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Amyloid fibril formation is associated with an array of degenerative diseases. While no real cure is currently available, evidence suggests that suppression of amyloid fibrillogenesis is an effective strategy toward combating these diseases. Brilliant blue R (BBR), a disulfonated triphenylmethane compound, has been shown to interact with fibril-forming proteins but exert different effects on amyloid fibrillogenesis. These inconsistent findings prompted us to further evaluate BBR's effect on the inhibition/suppresion of protein fibrillogenesis. Using 129-residue hen lysozyme, which shares high sequence homology to human lysozyme associated with hereditary non-neuropathic systemic amyloidosis, as a model, this study is aimed at thoroughly examining the influence of BBR on the in vitro protein fibrillogenesis. We first showed that BBR dose-dependently attenuated lysozyme fibril formation probably by affecting the fibril growth rate, with the value of IC 50 determined to be ~4.39 μM. Next, we employed tryptophan fluorescence quenching method to determine the binding constant and number of binding site(s) associated with BBR-lysozyme binding. In addition, we further conducted molecular docking studies to gain a better understanding of the possible binding site(s) and interaction(s) between lysozyme and BBR. We believe some of the information and/or knowledge concerning the structure-function relationship associated with BBR's suppressing activity obtained here can be applied for the future work in the subject matter related with the therapeutic strategies for amyloid diseases.

This study examined how mechanisms of moral disengagement (MD) were related to students' self-reported misbehaviors. Participants were 282 and 336 high school students enrolled in physical education classes. In Stage 1, results of regression analysis showed that advantageous comparison and non-responsibility positively predicted four misbehaviors (i.e., low engagement, failure to follow directions, poor self-management, and distracting behavior). In Stage 2, results of the structural equation modeling confirmed that advantageous comparison and non-responsibility were the significant predictors of student misbehavior in physical education. It is suggested that prevention and intervention programs should address students' advantageous comparison (e.g., compared to skipping class, it is not a big deal to be shirking in class) and non-responsibility (e.g., no one is taking the class seriously; I am just one of them) to reduce misbehaviors in the physical education context.

A new variant of the porcine epidemic diarrhea virus (PEDV) is an emerging swine disease, killing considerable numbers of neonatal piglets in North America and Asia in recent years. To generate immunogens mimicking the complex spike (S) protein folding with proper posttranslational modification to mount a robust immune response against the highly virulent PEDV, two baculoviruses displaying the full-length S protein (S-Bac) and the S1 protein (S1-Bac) of the virulent Taiwan genotype 2b (G2b) PEDV Pintung 52 (PEDV-PT) strain were constructed. Intramuscular immunizations of mice and piglets with the S-Bac and S1-Bac demonstrated significantly higher levels of systemic anti-PEDV S-specific IgG, as compared with control group. Our results also showed that piglets in the S-Bac group elicited superior PEDV-specific neutralizing antibodies than those of the S1-Bac and control groups. The highly virulent PEDV-PT strain challenge experiment showed that piglets immunized with S-Bac and S1-Bac showed milder clinical symptoms with significantly less fecal viral shedding as compared with non-immunized control piglets. More importantly, piglets immunized with the S-Bac exhibited no to mild clinical signs, with a delayed, minimal viral shedding. Our results demonstrated that the S-Bac could serve as a safe, easy to manipulate, and effective vaccine candidate against the PEDV infection.

Local Treg responses are involved in Helicobacter pylori-related inflammation and clinical outcomes after infection, and H. pylori-derived HSP60 (HpHSP60) is an important virulence factor associated with gastric carcinogenesis. This study to investigate the role of HpHSP60 in immunosuppression, particularly with regard to whether it could induce the production of Treg cells. For this purpose, human peripheral blood mononuclear cells (PBMCs) were treated with or without HpHSP60 in the presence of an anti-CD3 mAb to determine the effect of HpHSP60 on cell proliferation. In this report, HpHSP60 decreased the expression of CDK4 to significantly arrest the proliferation of mitogen-stimulated T-cells, which correlated with the induction of Treg cells. Moreover, monocytic cells were essential for the induction of HpHSP60-induced Treg cells via the secretion of IL-10 and TGF-β after treatment with HpHSP60. Blockage of HpHSP60 with specific monoclonal antibodies significantly reduced the colonization of H. pylori and the expression of Treg cells in vivo. Overall, our results suggest that HpHSP60 could act on macrophages to trigger the expression of IL-10 and TGF-β, thereby leading to an increase in Treg cells and inhibition of T-cell proliferation., (Copyright © 2018. Published by Elsevier Ltd.)

Amyloid aggregates of proteins are one of the most abundant and important naturally occurring self-associated assemblies. Formation of poly/peptide amyloid aggregates is also associated with the widely spread diseases, so called amyloidosis, which include Alzheimer's disease, diabetes mellitus and lysozyme amyloidosis. These disorders are still incurable and novel therapeutical approaches are focused on using small molecules for inhibition of amyloid aggregation. We have observed effect of three structurally distinct groups of tacrine/acridone - coumarin heterodimers on hen egg white (HEW) lysozyme fibrillization in vitro. The ability of heterodimers to interfere with lysozyme amyloid aggregation was examined using Thioflavin T fluorescence assay, atomic force microscopy and docking method. The obtained data suggest that inhibitory effect of heterodimers on lysozyme fibrillization depends on their composition. We have shown that tacrine-coumarin heterodimers with alkylenediamine linker are the most effective inhibitors of lysozyme fibrillization. The inhibitory activities were quantified through IC 50 values; the most potent heterodimers interfere with lysozyme aggregation in the scale of micromolar concentrations (19.2 μM-105.4 μM). The molecular docking showed that the modes of possible interactions involved in the binding are mainly hydrophobic interactions, hydrogen bonding and van der Waals interactions. Studied heterodimers had none or weak cytotoxic effect on human neuroblastoma cells. The obtained results can be helpful for the design and development of new therapeutics for amyloid-related diseases., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Because of the ubiquity of Internet of Things (IoT) devices, the power consumption and security of IoT systems have become very important issues. Advanced Encryption Standard (AES) is a block cipher algorithm is commonly used in IoT devices. In this paper, the power consumption and cryptographic calculation requirement for different payload lengths and AES encryption types are analyzed. These types include software-based AES-CB, hardware-based AES-ECB (Electronic Codebook Mode), and hardware-based AES-CCM (Counter with CBC-MAC Mode). The calculation requirement and power consumption for these AES encryption types are measured on the Texas Instruments LAUNCHXL-CC1310 platform. The experimental results show that the hardware-based AES performs better than the software-based AES in terms of power consumption and calculation cycle requirements. In addition, in terms of AES mode selection, the AES-CCM-MIC64 mode may be a better choice if the IoT device is considering security, encryption calculation requirement, and low power consumption at the same time. However, if the IoT device is pursuing lower power and the payload length is generally less than 16 bytes, then AES-ECB could be considered.

Piezoelectric materials have been widely used for sensors, actuators, electronics, and energy conversion. Two-dimensional (2D) ultrathin semiconductors, such as monolayer h-BN and MoS 2 with their atom-level geometry, are currently emerging as new and attractive members of the piezoelectric family. However, their piezoelectric polarization is commonly limited to the in-plane direction of odd-number ultrathin layers, largely restricting their application in integrated nanoelectromechanical systems. Recently, theoretical calculations have predicted the existence of out-of-plane and in-plane piezoelectricity in monolayer α-In 2 Se 3 . Here, we experimentally report the coexistence of out-of-plane and in-plane piezoelectricity in monolayer to bulk α-In 2 Se 3 , attributed to their noncentrosymmetry originating from the hexagonal stacking. Specifically, the corresponding d 33 piezoelectric coefficient of α-In 2 Se 3 increases from 0.34 pm/V (monolayer) to 5.6 pm/V (bulk) without any odd-even effect. In addition, we also demonstrate a type of α-In 2 Se 3 -based flexible piezoelectric nanogenerator as an energy-harvesting cell and electronic skin. The out-of-plane and in-plane piezoelectricity in α-In 2 Se 3 flakes offers an opportunity to enable both directional and nondirectional piezoelectric devices to be applicable for self-powered systems and adaptive and strain-tunable electronics/optoelectronics.

Rationale: Lapatinib (LAP) is a crucial alternative to trastuzumab upon the onset of drug resistance during treatment of metastatic human epidermal growth factor receptor 2-positive breast cancer. Like trastuzumab, LAP is commonly used alongside anthracyclines as a combination therapy, due to enhanced anti-cancer efficacy. However, this is notably associated with cardiotoxicity so it is imperative to understand the mechanisms driving this cardiotoxicity and develop cardioprotective strategies. To this end, here we utilize human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs), which exhibit several characteristics representative of in vivo cardiomyocytes that make them breakthrough models to study drug toxicity. Methods: We investigated LAP- and doxorubicin (DOX)-induced toxicity in hPSC-CMs and evaluated the involvement of inducible nitric oxide (NO) synthase (iNOS). The significance of iNOS-mediated cardiotoxicity was furthermore evaluated in animal studies. Results: LAP synergistically increased DOX toxicity in hPSC-CMs in a dose- and time-dependent manner. At concentrations that were otherwise non-apoptotic when administered separately, LAP significantly potentiated DOX-induced hPSC-CM apoptosis. This was accompanied by increased iNOS expression and pronounced production of NO. iNOS inhibition significantly reduced hPSC-CM sensitivity to LAP and DOX co-treatment (LAP-plus-DOX), leading to reduced apoptosis. Consistent with our observations in vitro , delivery of an iNOS inhibitor in mice treated with LAP-plus-DOX attenuated myocardial apoptosis and systolic dysfunction. Moreover, inhibition of iNOS did not compromise the anti-cancer potency of LAP-plus-DOX in a murine breast cancer xenograft model. Conclusions: Our findings suggest that iNOS inhibition is a promising cardioprotective strategy to accompany HER2-inhibitor/anthracycline combination therapies. Furthermore, these results support the promise of hPSC-CMs as a platform for investigating cardiotoxicity and developing cardioprotectants as a whole., Competing Interests: Competing Interests: Patrick Hsieh receives research grants from AstraZeneca, Gilead and Takeda, all of which did not participate in funding this work. The other authors report no conflicts.

Background: Gastric cancer is the eighth most common cancer in Taiwan, with a 40% 5-year survival rate. Approximately 40% of patients are refractory to chemotherapy. Currently, the anti-HER2 therapy is the only clinically employed targeted therapy. However, only 7% patients in Taiwan are HER2-positive. Identifying candidate target genes will facilitate the development of adjuvant targeted therapy to increase the efficacy of gastric cancer treatment., Methods: Clinical specimens were analyzed by targeted RNA sequencing to assess the expression levels of target genes. Statistical significance of differential expression and correlation between specimens was evaluated. The correlation with patient survival was analyzed as well. In vitro cell mobility was determined using wound-healing and transwell mobility assays., Results: Expression of BMP1, COL1A1, STAT3, SOX2, FOXA2, and GATA6 was progressively dysregulated through the stages of gastric oncogenesis. The expression profile of these six genes forms an ubiquitously biomarker signature that is sufficient to differentiate cancer from non-cancerous specimens. High expression status of BMP1 correlates with poor long-term survival of late-stage patients. In vitro, suppression of BMP1 inhibits the mobility of the gastric cancer cell lines, indicating a role of BMP1 in metastasis., Conclusions: BMP1 is upregulated in gastric cancer and is correlated with poor patient survival. Suppression of BMP1 reduced gastric cancer mobility in vitro. Our finding suggests that anti-BMP1 therapy will likely augment the efficacy of standard chemotherapy and improve the treatment outcome.

Van der Waals heterobilayers of transition metal dichalcogenides with spin-valley coupling of carriers in different layers have emerged as a new platform for exploring spin/valleytronic applications. The interlayer coupling was predicted to exhibit subtle changes with the interlayer atomic registry. Manually stacked heterobilayers, however, are incommensurate with the inevitable interlayer twist and/or lattice mismatch, where the properties associated with atomic registry are difficult to access by optical means. Here, we unveil the distinct polarization properties of valley-specific interlayer excitons using epitaxially grown, commensurate WSe 2 /MoSe 2 heterobilayers with well-defined (AA and AB) atomic registry. We observe circularly polarized photoluminescence from interlayer excitons, but with a helicity opposite to the optical excitation. The negative circular polarization arises from the quantum interference imposed by interlayer atomic registry, giving rise to distinct polarization selection rules for interlayer excitons. Using selective excitation schemes, we demonstrate the optical addressability for interlayer excitons with different valley configurations and polarization helicities.

Degeneration or loss of inner ear hair cells (HCs) is irreversible and results in sensorineural hearing loss (SHL). Human-induced pluripotent stem cells (hiPSCs) have been employed in disease modelling and cell therapy. Here, we propose a transcription factor (TF)-driven approach using ATOH1 and regulatory factor of x-box (RFX) genes to generate HC-like cells from hiPSCs. Our results suggest that ATOH1/RFX1/RFX3 could significantly increase the differentiation capacity of iPSCs into MYO7A mCherry -positive cells, upregulate the mRNA expression levels of HC-related genes and promote the differentiation of HCs with more mature stereociliary bundles. To model the molecular and stereociliary structural changes involved in HC dysfunction in SHL, we further used ATOH1/RFX1/RFX3 to differentiate HC-like cells from the iPSCs from patients with myoclonus epilepsy associated with ragged-red fibres (MERRF) syndrome, which is caused by A8344G mutation of mitochondrial DNA (mtDNA), and characterised by myoclonus epilepsy, ataxia and SHL. Compared with isogenic iPSCs, MERRF-iPSCs possessed ~42-44% mtDNA with A8344G mutation and exhibited significantly elevated reactive oxygen species (ROS) production and CAT gene expression. Furthermore, MERRF-iPSC-differentiated HC-like cells exhibited significantly elevated ROS levels and MnSOD and CAT gene expression. These MERRF-HCs that had more single cilia with a shorter length could be observed only by using a non-TF method, but those with fewer stereociliary bundle-like protrusions than isogenic iPSCs-differentiated-HC-like cells could be further observed using ATOH1/RFX1/RFX3 TFs. We further analysed and compared the whole transcriptome of M1 ctrl -HCs and M1-HCs after treatment with ATOH1 or ATOH1/RFX1/RFX3. We revealed that the HC-related gene transcripts in M1 ctrl -iPSCs had a significantly higher tendency to be activated by ATOH1/RFX1/RFX3 than M1-iPSCs. The ATOH1/RFX1/RFX3 TF-driven approach for the differentiation of HC-like cells from iPSCs is an efficient and promising strategy for the disease modelling of SHL and can be employed in future therapeutic strategies to treat SHL patients.

Background: Population-based studies evaluating outcomes of different approaches for rectal cancer are scarce., Methods: We conducted a retrospective cohort study using the Nationwide Inpatient Sample database between 2008 and 2012. We compared the outcomes and costs among rectal cancer patients undergoing robotic, laparoscopic, or open surgeries using propensity scores for adjusted and matched analysis., Results: We identified 194 957 rectal cancer patients. Over the 5-year period, the annual admission number decreased by 13.9%, the in-hospital mortality rate decreased by 32.2%, while the total hospitalization cost increased by 13.6%. Compared with laparoscopic surgery, robotic surgery had significantly lower length of stay (LOS) (OR 0.69, 95%CI 0.57-0.84), comparable wound complications (OR 1.08, 95%CI 0.70-1.65) and higher cost (OR 1.42, 95%CI 1.13-1.79), while open surgery had significantly longer LOS (OR 1.38, 95%CI 1.19-1.59), more wound complications (OR 1.49, 95%CI 1.08-1.79), and comparable cost (OR 0.92, 95%CI 0.79-1.07). There were no difference in in-hospital mortality among three approaches., Conclusions: Laparoscopic surgery was associated with better outcomes than open surgery. Robotic surgery was associated with higher cost, but no advantage over laparoscopic surgery in terms of mortality and complications. Studies on cost-effectiveness of robotic surgery may be warranted., (© 2017 Wiley Periodicals, Inc.)

Connectome-based predictive modeling (CPM; Finn et al., 2015; Shen et al., 2017) was recently developed to predict individual differences in traits and behaviors, including fluid intelligence (Finn et al., 2015) and sustained attention (Rosenberg et al., 2016a), from functional brain connectivity (FC) measured with fMRI. Here, using the CPM framework, we compared the predictive power of three different measures of FC (Pearson's correlation, accordance, and discordance) and two different prediction algorithms (linear and partial least square [PLS] regression) for attention function. Accordance and discordance are recently proposed FC measures that respectively track in-phase synchronization and out-of-phase anti-correlation (Meskaldji et al., 2015). We defined connectome-based models using task-based or resting-state FC data, and tested the effects of (1) functional connectivity measure and (2) feature-selection/prediction algorithm on individualized attention predictions. Models were internally validated in a training dataset using leave-one-subject-out cross-validation, and externally validated with three independent datasets. The training dataset included fMRI data collected while participants performed a sustained attention task and rested (N = 25; Rosenberg et al., 2016a). The validation datasets included: 1) data collected during performance of a stop-signal task and at rest (N = 83, including 19 participants who were administered methylphenidate prior to scanning; Farr et al., 2014a; Rosenberg et al., 2016b), 2) data collected during Attention Network Task performance and rest (N = 41, Rosenberg et al., in press), and 3) resting-state data and ADHD symptom severity from the ADHD-200 Consortium (N = 113; Rosenberg et al., 2016a). Models defined using all combinations of functional connectivity measure (Pearson's correlation, accordance, and discordance) and prediction algorithm (linear and PLS regression) predicted attentional abilities, with correlations between predicted and observed measures of attention as high as 0.9 for internal validation, and 0.6 for external validation (all p's < 0.05). Models trained on task data outperformed models trained on rest data. Pearson's correlation and accordance features generally showed a small numerical advantage over discordance features, while PLS regression models were usually better than linear regression models. Overall, in addition to correlation features combined with linear models (Rosenberg et al., 2016a), it is useful to consider accordance features and PLS regression for CPM., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The personality dimensions of neuroticism and extraversion are strongly associated with emotional experience and affective disorders. Previous studies reported functional magnetic resonance imaging (fMRI) activity correlates of these traits, but no study has used brain-based measures to predict them. Here, using a fully cross-validated approach, we predict novel individuals' neuroticism and extraversion from functional connectivity (FC) data observed as they simply rested during fMRI scanning. We applied a data-driven technique, connectome-based predictive modeling (CPM), to resting-state FC data and neuroticism and extraversion scores (self-reported NEO Five Factor Inventory) from 114 participants of the Nathan Kline Institute Rockland sample. After dividing the whole brain into 268 nodes using a predefined functional atlas, we defined each individual's FC matrix as the set of correlations between the activity timecourses of every pair of nodes. CPM identified networks consisting of functional connections correlated with neuroticism and extraversion scores, and used strength in these networks to predict a left-out individual's scores. CPM predicted neuroticism and extraversion in novel individuals, demonstrating that patterns in resting-state FC reveal trait-level measures of personality. CPM also revealed predictive networks that exhibit some anatomical patterns consistent with past studies and potential new brain areas of interest in personality.

Although we typically talk about attention as a single process, it comprises multiple independent components. But what are these components, and how are they represented in the functional organization of the brain? To investigate whether long-studied components of attention are reflected in the brain's intrinsic functional organization, here we apply connectome-based predictive modeling (CPM) to predict the components of Posner and Petersen's influential model of attention: alerting (preparing and maintaining alertness and vigilance), orienting (directing attention to a stimulus), and executive control (detecting and resolving cognitive conflict) [Posner, M. I., & Petersen, S. E. The attention system of the human brain. Annual Review of Neuroscience, 13, 25-42, 1990]. Participants performed the Attention Network Task (ANT), which measures these three factors, and rested during fMRI scanning. CPMs tested with leave-one-subject-out cross-validation successfully predicted novel individual's overall ANT accuracy, RT variability, and executive control scores from functional connectivity observed during ANT performance. CPMs also generalized to predict participants' alerting scores from their resting-state functional connectivity alone, demonstrating that connectivity patterns observed in the absence of an explicit task contain a signature of the ability to prepare for an upcoming stimulus. Suggesting that significant variance in ANT performance is also explained by an overall sustained attention factor, the sustained attention CPM, a model defined in prior work to predict sustained attentional abilities, predicted accuracy, RT variability, and executive control from task-based data and predicted RT variability from resting-state data. Our results suggest that, whereas executive control may be closely related to sustained attention, the infrastructure that supports alerting is distinct and can be measured at rest. In the future, CPM may be applied to elucidate additional independent components of attention and relationships between the functional brain networks that predict them.

Helicobacter pylori is recognised as a main risk factor for gastric cancer. However, approximately half of the patients with gastritis are negative for H. pylori infection, and the abundance of H. pylori decreases in patients with cancer. In the current study, we profiled gastric epithelium-associated bacterial species in patients with gastritis, intestinal metaplasia, and gastric cancer to identify additional potential pathogenic bacteria. The overall composition of the microbiota was similar between the patients with gastritis and those with intestinal metaplasia. H. pylori was present in half of the non-cancer group, and the dominant bacterial species in the H. pylori-negative patients were Burkholderia, Enterobacter, and Leclercia. The abundance of those bacteria was similar between the cancer and non-cancer groups, whereas the frequency and abundance of H. pylori were significantly lower in the cancer group. Instead, Clostridium, Fusobacterium, and Lactobacillus species were frequently abundant in patients with gastric cancer, demonstrating a gastric cancer-specific bacterial signature. A receiver operating characteristic curve analysis showed that Clostridium colicanis and Fusobacterium nucleatum exhibited a diagnostic ability for gastric cancer. Our findings indicate that the gastric microenvironment is frequently colonised by Clostridium and Fusobacterium in patients with gastric cancer.

ZnO, Al-doped ZnO (AZO), and Ga-doped ZnO (GZO) semiconductor thin films were deposited on glass substrates via a sol-gel spin-coating process for application in a photoconductive ultraviolet (UV) detector. The doping concentrations of Al and Ga were 1.0 at % in the precursor solutions. In this study, the microstructural features and the optical and electrical properties of sol-gel-derived ZnO, AZO, and GZO thin films were compared, and the performance of ZnO-based UV photodetectors under ultraviolet A (UVA) light were measured. Experimental results confirmed the synthesis of single-phase nanocrystalline ZnO-based thin films and the successful substitution of Al and Ga into Zn sites in ZnO crystals. The results also demonstrated that the optical transmittance and electrical properties of ZnO thin films could be improved by Al and Ga doping. UV photodetectors based on ZnO-based thin films, having a metal-semiconductor-metal (MSM) configuration, were fabricated with Al inter-digitated electrodes. All photodetectors showed an ohmic nature between semiconductor and electrode contacts and exhibited a sharp increase in photocurrent under illumination with UVA light. We found that the MSM UV photodetector based on the GZO semiconductor thin film exhibited the best UV response ( I UVA / I dark ) of 73.3 and the highest photocurrent responsivity of 46.2 A/W under UVA light (power density ~0.825 mW/cm²) at 5 V bias., Competing Interests: The authors declare no conflict of interest.

Background: Several clinical trials on hypertonic fluid administration have been completed, but the results have been inconclusive. The objective of this study is to summarize current evidence for treating hypovolemic patients with hypertonic solutions by performing a systematic review and meta-analysis., Methods: Major electronic databases were searched from inception through June 2014. We included only randomized controlled trials involving hemorrhagic shock patients treated with hypertonic solutions. After screening 570 trials, 12 were eligible for the final analysis. Pooled effect estimates were calculated with a random effect model., Results: The 12 studies included 6 trials comparing 7.5% hypertonic saline (HS) with 0.9% saline or Ringer's lactate solution and 11 trials comparing 7.5% hypertonic saline with dextran (HSD) with isotonic saline or Ringer's lactate. Overall, there were no statistically significant survival benefits for patients treated with HS (relative risk [RR], 0.96; 95% confidence interval [CI], 0.82-1.12) or HSD (RR, 0.92; 95% CI, 0.80-1.06). Treatment with hypertonic solutions was also not associated with increased complications (RR, 1.03; 95% CI, 0.78-1.36). Subgroup analysis on trauma patients in the prehospital or emergency department settings did not change these conclusions. There was no evidence of significant publication bias. Meta-regression analysis did not find any significant sources of heterogeneity., Conclusions: Current evidence does not reveal increased mortality when the administration of isotonic solutions is compared to HS or HSD in trauma patients with hemorrhagic shock. HS or HSD may be a viable alternative resuscitation fluid in the prehospital setting. Further studies are needed to determine the optimum volume and regimen of intravenous fluids for the treatment of trauma patients.

Monolayer transition metal dichalcogenides, such as MoS 2 and WSe 2 , have been known as direct gap semiconductors and emerged as new optically active materials for novel device applications. Here we reexamine their direct gap properties by investigating the strain effects on the photoluminescence of monolayer MoS 2 and WSe 2 . Instead of applying stress, we investigate the strain effects by imaging the direct exciton populations in monolayer WSe 2 -MoS 2 and MoSe 2 -WSe 2 lateral heterojunctions with inherent strain inhomogeneity. We find that unstrained monolayer WSe 2 is actually an indirect gap material, as manifested in the observed photoluminescence intensity-energy correlation, from which the difference between the direct and indirect optical gaps can be extracted by analyzing the exciton thermal populations. Our findings combined with the estimated exciton binding energy further indicate that monolayer WSe 2 exhibits an indirect quasiparticle gap, which has to be reconsidered in further studies for its fundamental properties and device applications.Monolayer transition metal dichalcogenides have so far been thought to be direct bandgap semiconductors. Here, the authors revisit this assumption and find that unstrained monolayer WSe 2 is an indirect-gap material, as evidenced by the observed photoluminescence intensity-energy correlation.

Purpose: The prevalence of gastroesophagel reflux disease (GERD) has steadily increased. However, the association between GERD itself and the risk of pneumonia remains unclear. This study aimed to investigate the association between GERD and long-term risk of pneumonia and to identify the major risk factors for pneumonia in GERD patients., Methods: Using the Taiwan National Health Insurance Research Database, we identified patients who were newly diagnosed with GERD and treated with proton pump inhibitors (PPIs) from January 1, 2004 through December 31, 2010. Two groups comprising 15,715 GERD cases and 15,715 non-GERD matched controls were generated using propensity score matching, thereby making the differences in basic demographics, concomitant medication use, and comorbidities between the two groups inconsiderable., Results: Cumulative incidence of pneumonia was significantly higher in the patients with GERD than that in the non-GERD matched controls, with an adjusted HR of 1.48 (95% confidence interval [CI] = 1.31-1.67; P < 0.001) within 6-year follow-ups. Multivariate stratified analyses revealed similar results in many subgroups, with a highest risk in individuals younger than 40 years of age (HR = 2.17, 95% CI = 1.48-3.19). Crucially, patients with GERD using PPIs longer than 4 months were at a significantly increased risk of pneumonia than those who did not use PPIs or took PPIs less than 4 months., Conclusions: GERD was significantly associated with long-term risk of pneumonia, especially in GERD with PPI use longer than 4 months or in the young population. Further prospective longitudinal studies should be conducted for validation and implementing clinical practice guidelines.

This study aimed to determine whether goal orientations were related to students' self-reported misbehaviors in physical education and to examine whether the effects were mediated by moral disengagement. A two-study project employing structural equation modeling was conducted with high school students (Study 1, n = 287; Study 2, n = 296). In Study 1, the results showed that mastery-avoidance goals were unable to predict five misbehaviors (i.e., aggressive behavior, low engagement, failure to follow directions, poor self-management, and distracting behavior). Mastery-approach goals negatively predicted low engagement, failure to follow directions, and poor self-management. Performance-approach goals positively predicted aggressive and distracting behaviors, while performance-avoidance goals positively predicted all five misbehaviors. In Study 2, the results indicated that the positive relationships between performance-approach goals and misbehaviors and between performance-avoidance goals and misbehaviors were mediated by moral disengagement. These results are discussed in terms of the model of achievement goals, and implications for physical education are also highlighted.

Background: Studies investigating the association between antipsychotic use and the risk of cerebrovascular accident (CVA) showed inconsistent results., Aim: Conduct a systematic review and meta-analysis to evaluate whether use of antipsychotics is associated with increased risk of CVA., Methods: Major electronic databases were searched from 1970 to October 2016 for observational studies investigating the risk of CVA among users of antipsychotics. Pooled estimates of odds ratios (ORs) and 95% confidence intervals (CIs) were obtained by random effects meta-analysis., Results: Of 1171 citations identified, 10 studies were considered eligible. Significant increase in risk of CVA was associated with first-generation antipsychotics (OR 1.49; 95% CI 1.24-1.77) but not with second-generation antipsychotics (OR 1.31; 95% CI 0.74-2.30). Use of any antipsychotics in patients with dementia was associated with a low risk of CVA (OR 1.17; 95% CI 1.08-1.26)., Conclusions: The available evidence suggests use of with first-generation antipsychotics as opposed to second-generation antipsychotics significantly increased the risk of CVA., (Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

A man with cytopenias, dysplasia, excess blasts, P53 and RUNX1 mutations, and ring chromosome 7 recovered after stopping lenalidomide., Competing Interests: Conflict-of-interest disclosure: The authors declare no competing financial interests.

Formation of amyloid fibrils has been associated with at least 30 different protein aggregation diseases. The 129-residue polypeptide hen lysozyme, which is structurally homologous to human lysozyme, has been demonstrated to exhibit amyloid fibril-forming propensity in vitro. This study is aimed at exploring the influence of erythrosine B on the in vitro amyloid fibril formation of hen lysozyme at pH 2.0 and 55°C using ThT binding assay, transmission electron microscopy, far-UV circular dichroism absorption spectroscopy, 1-anilinonaphthalene-8-sulfonic acid fluorescence spectroscopy, and synchronous fluorescence study. We found that lysozyme fibrillogenesis was dose-dependently suppressed by erythrosine B. In addition, our far-UV CD and ANS fluorescence data showed that, as compared with the untreated lysozyme control, the α-to-ß transition and exposure of hydrophobic clusters in lysozyme were reduced upon treatment with erythrosine B. Moreover, it could be inferred that the binding of erythrosine B occurred in the vicinity of the tryptophan residues. Finally, molecular docking and molecular dynamics simulations were further employed to gain some insights into the possible binding site(s) and interactions between lysozyme and erythrosine B. We believe the results obtained here may contribute to the development of potential strategies/approaches for the suppression of amyloid fibrillogenesis, which is implicated in amyloid pathology., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Age-related hearing loss (ARHL) is postulated to affect dementia. Our study aims to investigate the relationship between ARHL and the prevalence, and 10-year incidence of dementia in the Taiwan National Health Insurance Research Database (NHIRD). We selected patients diagnosed with ARHL from the NHIRD. A comparison cohort comprising of patients without ARHL was frequency-matched by age, sex, and co-morbidities, and the occurrence of dementia was evaluated in both cohorts. The ARHL cohort consisted of 4108 patients with ARHL and the control cohort consisted of 4013 frequency-matched patients without ARHL. The incidence of dementia [hazard ratio (HR), 1.30; 95% confidence interval (CI 1.14-1.49); P = 0.002] was higher among ARHL patients. Cox models showed that being female (HR, 1.34; 95% CI 1.07-1.68), as well as having co-morbidities, including chronic liver disease and cirrhosis, rheumatoid arthritis, hypertension, diabetes mellitus, stroke, head injury, chronic kidney disease, coronary artery disease, alcohol abuse/dependence, and tobacco abuse/dependence (HR, 1.27; 95% CI 1.11-1.45), were independent risk factors for dementia in ARHL patients. We found ARHL may be one of the early characteristics of dementia, and patients with hearing loss were at a higher risk of subsequent dementia. Clinicians should be more sensitive to dementia symptoms within the first 2 years following ARHL diagnosis. Further clinical studies of the relationship between dementia and ARHL may be necessary.

Our systematic review and meta-analysis of observational studies indicated that the use of antipsychotics was associated with a nearly 1.5-fold increase in the risk of fracture. First-generation antipsychotics (FGAs) appeared to carry a higher risk of fracture than second-generation antipsychotics (SGAs)., Introduction: The risk of fractures associated with the use of antipsychotic medications has inconsistent evidence between different drug classes. A systematic review and meta-analysis was conducted to evaluate whether there is an association between the use of antipsychotic drugs and fractures., Methods: Searches were conducted through the PubMed and EMBASE databases to identify observational studies that had reported a quantitative estimate of the association between use of antipsychotics and fractures. The summary risk was derived from random effects meta-analysis., Results: The search yielded 19 observational studies (n = 544,811 participants) with 80,835 fracture cases. Compared with nonuse, use of FGAs was associated with a significantly higher risk for hip fractures (OR 1.67, 95% CI, 1.45-1.93), and use of second generation antipsychotics (SGAs) was associated with an attenuated but still significant risk for hip fractures (OR 1.33, 95% CI, 1.11-1.58). The risk of fractures associated with individual classes of antipsychotic users was heterogeneous, and odds ratios ranged from 1.24 to 2.01. Chlorpromazine was associated with the highest risk (OR 2.01, 95% CI 1.43-2.83), while Risperidone was associated with the lowest risk of fracture (OR 1.24, 95% CI 0.95-1.83)., Conclusions: FGA users were at a higher risk of hip fracture than SGA users. Both FGAs and SGAs were associated with an increased risk of fractures, especially among the older population. Therefore, the benefit of the off-label use of antipsychotics in elderly patients should be weighed against any risks for fracture.

Background: General anesthesia (GA) as a pediatric dental procedure is a well-established method of behavior management. However, studies of pediatric dentistry under GA have mostly focused on handicapped patients, and various retrospective studies in Taiwan have mainly reviewed only a limited number of years. The purpose of the present study was to report trends in pediatric dental treatment performed under GA over the past 10 years., Methods: A retrospective review of the hospital records of patients receiving dental treatment under GA from 2006 until 2015 was performed. The patients were divided into three age groups: < 3 years, 3-6 years, and > 6 years. A range of information including basic patient characteristics and types of dental treatment was identified and then analyzed., Results: A total of 791 cases (< 3 years old: 65 cases, 3-6 years old: 492, > 6 years old: 235; 549 male, 242 female) were treated under GA. The case number was found to have increased from 94 during 2006-2007 to 238 during 2014-2015, with the increase being especially pronounced among those aged 3-6 years (2006-2007: 49, 2014-2015: 165). The most common treatments (extraction, restoration, and pulp therapy) were associated with multiple dental caries (684, 86.4%). The < 3-years-old group was characterized by the highest decayed, extracted, and filled surface and decayed, missing, and filled surface indices; the highest mean number of treated teeth; and the highest mean number of treated teeth by composite resin fillings. The 3-6-years-old group had the highest number of primary teeth extractions. The > 6-years-old group had the lowest mean number of treated teeth by stainless-steel crowns (SSCs) and fewest cases treated with pulp therapy. From 2011 onwards, the number of primary tooth extractions significantly increased, while in 2013, there was a crossover whereby the SSC count surpassed the composite resin filling count., Conclusion: Over the past 10 years, there has been an increased use of GA for pediatric dental treatments, in particular, in cases with multiple dental caries. In addition, there has also been an increasing trend towards extraction of primary teeth and the use of SSCs., (Copyright © 2017. Published by Elsevier Taiwan LLC.)

The p85α subunit of phosphatidylinositol 3-kinase (PI3K) acts as a key regulator of cell proliferation and motility, which mediates signals that confer chemoresistance to many human cancer cells. Using small interfering RNAs against matrix metalloproteinase-2 (MMP-2) and the MMP-2 promoter-driven luciferase assay, we showed that the new synthetic bichalcone analog TSWU-CD4 inhibits the invasion of human cancer cells by down-regulating MMP-2 expression. Treatment with TSWU-CD4 inhibited MMP-2 expression and cell invasion, which were restored by ectopic wild type (wt) p85α or a constitutively active form of MAPK kinase 3 (CA MKK3), CA MKK6, or CA p38α mitogen-activated protein kinase (MAPK). The attenuated formation of lipid raft-associated phospho (p)-p85α-GTP-Rac1 complexes, protein kinase B (Akt) Ser 473 phosphorylation, and cell invasion by TSWU-CD4 was reversed by overexpression of wt p85α or the p85α Brc-homology (BH) domain. The ectopic expression of CA Rac1 L61 (but not wt Rac1) could overcome the suppression of Ser 473 phosphorylation, lipid raft association of Akt, the interaction between GTP-bound Rac1 and p85α in lipid rafts, and cell invasion by TSWU-CD4. The involvement of Akt activity in the functions of NF-κB-mediated MMP-2 was further confirmed through the attenuation of Akt phosphorylation signaling using the Akt-specific inhibitor MK-2206 and ectopic expression of NF-κB p65. Collectively, the inhibitory effect of TSWU-CD4 on cancer cell invasion was likely to suppress the p-p85α-GTP-Rac1 interaction in lipid rafts by targeting the p85α BH domain, which resulted in the suppression of MMP-2 expression via the PI3K-Akt-mediated ERK-MKK3/MKK6-p38 MAPK-NF-κB signaling pathway. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

The characteristics of PAHs that are emitted by a municipal waste incinerator (MWI) and coal-fired power plant are examined via intensive sampling. Results of flue gas sampling reveal the potential for PAH formation within the selective catalytic reduction (SCR) system of a coal-fired power plant. In the large-scale MWI, the removal efficiency of PAHs achieved with the pilot-scaled catalytic filter (CF) exceeds that achieved by activated carbon injection with a bag filter (ACI+BF) owing to the effective destruction of gas-phase contaminants by a catalyst. A significantly lower PAH concentration (1640ng/g) was measured in fly ash from a CF module than from an ACI+BF system (5650ng/g). Replacing the ACI+BF system with CF technology would significantly reduce the discharge factor (including emission and fly ash) of PAHs from 251.6 to 77.8mg/ton-waste. The emission factors of PAHs that are obtained using ACI+BF and the CF system in the MWI are 8.05 and 7.13mg/ton, respectively. However, the emission factor of MWI is significantly higher than that of coal-fired power plant (1.56mg/ton). From the perspective of total environmental management to reduce PAH emissions, replacing the original ACI+BF process with a CF system is expected to reduce environmental impact thereof., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Molecular-level differences ranging from genomes to proteomes, but not N-glycoproteomes, between human induced pluripotent stem cells (hiPSCs) and embryonic stem cells (hESCs) have been assessed to gain insights into cell reprogramming and induced pluripotency. Our multiplexed quantitative N-glycoproteomics study identified altered N-glycoproteins that significantly regulate cell adhesion processes in hiPSCs compared to hESCs. The integrative proteomics and functional network analyses of the altered N-glycoproteins revealed their significant interactions with known PluriNet (pluripotency-associated network) proteins. We found that these interactions potentially regulate various signaling pathways including focal adhesion, PI3K-Akt signaling, regulation of actin cytoskeleton, and spliceosome. Furthermore, the integrative transcriptomics analysis revealed that imperfectly reprogrammed subunits of the oligosaccharyltransferase (OST) and dolichol-phosphate-mannose synthase (DPM) complexes were potential candidate regulatory events for the altered N-glycoprotein levels. Together, the results of our study suggest that imperfect reprogramming of the protein complexes linked with the N-glycosylation process may result in N-glycoprotein alterations that affect induced pluripotency through their functional protein interactions.

Acquired sensory hearing loss (SHL) is suggested to be associated with depression. However, some studies have reported conflicting results. Our study investigated the relationship between the prevalence of SHL and the incidence of depression over 12 years of follow-up by using data from the Taiwan National Health Insurance Research Database (NHIRD). We sought to determine the association between SHL and subsequent development of depression and discuss the pathophysiological mechanism underlying the association.Patients with SHL were identified from the NHIRD (SHL cohort). A non-SHL cohort, comprising patients without SHL frequency-matched with the SHL patients according to age group, sex, and the year of diagnosis of SHL at the ratio of 1:4, was constructed, and the incidence of depression was evaluated in both cohorts. A multivariable model was adjusted for age, sex, and comorbidity.The SHL cohort and non-SHL cohort comprised 5043 patients with SHL and 20,172 patients without SHL, respectively. The incidences density rates were 9.50 and 4.78 per 1000 person-years in the SHL cohort and non-SHL cohort, respectively. After adjustment for age, sex, and comorbidities, the risk of depression was higher in the SHL cohort than in the non-SHL cohort (hazard ratio = 1.73, 95% confidence interval = 1.49-2.00).Acquired SHL may increase the risk of subsequent depression. The results demonstrated that SHL was an independent risk factor regardless of sex, age, and comorbidities. Moreover, a strong association between hearing loss and subsequent depression among Taiwanese adults of all ages, particularly those aged ≤49 and >65 years and without using steroids for the treatment of SHL was observed. Prospective clinical and biomedical studies on the relationship between hearing loss and depression are warranted for determining the etiopathology.

The healing of a corneal epithelial defect is essential for preventing infectious corneal ulcers and subsequent blindness. We previously demonstrated that mesenchymal stem cells (MSCs) in the corneal stroma, through a paracrine mechanism, yield a more favorable therapeutic benefit for corneal wound re-epithelialization than do MSCs in the corneal epithelium. In this study, MSCs were grown on a matrix with the rigidity of the physiological human vitreous (1 kPa), corneal epithelium (8 kPa), or corneal stroma (25 kPa) for investigating the role of corneal tissue rigidity in MSC functions regarding re-epithelialization promotion. MSC growth on a 25-kPa dish significantly promoted the wound healing of human corneal epithelial (HCE-T) cells. Among growth factors contributing to corneal epithelial wound healing, corneal stromal rigidity selectively enhanced transforming growth factor-beta (TGF-β) secretion from MSCs. Inhibitors of TGF-β pan receptor, TGF-β receptor 1, and Smad2 dose dependently abrogated MSC-mediated HCE-T wound healing. Furthermore, MSCs growth on a matrix with corneal stromal rigidity enhanced the ability of themselves to promote corneal re-epithelialization by activating matrix metalloproteinase (MMP) expression and integrin β1 production in HCE-T cells through TGF-β signaling pathway activation. Smad2 activation resulted in the upregulation of MMP-2 and -13 expression in HCE-T cells, whereas integrin β1 production favored a Smad2-independent TGF-β pathway. Altogether, we conclude that corneal stromal rigidity is a critical factor for MSC-induced promotion of corneal re-epithelialization. The activation of the TGF-β signaling pathway, which maintains the balance between integrin and MMP expression, in HCE-T cells is the major pathway responsible for MSC-mediated wound healing. Stem Cells 2016;34:2525-2535., (© 2016 AlphaMed Press.)

Unlabelled: Recent work has demonstrated that human whole-brain functional connectivity patterns measured with fMRI contain information about cognitive abilities, including sustained attention. To derive behavioral predictions from connectivity patterns, our group developed a connectome-based predictive modeling (CPM) approach (Finn et al., 2015; Rosenberg et al., 2016). Previously using CPM, we defined a high-attention network, comprising connections positively correlated with performance on a sustained attention task, and a low-attention network, comprising connections negatively correlated with performance. Validating the networks as generalizable biomarkers of attention, models based on network strength at rest predicted attention-deficit/hyperactivity disorder (ADHD) symptoms in an independent group of individuals (Rosenberg et al., 2016). To investigate whether these networks play a causal role in attention, here we examined their strength in healthy adults given methylphenidate (Ritalin), a common ADHD treatment, compared with unmedicated controls. As predicted, individuals given methylphenidate showed patterns of connectivity associated with better sustained attention: higher high-attention and lower low-attention network strength than controls. There was significant overlap between the high-attention network and a network with greater strength in the methylphenidate group, and between the low-attention network and a network with greater strength in the control group. Network strength also predicted behavior on a stop-signal task, such that participants with higher go response rates showed higher high-attention and lower low-attention network strength. These results suggest that methylphenidate acts by modulating functional brain networks related to sustained attention, and that changing whole-brain connectivity patterns may help improve attention., Significance Statement: Recent work identified a promising neuromarker of sustained attention based on whole-brain functional connectivity networks. To investigate the causal role of these networks in attention, we examined their response to a dose of methylphenidate, a common and effective treatment for attention-deficit/hyperactivity disorder, in healthy adults. As predicted, individuals on methylphenidate showed connectivity signatures of better sustained attention: higher high-attention and lower low-attention network strength than controls. These results suggest that methylphenidate acts by modulating strength in functional brain networks related to attention, and that changing whole-brain connectivity patterns may improve attention., (Copyright © 2016 the authors 0270-6474/16/369547-11$15.00/0.)

Aberrant Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling is crucial to the development of gastric cancer. In this study, we examined the role of STAT3 in the expression and methylation of its targets in gastric cancer patients. Results from RNA sequencing identified an inverse correlation between the expression of STAT3 and GATA6 in 23 pairs of gastric cancer patient samples. We discovered that the expression of GATA6 is epigenetically silenced through promoter methylation in gastric cancer cell lines. Interestingly, the inhibition of STAT3 using a novel STAT3 inhibitor restored the expression of GATA6 and its targets, trefoil factors 1 and 2 (TFF1/2). Moreover, disruption of STAT3 binding to GATA6 promoter by small hairpin RNA restored GATA6 expression in AGS cells. A clinically significant correlation was also observed between the expression of GATA6 and TFF1/2 among tissue samples from 60 gastric cancer patients. Finally, bisulfite pyrosequencing revealed GATA6 methylation in 65% (39/60) of the patients, and those with higher GATA6 methylation tended to have shorter overall survival. In conclusion, we demonstrated that aberrant JAK/STAT signaling suppresses TFF1/2 partially through the epigenetic silencing of GATA6. Therapeutic intervention of STAT3 in reversing the epigenetic status of GATA6 could benefit the treatment of gastric cancer and is worthy of further investigation., Competing Interests: The authors declare no conflict of interest.

Background: Epidemiological data suggest that statins improve the clinical outcome of respiratory infections. We sought to examine whether statin therapy decreases the risk of active TB., Methods: We conducted a nested case-control study on data obtained from a national health insurance claims database between 1999 and 2011. The use of statins was classified as current, recent, past or chronic use. Three conditional logistic regression models were used to estimate the incidence rate ratios (RRs). The first assessed the effect of statin use without further adjustment; the second adjusted (individually) for 75 potential confounders; and the third adjusted for the Disease Risk Score (DRS)., Results: A total of 8098 new TB cases and 809 800 control patients were examined. All four types of statin users showed a decreased risk of active TB. Chronic use (>90 days in a calendar year) of statins was associated with the lowest unadjusted risk of TB (RR 0.74; 95% CI 0.63 to 0.87). The protective effect of active TB remained after adjusting for individual confounders (RR 0.66; 95% CI 0.56 to 0.78) and after DRS adjustment (RR 0.62; 95% CI 0.53 to 0.72). The effect estimates obtained for chronic and current use of statins were very similar. We also found that the active TB protection increased with increasing length of statin prescription., Conclusions: We found that statin therapy was associated with a decreased risk of active TB, and the length of statin therapy affected the TB protection. Given the observational nature of this study, the protective effect against active TB must be confirmed in future randomised trials., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Sex-determining region Y (SRY)-box protein 2 (SOX2) plays a critical role in stem cell maintenance and carcinogenesis. In addition to its function as a minor-groove DNA binding transcription factor, our previous study showed that SOX2 also acts as a RNA binding protein. In current study, we first showed that SOX2 displayed high affinity toward the mRNA encoding S100A14 in BFTC905 and that depletion of SOX2 resulted in a decrease of S100A14 mRNA and protein level. To characterize the RNA binding sequence recognized by SOX2, oligomer-directed RNase H digestion was coupled to the cross-linking before immunoprecipitation assay to demonstrate that SOX2 preferentially binds to the 3'-UTR of the S100A14 mRNA. Using EGFP-S100A14 3'-UTR reporters and mobility shift assay, we identified that the binding sequence on the 3'-UTR of the S100A14 mRNA exhibits a stem-loop structure. Together, our data indicates that SOX2 enhances S100A14 expression by binding to the 3'-UTR of the S100A14 mRNA. Functionally, depletion of SOX2 increases growth and mobility of BFTC905. Knock-down of S100A14 in BFTC905 also leads to an increase in the number of the cells in the S phase and higher mobility, suggesting that SOX2 suppresses cell growth and mobility through promoting the expression of S100A14. Together, our experimental evidence indicates that SOX2 is capable of exerting its cellular functions by functioning as an RNA binding protein in post-transcriptional regulation.

Background/purpose: Heart failure (HF) patients are at high risk of having drug-related problems (DRPs). We aim to describe the frequency, types, and temporal occurrence of DRPs in Taiwanese HF outpatients receiving case management., Methods: In this study, we included 141 patients from HF clinics in three hospitals in Taiwan from October 2008 to December 2010. Nurse case managers at each of the participating sites registered case report forms (CRFs) for patients during clinic visits. DRPs were classified using the Pharmaceutical Care Network Europe Foundation (PCNE) classification system and documented by pharmacists after reviewing CRFs and participating in multidisciplinary team discussions., Results: For 141 clinic participants, the average duration of medication use was 17 months, and 796 DRPs were reported. The DRPs most frequently recorded were the need for laboratory tests (32.7% of total DRPs), followed by potential interaction (29.6%), nonallergic side effects (13.3%), and insufficient awareness of health and disease (9.5%). The drugs most frequently causing a DRP were angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, diuretics, warfarin, spironolactone, and β-blockers. The incidence rates of total DRPs was maximal during the initial 3 months of medication treatment, whereas the incidence rates of each category of DRPs showed multiform changes over time among various drug classes., Conclusion: In Taiwan where the clinical pharmacist system is not well organized, HF outpatients still had a high prevalence of DRPs despite intensive monitoring by nurse case managers. Clinical pharmacists play critical roles in detecting potential DRPs during long-term medication treatment for this population., (Copyright © 2015. Published by Elsevier B.V.)

Rheumatoid arthritis (RA) is an autoimmune disease in which dysregulated immune cells primarily target synovial joints. Despite recent advances in the treatment of RA, including the introduction of biologic therapies and employment of combination disease-modifying antirheumatic drug strategies, remission rates remain suboptimal. Previous studies have demonstrated that the adoptive transfer of induced regulatory T cells (iTregs) was effective in treating a murine model of collagen-induced arthritis (CIA). The objective of this study was to develop optimal potential iTreg-based therapy for CIA by adoptively transferring LAG3(+) Treg-of-B cells. B-cell-induced Treg-of-B cells expressed LAG3 but not Foxp3 (designated LAG3(+) Treg-of-B), and secreted IL-4, IL-10, and TGF-β. Furthermore, LAG3(+) Treg-of-B cells suppressed the proliferation of CD4(+)CD25(-) responder T cells through both LAG3 and IL-10 production. In the murine CIA model, adoptive transfer of LAG3(+) Treg-of-B cells alleviated the joint severity as well as local and systemic inflammation. Treatment with LAG3(+) Treg-of-B cells also promoted IL-10 production in lymphocytes isolated from the spleen and draining lymph nodes. Moreover, mice receiving LAG3(+) Treg-of-B cell treatment showed significantly less pronounced osteolysis in the hind footpads, which correlated with the downregulation of tartrate-resistant acid phosphatase expression. In conclusion, we identified a novel subset of Tregs for CIA treatment. This insight may facilitate exploring novel regulatory T-cell-based therapies for human autoimmune diseases., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Endovascular aortic aneurysm repair (EVAR) is a predominant surgical procedure to reduce the risk of aneurysm rupture in abdominal aortic aneurysm (AAA) patients. Endoleak formation, which eventually requires additional surgical reoperation, is a major EVAR complication. Understanding the etiology and evolution of endoleak from the hemodynamic perspective is crucial to advancing the current posttreatments for AAA patients who underwent EVAR. Therefore, a comprehensive flow assessment was performed to investigate the relationship between endoleak and its surrounding pathological flow fields through computational fluid dynamics and image processing. Six patient-specific models were reconstructed, and the associated hemodynamics in these models was quantified three-dimensionally to calculate wall stress. To provide a high degree of clinical relevance, the mechanical stress distribution calculated from the models was compared with the endoleak positions identified from the computed tomography images of patients through a series of imaging processing methods. An endoleak possibly forms in a location with high local wall stress. An improved stent graft (SG) structure is conceived accordingly by increasing the mechanical strength of the SG at peak wall stress locations. The presented analytical paradigm, as well as numerical analysis using patient-specific models, may be extended to other common human cardiovascular surgeries.

Background: The pendulum test is a standard clinical test for quantifying the severity of spasticity. In the test, an electrogoniometer is typically used to measure the knee angular motion. The device is costly and difficult to set up such that the pendulum test is normally time consuming., Objective: The goal of this study is to determine whether a Nintendo Wii remote can replace the electrogroniometer for reliable assessment of the angular motion of the knee in the pendulum test., Methods: The pendulum test was performed in three control participants and 13 hemiplegic stroke patients using both a Wii remote and an electrogoniometer. The correlation coefficient and the Bland-Altman difference plot were used to compare the results obtained from the two devices. The Wilcoxon signed-rank test was used to compare the difference between hemiplegia-affected and nonaffected sides in the hemiplegic stroke patients., Results: There was a fair to strong correlation between measurements from the Wii remote and the electrogoniometer (0.513

Aim: Galectin-3 (Gal-3) is a new biomarker for assessing prognosis of heart failure (HF) patients. This systemic review and meta-analysis aims to examine Gal-3's ability in assessing prognosis of HF patients., Method: We searched MEDLINE and Embase up to November 2014. Test performance characteristics were summarized using forest plots and hierarchical summary receiver operating characteristic curves., Results: The diagnostic odds ratio of Gal-3 in predicting mortality in chronic HF patients was 2.36 (95% CI: 1.71-3.26) and 2.30 (95% CI: 1.76-3.01) in acute HF patients., Conclusion: Elevated levels of Gal-3 are associated with mortality in both acute and chronic HF patients. However, current evidence does not support sole use of Gal-3 for prognosis evaluation of HF patients.

This study investigates the removal efficiencies of PCDD/Fs achieved with a catalytic filter (CF) and with activated carbon injection followed by bag filter (ACI+BF) as applied in an industrial waste incinerator (IWI) and a hazardous waste incinerator (HWI), respectively. Catalytic filtration has been successfully applied to remove PCDD/Fs from gas streams. Comparing the CF to the ACI+BF system, it appears that the PCDD/F removal efficiency achieved with a CF is higher than that of an ACI+BF system. The PCDD/F emissions from both incinerators are well controlled to meet the regulatory limit of 0.1 ng I-TEQ/Nm(3). Additionally, the PCDD/F concentration in BF ash is higher than the regulation limit of Taiwan (1.0 ng I-TEQ/g). In contrast, the PCDD/F concentration in CF ash is only 0.274 ng I-TEQ/g. The difference is attributed to the fact that the ACI+BF system just transfers PCDD/Fs from gas phase to solid phase and further increases the PCDD/F concentration in fly ash, while CF technology effectively destroys the gas-phase PCDD/Fs. Therefore, the disposal of the fly ash discharged from CF would be less expensive compared with the fly ash discharged from the ACI+BF system. In this study, the PCDD/F emission factors of both incinerators are also established., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

A robust valley polarization is a key prerequisite for exploiting valley pseudospin to carry information in next-generation electronics and optoelectronics. Although monolayer transition metal dichalcogenides with inherent spin-valley coupling offer a unique platform to develop such valleytronic devices, the anticipated long-lived valley pseudospin has not been observed yet. Here we demonstrate that robust valley-polarized holes in monolayer WSe2 can be initialized by optical pumping. Using time-resolved Kerr rotation spectroscopy, we observe a long-lived valley polarization for positive trion with a lifetime approaching 1 ns at low temperatures, which is much longer than the trion recombination lifetime (∼10-20 ps). The long-lived valley polarization arises from the transfer of valley pseudospin from photocarriers to resident holes in a specific valley. The optically initialized valley pseudospin of holes remains robust even at room temperature, which opens up the possibility to realize room-temperature valleytronics based on transition metal dichalcogenides.

This study was conducted to determine the effect of dietary supplement of bacterial lycopene (BL) produced by Escherichia coli on the egg quality and blood characteristics of laying quails. The antioxidant activity measurement showed that BL exhibited 100% 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging capacity at a concentration of 4.65 μg/ml, which was more effective than butylated hydroxytoluene (BHT) and commercial lycopene (CL). Moreover, seven dietary groups of laying quails consisting of 10 100-day-old quails (Coturnix coturnix japonica) each were fed with the basal diet supplemented with BL, CL or canthaxanthin (CA) for 4 weeks. Consequently, the triglyceride content of yolk was significantly lower in the group with BL and CL supplement. The serum malondialdehyde (MDA) level of the BL- and CA-supplemented groups at 18 mg/kg was lower than the control group. In conclusion, BL has a high antioxidant activity and is promising as a feed additive in the diet of laying quails., (Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

Lung fibrosis is a poor prognostic factor for pulmonary adenocarcinoma, and the effect of a rigid microenvironment on cancer behavior is unclear. We cultured A549 cells on matrices of 0.2, 2, and 25 kPa to mimic the rigidities of normal lung parenchyma, progressive fibrotic change, and lung fibrosis, respectively. Lung tissue from patients with pulmonary adenocarcinoma was used to confirm the in vitro findings. Increased matrix rigidity promoted cell proliferation and upregulated the epidermal growth factor receptor (EGFR), hepatocyte growth factor receptor (c-Met), and Snail expression in A549 cells. A549 cells became more resistant to the EGFR inhibitor (Erlotinib) and c-Met inhibitor (PHA-665752) when matrix rigidity increased; however, a high concentration of PHA-665752 reversed the rigidity-induced morphological pleomorphism. In human lung tissue, expression of type I collagen was more consistent with clinical fibrosis than the expression of alpha-smooth muscle antibody was. c-Met- and Snail-expressing tumor cells, rather than EGFR-experssing cells, were localized with lung parenchyma rich in type I collagen. Our findings suggest that c-Met causes the rigidity-induced biophysical reaction in pulmonary adenocarcinoma. Treatment targeting both EGFR and c-Met should be considered for patients with lung fibrosis and who are abundant type I collagen expression in the tumor mass., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Nicorandil is a vasodilatory drug used to relieve angina symptoms. Several healthcare products regulatory agencies have issued a warning associating the use of nicorandil and gastrointestinal (GI) ulceration. We aimed to evaluate the association between use of nicorandil and GI ulceration/perforation. A population-based cohort study involving 1 million randomly sampled participants in Taiwan's National Health Insurance Research Database was carried out. We estimated the association between use of nicorandil and GI ulceration/perforation by a Cox proportional hazards regression model. A nicorandil-specific propensity score (PS) was also created for adjustment of 75 covariates and matching. 25.8% (183/710) of nicorandil-treated patients developed new GI ulcer events and 1.6% (20/1254) developed new GI perforation events in the three-year follow-up period, as compared to 9.3% (61,281/659,081) and 0.3% (2,488/770,537) in the general population comparator cohort. Patients treated with nicorandil were at significantly increased risk of GI ulcer (PS adjusted hazard ratio 1.43, 95% CI, 1.23 to 1.65, 6848 excess cases per 100,000 person years) or GI perforation (aHR 1.60, 95% CI 1.02-2.51, 315 excess cases per 100,000 person years) compared with the nicorandil unexposed population. Our finding may warn the clinicians to weigh the overall risk-benefit balance of nicorandil treatment in patients.

The primary objective of this study was to determine the association between the use of gastric acid suppressants (GAS) and the risk of developing spontaneous bacterial peritonitis (SBP) in patients with advanced liver cirrhosis (LC). A case-control study nested within a cohort of 480,000 representatives of Taiwan National Health Insurance beneficiaries was carried out. A case was matched with 100 controls on age, gender, and index date of SBP diagnosis. GAS use was identified from the 1-year period before the index date. Conditional logistic regression analysis was used to adjust for various unbalanced covariates between users and nonusers of GAS. A total of 947 cases of SBP were identified among the 86,418 patients with advanced LC. A significant increased risk of developing SBP was found to be associated with current (within 30 days), and recent (within 30-90 day) use of 2 different classes of GAS: proton pump inhibitors (PPIs) and histamine 2 receptor antagonists (H2RAs). The confounder adjusted rate ratio (aRR) for the current use of PPIs was 2.77 (95% CI: 1.90-4.04) and H2RAs was 2.62 (95% CI: 2.00-3.42). The risk of SBP attenuated for the recent use of PPIs (aRR: 2.20, 95%CI: 1.60-3.02) or H2RAs (aRR: 1.72, 95% CI: 1.25-2.37). In addition, sensitivity analysis using hospitalized SBP as the primary outcome showed a similar risk for the current use of PPIs (aRR, 3.24; 95% CI: 2.08-5.05) and H2RAs (aRR 2.43; 95% CI 1.71-3.46). Furthermore, higher cumulative days of gastric acid suppression were associated with a higher risk of SBP (trend P < 0.0001). To conclude, exposure to GAS was associated with an increased risk of SBP in patients with advanced LC. The association was more pronounced in current PPI users compared with nonusers.