants. Six male mixed foxhounds underwent extraction of mandibular premolars and first molars, and the sockets healed for 42 days. Canine mandibles were randomized to receive either plasma-treated (test) or non-plasma-treated (control) dental implants. A total of 36 implants were placed in six animals, and they were sacrificed at 2 weeks (two animals), 4 weeks (two animals), and 6 weeks (two animals) after the implant surgery. When the radiographic analysis was performed, the changes in bone level were not statistically significant between the two groups at 2 weeks and 4 weeks. The difference became significant at 6 weeks (p = 0.016), indicating more bone loss from baseline to 6 weeks for the control group. The bone-to-implant contact (BIC) appeared to be higher for the test groups at all time points, and the BIC was significantly higher for the test group at 4 weeks (p = 0.046). In conclusion, this study underscored the potential of nonthermal plasma treatment in enhancing implant osseointegration.

Abstract Background This study aimed to collect data regarding patient perception and knowledge of dental implants. It was conducted with the hope that the data would provide dental professionals and policymakers with a better understanding of ways to promote implant therapy. Methods An anonymous online survey with 10 questions was distributed through 12 dental offices in Tokyo and provincial cities in Japan to assess patient perception and knowledge of dental implants. Harvard Medical School’s IRB approved this study. Results We collected data from 1172 patients (59% female, 41% male). The most common perceptions of implant therapy were that it was “expensive,” “advanced,” and “scary”. Patients’ implant knowledge came primarily from magazines or books, while professional dental societies/associations were the least sought out source of information. Patients believed that the purpose of dental implants was to avoid dentures and improve chewing function. Their primary concerns about dental implants were the cost and longevity. Approximately 12% of patients with dental implants and 61% of patients without implants did not know that bone grafts may be required and that sedation during surgery was an option. For patients who experienced sedation during the procedure, 60% of them want it for future surgeries. Patients also had limited knowledge of bone-graft materials and the effects of CBCT radiation; 75% of the patients expressed concerns over the safety of graft materials and radiation exposure. For patients with a history of dental implant therapy, 80% of them would recommend dental implants to their family and friends. Conclusions Overall, patients’ experiences with dental implant therapy were positive, but there was a lack of patient education regarding dental implants and their associated procedures. Dental professionals need to take the initiative to improve patient education.

This study aimed to assess the accuracy of a method of predicting post-movement root position during orthodontic treatment using a 3D digital crown/root model (3DCRM) created with pre-movement records of both cone-beam computed tomography (CBCT) and dental arch digital scans. Pre- and post-movement CBCT scans and dental arch digital scans of five patients who had completed orthodontic treatments were used in this study. The 3DCRM was superimposed onto the post-movement scanned dental arch to identify the post-movement root position (test method). Post-movement CBCT (referenced as the current method) served as the control to identify the actual post-movement root position. 3D-coordinate analysis revealed no significant differences between the test and current methods along the X and Y axes. However, the discrepancy on the Z axis (especially in cases of intrusion) was greater than that in all other directions for all three tooth types examined (p < 0.05). A strong positive correlation between the degree of discrepancy and the distance of tooth movement was observed on the Z axis (r = 0.71). The 3DCRM method showed promising potential to accurately predict root position during orthodontic treatments without the need for a second CBCT. However, root resorption, which affected the Z axis prediction, needs to be closely monitored using periapical radiographs to complement this method.

Objective(s): Protective effects of s-methyl cysteine (SMC) alone, protocatechuic acid (PCA) alone, and SMC plus PCA against chronic ethanol consumption induced hepatic steatosis and inflammation were investigated. Materials and Methods: Mice were divided into six groups: normal diet (ND) group, Lieber-DeCarli liquid diet without ethanol (LD diet) group, LD diet with ethanol (LED diet) group, SMC group (LED diet plus 0.25% SMC), PCA group (LED diet plus 0.25% PCA), and SMC+PCA group (LED diet plus 0.125% SMC + 0.125% PCA). After 8 weeks of supplementation, blood and liver were used for analysis. Results: Biochemical and histological data showed that SMC plus PCA led to a greater reduction in lipid droplets in the liver than SMC or PCA treatment alone. SMC plus PCA resulted in greater suppression in hepatic mRNA expression of peroxisome proliferator-activated receptor-gamma, sterol regulatory element-binding protein 1c, stearoyl-CoA desaturase-1, cyclooxygenase-2, and myeloperoxidase than SMC or PCA treatment alone. SMC plus PCA led to a greater decrease in hepatic reactive oxygen species and inflammatory cytokine levels than SMC or PCA treatment alone. Conclusion: These novel findings suggest that the combination of SMC and PCA was a potent remedy for alcoholic liver disorders.

Despite the global decline in the standardized mortality rate of multiple sclerosis (MS), recent research on MS patient survival, especially in Taiwan, remains limited. This study aimed to investigate survival, mortality causes, and associated factors among MS patients in Taiwan. The Taiwan National Health Insurance Research Database was used as the primary data source, and a Cox proportional hazard model was employed to estimate and analyze factors related to survival. We analyzed data from 1444 MS patients diagnosed between 2000 and 2018. Age at diagnosis was positively correlated with the risk of death. Among the 190 patients who died, the leading causes of disease-related deaths were nervous system diseases (n = 83, 43.68%), followed by respiratory system diseases and certain infectious and parasitic diseases. The 8-, 13-, and 18-year survival rates for MS patients were 0.97, 0.91, and 0.81, respectively. This study highlights that the MS patient’s socioeconomic status, environmental factors, comorbidity severity, and related medical variables were not significantly associated with survival.

Objective: Cervical cancer is the fourth most prevalent cancer in women worldwide. It is vital to achieve a high cervical cancer screening rate among women. We compared the Pap smear test (PST) used between individuals with disabilities and those without disabilities in Taiwan. Methods: Individuals registered in the Taiwan Disability Registration File and the National Health Insurance Research Database (NHIRD) were screened for this nationally representative retrospective cohort study. Women aged 30 and above in 2016 and who were still alive in 2016 were matched in a 1:1 ratio via propensity score matching (PSM); 186,717 individuals with disabilities and 186,717 individuals without disabilities were included. Controlling for relevant variables, the odds of receiving PST were compared using conditional logistic regression analysis. Results: A lower percentage of individuals with disabilities (16.93%) received PST than those without disabilities (21.82%). The odds of individuals with disabilities receiving PST were 0.74 times that of individuals without disabilities (OR = 0.74, 95% CI = 0.73–0.76). Compared to individuals without disabilities, individuals with intellectual and developmental disabilities had the lower odds of receiving PST (OR = 0.38, 95% CI = 0.36–0.40), followed by individuals with dementia (OR = 0.40, 95% CI = 0.33–0.48) or multiple disabilities (OR = 0.52, 95% CI = 0.49–0.54). Conclusions: We highly recommend that healthcare practitioners recognize the unique needs of individuals with different types of disabilities, especially those with cognitive impairments.

Hsien-Ya Lin, Chia-Yu Chen, Ting-Chien Lin and colleagues perform structure-guided modifications of the compound uronic isofagomaine in order to engineer a highly specific and potent inhibitor of gut bacterial β-glucuronidases (GUSs). The authors present eight crystal structures and demonstrate in vivo efficacy of the optimised C6-alkyl derivative inhibitor in mice models. This study may enhance the development of inhibitors of microbial GUS for use in colorectal cancer therapy to minimize the undesired side effects of irinotecan treatment.

Nutritional modification including fasting has been shown to reduce cardiometabolic risk linked to western diet. Here the authors show implementation of fasting resulted in alterations to the intestinal microbiota, and circulating immune cells, improving blood pressure and body weight in patients with metabolic syndrome.

Abstract The aim of this study was to evaluate the biological efficacy of a unique perpendicular protrusion of type-I collagen (Col-I) from TiO2 nanotubes (NT-EPF surface). We hypothesized that the NT-EPF surface would play bifunctional roles in stimulating platelet-mediated fibroblast recruitment and anchoring fibroblast-derived Col-I to form a perpendicular collagen assembly, mimicking the connective tissue attachment around natural teeth for the long-term maintenance of dental implants. Ti surface modification was accomplished in two steps. First, TiO2 nanotubes (NT) array was fabricated via anodization. Diameters and depths of NTs were controlled by applied voltage and duration. Subsequently, an electrophoretic fusion (EPF) method was applied to fuse Col-I into nanotube arrays in a perpendicular fashion. Surface wettability was assessed by contact angle measurement. The bioactivity of modified TiO2 surfaces was evaluated in terms of NIH3T3 fibroblast attachment, platelet activation, and collagen extension. Early attachment, aggregation, and activation of platelets as well as release of platelet-related growth factors were demonstrated on NT-EPF surfaces. Platelet-mediated NIH3T3 cells migration toward NT-EPF was significantly increased and the attached cells showed a typical fibrous morphology with elongated spindle shape. A direct linkage between pseudopod-like processes of fibroblasts to NT-EPF surfaces was observed. Furthermore, the engineered EPF collagen protrusion linked with cell-derived collagen in a perpendicular fashion. Within the limitation of this in vitro study, the TiO2 nanotube with perpendicular Col-I surface (NT-EPF) promoted better cell attachment, induced a strong platelet activation which suggested the ability to create a more robust soft tissue seal.

Abstract Acinetobacter baumannii is a prevalent pathogen that can rapidly acquire resistance to antibiotics. Indeed, multidrug-resistant A. baumannii is a major cause of hospital-acquired infections and has been recognised by the World Health Organization as one of the most threatening bacteria to our society. Resistance-nodulation-division (RND) type multidrug efflux pumps have been demonstrated to convey antibiotic resistance to a wide range of pathogens and are the primary resistance mechanism employed by A. baumannii. A component of an RND pump in A. baumannii, AdeT1, was previously demonstrated to enhance the antimicrobial resistance of Escherichia coli. Here, we report the results of experiments which demonstrate that wild-type AdeT1 does not confer antimicrobial resistance in E. coli, highlighting the importance of verifying protein production when determining minimum inhibitory concentrations (MICs) especially by broth dilution. Nevertheless, using an agar-based MIC assay, we found that propionylation of Lys280 on AdeT1 renders E. coli cells more resistant to erythromycin.

There has been an increase in utilizing 3D printers in dental restorations. The purpose of the study is to compare mechanical properties of 3D-printed prostheses to those of self-cured and/or computer-aided design-computer-aided manufacturing (CAD-CAM) restorations. A metal master typodont was prepared for the mandibular left sextant with implant analogs embedded at the first premolar and first molar positions with a missing second premolar. Three-unit provisional fixed dental prosthesis (FDP) was designed utilizing the 3Shape tooth library and forty-five uniform specimens were fabricated with different materials: self-cured poly(methyl methacrylate) (PMMA) (N = 15), milled PMMA CAD-CAM blocks (N = 15) and 3D-printed resin (N = 15). All specimens were tested using an Instron machine at a crosshead speed of 0.5 mm/min by an axial load on the occlusal surface of the second premolar pontic site. Statistical analysis was completed with Shapiro-Wilk, ANOVA and Tukey post-hoc tests. Mean fracture force was 300.61 N, 294.64 N and 408.49 N for self-cured PMMA, milled PMMA and 3D-printed resin, respectively. Mean force at FDP fracture of 3D-printed resin was significantly greater than the mean fracture force of either self-cured (p = 0.016, 95% CI [17.86, 197.91]) or milled (p = 0.010, 95% CI [23.83, 203.88]) PMMA.

Endozoicomonas, a core bacterial group in corals, may also be a coral symbiont. Endozoicomonas communities often decrease rapidly in corals under heat stress. However, how the bacteria respond to changes in temperature and coral host during heat stress is unknown. Here, we employed the cultivable, dominant species E. montiporae as a working organism to explore how Endozoicomonas responds to heat stress. We designed two experiments to clarify the extent to which E. montiporae is influenced by temperature and coral host. We detected differentially expressed protein (DEP) profiles in this bacterium at 31 and 33°C compared to 25°C by tandem mass tags-based quantitative proteome analysis. Fifty DEPs, including many heat shock proteins, were detected when the temperature changed. The expression of antioxidant defense proteins and key pyruvate synthase proteins decreased, suggesting that E. montiporae were in a physiology of stress at 33°C. Furthermore, some proteins were differentially expressed because of the heat-stress-treated coral lysate specifically, suggesting that not only heat but also heat-induced host factors can affect the protein expression of the bacterium. This study provides an in-depth analysis of how the molecular mechanisms of Endozoicomonas are affected by heat stress and coral host.

Evaluating several vital signs and chest X-ray (CXR) reports regularly to determine the recovery of the pneumonia patients at general wards is a challenge for doctors. A recent study shows the identification of pneumonia by the history of symptoms and signs including vital signs, CXR, and other clinical parameters, but they lack predicting the recovery status after starting treatment. The goal of this paper is to provide a pneumonia status prediction system for the early affected patient’s discharge from the hospital within 7 days or late discharge more than 7 days. This paper aims to design a multimodal data analysis for pneumonia status prediction using deep learning classification (MDA-PSP). We have developed a system that takes an input of vital signs and CXR images of the affected patient with pneumonia from admission day 1 to day 3. The deep learning then classifies the health status improvement or deterioration for predicting the possible discharge state. Therefore, the scope is to provide a highly accurate prediction of the pneumonia recovery on the 7th day after 3-day treatment by the SHAP (SHapley Additive exPlanation), imputation, adaptive imputation-based preprocessing of the vital signs, and CXR image feature extraction using deep learning based on dense layers-batch normalization (BN) with class weights for the first 7 days’ general ward patient in MDA-PSP. A total of 3972 patients with pneumonia were enrolled by de-identification with an adult age of 71 mean ± 17 sd and 64% of them were male. After analyzing the data behavior, appropriate improvement measures are taken by data preprocessing and feature vectorization algorithm. The deep learning method of Dense-BN with SHAP features has an accuracy of 0.77 for vital signs, 0.92 for CXR, and 0.75 for the combined model with class weights. The MDA-PSP hybrid method-based experiments are proven to demonstrate higher prediction accuracy of 0.75 for pneumonia patient status. Henceforth, the hybrid methods of machine and deep learning for pneumonia patient discharge are concluded to be a better approach.

Soft tissue sealing around zirconia (ZrO2) abutment is critical for the long-term stability of dental implants. The goal of the study is to develop a strong basal lamina (BL)-mediated epithelial attachment to ZrO2 via a novel physicochemical immobilization method. An electrophoretic fusion (EPF) method was applied to fuse a phosphonic acid (PA) linker to ZrO2 discs. Bindings of the PA linker and the following protease activated receptor 4 (PAR4) were verified by Fourier-transform infrared spectroscopy (FITR). Then, ZrO2 discs were doped in platelet-rich plasma (PRP). Platelet-derived growth factor (PDGF) was measured to assess platelet activation. PRP-doped discs were subsequently co-cultured with human gingival epithelial cells (OBA9) to evaluate establishment of basal lamina-mediated epithelial attachment. The EPF method achieved robust immobilization of the PA linker and PAR4 onto the ZrO2 surface. The resultant PAR4-coupled ZrO2 successfully induced platelet aggregation and activation. Furthermore, a BL-mediated epithelial attachment was established. The results are significant for clinical application to minimize the risk of developing peri-implant diseases.

Abstract Natural teeth are supported by connective tissue collagen fibers that insert perpendicularly in the tooth cementum. Perpendicular insertion plays an important role in the maintenance of the junction between the oral epithelium and the periodontal connective tissue. Most titanium dental implant surfaces have no micro or macro structure to support perpendicularly oriented collagen attachment. Without this tight biologic seal to resist bacterial invasion and epithelial downgrowth, progressive bone loss in peri-implantitis is seen around dental implants. The purpose of this study was to establish the perpendicularly oriented collagen attachment to titanium oxide nanotube (TNT), and to assess its binding stability. TNT was prepared on the titanium-surface by anodization. Scanning electron microscopy (SEM) showed a regularly aligned TNT with an average 67 nm-diameter when anodized at 30 V for 3 h. Subsequently, collagen type I (CoI) was electrophoretically fused to anodic TNT in native polyacrylamide gel system where negatively charged CoI-C term was perpendicularly navigated to TNT. SEM and atomic force microscopy (AFM) were used to analyze CoI on the TiO2 and TNT surface. Several tens of nanometers of CoI protrusion were recorded by AFM. These protrusions may be long enough to be priming sites for cell-secreted CoI. CoI laid parallel to the titanium surface when fused by a chemical linker. Binding resistance of CoI against drastic ultrasonication was measured by Fourier-transform infrared spectroscopy attenuated total reflection (FTIR-ATR). The electrophoretically fused CoI in the titanium nanotube (TNT–CoIEPF) showed the significantly greatest binding resistance than the other groups (P

(1) Background: The tongue plays a key role in the stomatognathic system in carrying out oral functions. The aim of this study was to identify the association between tongue pressure and orthodontic parameters. (2) Methods: This study is a cross-sectional multicentered cohort study with IRB approval. During routine orthodontic initial examinations, the following data were recorded: age, sex, angle classification, overjet (OJ), overbite (OB), arch sizes, tongue width, and maximum tongue pressure (MTP). The association between MTP and orthodontic parameters was analyzed using Pearson’s correlation analysis and the Student’s t-test. (3) Results: There is a positive correlation between MTP and age between ages 10 and 20 (R = 0.47, p < 0.01). There is a negative correlation with MTP and age between 20 and 40 (R = −0.30, p < 0.05). There are negative correlations between MTP and OJ (R = −0.278, p < 0.01)) and OB (R = −0.374, p < 0.01). While there is no statistical significance between MTP and tongue width, there is a statistically significant difference between age and tongue width (R = 0.22482, p < 0.05). There is no statistical significance between MTP and sex, angle classification, arch length, intercanine width, and intermolar width. (4) Conclusion: An earlier decline in MTP is observed with patients with malocclusion. This implies that patients with malocclusion should seek early treatment for the malocclusion.

High salt intake ranks among the most important risk factors for noncommunicable diseases. Western diets, which are typically high in salt, are associated with a high prevalence of obesity. High salt is thought to be a potential risk factor for obesity independent of energy intake, although the underlying mechanisms are insufficiently understood. A high salt diet could influence energy expenditure (EE), specifically diet-induced thermogenesis (DIT), which accounts for about 10% of total EE. We aimed to investigate the influence of high salt on DIT. In a randomized, double-blind, placebo-controlled, parallel-group study, 40 healthy subjects received either 6 g/d salt (NaCl) or placebo in capsules over 2 weeks. Before and after the intervention, resting EE, DIT, body composition, food intake, 24 h urine analysis, and blood pressure were obtained. EE was measured by indirect calorimetry after a 12 h overnight fast and a standardized 440 kcal meal. Thirty-eight subjects completed the study. Salt intake from foods was 6 g/d in both groups, resulting in a total salt intake of 12 g/d in the salt group and 6 g/d in the placebo group. Urine sodium increased by 2.29 g/d (p < 0.0001) in the salt group, indicating overall compliance. The change in DIT differed significantly between groups (placebo vs. salt, p = 0.023). DIT decreased by 1.3% in the salt group (p = 0.048), but increased by 0.6% in the placebo group (NS). Substrate oxidation indicated by respiratory exchange ratio, body composition, resting blood pressure, fluid intake, hydration, and urine volume did not change significantly in either group. A moderate short-term increase in salt intake decreased DIT after a standardized meal. This effect could at least partially contribute to the observed weight gain in populations consuming a Western diet high in salt.

BackgroundIn pancreatic cancer, toxicities associated with current chemotherapeutic regimens remain concerning. A modified combination of gemcitabine, S-1, and leucovorin (GSL) was used as the first-line treatment for newly diagnosed locally advanced or metastatic pancreatic adenocarcinoma patients.MethodsGSL was administered every 2 weeks-intravenous gemcitabine 800 mg/m2 at a fixed-dose rate of 10 mg/m2/min on day 1 and oral S-1 (80-120 mg/day) plus leucovorin 30 mg twice daily on days 1-7. We retrospectively analyzed the feasibility of GSL and patient outcomes in three medical centers in Taiwan.ResultsOverall, 49 patients received GSL with a median follow-up of 24.9 months from May 2015 to March 2019. The median patient age was 68 years (range, 47-83 years), with a marginally higher number of females (57.1%). Among the 44 patients who underwent image evaluation, 13 demonstrated a partial response (29.5%) and 17 presented with stable disease (38.6%). The partial response rate and stable disease rate was 26.5% and 34.7%, respectively, in the intent-to-treat analysis. The median time-to-treatment failure was 5.79 months (95% C.I., 2.63-8.94), progression-free survival was 6.94 months (95% C.I., 5.55-8.33), and overall survival time was 11.53 months (95% C.I., 9.94-13.13). For GSL treatment, the most common grade 3 or worse toxicities were anemia (18.3%), neutropenia (6.1%), nausea (4.1%), and mucositis (4.1%). Treatment discontinuation was mostly due to disease progression (65.3%).ConclusionsThe modified GSL therapy can be a promising and affordable treatment for patients with advanced and metastatic pancreatic cancer in Taiwan. A prospective trial of modified GSL for elderly patients is currently ongoing in Taiwan.

Background: Antinuclear antibody pattern recognition is vital for autoimmune disease diagnosis but labor-intensive for manual interpretation. To develop an automated pattern recognition system, we established machine learning models based on the International Consensus on Antinuclear Antibody Patterns (ICAP) at a competent level, mixed patterns recognition, and evaluated their consistency with human reading. Methods: 51,694 human epithelial cells (HEp-2) cell images with patterns assigned by experienced medical technologists collected in a medical center were used to train six machine learning algorithms and were compared by their performance. Next, we choose the best performing model to test the consistency with five experienced readers and two beginners. Results: The mean F1 score in each classification of the best performing model was 0.86 evaluated by Testing Data 1. For the inter-observer agreement test on Testing Data 2, the average agreement was 0.849 (κ) among five experienced readers, 0.844 between the best performing model and experienced readers, 0.528 between experienced readers and beginners. The results indicate that the proposed model outperformed beginners and achieved an excellent agreement with experienced readers. Conclusions: This study demonstrated that the developed model could reach an excellent agreement with experienced human readers using machine learning methods.

STEAP1 (six transmembrane epithelial antigen of the prostate 1) is a transmembrane protein that functions as a potential channel or transporter protein. It is overexpressed in certain cancers and is viewed as a promising therapeutic target. However, the prognostic role of STEAP1 is still controversial, and no role for STEAP1 has yet been indicated in colorectal cancer. The aim of this study was to investigate the possible association of STEAP1 expression with colorectal cancer prognosis. STEAP1 expression was analyzed by immunohistochemical staining of a tissue array of 165 cancer specimens from primary colorectal cancer patients. The mean and medium follow-up times after surgery were 5.1 and 3.9 years, respectively. A total of 139 patients died during the 13 years of follow-up in the survey period. The prognostic value of STEAP1 with respect to overall survival was analyzed by Kaplan-Meier analysis and Cox proportional hazard models. In total, 164 samples displayed detectable STEAP1 expression in the cytoplasm and membrane. Low STEAP1 expression was correlated with poor overall survival (five-year survival: 33.7% vs. 57.0%, low expression vs. high expression, p = 0.020). Accordingly, multivariate analysis identified low STEAP1 expression as an independent risk factor (hazard ratio = 1.500, p = 0.018), especially in elderly patients or those with late stage cancers, late T values, and early N values. We suggest that analysis of STEAP1 expression by immunohistochemical staining could serve as an independent prognostic marker for colorectal patients. This finding should be validated by other investigative groups.

Human placental multipotent mesenchymal stromal cells (hPMSCs) can be isolated from term placenta, but their angiogenic ability and the regulatory pathways involved are not known. hPMSCs were shown to express integrins alpha(v), alpha(4), alpha(5), beta(1), beta(3), and beta(5) and could be induced to differentiate into cells expressing endothelial markers. Increases in cell surface integrins alpha(5) and beta(1), but not alpha(4), alpha(v)beta(3), or alpha(v)beta(5), accompanied endothelial differentiation. Vascular endothelial growth factor-A augmented the effect of fibronectin in enhancing adhesion and migration of differentiated hPMSC through integrin alpha(5)beta(1), but not alpha(v)beta(3) or alpha(v)beta(5). Formation of capillary-like structures in vitro from differentiated cells was inhibited by pre-treatment with function-blocking antibodies to integrins alpha(5) and beta(1). When hPMSCs were seeded onto chick chorioallantoic membranes (CAM), human von Willebrand factor-positive cells were observed to engraft in the chick endothelium. CAMs transplanted with differentiated hPMSCs had a greater number of vessels containing human cells and more incorporated cells per vessel compared to CAMs transplanted with undifferentiated hPMSCs, and overall angiogenesis was enhanced more by the differentiated cells. Function-blocking antibodies to integrins alpha(5) and beta(1) inhibited angiogenesis in the CAM assay. These results suggest that differentiated hPMSCs may contribute to blood vessel formation, and this activity depends on integrin alpha(5)beta(1).

The Longitudinal Valley in Eastern Taiwan sits at the collision suture between the Eurasian and Philippine Sea plates. Based on repeated GPS campaigned measurements from 25 stations six times in 2007 - 2009, we characterize the surface deformation in the northernmost Longitudinal Valley where the Coastal Range of the Philippine Sea plate turns northward diving under the Eurasian plate producing two major active faults: the Milun fault and the Longitudinal Valley fault. We reconstructed a GPS velocity field and conducted strain analyses and elastic block modeling. Our results suggest a rapid clockwise rotation of 33° Myr-1 and an eastward tectonic escape in the small Hualien City block (HUAL) area of ~10 × 10 km, which is apparently detached from the regional rotating RYUK block defined by previous studies. We interpret it as being initiated locally by the northwest indentation of the Coastal Range, which pushed the HUAL block to move upward and eastward. According to our strain analyses, the HUAL block shows a significant internal elastic strain inside the Milun Tableland, the hanging wall of the Milun fault. No significant deformation was observed across the surface trace of the fault, indicating that the Milun fault is now probably locked in the near surface. The deformation in the footwall of the fault was accommodated by pure-shear strain with a major NNW-compression and a minor ENE-extension. The deformation in the hanging wall is characterized by simple-shear strain with ENE-extension in its northern part and little deformation in the southern part, separated by a little known NW-trending active fault zone (Dongmingyi fault), which needs further investigation.