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Purpose To clarify and investigate the prevalence and clinical impact of hepatitis D virus (HDV) infection in Taiwan’s communities. Methods HDV infection in patients with chronic hepatitis B viral (HBV) infection was examined using an anti-HDV antibody in Yonghe Cardinal Tien Hospital (YCTH), a district hospital in Taiwan. Clinical characteristics of anti-HDV-positive and anti-HDV-negative patients were collected and compared. These characteristics were also compared with the data collected from a medical center. Continuous variables and confounding factor adjustments were compared using the analysis of covariance method, whereas categorical variables were compared using the logistic regression method. Results A total of 346 patients with chronic HBV infection were assessed from 2018 to 2019. Among them, 4 (1.15%) were positive for anti-HDV. The clinical, virological, and biochemical characteristics were similar between anti-HDV-positive and anti-HDV-negative groups. None of the four patients was positive for serum HDV RNA. Another 18 anti-HDV-positive patients were identified from National Taiwan University Hospital (NTUH). The clinical, virological, and biochemical characteristics of anti-HDV-positive patients from YCTH and NTUH were also similar. Conclusion The prevalence of HDV and the serum HDV RNA-positive rate were low in district hospitals in Taiwan. Coexisting HDV infection did not influence the clinical manifestation of patients with chronic HBV infection in Taiwan. However, because the number of HDV RNA cases was very small, our findings may not be conclusive. Besides, since the sensitivity of current anti-HDV kit is not 100%, more sensitive methods are needed to achieve reliable prevalence data.

Sonogenetics is a promising strategy allowing the noninvasive and selective activation of targeted neurons in deep brain regions; nevertheless, its therapeutic outcome for neurodegeneration diseases that need long-term treatment remains to be verified. We previously enhanced the ultrasound (US) sensitivity of targeted cells by genetic modification with an engineered auditory-sensing protein, mPrestin (N7T, N308S). In this study, we expressed mPrestin in the dopaminergic neurons of the substantia nigra in Parkinson's disease (PD) mice and used 0.5 MHz US for repeated and localized brain stimulation. The mPrestin expression in dopaminergic neurons persisted for at least 56 days after a single shot of adeno-associated virus, suggesting that the period of expression was long enough for US treatment in mice. Compared to untreated mice, US stimulation ameliorated the dopaminergic neurodegeneration 10-fold and mitigated the PD symptoms of the mice 4-fold, suggesting that this sonogenetic strategy has the clinical potential to treat neurodegenerative diseases.

Objective To identify predictor microRNAs (miRNAs) from patients with repeated implantation failure (RIF). Design Systemic analysis of miRNA profiles from the endometrium of patients undergoing in vitro fertilization (IVF). Setting University research institute, private IVF center, and molecular testing laboratory. Patient(s) Twenty five infertile patients in the discovery cohort and 11 patients in the validation cohort. Interventions(s) None. Main Outcome Measure(s) A signature set of miRNA associated with the risk of RIF. Result(s) We designed a reproductive disease-related PanelChip to access endometrium miRNA profiles in patients undergoing IVF. Three major miRNA signatures, including hsa-miR-20b-5p, hsa-miR-155-5p, and hsa-miR-718, were identified using infinite combination signature search algorithm analysis from 25 patients in the discovery cohort undergoing IVF. These miRNAs were used as biomarkers in the validation cohort of 11 patients. Finally, the 3-miRNA signature was capable of predicting patients with RIF with an accuracy >90%. Conclusion(s) Our findings indicated that specific endometrial miRNAs can be applied as diagnostic biomarkers to predict RIF. Such information will definitely help to increase the success rate of implantation practice.

Hemangioblastomas (HBs) are uncommon tumors that occur as sporadic lesions or multiple lesions associated with von Hippel–Lindau (VHL) disease. We report a case of a 77-year-old male with an unusual clinical presentation of HB mimicking meningioma, involving the left anterior temporal fossa, skull, infratemporal fossa, and orbit, and compressing the lateral rectus muscle and optic nerve causing exophthalmos, without a diagnosis of VHL-related HB.

Background: Autophagy has been suggested to be involved in the pathogenesis of protists. While the molecular mechanisms of autophagy are mainly studied in model organisms, functional characterization of autophagy-related (Atg) proteins is poorly understood in deep-branching protists. Trichomoniasis is the most common nonviral sexually transmitted infection caused by Trichomonas vaginalis. Bioinformatics analysis of the T. vaginalis genome reveals that the parasite possesses the genes encoding proteins of the Atg8 conjugation system. Herein, we sought to characterize whether the T. vaginalis Atg3 ortholog (TVAG_447140), a putative component of the TvAtg8 conjugation system, regulates autophagy in this parasite. Methods: The recombinant protein of T. vaginalis Atg3 ortholog (TvAtg3) (rTvAtg3) and the polyclonal antibody against rTvAtg3 were generated. The expression and localization was monitored upon autophagy induction by glucose restriction (GR) compared with glucose-rich cultivation. The role of TvAtg3 in autophagy was clarified using small interfering RNA targeting TvAtg3 gene. Results: Phylogenic analysis of Atg3 proteins from different organisms showed that T. vaginalis was not in a close evolutionary relationship with any other protozoan. The expression of TvAtg3 was upregulated in the late-stationary phase of GR culture, implying its involvement in autophagy. Immunofluorescence analysis revealed a much higher TvAtg3 fluorescent intensity located on the round and/or linear structures close to the nucleus. Silencing Tvatg3 expression suppressed GR-induced TvAtg8 expression and autophagic vacuoles formation. Conclusions: These findings suggest the potential role of TvAtg3 in T. vaginalis autophagy and enhance our understanding of the autophagy regulatory network in the deep-branching eukaryotes.

Objectives: This study investigates whether self-reported nutritional status affects falling among middle-aged and older adults. Method: We used 8-year follow-up data from the Taiwan Longitudinal Study on Aging. At baseline, respondents’ appetite, changes in amount of food intake, and eating difficulties were assessed in a questionnaire-based survey in addition to anthropometric measurements (body mass index, mid-arm circumferences, and involuntary body weight loss). Their associations with falls in the follow-up were examined using multivariable log-binomial regression. Results: The study included 2,519 respondents aged 50 years and older. Poor appetite (prevalence ratio [PR] = 1.25, 95% confidence interval [CI] = [1.07, 1.46]) and eating difficulties (PR = 1.16, 95% CI = [1.02, 1.32]) significantly predicted falling 8 years later with adjustments for sociodemographics, health behaviors, comorbidities, and anthropometric measures by taking into account probabilities of follow-up. Conclusion: Poor appetite and eating difficulties can predict falling in the long-term independent of anthropometric measurements among middle-aged and older adults.

Background A country’s spending on healthcare significantly improves its population health status. No comparative study has examined how the threat perceived by leaders influences health expenditure and cross-national analyses of authoritarian regimes. The objectives of this study are to examine how time horizons of autocrats influence health expenditure. Methods We designed a mixed methods research approach. First, the study used panel data from 1995 to 2010 covering 95 countries (n = 1208) and applied fixed effects regression models. As a proxy for time horizons, the study generated the predicted survival time for each regime-year using parametric survival analysis and the predictors to model regime failure. Second, we chose Chad, Rwanda and Ivory Coast to apply synthetic control methods for comparative case studies. Armed conflict had significant effects on regime duration and was used for an intervention. We constructed a synthetic version of each country, combining counties that did not or did experience armed conflict to resemble the values of health expenditure predictors for the actual country prior to the intervention. Results We found that an increase in the natural log form of survival time by 1 resulted in a 1.14 percentage point increase in health expenditure (% of GDP) (1.14, 95% CI = 0.60–1.69). Furthermore, we found that the difference in health expenditure between the actual Chad and its synthetic version starts to grow following the civil war in 2004 (in 2004, actual: 5.72%, synthetic: 5.91%; in 2005, actual: 3.91%, synthetic: 6.74%). Similarly, a large health expenditure gap between the actual Rwanda and its synthetic control resulted after the peace deal was signed in 2002 (in 2002, actual: 4.18%, synthetic: 4.77%; in 2003, actual: 6.34%, synthetic: 5.03%). In Ivory Coast, the two series diverge substantially during the civil war from 1999 to 2005 (in 1998, actual: 7.30%, synthetic: 7.11%; in 2002, actual: 4.47%, synthetic: 7.43%; in 2007, actual: 6.35%, synthetic: 6.50%). Conclusions The findings suggest that health expenditure decreases as regime time horizons shrink, and reducing armed conflict is a way to promote regime stability.

The Taiwan Adverse Drug Reaction Reporting System for Herbal Medicine (TADRRS-HM) has systematically documented suspected adverse events from adverse drug reaction (ADR) reports from 1998 (prior to its formal establishment in 2001) and evaluates safety profiles of herbal medicines. This article describes findings from 2079 ADR reports filed between 1998 and 2016: 941 reports involved single herbs and 87 involved folk herbals; 842 were generated from clinical trials, while 209 ADR reports involving foods, health foods, dietary supplement foods and herbal cuisine were grouped as Other. Severity assessments using the Modified Hartwig and Siegel scale classified 72.4% of ADRs as mild, 17.4% as moderate and 6.5% as severe. System Organ Class classification of the ADRs identified gastrointestinal system disorders as the most common (33.4%), followed by skin and subcutaneous tissue disorders (21.2%). The TADRRS-HM records indicate that herbal medicines may cause a wide range of ADRs. Aconiti Radix, Xiao-Qing-Long-Tang, and Datura suaveolens were the most commonly reported single herb, herbal formula, and folk herbal, respectively. The data indicate that herbal medicines may cause a wide range of ADRs. This system will confer long-term benefits for the development of Taiwan’s herbal medicines adverse reaction database and facilitate epidemiological analysis.

Background The study aimed to investigate the association between socioeconomic status and severity of oral epithelial dysplasia (OED) using current data from the Taiwanese Nationwide Oral Mucosal Screening Program (TNOMSP). Methods This retrospective analysis was conducted in the Department of Oral and Maxillofacial Surgery at a general hospital in Taipei, Taiwan. A total of 134 participants were analysed from a previous study database of 150 patients. The inclusion criteria included age > 20 years and a history of either tobacco or betel nut use. Background information, including para-habits such as betel and tobacco use, was analysed using the Pearson chi-square (χ2) test; furthermore, the correlation of background information with OED severity was investigated using logistic regression (mild or moderate/severe). Results High school education level (P P = 0.002), current betel use (P P = 0.003) were highly correlated with moderate- and severe OED (P P ), while that of junior high school was 1. Current betel chewing (OR 6.57 [95% CI 1.17–37.0], P = 0.033) was significantly associated with OED severity compared with never or ex-use of betel. Conclusions We found a strong correlation between the severity of OED and current betel use and low education status. The current study revealed that the socioeconomic status, poor self-awareness, and para-habit history of the patients with OED should be evaluated to identify high-risk individuals using TNOMSP.

Objective: Heat stroke (HS) elicits the systemic inflammatory responses that result in multiple organ dysfunction (MOD). Heat shock response and autophagy are activated during heat stress for removal of damaged organelles and proteins, emerging as a major regulator of cellular homeostasis. Ethyl pyruvate (EP) is a derivative of pyruvic acid and possesses antioxidant and anti-inflammatory effects. This study aims to investigate the effects of EP on MOD in HS rats and explore the possible mechanisms. Method: Anesthetized rats were placed in a heating chamber (42 °C) to elevate the core body temperature attaining to 42.9 °C. Rats were then moved to room temperature and monitored for 6 h. EP (60 mg/kg, i.v.) was administered 30 min prior to heat exposure. Results: Results showed that EP significantly reduced HS-induced increases in plasma levels of LDH, CPK, GPT and CK-MB, reversed the decrease of platelet counts, and alleviated intestinal mucosal and pulmonary damage. Moreover, EP reduced pro-inflammatory protein, including TNF-α, IL-6, IL-1β, HMGB1 and iNOS, and induced stress proteins, heme oxygenase-1 (HO-1), heat shock protein (HSP) 70 and HSP90 in the liver of HS rats. The levels of HS-activated autophagy-regulatory proteins were affected by EP, in which the phosphorylated mTOR and AKT were reduced, and the phosphorylated AMPK increased, accompanied with upregulation in ULK1, Atg7, Atg12 and LC3II, and downregulation of p62. Conclusion: In conclusion, EP ameliorated HS-induced inflammatory responses and MOD, and the underlying mechanism is associated with the induction of the stress proteins HO-1 and HSP70 as well as restorage of autophagy.

Pancreatic cancer (PC) is the seventh leading cause of cancer death worldwide, and remains one of our most recalcitrant and dismal diseases. In contrast to many other malignancies, there has not been a significant improvement in patient survival over the past decade. Despite advances in our understanding of the genetic alterations associated with this disease, an incomplete understanding of the underlying biology and lack of suitable animal models have hampered efforts to develop more effective therapies. LKB1 is a tumor suppressor that functions as a primary upstream kinase of adenine monophosphate-activated protein kinase (AMPK), which is an important mediator in the regulation of cell growth and epithelial polarity pathways. LKB1 is mutated in a significant number of Peutz–Jeghers syndrome (PJS) patients and in a small proportion of sporadic cancers, including PC, however, little is known about how LKB1 loss contributes to PC development. Here, we report that a reduction in Wnt/β-catenin activity is associated with LKB1 tumor-suppressive properties in PC. Remarkably, in vivo functional analyses of β-catenin in the Pdx-1-Cre LKB1L/L β-cateninL/L mouse model compared to LKB1 loss-driven cystadenoma demonstrate that the loss of β-catenin impairs cystadenoma development in the pancreas of Pdx-1Cre LKB1L/L mice and dramatically restores the normal development and functions of the pancreas. This study further determined the in vivo and in vitro therapeutic efficacy of the β-catenin inhibitor FH535 in suppressing LKB1 loss-driven cystadenoma and reducing PC progression that delineates the potential roles of Wnt/β-catenin signaling in PC harboring LKB1 deficiency.

Background and aim Several strategies have been proposed to increase the eradication rate of Helicobacter pylori. However, the widespread increasing resistance rates to current multiple-dose oral antibiotic therapies call for alternative therapeutic approaches. We aim to develop a novel intraluminal therapy for H. pylori infection (ILTHPI). Methods From April 2017 to December 2017, 100 H. pylori-infected treatment-naive patients with upper abdominal pain or discomfort underwent endoscopic examinations and concomitant ILTHPI, which comprised the control of intragastric pH, the irrigation of gastric mucosal surface with a mucolytic agent, and the application of single-dose medicaments containing antibiotic powders. The safety profiles while conducting ILTHPI and adverse events after ILTHPI were evaluated. The success of eradication was assessed based on the result of the 13 C-urea breath test 6 weeks after ILTHPI. In addition, a patient with successful ILTHPI was reconfirmed by a negative H. pylori stool antigen test four to 6 months after ILTHPI to exclude short-term recurrence. Results All the 100 enrolled patients completed the ILTHPI with good safety profiles and mild adverse events (6%). Five patients dropped out, and 51 of 95 patients (53.7%) achieved successful eradication immediately after endoscopic examinations. All 51 patients revealed negative stool H. pylori antigen tests four to 6 months after successful ILTHPI. No short-term recurrence was observed. Conclusions We have developed a novel therapeutic approach. With the ILTHPI, H. pylori can be eradicated immediately by administrating a single-dose regimen while conducting an endoscopic examination. Clinical trials number NCT03124420.

Autofluorescence imaging is gaining popularity as an adjunctive test for oral potentially malignant disorders (OPMD). This study evaluated the efficacy of autofluorescence imaging based on the current standard oral mucosal disorder checklist in Taiwan. In total, 126 patients suspected to have mucosal disorders at the Division of Oral and Maxillofacial Surgery, Tri-Service General Hospital, Taipei, Taiwan, were enrolled. Following a conventional oral examination by using the oral mucosal disorder checklist and an autofluorescence imaging examination, all participants underwent histopathological examination to access epithelial dysplasia. Among 126 patients, 68 patients were diagnosis as having an OPMD and 63 having epithelial dysplasia. Autofluorescence imaging exhibited a sensitivity, specificity, positivity predictive value (PPV), negative predictive value (NPV), and accuracy of 77.94%, 35.42%, 63.10%, 53.13%, and 60.34%, respectively, for OPMD and of 88.89%, 43.86%, 63.64%, 78.13%, and 67.50%, respectively, for epithelial dysplasia. After the exclusion of 48 non-OPMD cases according to the checklist, the sensitivity, specificity, PPV, NPV, and accuracy of autofluorescence imaging became 87.50%, 72.73%, 94.23%, 53.33%, and 85.07%, respectively, for epithelial dysplasia. The efficacy of epithelial dysplasia identification and OPMD risk assessment can be increased after the exclusion of the non-OPMD cases through autofluorescence imaging. Autofluorescence imaging is a useful adjunct that can assist specialists in assessing OPMD patients prone to dysplasia without compromising patient care.

Precise risk stratification in lymphadenectomy is important for patients with endometrial cancer (EC), to balance the therapeutic benefit against the operation-related morbidity and mortality. We aimed to investigate added values of computer-aided segmentation and machine learning based on clinical parameters and diffusion-weighted imaging radiomics for predicting lymph node (LN) metastasis in EC. This prospective observational study included 236 women with EC (mean age ± standard deviation, 51.2 ± 11.6 years) who underwent magnetic resonance (MR) imaging before surgery during July 2010–July 2018, randomly split into training (n = 165) and test sets (n = 71). A decision-tree model was constructed based on mean apparent diffusion coefficient (ADC) value of the tumor (cutoff, 1.1 × 10−3 mm2/s), skewness of the relative ADC value (cutoff, 1.2), short-axis diameter of LN (cutoff, 1.7 mm) and skewness ADC value of the LN (cutoff, 7.2 × 10−2), as well as tumor grade (1 vs. 2 and 3), and clinical tumor size (cutoff, 20 mm). The sensitivity and specificity of the model were 94% and 80% for the training set and 86%, 78% for the independent testing set, respectively. The areas under the receiver operating characteristics curve (AUCs) of the decision-tree was 0.85—significantly higher than the mean ADC model (AUC = 0.54) and LN short-axis diameter criteria (AUC = 0.62) (both p &lt, 0.0001). We concluded that a combination of clinical and MR radiomics generates a prediction model for LN metastasis in EC, with diagnostic performance surpassing the conventional ADC and size criteria.

BACKGROUND This study assessed the safety of adalimumab in different dosages and durations of treatment. METHODS We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to explore the infection risk in people who received adalimumab. We searched the Cochrane Library, PubMed, and EMBASE from inception to December 8, 2020. Summary estimates were obtained using meta-analysis with a random-effects model. RESULTS Twenty-one RCTs, considered to be of high quality, were analyzed. We found that there was a risk of infection (RR: 1.10, 95% CI: 1.02-1.18). In the stratified analysis, we found an increase in infection among those that received normal dosage (RR: 1.13, 95% CI: 1.04-1.23), and in patients with psoriasis (RR: 1.13, 95% CI: 1.00-1.35) and rheumatoid arthritis (RR: 1.23, 95% CI: 1.06-1.41), but not in those that received high doses and other criteria. In the meta-regressions, intervention duration was not related to changes in incidence risk. CONCLUSIONS Trials that have a longer treatment duration and higher doses are needed to clarify whether patients that received adalimumab had an elevated risk of general infection.

Obesity and its associated conditions, such as type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD), are a particular worldwide health problem at present. Momordica cochinchinensis (MC) is consumed widely in Southeast Asia. However, whether it has functional effects on fat-induced metabolic syndrome remains unclear. This study was conducted to examine the prevention effect of Momordica cochinchinensis aril (MCA) on obesity, non-alcoholic fatty liver and insulin resistance in mice. MCA protected the mice against high-fat diet (HFD)-induced body weight gain, hyperlipidemia and hyperglycemia, compared with mice that were not treated. MCA inhibited the expansion of adipose tissue and adipocyte hypertrophy. In addition, the insulin sensitivity-associated index that evaluates insulin function was also significantly restored. MCA also regulated the secretion of adipokines in HFD-induced obese mice. Moreover, hepatic fat accumulation and liver damage were reduced, which suggested that fatty liver was prevented by MCA. Furthermore, MCA supplementation suppressed hepatic lipid accumulation by activation of the AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-alpha (PPAR-alpha) signaling pathway in the human fatty liver HuS-E/2 cell model. Our data indicate that MCA altered the microbial contents of the gut and modulated microbial dysbiosis in the host, and consequently is involved in the prevention of HFD-induced adiposity, insulin resistance and non-alcoholic fatty liver disease.

Introduction: White matter degeneration may contribute to clinical symptoms of parkinsonism.Objective: We used fixel-based analysis (FBA) to compare the extent and patterns of white matter degeneration in different parkinsonian syndromes—including idiopathic Parkinson's disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP).Methods: This is a retrospective interpretation of prospectively acquired data of patients recruited in previous studies during 2008 and 2019. Diffusion-weighted images were acquired on a 3-Tesla scanner (diffusion weighting b = 1000 s/mm2–applied along either 64 or 30 non-collinear directions) from 53 patients with PD (men/women: 29/24; mean age: 65.06 ± 5.51 years), 47 with MSA (men/women: 20/27; mean age: 63.00 ± 7.19 years), and 50 with PSP men/women: 20/30; mean age: 65.96 ± 3.14 years). Non-parametric permutation tests were used to detect intergroup differences in fixel-related indices—including fiber density, fiber cross-section, and their combination.Results: Patterns of white matter degeneration were significantly different between PD and atypical parkinsonisms (MSA and PSP). Compared with patients with PD, those with MSA and PSP showed a more extensive white matter involvement—noticeably descending tracts from primary motor cortex to corona radiata and cerebral peduncle. Lesions of corpus callosum were specific to PSP and absent in both MSA and PD.Discussion: FBA identified specific patterns of white matter changes in MSA and PSP patients compared to PD. Our results proved the utility of FBA in evaluation of implied biological processes of white matter changes in parkinsonism. Our study set the stage for future applications of this technique in patients with parkinsonian syndromes.

PurposeTo elucidate the usefulness of intravoxel incoherent motion (IVIM)/apparent diffusion coefficient (ADC) parameters in preoperative risk stratification using International Society of Urological Pathology (ISUP) grades.Materials and MethodsForty-five prostate cancer (PCa) patients undergoing radical prostatectomy (RP) after prostate multiparametric magnetic resonance imaging (mpMRI) were included. The ISUP grades were categorized into low-risk (I-II) and high-risk (III-V) groups, and the concordance between the preoperative and postoperative grades was analyzed. The largest region of interest (ROI) of the dominant tumor on each IVIM/ADC image was delineated to obtain its histogram values (i.e., minimum, mean, and kurtosis) of diffusivity (D), pseudodiffusivity (D*), perfusion fraction (PF), and ADC. Multivariable logistic regression analysis of the IVIM/ADC parameters without and with preoperative ISUP grades were performed to identify predictors for the postoperative high-risk group.ResultsThirty-two (71.1%) of 45 patients had concordant preoperative and postoperative ISUP grades. Dmean, D*kurtosis, PFkurtosis, ADCmin, and ADCmean were significantly associated with the postoperative ISUP risk group (all p < 0.05). Dmean and D*kurtosis (model I, both p < 0.05) could predict the postoperative ISUP high-risk group with an area under the curve (AUC) of 0.842 and a 95% confidence interval (CI) of 0.726–0.958. The addition of D*kurtosis to the preoperative ISUP grade (model II) may enhance prediction performance, with an AUC of 0.907 (95% CI 0.822–0.992).ConclusionsThe postoperative ISUP risk group could be predicted by Dmean and D*kurtosis from mpMRI, especially D*kurtosis. Obtaining the biexponential IVIM parameters is important for better risk stratification for PCa.

Ultrasound is acoustic waves that can penetrate deeply into tissue in a focused manner with limited adverse effects on cells. As such, ultrasound has been widely used for clinical diagnosis for several decades. Ultrasound induces bioeffects in tissues, providing potential value in therapeutic applications. However, the intrinsic millimeter scale of the ultrasound focal zone represents a challenge with respect to minimizing the illuminated regions to perturb target cells in a precise manner. To control a specific cell population or even single cells, sonogenetic tools that combine ultrasound and genetic methods have been recently developed. With these approaches, several ultrasound-responsive proteins are heterologously introduced into target cells, which enhances the cells' ability to respond to ultrasound stimulation. With optimization of the ultrasound parameters, these tools can specifically manipulate activities in genetically defined cells but not in unmodified cells present in the ultrasound-illuminated regions. These approaches provide new strategies for noninvasive modulation of target cells in various therapeutic applications.

Endometrial carcinoma (EC) is the most common gynecological cancer. However, there is currently no routinely used biomarker for differential diagnosis of malignant and premalignant endometrial lesions. Ten-eleven translocation (TET) proteins, especially TET1, were found to play a significant role in DNA demethylation, via conversion of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC). TET1, 5-mC, and 5-hmC expression profiles in endometrial carcinogenesis are currently unclear. We conducted a hospital-based retrospective review of the immunohistochemical expression of TET1, 5-mC, and 5-hmC in 181 endometrial samples. A “high” TET1 and 5-hmC expression score was observed in all cases of normal endometrium (100.0% and 100.0%, respectively) and in most samples of endometrial hyperplasia without atypia (90.9% and 78.8%, respectively) and atypical hyperplasia (90.6% and 93.8%, respectively), but a “high” score was found in only less than half of the EC samples (48.8% and 46.5%, respectively). The TET1 and 5-hmC expression scores were significantly higher in normal endometrium and premalignant endometrial lesions than in ECs (p < 0.001). A “high” 5-mC expression score was observed more frequently for ECs (81.4%) than for normal endometrium (40.0%), endometrial hyperplasia without atypia (51.5%), and atypical hyperplasia (53.1%) (p < 0.001). We also found that TET1 mRNA expression was lower in ECs compared to normal tissues (p = 0.0037). TET1 immunohistochemistry (IHC) scores were highly proportional to the TET1 mRNA levels and we summarize that the TET1 IHC scoring can be used for biomarker determinations. Most importantly, a higher TET1 score in EC cases was associated with a good overall survival (OS) rate, with a hazard ratio (HR) of 0.31 for death (95% confidence interval: 0.11–0.84). Our findings suggest that TET1, 5-mC, and 5-hmC expression is a potential histopathology biomarker for the differential diagnosis of malignant and premalignant endometrial lesions. TET1 is also a potential prognostic marker for EC.

Background: Due to the lack of an evidence-based consensus, managing refractory myofascial pain syndrome is challenging for clinicians. Dextrose injection (dextrose prolotherapy) emerged as a promising, cost-effective treatment. This study evaluated the efficacy of targeted ultrasound-guided dextrose injection for localized myofascial pain syndrome. Methods: We retrospectively reviewed the clinical outcomes of 45 patients with myofascial pain syndrome refractory to alternative treatments with targeted ultrasound-guided dextrose injection. Pretreatment symptom severity and symptomatic response 1 month after treatment were statistically analyzed using a visual analog scale (VAS)-based scoring system. Results: Of 45 patients, 8 (24.4%) reported complete resolution of symptoms at the treated site. In total, 36 (80.0%) patients reported greater than 50% improvement in their symptoms. The mean pretreatment and posttreatment VAS scores were 7.0 and 2.44 (p < 0.001), indicating an overall 65.0% reduction in symptom severity. Conclusion: Targeted ultrasound-guided dextrose injection was remarkably effective for refractory localized myofascial pain syndrome, significantly reducing symptom intensities in the majority of treated patients within 1 month after a single injection.

As cloud gaming and Virtual Reality (VR) games become popular in the game industry, game developers engage in these fields to boost their sales. Because cloud gaming possesses the merit of lifting computation loads from client devices to servers, it solves the high resource consumption issue of VR games on regular clients. However, it is important to know where is the bottleneck of the cloud VR gaming platform and how can it be improved in the future. In this paper, we conduct extensive experiments on the state-of-the-art cloud VR gaming platform--Air Light VR (ALVR). In particular, we analyze the performance of ALVR using both Quality-of-Service and Quality-of-Experience metrics. Our experiments reveal that latency (up to 90 ms RTT) has less influence on user experience compared to bandwidth limitation (as small as 35 Mbps) and packet loss rate (as high as 8%) . Moreover, we find that VR gamers can hardly notice the difference between the gaming experience with different latency values (between 0 and 90 ms RTT). Such findings shed some lights on how to further improve the cloud VR gaming platform, e.g., a budget of up to 90 ms RTT may be used to absorb network dynamics when bandwidth is insufficient.

In this information-based era, online shopping has become prevalent. A well-designed webpage interface (visual appeal) could promote consumers’ emotions (pleasure and arousal), thus stimulating their impulse buying. However, existing researches regarding online impulse buying are mainly focused on the influence of website attribute stimulation on impulse buying, without probing into consumers’ post-purchase cognitive dissonance (product dissonance and emotional dissonance), and their return intention. Therefore, this study aims to integrate external websites stimuli (visual appeal), emotional responses (pleasure and arousal), and consumers’ impulse buying tendencies, in order to explore the effect on impulse buying and the subsequent effect of post-purchase behavior (post-purchase dissonance and return intention). An online survey was conducted on 428 participants who had purchased apparel products online, in order to empirically examine the proposed research model. Partial Least Squares (PLS) was employed to analyze the research model. The results show that (1) pleasure directly and positively influences consumers’ impulse buying, whereas arousal indirectly influences consumers’ impulse buying through pleasure, (2) impulse buying directly and positively influences consumers’ product dissonance, whereas impulse buying indirectly influences consumers’ emotional dissonance through product dissonance, (3) consumers’ emotional dissonance directly and positively influences consumers’ return intention, whereas product dissonance indirectly influences consumers’ return intention through emotional dissonance.

Chronic obstructive pulmonary disease (COPD) is an inflammatory disease that is associated with increased risk of lung cancer. Pseudomonas aeruginosa (PA) infections are frequent in patients with COPD, which increase lung inflammation and acute exacerbations. However, the influences of PA-induced inflammation on lung tumorigenesis and the efficacy of immune checkpoint blockade remain unknown. In this study, we initiated a murine model of lung cancer by treating FVB/NJ female mice with tobacco carcinogen nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) alone or in combination with PA-lipopolysaccharide (LPS). LPS-mediated chronic inflammation induced T-cell exhaustion, increased the programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) axis, and enhanced NNK-induced lung tumorigenesis through an immunosuppressive microenvironment characterized by accumulation of myeloid-derived suppressive cells (MDSC) and regulatory T cells. Anti–PD-1 antibody treatment reduced tumors in NNK/LPS-treated mice with a 10-week LPS treatment but failed to inhibit tumor growth when LPS exposure was prolonged to 16 weeks. Anti-Ly6G antibody treatment coupled with depletion of MDSC alone reduced tumor growth; when combined with anti–PD-1 antibody, this treatment further enhanced antitumor activity in 16-week NNK/LPS-treated mice. Immune gene signatures from a human lung cancer dataset of PD-1 blockade were identified, which predicted treatment responses and survival outcome and overlapped with those from the mouse model. This study demonstrated that LPS-mediated chronic inflammation creates a favorable immunosuppressive microenvironment for tumor progression and correlates with the efficacy of anti–PD-1 treatment in mice. Immune gene signatures overlap with human and mouse lung tumors, providing potentially predictive markers for patients undergoing immunotherapy. Significance: This study identifies an immune gene signature that predicts treatment responses and survival in patients with tobacco carcinogen–induced lung cancer receiving immune checkpoint blockade therapy.

Pancreatic cancer (PC) is a highly lethal malignancy due to the cancer routinely being diagnosed late and having a limited response to chemotherapy. Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic malignant tumor, representing more than 85% of all pancreatic cancers. In the present study, we characterized the phenotypes of concomitant P53 and APC mutations in pancreatic neoplasms driven by the oncogene KRAS in genetically modified mice (GEMM). In this GEMM setting, APC haploinsufficiency coupled with P53 deletion and KRASG12D activation resulted in an earlier appearance of pancreatic intraepithelial neoplasia (PanIN) lesions and progressed rapidly to highly invasive and metastatic PDAC. Through a microarray analysis of murine PDAC cells derived from our APC-deficient PDAC model, we observed that APC loss leads to upregulated CD34 expression in PDAC. CD34 is a member of a family of single-pass transmembrane proteins and is selectively expressed in hematopoietic progenitor cells, vascular endothelial cells, interstitial precursor cells, and various interstitial tumor cells. However, the functional roles of CD34 in pancreatic cancer remain unclear. Thus, in this study, we explored the mechanisms regarding how CD34 promotes the deterioration of pancreatic malignancy. Our results demonstrated that the increased expression of CD34 induced by APC inactivation promotes the invasion and migration of PDAC cells, which may relate to PDAC metastasis in vivo. Collectively, our study provides first-line evidence to delineate the association between CD34 and the APC/Wnt pathway in PDAC, and reveals the potential roles of CD34 in PDAC progression.

Increasing occlusal vertical dimension (OVD) is often indicated in complex prosthodontic rehabilitations to gain restorative space and improve the occlusal relationship and esthetics. The effect of increasing occlusal vertical dimension on lower facial height (distance from subnasale to soft-tissue menton) and perceived facial esthetics is not well understood.The purpose of this clinical study was to investigate the effect of incremental increases in the occlusal vertical dimension on lower facial height and perceived facial esthetics by using a digital approach.Twenty-five participants with Class I jaw relationship and no loss of OVD participated in the study. Custom mandibular devices were digitally designed and 3-dimensionally printed to increase the OVD by 3, 6, and 9 mm in each participant. Three-dimensional facial scans and frontal photographs were made with the participants wearing a specific device to achieve the desired OVD increase. The lower facial height, total facial height (distance between nasion to soft-tissue menton), nasolabial angle, lip width, and lip height were digitally measured on facial scans. All measurements were recorded in a computer-aided design (CAD) software program and were repeated 3 times. Subsequently, frontal photographs of 10 participants were randomly selected for survey. Three groups each of 10 prosthodontists, general dentists, or laypersons participated in the survey and were asked to detect OVD difference in 2 photographs of the same participant and to rank facial esthetics at varying OVDs. One-way repeated measures ANOVA (α=.05) for the facial measurements and descriptive statistics for the survey results were used.Lower facial height, the ratio of lower facial height to total facial height, lip height, and nasolabial angle increased with an OVD increase, whereas lip width decreased (P.001). Bonferroni corrected paired t tests revealed all groups of OVD increase to be significantly different from each other (P.001) except for an OVD increase to 6 mm versus 9 mm in lip height (P=.540) and lip width (P=.019), respectively. Prosthodontists, general dentists, and laypersons could detect a +3 mm OVD increase 63.9%, 62.5%, and 56.5% of the time, respectively. The participants' original OVD was considered the most esthetic (60.0%, 45.0%, and 68.0%) by prosthodontists, general dentists, and laypersons, respectively.Increased OVD increases lower facial height, the ratio of lower facial height to total facial height, lip height, and nasolabial angle but decreases lip width. Prosthodontists are more sensitive to a smaller increase in OVD, closely followed by general dentists and then laypersons. In case of no loss of OVD, a vertical increase as small as 3 mm can be detected by both dentists and the general public and perceived as less esthetic. The larger the increase in OVD, the more detectable the difference and the less the faces are perceived as esthetic.

Aim This study aimed to explore the association between socioeconomic status and urinary incontinence (UI). Methods We used data from the three waves of the Taiwan Longitudinal Study on Aging. This study included 2458 women and 2866 men aged ≥50 years. We used logistic random effects models to examine the associations of interest, adjusting for demographics, health-related behaviors, disability, number of health conditions and prostate problems for men and numbers of children for women. Results In adjusted analysis, women with secondary education least frequently reported UI compared with women with no formal education (adjusted odds ratio [AOR] 0.41, 95% confidence interval [95% CI] 0.22-0.79). Those with severe economic hardships (vs those with no economic hardships) had an increased risk of UI among men and women (AOR 2.71, 95% CI 1.72-4.25 and AOR 1.94, 95% CI 1.31-2.88, respectively). Compared with men doing mentally demanding jobs, service workers/salesperson and retired men were more prone to UI (AOR 2.67, 95% CI 1.14-6.36 and AOR 2.41, 95% CI 1.19-4.87, respectively). Further analysis showed that the associations of economic hardship with UI were attenuated when adjusting for access to healthcare. Conclusion No formal education in women and severe economic hardship in both the sexes were associated with an increased risk of UI among middle-aged and older persons. The disparities should be taken into account in interventions for prevention, treatment and management of UI. Geriatr Gerontol Int 2021; 21: 245-253.

Quantitative maps from cardiac MRI provide objective information for myocardial tissue. The study aimed to report the T1 and T2∗ relaxation time and its relationship with clinical parameters in healthy Taiwanese participants.Ninety-three participants were enrolled between 2014 and 2016 (Males/Females: 43/50; age: 49.7 ± 11.3/49.9 ± 10.3). T1 and T2∗ weighted images were obtained by MOLLI recovery and 3D fully flow compensated gradient echo sequences with a 3T MR scanner, respectively. The T1 map of the myocardium was parcellated into 16 partitions from the American Heart Association. The septal part of basal, mid-cavity, and apical view was selected for the T2∗ map. The difference of quantitative map by sex and age groups were evaluated by Student's TTEST and ANOVA, respectively. The relationship between T1, T2∗ map, and clinical parameters, such as ejection fraction, pulse rate, and blood pressures, were evaluated with partial correlation by controlling BMI and age.Male participants decreased T1 relaxation time in partitions which located in the mid-cavity and apical before 55 years old compared with females (Male/Female: 1143.1.4 ± 72.0-1191.1 ± 37.0/1180.1 ± 54.5-1326.1 ± 113.3 msec, p 0.01). For female participants, T1 relaxation time was correlated negatively with systolic pressure (p 0.01) and pulse rate (p 0.01) before 45 years old. Besides, T1 and T2∗ relaxation time were positively and negatively correlated with ejection fraction and pulse rate after 45 years old in male participants, respectively. Decreased T2∗ relaxation time could be noticed in participants after 45 years old compared with youngers (26.0 ± 6.5/21.9 ± 8.0 msec; 25.2 ± 5.0/21.6 ± 7.2 msec, p 0.05).Reference T1 and T2∗ relaxation time from cardiac MRI in healthy Taiwanese participants were provided with sex and age-dependent manners. The relationship between clinical parameters and T1 or T2∗ relaxation time was also established and could be further investigated for its potential application in healthy/sub-healthy participants.

Robust early prediction of clinical outcomes in Parkinson&rsquo, s disease (PD) is paramount for implementing appropriate management interventions. We propose a method that uses the baseline MRI, measuring diffusion parameters from multiple parcellated brain regions, to predict the 2-year clinical outcome in Parkinson&rsquo, s disease. Diffusion tensor imaging was obtained from 82 patients (males/females = 45/37, mean age: 60.9 &plusmn, 7.3 years, baseline and after 23.7 &plusmn, 0.7 months) using a 3T MR scanner, which was normalized and parcellated according to the Automated Anatomical Labelling template. All patients were diagnosed with probable Parkinson&rsquo, s disease by the National Institute of Neurological Disorders and Stroke criteria. Clinical outcome was graded using disease severity (Unified Parkinson&rsquo, s Disease Rating Scale and Modified Hoehn and Yahr staging), drug administration (levodopa equivalent daily dose), and quality of life (39-item PD Questionnaire). Selection and regularization of diffusion parameters, the mean diffusivity and fractional anisotropy, were performed using least absolute shrinkage and selection operator (LASSO) between baseline diffusion index and clinical outcome over 2 years. Identified features were entered into a stepwise multivariate regression model, followed by a leave-one-out/5-fold cross validation and additional blind validation using an independent dataset. The predicted Unified Parkinson&rsquo, s Disease Rating Scale for each individual was consistent with the observed values at blind validation (adjusted R2 0.76) by using 13 features, such as mean diffusivity in lingual, nodule lobule of cerebellum vermis and fractional anisotropy in rolandic operculum, and quadrangular lobule of cerebellum. We conclude that baseline diffusion MRI is potentially capable of predicting 2-year clinical outcomes in patients with Parkinson&rsquo, s disease on an individual basis.

Background: This prospective study was designed to investigate whether myocardial triglyceride (TG) content from proton magnetic resonance spectroscopy (MRS) and left ventricular (LV) function parameters from cardiovascular magnetic resonance imaging (CMR) can serve as imaging biomarkers in predicting future major cardiovascular adverse events (MACE) and readmission in patients who had been hospitalized for acute heart failure (HF). Methods: Patients who were discharged after hospitalization for acute HF were prospectively enrolled. On a 3.0 T MR scanner, myocardial TG contents were measured using MRS, and LV parameters (function and mass) were evaluated using cine. The occurrence of MACE and the HF-related readmission served as the endpoints. Independent predictors were identified using univariate and multivariable Cox proportional hazard regression analyses. Results: A total of 133 patients (mean age, 52.4 years) were enrolled. The mean duration of follow-up in surviving patients was 775 days. Baseline LV functional parameters&mdash, including ejection fraction, LV end-diastolic volume, LV end-diastolic volume index (LVEDVI), and LV end-systolic volume (p &lt, 0.0001 for all), and myocardial mass (p = 0.010)&mdash, were significantly associated with MACE. Multivariable analysis revealed that LVEDVI was the independent predictor for MACE, while myocardial mass was the independent predictor for 3- and 12-month readmission. Myocardial TG content (lipid resonances &delta, 1.6 ppm) was significantly associated with readmission in patients with ischemic heart disease. Conclusions: LVEDVI and myocardial mass are potential imaging biomarkers that independently predict MACE and readmission, respectively, in patients discharged after hospitalization for acute HF. Myocardial TG predicts readmission in patients with a history of ischemic heart disease.

Employee perceptions of performance appraisal processes have received considerable attention in the public management literature, but the views of supervisors who actually conduct the appraisals have received relatively little consideration. This article addresses that gap in the literature by examining supervisors’ perceptions of individual employee performance appraisal in the U.S. federal service in an attempt to identify structural and operational problems associated with that system as viewed by those responsible for making it work. Data are drawn from a Merit Systems Protection Board (MSPB), Merit Principles Survey, which contained a section asking supervisors to evaluate nine potential problems associated with performance appraisal. Responses indicated that inflated ratings, flawed standards, and a lack of support were the most problematic aspects of the appraisal process. An agency’s use of performance-based rewards, a supervisor’s belief that his or her own performance is assessed objectively, and supervisor age are consistent predictors of supervisors’ perceptions.

Progressive supranuclear palsy (PSP) is characterized by a rapid and progressive clinical course. A timely and objective image-based evaluation of disease severity before standard clinical assessments might increase the diagnostic confidence of the neurologist. We sought to investigate whether features from diffusion tensor imaging of the entire brain with a machine learning algorithm, rather than a few pathogenically involved regions, may predict the clinical severity of PSP. Fifty-three patients who met the diagnostic criteria for probable PSP were subjected to diffusion tensor imaging. Of them, 15 underwent follow-up imaging. Clinical severity was assessed by the neurological examinations. Mean diffusivity and fractional anisotropy maps were spatially co-registered, normalized, and parcellated into 246 brain regions from the human Brainnetome atlas. The predictors of clinical severity from a stepwise linear regression model were determined after feature reduction by the least absolute shrinkage and selection operator. Performance estimates were obtained using bootstrapping, cross-validation, and through application of the model in the patients who underwent repeated imaging. The algorithm confidently predicts the clinical severity of PSP at the individual level (adjusted R2: 0.739 and 0.892, p &lt, 0.001). The machine learning algorithm for selection of diffusion tensor imaging-based features is accurate in predicting motor subscale of unified Parkinson&rsquo, s disease rating scale and postural instability and gait disturbance of PSP.

Background There has been much speculation about social environments causing an epidemic of depression. The objectives of this study are to examine how media freedom influences prevalence of depressive disorders. A direct effect of free media is great levels of information complexity causing poor mental health. Two indirect effects are that media freedom facilitates modernization, which is associated with competition-related stress, and government investment in social protection, which impedes the person’s ability to manage stress. Methods The study used a cross-sectional analysis on determinants of prevalence of depressive disorders in 2015 covering 98 democratic countries. Media freedom was measured as the degree to which a country allows the freedom of news and information of print media, television, and radio broadcasting (0-100: least to most free). Control variables were then added, including GDP per capita growth, population density, country latitude, and religious affiliations. Further, a mediation analysis was applied to test if there is a causal pathway that links the degrees of media freedom and the levels of economic development or/and social protection to prevalence of depression. Results We found that an increase in the score of media freedom by 10 resulted in a 0.20 percentage point increase in prevalence of depressive disorders (%) (0.20, CI = 0.10-0.30). Our theoretical expectations were still confirmed when this study examined the relationship for each year between 2011 and 2014 (e.g. in 2014, 0.19, CI = 0.09-0.29), used an alternative index of media freedom from a practitioners’ view (0.17, CI = 0.02-0.32), or measured each country’s level of internet and digital media freedom (0.30, CI = 0.10-0.49). Further, a mediation test showed that 39.88% and 21.38% of the total effect was mediated through the economic and social pathway respectively. Conclusions The findings suggest that great levels of media freedom matter in increasing prevalence of depression. Key messages Great levels of media freedom matter in increasing prevalence of depression. There are direct and two indirect effects of media freedom on prevalence of depression.

OBJECTIVES To investigate the effectiveness of Chinese herbal medicine for the treatment of urinary incontinence in patients with chronic obstructive pulmonary disease. METHODS We carried out a retrospective cohort study using the National Health Insurance Research Database. From a cohort of 1 million records between 1996 and 2013, a total of 202 279 patients with newly onset chronic obstructive pulmonary disease were initially recruited. We matched with propensity score 3967 patients who received Chinese herbal medicine by age, sex, year of chronic obstructive pulmonary disease diagnosis, urbanization, comorbidities and chronic obstructive pulmonary disease medications. All participants received follow-up visits until the end of 2013 to record the incidence rate of urinary incontinence. The Cox proportional hazards model was applied to assess the association between Chinese herbal medicine use and the risk of urinary incontinence among chronic obstructive pulmonary disease patients. RESULTS The incidence rates of urinary incontinence were 57.33 and 108.15 (per 10 000 person-years) in the Chinese herbal medicine and non-Chinese herbal medicine cohorts, respectively, showing a significantly lower risk of urinary incontinence in Chinese herbal medicine users (aHR = 0.56, 95% CI = 0.45-0.69, P

Rationale: Pulmonary arterial hypertension (PH) is a life-threatening condition associated with immune dysregulation and abnormal regulatory T cell (Treg) activity, but it is currently unknown whether and how abnormal Treg function differentially affects males and females. Objective: To evaluate whether and how Treg deficiency differentially affects male and female rats in experimental PH. Methods and Results: Male and female athymic rnu/rnu rats, lacking Tregs, were treated with the VEGFR2 (vascular endothelial growth factor receptor 2) inhibitor SU5416 or chronic hypoxia and evaluated for PH; some animals underwent Treg immune reconstitution before SU5416 administration. Plasma PGI 2 (prostacyclin) levels were measured. Lung and right ventricles were assessed for the expression of the vasoprotective proteins COX-2 (cyclooxygenase 2), PTGIS (prostacyclin synthase), PDL-1 (programmed death ligand 1), and HO-1 (heme oxygenase 1). Inhibitors of these pathways were administered to athymic rats undergoing Treg immune reconstitution. Finally, human cardiac microvascular endothelial cells cocultured with Tregs were evaluated for COX-2, PDL-1, HO-1, and ER (estrogen receptor) expression, and culture supernatants were assayed for PGI 2 and IL (interleukin)-10. SU5416-treatment and chronic hypoxia produced more severe PH in female than male athymic rats. Females were distinguished by greater pulmonary inflammation, augmented right ventricular fibrosis, lower plasma PGI 2 levels, decreased lung COX-2, PTGIS, HO-1, and PDL-1 expression and reduced right ventricular PDL-1 levels. In both sexes, Treg immune reconstitution protected against PH development and raised levels of plasma PGI 2 and cardiopulmonary COX-2, PTGIS, PDL-1, and HO-1. Inhibiting COX-2, HO-1, and PD-1 (programmed death 1)/PDL-1 pathways abrogated Treg protection. In vitro, human Tregs directly upregulated endothelial COX-2, PDL-1, HO-1, ERs and increased supernatant levels of PGI 2 and IL-10. Conclusions: In 2 animal models of PH based on Treg deficiency, females developed more severe PH than males. The data suggest that females are especially reliant on the normal Treg function to counteract the effects of pulmonary vascular injury leading to PH.

Background and aim To assess the detection rates of Helicobacter pylori colonization in the gastric cardia with two commercial kits of rapid urease test: 5 min UFT300 and 24 h CLO test in H. pylori-infected patients. Methods Eighty consecutive dyspeptic patients with confirmed H. pylori infection (serology and 13C-urea breath test) were prospectively studied. During endoscopy, tissue samples using separate biopsy forceps from the cardia were taken for the UFT300 and CLO tests. The results of the UFT300 were read at 5 and 30 min, and those of the CLO test were read at 24 h. Results Of 80 enrolled patients, 17 (21.3%) and 44 (55%) had positive findings with the UFT300 at 5 and 30 min, respectively, while 72 (90%) had positive findings with the CLO test at 24 h. The CLO test is significantly more sensitive than the UFT300 in evaluating H. pylori status in the cardia. On comparing patients with and without carditis, the detection rates of the CLO test were similar (91.1% vs 88.6%; P = 0.724), and the rates of the UFT300 were also similar at 5 and 30 min. Conclusions The rate of H. pylori colonization in the gastric cardia was 90% in H. pylori-infected patients detected with the CLO test. Although the UFT300 provides a more rapid reading of H. pylori status, the diagnostic yield of the CLO test is much higher than that of the UFT300. However, a positive result of the UFT300 may indicate a higher bacterial load in the cardia, which warrants a more effective therapeutic strategy.

Purpose This study aims to examine the consequences when audit committees have different economic incentives (i.e. incentive-based compensation) to switch auditors. Design/methodology/approach The author focuses on companies experiencing an auditor switching event (client-initiated dismissals) and uses Heckman’s (1997) two-stage estimation procedure to control endogenous bias. Audit committee quality is measured by the level of incentive-based compensation. Accrual quality and abnormal audit fees are examined over the periods of auditor switches. Findings Using 1,087 US companies between 2006 and 2014, the author found that audit committees’ incentive-based compensation is negatively (positively) associated with accruals quality (abnormal audit fees) only when companies switch from Big 4 to non-Big 4 auditors or switch within non-Big 4 auditors. For companies that switch from non-Big 4 to Big 4 auditors, she found no evidence. Research limitations/implications This study provides a detailed discussion of the consequences of audit committee quality. The findings also contribute to the literature by concluding that economic incentives are associated with ineffective oversight, particularly after auditor switches. Practical implications Sarbanes–Oxley Act and its associated regulations significantly expanded the oversight role of audit committees. However, regulators bypassed restrictions on audit committee compensation. Accordingly, the author suggests that regulators focus on the issue of economic incentives to improve audit committee quality. Originality/value Minimal research has been conducted on the role of audit committees when companies switch to a new external auditor. The author shows that when companies switch auditors, incentive-based compensation significantly affects the monitoring quality of audit committees.

Background A triage test to assist clinical decision-making on choosing primary chemoradiation for cervical carcinomas or primary surgery for endometrial carcinomas is important. Purpose or Hypothesis To develop and validate a multiparametric prediction model based on MR imaging and spectroscopy in distinguishing adenocarcinomas of uterine cervical or endometrial origin. Study Type Prospective diagnostic accuracy study. Population Eighty-seven women: 25 cervical and 62 endometrial adenocarcinomas divided into training (n = 43; cervical/endometrial adenocarcinomas = 11/32) and validation (n = 44; 14/30) datasets. Field Strength/Sequence The 3T diffusion-weighted (DW) MR imaging and MR spectroscopy. Assessment Morphology, volumetric DW MR imaging and spectroscopy (MDS) scoring system with total points 0–5, based on presence of the following MR features assessed independently by two radiologists: (a) epicenter at the cervix, (b) rim enhancement, (c) disrupted cervical stromal integrity, (d) mean volumetric apparent diffusion coefficient values (ADCmean) higher than 0.98 × 10-3 mm2/s, (e) fatty acyl δ 1.3 ppm more than 161.92 mM. Histopathology as gold standard. Statistical Tests Logistic regression and receiver operator characteristic (ROC) curves analysis. Results For both the training and validation datasets, the MDS score achieved an accuracy of 93.0% and 84.1%, significantly higher than that of morphology (88.4% and 79.5%), ADC value (74.4% and 68.2%), and spectroscopy (81.4% and 68.2%; P

The coexistence of imperforate hymen and vaginal septum is rare and their ability to mimic malignant manifestations have not been frequently reported. This current case report describes a 13-year-old girl that presented with cyclic abdominal pain for 6 months. She was found to have a huge mass via abdominal plain film X-ray and sonography, with inexplicably high levels of serum carcinoembryonic antigen, cancer antigen (CA)-19-9 and CA-125. Pelvic computed tomography imaging disclosed two huge cystic lesions in the uterine and upper vaginal cavities. Surgical intervention conformed the diagnosis of a concurrent imperforate hymen and transverse vaginal septum, echoing the imaging findings of haematocolpometra. Her tumour marker levels gradually returned to normal after surgery. This rare case of concomitant imperforate hymen and transverse vaginal septum highlights that haematocolpometra, a benign disease that might mimic malignancy, should be taken into consideration in any adolescent females with an abdominal mass and amenorrhoea to ensure an early diagnosis and timely appropriate management.

Ischemic stroke, and the consequent brain cell death, is a common cause of death and disability worldwide. Current treatments that primarily aim to relieve symptoms are relatively inefficient in achieving brain tissue regeneration and functional recovery, and thus novel therapeutic options are urgently needed. Although cell-based therapies have shown promise for treating the infarcted brain, a recurring challenge is the inadequate retention and engraftment of transplanted cells at the target tissue, thereby limiting the ultimate therapeutic efficacy. Here, we show that transplantation of preassembled three-dimensional (3D) spheroids of mesenchymal stem cells (MSCs) and vascular endothelial cells (ECs) results in significantly improved cell retention and survival compared with conventional mixed-cell suspensions. The transplanted 3D spheroids exhibit notable neuroprotective, proneurogenic, proangiogenic and anti-scarring potential as evidenced by clear extracellular matrix structure formation and paracrine factor expression and secretion; this ultimately results in increased structural and motor function recovery in the brain of an ischemic stroke mouse model. Therefore, transplantation of MSCs and ECs using the 3D cell spheroid configuration not only reduces cell loss during cell harvesting/administration but also enhances the resultant therapeutic benefit, thus providing important proof-of-concept for future clinical translation.

Research and development (R&D) investment affects firms’ growth and reflects their investment energy. However, it is recorded as an expense in financial statements, according to generally accepted accounting principles (e.g., International Financial Statements Standards). This study examines whether firms’ R&D investment has a positive effect on their performance, when they engage in corporate social responsibility. The author focuses on firms that have earned corporate social responsibility awards from Global Views Magazine, Common Wealth Magazine, and the Taiwan Institute for Sustainable Energy in order to measure firms’ levels of corporate social responsibility engagement. Tobin’s Q is used as a proxy for firm performance. Because corporate social responsibility engagement is not mandatory in Taiwan, the Heckman two-stage process is used to control for an endogeneity bias. In the first stage, logit regression is employed, using a dummy variable as a proxy for a firm’s social responsibility engagement. In the second stage, the impact of corporate social responsibility on firm value is estimated by regressing Tobin’s Q on various governance and firm characteristics and on a dummy variable for social responsibility engagement. Based on all public traded companies in Taiwan for the period 2005 – 2014, and after controlling for an endogeneity bias, it is found that R&D investment is positively associated with Tobin’s Q, but only when firms engage in corporate social responsibility. Therefore, an investment strategy that meets corporate social responsibility objectives benefits firm performance. The empirical results provide policy implications for firm R&D investment and corporate social responsibility implementation.

Fibrosis after solid organ transplantation is considered an irreversible process and remains the major cause of graft dysfunction and death with limited therapies. This remodeling is characterized by aberrant accumulation of contractile myofibroblasts that deposit excessive extracellular matrix (ECM) and increase tissue stiffness. Studies demonstrate, however, that a stiff ECM itself promotes fibroblast-to-myofibroblast differentiation, stimulating further ECM production. This creates a positive feedback loop that perpetuates fibrosis. We hypothesized that simultaneously targeting myofibroblast contractility with relaxin and ECM stiffness with lysyl oxidase inhibitors could break the feedback loop, reversing established fibrosis. To test this, we used the orthotopic tracheal transplantation (OTT) mouse model, which develops robust fibrotic airway remodeling. Mice with established fibrosis were treated with saline, mono-, or combination therapies. Although monotherapies had no effect, combining these agents decreased collagen deposition and promoted re-epithelialization of remodeled airways. Relaxin inhibited myofibroblast differentiation and contraction in a matrix-stiffness-dependent manner through prostaglandin E2 (PGE2 ). Furthermore, the effect of combination therapy was lost in PGE2 receptor knockout and PGE2 -inhibited OTT mice. This study revealed the important synergistic roles of cellular contractility and tissue stiffness in the maintenance of fibrotic tissue and suggests a new therapeutic principle for fibrosis.

This paper is aimed to inspect the chapel’s overall structural system based on nondestructive testing (NDT), and a rebound hammer test and a ground-penetrating radar (GPR) system are employed to conduct a nondestructive testing. It is important before the chapel’s structural performance was assessed, the structure was inspected to investigate the current state and was constructed according to its original structural designs. According to the inspection, it is found the concrete compressive strength of all the components is larger than the original design strength. Moreover, the total numbers of the reinforcing bars of Slabs S1 and N1 are consistent with the number in the original design (246). However, the total numbers of the reinforcing bars of Slabs S2 and N2 are 167 and 174, respectively, whereas those of the original design were 150, indicating additional vertical reinforcing bars were applied in the chapel’s construction. Based on the results of inspection, the future structural performance assessment and retrofitting are expected to be set-up properly.

Manuscript Type Empirical Research Question/Issue This study tests whether the adoption of clawback provisions mitigates overinvestment. A clawback provision is a recoupment policy that allows certain bonuses previously paid to executives to be cancelled or “clawed back” if financial statements are restated. Research Findings/Insights This study focuses on 1,093 voluntary clawback adopters in the U.S. during 2006–2012 and uses propensity score matching to obtain a matched sample. We then perform a difference-in-differences analysis to assess pre- and post-adoption changes in overinvestment. The empirical results show that (i) clawback provisions mitigate overinvestment, and (ii) overinvestment decreases most for those executives identified as overconfident or receiving higher option compensation. Theoretical/Academic Implications Agency conflict between shareholders and executives distorts a firm's investment decisions. According to the agency-based explanation, better financial reporting quality decreases information asymmetry. Clawback provisions improve financial reporting and mitigate potential overinvestment under agency conflict. To the best of our knowledge, no other published study has discussed executives’ investment behavior or has reported that one benefit of clawback provisions is mitigating ex post overinvestment. It is important for regulators and academics to understand how clawback provisions impact executives’ behavior. Practitioner/Policy Implications The results of this study provide political implications for mandatory clawback provisions under Section 954 of the Dodd-Frank Act after 2016 in the U.S. Given that we show that voluntarily adopting clawback provisions curbs overinvestment, it is important to examine whether this new act should place restrictions on the form of executive pay.

Purpose To investigate the biological meaning of apparent diffusion coefficient (ADC) values in tumors following radiotherapy. Materials and Methods Five mice bearing TRAMP-C1 tumor were half-irradiated with a dose of 15 Gy. Diffusion-weighted images, using multiple b-values from 0 to 3000 s/mm2, were acquired at 7T on day 6. ADC values calculated by a two-point estimate and monoexponential fitting of signal decay were compared between the irradiated and nonirradiated regions of the tumor. Pixelwise ADC maps were correlated with histological metrics including nuclear counts, nuclear sizes, nuclear spaces, cytoplasmic spaces, and extracellular spaces. Results As compared with the nonirradiated region, the irradiated region exhibited significant increases in ADC, extracellular space, and nuclear size, and a significant decrease in nuclear counts (P < 0.001 for all). Optimal ADC to differentiate the irradiated from nonirradiated regions was achieved at a b-value of 800 s/mm2 by the two-point method and monoexponential curve fitting. ADC positively correlated with extracellular spaces (r = 0.74) and nuclear sizes (r = 0.72), and negatively correlated with nuclear counts (r = –0.82, P < 0.001 for all). Conclusion As a radiomic biomarker, ADC maps correlating with histological metrics pixelwise could be a means of evaluating tumor heterogeneity and responses to radiotherapy. Level of Evidence: 1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:483–489

Pancreatic cancer is often treatment-resistant, with the emerging standard of care, gemcitabine, affording only a few months of incrementally-deteriorating survival. Reflecting on the history of failed clinical trials, genetically engineered mouse models (GEMMs) in oncology research provides the inspiration to discover new treatments for pancreatic cancer that come from better knowledge of pathogenesis mechanisms, not only of the derangements in and consequently acquired capabilities of the cancer cells, but also in the aberrant microenvironment that becomes established to support, sustain, and enhance neoplastic progression. On the other hand, the existing mutational profile of pancreatic cancer guides our understanding of the disease, but leaves many important questions of pancreatic cancer biology unanswered. Over the past decade, a series of transgenic and gene knockout mouse modes have been produced that develop pancreatic cancers with features reflective of metastatic pancreatic ductal adenocarcinoma (PDAC) in humans. Animal models of PDAC are likely to be essential to understanding the genetics and biology of the disease and may provide the foundation for advances in early diagnosis and treatment.

To develop and evaluate the performance of U-Net for fully automated localization and segmentation of cervical tumors in magnetic resonance (MR) images and the robustness of extracting apparent diffusion coefficient (ADC) radiomics features. This retrospective study involved analysis of MR images from 169 patients with cervical cancer stage IB–IVA captured; among them, diffusion-weighted (DW) images from 144 patients were used for training, and another 25 patients were recruited for testing. A U-Net convolutional network was developed to perform automated tumor segmentation. The manually delineated tumor region was used as the ground truth for comparison. Segmentation performance was assessed for various combinations of input sources for training. ADC radiomics were extracted and assessed using Pearson correlation. The reproducibility of the training was also assessed. Combining b0, b1000, and ADC images as a triple-channel input exhibited the highest learning efficacy in the training phase and had the highest accuracy in the testing dataset, with a dice coefficient of 0.82, sensitivity 0.89, and a positive predicted value 0.92. The first-order ADC radiomics parameters were significantly correlated between the manually contoured and fully automated segmentation methods (p

Biomolecules that respond to different external stimuli enable the remote control of genetically modified cells. Chemogenetics and optogenetics, two tools that can control cellular activities via synthetic chemicals or photons, respectively, have been widely used to elucidate underlying physiological processes. These methods are, however, very invasive, have poor penetrability, or low spatiotemporal precision, attributes that hinder their use in therapeutic applications. We report herein a sonogenetic approach that can manipulate target cell activities by focused ultrasound stimulation. This system requires an ultrasound-responsive protein derived from an engineered auditory-sensing protein prestin. Heterogeneous expression of mouse prestin containing two parallel amino acid substitutions, N7T and N308S, that frequently exist in prestins from echolocating species endowed transfected mammalian cells with the ability to sense ultrasound. An ultrasound pulse of low frequency and low pressure efficiently evoked cellular calcium responses after transfecting with prestin(N7T, N308S). Moreover, pulsed ultrasound can also non-invasively stimulate target neurons expressing prestin(N7T, N308S) in deep regions of mice brains. Our study delineates how an engineered auditory-sensing protein can cause mammalian cells to sense ultrasound stimulation. Moreover, owing to the great penetration of low-frequency ultrasound (∼400 mm in depth), our sonogenetic tools will serve as new strategies for non-invasive therapy in deep tissues of large animals like primates.

A 50Gb/s all-digital adaptive noise-suppression (NS) feed-forward equalizer (AFFE) and adaptive decision feedback equalizer (ADFE) for 2-level pulse amplitude modulation (2-PAM) serial link systems is presented. Based on a parallel extended incremental coefficients-lookahead scheme (EICL), we propose a Dual Data-paths Self-Lookahead Filter (DD-SLF) for ADFE. DD-SLF architecture has better energy efficiency and hardware area than an original SLF architecture due to the number of delay elements in the feedback loop is reduced. Furthermore, gated clock technique with the design idea of register file architecture is used to replace the pipelined delay elements to save power. The whole equalizer which operates at 1GHz system clock rate with 50 parallelisms is implemented in 40nm CMOS technology with a 0.38mm2 core area. The equalizer with 50Gb/s throughput rate achieves 2.6pJ/bit energy efficiency under 0.81V supply measurement results.