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Pulse wave velocity (PWV) was a good marker of arterial stiffness and could predict cardiovascular (CV) outcomes. Recently, estimated PWV (ePWV) calculated by equations using age and mean blood pressure was reported to be an independent predictor of major CV events. However, there was no study comparing ePWV with brachial‐ankle PWV (baPWV) for CV and overall mortality prediction. We included 881 patients arranged for echocardiographic examination. BaPWV and blood pressures were measured by ankle‐brachial index‐form device. The median follow‐up period to mortality was 94 months. Mortality events were documented during the follow‐up period, including CV mortality (n = 66) and overall mortality (n = 184). Both of ePWV and baPWV were associated with increased CV and overall mortality after the multivariable analysis. ePWV had better predictive value than Framingham risk score (FRS) for CV and overall mortality prediction, but baPWV did not. In direct comparison of multivariable analysis using FRS as basic model, ePWV had a superior additive predictive value for CV mortality than baPWV (p = .030), but similar predictive valve for overall mortality as baPWV (p = .540). In conclusion, both ePWV and baPWV were independent predictors for long‐term CV and overall mortality in univariable and multivariable analysis. Besides, ePWV had a better additive predictive value for CV mortality than baPWV and similar predictive value for overall mortality as baPWV. Therefore, ePWV obtained without equipment deserved to be calculated for overall mortality prediction and better CV survival prediction.

Four-limb blood pressure measurement could improve mortality prediction in the elderly. However, there was no study to evaluate whether such measurement was still useful in predicting overall and cardiovascular (CV) mortality in acute myocardial infarction (AMI). Two hundred AMI patients admitted to cardiac care unit were enrolled. The 4-limb blood pressures, inter-limb blood pressure differences, and ankle brachial index (ABI) were measured using an ABI-form device. The median follow-up to mortality was 64 months (25th-75th percentile: 5-174 months). There were 40 and 138 patients documented as CV and overall mortality, respectively. After multivariable adjustment, the ankle diastolic blood pressure (DBP) on the lower side, ABI value, ABI < 0.9, interarm DBP difference, interankle systolic blood pressure (SBP) and DBP differences, interankle SBP difference ≥ 15 mmHg, and interankle DBP difference ≥ 10 mmHg could predict overall mortality (P ≤ 0.025). The ankle DBP on the lower side, interankle DBP difference, and interankle DBP difference ≥ 10 mmHg could predict CV mortality (P ≤ 0.031). In addition, in the Nested Cox model, the model including the ankle DBP on the lower side and the model including interankle DBP difference had the best value for overall and CV mortality prediction, respectively (P ≤ 0.031). In AMI patients, 4-limb blood pressure measurement could generate several useful parameters in predicting overall and CV mortality. Furthermore, ankle DBP on the lower side and interankle DBP difference were the most powerful parameters in prediction of overall and CV mortality, respectively.

Stumpless chronic total occlusion is associated with a higher failure rate of recanalization. Intravascular ultrasound (IVUS) is useful for identifying the entry point; however, 8-F guide catheters are necessary for real-time IVUS-guided wiring. This case reports the novel use of the “ping-pong” guide catheter technique to facilitate real-time IVUS-guided wiring for a stumpless chronic total occlusion. (Level of Difficulty: Advanced.), Graphical abstract, Stumpless chronic total occlusion is associated with a higher failure rate of recanalization. Intravascular ultrasound (IVUS) is useful for…

The current fusion-based methods transform LiDAR data into bird’s eye view (BEV) representations or 3D voxel, leading to information loss and heavy computation cost of 3D convolution. In contrast, we directly consume raw point clouds and perform fusion between two modalities. We employ the concept of region proposal network to generate proposals from two streams, respectively. In order to make two sensors compensate the weakness of each other, we utilize the calibration parameters to project proposals from one stream onto the other. With the proposed multi-scale feature aggregation module, we are able to combine the extracted regionof-interest-level (RoI-level) features of RGB stream from different receptive fields, resulting in fertilizing feature richness. Experiments on KITTI dataset show that our proposed network outperforms other fusion-based methods with meaningful improvements as compared to 3D object detection methods under challenging setting.

(1) Background: The autonomic imbalance plays a role in vasovagal syncope (VVS) diagnosed by head-up tilting test (HUT). neuECG is a new method of recording skin electrical signals to simultaneously analyze skin sympathetic nerve activity (SKNA) and electrocardiogram. We hypothesize that SKNA is higher in subjects with tilt-positive than tilt-negative and the SKNA surges before syncope. (2) Methods: We recorded neuECG in 41 subjects who received HUT (according to the “Italian protocol”), including rest, tilt-up, provocation and recovery phases. Data were analyzed to determine the average SKNA (aSKNA, μV) per digitized sample. Electrocardiogram was used to calculate standard deviation of normal-to-normal beat intervals (SDNN). The “SKNA-SDNN index” was calculated by rest aSKNA multiplied by the ratio of tilt-up to rest SDNN. (3) Results: 16 of 41 (39%) subjects developed syncope. The aSKNA at rest phase is significantly higher in the tilt-positive (1.21 ± 0.27 µV) than tilt-negative subjects (1.02 ± 0.29 µV) (p = 0.034). There are significant surges and withdraw of aSKNA 30 s before and after syncope (both p ≤ 0.006). SKNA-SDNN index is able to predict syncope (p &lt, 0.001). (4) Conclusion: Higher SKNA at rest phase is associated with positive HUT. The SKNA-SDNN index is a novel marker to predict syncope during HUT.

Background: Upper tract urothelial carcinoma (UTUC) is a relatively rare type of urothelial carcinoma. Additionally, only few reports have examined the sex differences in patients with UTUC. Therefore, the present study aimed to identify the sex factors affecting renal function in patients with UTUC.Methods: Patients who underwent radical nephroureterectomy for non-metastatic UTUC between 2000 and 2013 were retrospectively reviewed and divided into two groups by sex. The Kaplan–Meier method was applied to evaluate the effects of sex on survival, whereas for the other clinicopathological parameters, hazard ratios were evaluated using the Cox regression model. The analyses were also performed in patients with different chronic kidney disease (CKD) stages.Results: A total of 368 patients were included, 147 men and 221 women. Female patients had a higher rate of anemia, advanced CKD stage, and dialysis. Male patients predominantly had a higher rate of smoking. The Kaplan–Meier analysis revealed no differences between sexes on metastasis-free survival (MFS) and cancer-specific survival. Multivariate analysis confirmed that ureteral tumors, advanced pathological tumor stage, and adjuvant chemotherapy indicated significantly worse survival outcomes in both sexes. However, only female patients with advanced CKD showed poorer MFS. After adjusting for renal function, the analysis found men had worse MFS.Conclusions: The female sex is significantly associated with a higher prevalence of advanced CKD among patients with UTUC in Taiwan. The impact of sex differences on renal function needs to be considered when evaluating survival.

DNA barcodes with short sequence fragments are used for species identification. Because of advances in sequencing technologies, DNA barcodes have gradually been emphasized. DNA sequences from different organisms are easily and rapidly acquired. Therefore, DNA sequence analysis tools play an increasingly crucial role in species identification. This study proposed deep barcoding, a deep learning framework for species classification by using DNA barcodes. Deep barcoding uses raw sequence data as the input to represent one-hot encoding as a one-dimensional image and uses a deep convolutional neural network with a fully connected deep neural network for sequence analysis. It can achieve an average accuracy of90 percent for both simulation and real datasets. Although deep learning yields outstanding performance for species classification with DNA sequences, its application remains a challenge. The deep barcoding model can be a potential tool for species classification and can elucidate DNA barcode-based species identification.

Background Urolithiasis is considered a vital public health issue with a substantial burden on kidney function. Additionally, only few reports focused on the gender difference in patients with urolithiasis. Therefore, this study aimed to compare the clinical characteristics of sex difference and their potential risk for chronic kidney disease (CKD) in patients with urolithiasis. Methods Patients diagnosed with stone disease from 2013 to 2018 were retrospectively reviewed and divided into two groups by gender. Clinical demographic characteristics, stone location, stone composition, urine chemistries, and renal function were investigated. Univariate and multivariate analyses were used to assess the relationship and potential risk of CKD between sex groups. Results A total of 1802 patients were included: 1312 from men and 490 from women. Female patients had a higher rate of hypertension, diabetes, and dyslipidemia. Male patients predominantly had calcium-containing stones, especially calcium oxalate stone, uric acid stone, and struvite stone. Carbonate apatite stone was more frequently found in women. Complex surgeries such as percutaneous nephrolithotomy (PCNL) and ureteroscopic lithotripsy (URSL) were more frequently performed in women than that in men. Multivariate analysis confirmed that age > 60 years (odds ratios [ORs] = 6.36; 95% confidence interval [CI], 3.8–10.8), female sex (ORs = 5.31; 95% CI 3.3–8.4), uric acid stone (ORs = 3.55; 95% CI 2.0–6.4), hypertension (OR = 7.20; 95% CI 3.8–13.7), and diabetes (OR = 7.06; 95% CI 3.1–16.2) were independent predictors of poor prognoses in CKD. Conclusions The female gender is significantly associated with a higher prevalence of CKD among patients with urolithiasis. Therefore, women with stone disease may need close renal function monitoring during follow-up.

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase 3 randomized trials. The EXPosurE Registry RiociguaT in patients with pulmonary hypertension (EXPERT) study was designed to monitor the long-term safety of riociguat in clinical practice. Methods: EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study of patients treated with riociguat. Patients were followed for at least 1 year and up to 4 years from enrollment or until 30 days after stopping riociguat treatment. Primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs) coded using Medical Dictionary for Regulatory Activities preferred terms and System Organ Classes version 21.0, collected during routine clinic visits and collated via case report forms. Results: In total, 956 patients with CTEPH were included in the analysis. The most common AEs in these patients were peripheral edema/edema (11.7%), dizziness (7.5%), right ventricular (RV)/cardiac failure (7.7%), and pneumonia (5.0%). The most common SAEs were RV/cardiac failure (7.4%), pneumonia (4.1%), dyspnea (3.6%), and syncope (2.5%). Exposure-adjusted rates of hemoptysis/pulmonary hemorrhage and hypotension were low and comparable to those in the long-term extension study of riociguat (Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase–Stimulator Trial [CHEST-2]). Conclusion: Data from EXPERT show that in patients with CTEPH, the safety of riociguat in routine practice was consistent with the known safety profile of the drug, and no new safety concerns were identified. © 2020 The Authors Eli Lilly and Company; Pfizer; Bayer; GlaxoSmithKline; Merck; Actelion Pharmaceuticals; Meso Scale Diagnostics; United Therapeutics Corporation; Novartis Pharma; Merck Sharp and Dohme; GlaxoSmithKline Australia; Deutsche Forschungsgemeinschaft; Grupo Ferrer Internacional, S.A The EXPERT registry was funded by Bayer AG (Berlin, Germany) and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Kenilworth, NJ, USA. The authors acknowledge the database administration by Torsten Tille, Dresden, and the project administration of Mrs Romy Hoppenz and Mrs Linda Kottke at GWT-TUD GmbH, Dresden. Medical writing services provided by Richard Murphy PhD of Adelphi Communications Ltd, Macclesfield, UK were funded by Bayer AG in accordance with Good Publication Practice (GPP3) guidelines. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prof Marius M. Hoeper reports personal fees from Bayer AG, during the conduct of the study; personal fees from Actelion, personal fees from Acceleron, personal fees from MSD, personal fees from Jansen, personal fees from Pfizer, outside the submitted work. Dr Hans Klose reports speaker and consultancy fees from Actelion, Bayer AG, GSK, Novartis, Pfizer, and United Therapeutics and research support from Actelion, Bayer AG, GSK, Pfizer, and MSD. Dr Michael Halank reports personal fees and non-financial support from Actelion, AstraZeneca, Bayer AG, Berlin-Chemie, GSK, OMT, MSD, and Novartis. Dr George Giannakoulas reports speaker and consultancy fees from Actelion, Bayer, ELPEN Pharmaceuticals, GSK, Pfizer, Lilly, and United Therapeutics, and research support from GSK, ELPEN Pharmaceuticals, and Galenica. Dr Henning Gall has received honoraria and/or other support from Actelion, AstraZeneca, Bayer, BMS, GSK, Janssen-Cilag, Lilly, MSD, Novartis, OMT, Pfizer, and United Therapeutics. Dr Pavel Jansa reports consultancy and speaker fees from MSD, AOP Orphan, and Actelion. Prof Ekkehard Grünig reports research grants and speaker honoraria/consultancy fees from Actelion and Bayer/MSD, research grants from GSK, United Therapeutics, Bellerophon, OMT GmbH, Pfizer, Reata, and Novartis, and speaker honoraria from Bial, Medscape, and OrPha Swiss GmbH. Prof David Pittrow reports personal fees from Actelion, Bayer AG, Aspen, Boehringer Ingelheim, Sanofi, Biogen, Shire, and MSD outside the submitted work. Silvia Ulrich reports research grants and personal fees from Actelion, Bayer, MSD, and Orpha Swiss. Tobias J. Lange has received personal fees from Actelion, MSD, Pfizer, and OMT orphan. Dr Iraklis Tsangaris reports speaker and consultancy fees from Actelion, Bayer AG, ELPEN, GSK, MSD, Pfizer, and United Therapeutics. Stephan Rosenkranz reports remunerations for lectures and/or consultancy from Abbott, Actelion, Arena, Bayer, Ferrer, GSK, MSD, Novartis, Pfizer, and United Therapeutics; and research support to his institution from Actelion, Bayer, Novartis, Pfizer, and United Therapeutics. Repke J. Snijder reports grants from Pfizer and Actelion Pharmaceuticals. Prof Iveta Šimková reports consultancy and speaker fees from MSD, AOP Orphan, and Actelion. Dr Marc Humbert reports grants and personal fees from Bayer and GSK, and personal fees from Actelion, Merck, and United Therapeutics. Marion Delcroix has received investigator, speaker, consultant, and steering committee member fees from Actelion, Bayer AG, Bellerophon, Eli Lilly, GlaxoSmithKline, MSD, Pfizer, and Reata, and research grants from Actelion. Joan A. Barberà reports receipt of honoraria for consultation or speaker fees from Actelion and Merck; and research support through his institution from Actelion, Merck, GlaxoSmithKline, and Ferrer. Joanna Pepke-Zaba reports research grants and speaker honoraria/consultancy fees from Actelion, Bayer/MSD, and GSK. Jean-Luc Vachiéry reports ongoing consultancies to Actelion, Sonnivie, Arena Pharma, Bial Portela, and Respira Therapeutics, past consultancies to AstraZeneca, BayerShering, CardioMEMS, GlaxoSmithKline, Pfizer, Merck, and United Therapeutics, and current membership of an advisory board or similar group for Actelion and GlaxoSmithKline. Jean-Luc Vachiéry's institution receives funding from Actelion Pharmaceuticals for performing clinical studies. Regina Steringer-Mascherbauer, Jens Klotsche, and Miguel-Angel Gomez Sanchez have no conflicts of interest relevant to the EXPERT study. Hossein-Ardeschir Ghofrani reports personal fees for advisory board work, and payment for lectures including service on speaker bureaus, from Actelion, Bayer, GSK, Novartis, and Pfizer; consultancy fees from Actelion, Bayer, Bellerophon Pulse Technologies, GSK, MSD, Novartis, and Pfizer; and grants from Deutsche Forschungsgemeinschaft (DFG). Pilar Escribano Subias reports personal fees from Actelion, Bayer AG, GlaxoSmithKline, and Merck Sharp & Dohme, and grants from Actelion, Bayer AG, GlaxoSmithKline, and Ferrer, outside the submitted work. Gérald Simonneau reports personal fees and non-financial support from Actelion, personal fees and non-financial support from Bayer, personal fees and non-financial support from MSD, outside the submitted work. Douglas S. Helmersen reports industry-sponsored research with Bayer AG, United Therapeutics, and Gilead Sciences, Inc., and advisory board/speaker fees from Bayer AG and Actelion. David Langleben reports honoraria, consultation fees, research support, and/or travel expenses from Actelion, Arena, Bayer AG, Northern Therapeutics, PhaseBio, Acceleron, Janssen, and United Therapeutics. Anco Boonstra reports consultancy fees from Pfizer BV and hospitality from Teva Nederland. Lisa M. Mielniczuk reports speaker fees and honoraria from Bayer AG, and speaker fees, consultancy fees, and travel fees from Actelion. Evgenia Williams and Christian Meier are employees of Bayer AG.

The aim of this study was to examine the effect of extract of pre-germinated brown rice (EP) on metabolic and cardiovascular dysfunction in a rat model of T2DM. Hypertensive rats were divided into: (1) normal diet (ND group), (2) induced T2DM (DM group), and T2DM rats that were treated with (3) EP30 mg/kg (EP30 group) or (4) EP300 mg/kg (EP300 group) per day for 4 weeks. T2DM symptoms included: weight loss, hyperglycaemia, hypoinsulinemia, hyperlipidaemia, higher HbA1c, glucose in urine, and lower GLP-1. EP treatment improved metabolic parameters, activated insulin signalling, and increased lipid metabolism, and also ameliorated T2DM-associated increases in levels of inflammation, free radicals, cardiac hypertrophy and fibrosis. EP reduced T2DM and related cardiovascular complications by increasing insulin signalling and lipid metabolism, and reducing levels of inflammation and free radicals. Thus, EP may be a potential candidate for the treatment of metabolic syndrome and related cardiovascular complications.

In non-haemodialysis (HD) patients, increased epicardial adipose tissue (EAT) thickness was significantly associated with adverse cardiovascular (CV) events. This study was designed to investigate whether EAT thickness was a useful parameter in the prediction of adverse CV events in HD patients. In addition, we also evaluated the major correlates of EAT thickness in these patients. In 189 routine HD patients, we performed a comprehensive transthoracic echocardiographic examination with assessment of EAT thickness. The definition of CV events included CV death, non-fatal stroke, non-fatal myocardial infarction, peripheral artery disease, and hospitalization for heart failure. The follow-up period for CV events was 2.5 ± 0.7 years. Thirty-one CV events were documented. The multivariable analysis demonstrated that older age, smoking status, the presence of diabetes mellitus and coronary artery disease, and low albumin levels were independently correlated with adverse CV events. However, increased EAT thickness was not associated with adverse CV events (P = 0.631). Additionally, older age, female sex, low haemoglobin, and low early diastolic mitral annular velocity were correlated with high EAT thickness in the univariable analysis. In the multivariable analysis, older age and female sex were still correlated with high EAT thickness. In conclusion, high EAT thickness was associated with older age and female sex in the multivariable analysis in our HD patients. However, EAT thickness was not helpful in predicting adverse CV events in such patients. Further large-scale studies are necessary to verify this finding.

This research aims to delineate the anti-inflammatory effect of pregerminated brown rice extract (PE) and γ-oryzanol on improving metabolic features of high-fat diet (HFD)-induced metabolic syndrome (MetS) mouse model. C57BL/6 mice were randomly divided into eight groups: regular diet (RD), HFD, HFD-combined treatment of 0.5, 5, or 10 mg kg-1 day-1 oral gavage γ-oryzanol, and 30, 300, or 600 mg kg-1 day-1 PE for 18 weeks. HFD-fed mice showed overweight, hyperglycemia, hyperlipidemia signs of metabolic disorder, and elevation of inflammatory cytokines such as IL-6, TNF-α, IFN-γ, NO, PGE2 in serum and MAPKs, transcription factor p65, iNOS, and MDA in the liver. In contrast, HFD-fed mice showed lower levels of adiponectin in serum and antiperoxidation enzymes GPx, SOD, and catalase in the liver. While HFD-fed mice cotreated with PE or γ-oryzanol, HFD-induced metabolic disorders, ROS, and inflammation were improved. The anti-MetS, antioxidative stress and anti-inflammation properties of PE were more potent than γ-oryzanol. PRACTICAL APPLICATIONS: Our study showed that PE or γ-oryzanol supplement could help control metabolic disorders, oxidative stress, chronic inflammation, and related complications.

Low ankle-brachial index (ABI) calculated using systolic blood pressure (SBP) is associated with poor prognosis. However, there is no study assessing ABI calculated using mean artery pressure (MAP) and diastolic blood pressure (DBP) in predicting mortality.Two cohort populations were enrolled. The first population comprised 379 patients (106 patients with angiography-proved peripheral artery disease (PAD) and 273 relative normal patients) to evaluate the best cutoff values of ABImbp and ABIdbp for prediction of PAD. The second population included 941 patients undergoing echocardiographic examinations to assess the ability of different ABIs in predicting mortality. ABIs were measured using an ABI-form device.The best cutoff values of ABImbp and ABIdbp for prediction of PAD were 0.92 and 0.88. In our second population, median follow-up to mortality was 93 months. There were 87 cardiovascular and 228 overall deaths. Multivariable analysis showed ABIsbp, ABImap, ABIdbp, ABIsbp0.9, and ABImap0.92 could predict overall and cardiovascular mortality (all p 0.001). ABIdbp0.88 could only predict CV mortality (p = 0.033). In a direct comparison of 6 multivariable models, the basic model consisting of significant variables in the univariable analysis plus ABImap0.92 had the highest predictive value for overall and cardiovascular mortality (all p 0.001).In a direct comparison of 6 multivariable models, the basic model + ABImap 0.92 was the best model in predicting overall and cardiovascular mortality. Hence, calculation of ABI using MAP except SBP might provide extra benefit in survival prediction.

Pulse volume recording is an accurate modality for detecting arterial occlusion in the lower extremities. There are two indexes of pulse volume recording measured at ankle, percentage of mean arterial pressure (%MAP) and upstroke time (UT). The aim of the study was to examine the ability of %MAP and UT for the prediction of overall and cardiovascular mortality in hemodialysis (HD) patients. In 197 routine HD patients, ankle %MAP, ankle UT, and ankle&ndash, brachial index (ABI) were automatically measured by Colin VP-1000 instrument. Fourteen cardiovascular mortality and 29 overall mortalities were documented during 2.7 &plusmn, 0.6 years follow-up. In the univariate analysis, in addition to co-morbidities and traditional clinical parameters, increased total mortality was associated with decreased ABI, ABI &lt, 0.9, increased %MAP and UT, %MAP &gt, 50%, and UT &gt, 169 ms (p &lt, 0.041) and increased cardiovascular mortality was associated with increased UT and %MAP &gt, 50% (p &lt, 0.022). After multivariate analysis, increased %MAP and %MAP &gt, 0.047) were still the predictors of total mortality and %MAP &gt, 50% (p = 0.024) was still the predictor of cardiovascular mortality. In HD patients, we found that ankle %MAP and %MAP &gt, 50% could predict total mortality and ankle %MAP &gt, 50% could predict cardiovascular mortality in the multivariate analysis. Hence, assessment of %MAP from pulse volume recording at ankle might be helpful in identifying the high-risk group for poor prognosis in HD patients.

This study examined the effects of eugenosedin-A (Eu-A) in a streptozotocin (STZ)/nicotinamide-induced rat model of type II diabetes mellitus (T2DM). Six-week-old Sprague–Dawley rats were randomly divided into three groups: (1) RD group, normal rats fed a regular diet (RD), (2) DM group, T2DM rats fed a high-fat diet, and (3) Eu-A group, T2DM rats fed a high fat diet plus oral Eu-A (5 mg/kg/day). After 30 days, the DM group had higher body weight, higher blood glucose and lower insulin levels than the RD group. The DM group also had increased protein expression of glycogen synthase kinase (GSK) in liver and skeletal muscle and decreased protein expression of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), IRS-2, AMP-activated protein kinase (AMPK), glucose transporter-4 (GLUT-4), glucokinase (GCK), and peroxisome proliferator-activated receptor γ (PPAR-γ). STZ/nicotinamide-induced T2DM increased the expression of mitogen-activated protein kinases (MAPKs: p38, ERK, JNK) and inflammatory p65 protein. In the Eu-A treated T2DM rats, however, blood glucose was attenuated and the insulin concentration stimulated. Changes in IR, IRS-1 and IRS-2 proteins as well as AMPK, GLUT-4, GCK, GSK, PPAR-γ, MAPKs, and inflammatory p65 proteins were ameliorated. These results suggested that Eu-A alleviates STZ/nicotinamide-induced hyperglycemia by improving insulin levels and glucose metabolism, and inhibiting the MAPKs- and p65-mediated inflammatory pathway.

A novel logic non-volatile memory (NVM), which is fabricated by generic logic CMOS process without any additional thermal budget and with only two additional mask layers for well implantation, is proposed in this paper. Compared to the traditional cell structure, the proposed memory cell features 45% cell size reduction and overall memory macro has 37.5% area shrinkage. In addition, the NVM macro performs excellent programming/erase endurance capability up to 10K cycles and good data retention at 175°C. The NVM macro can fulfill the autotronic reliability requirements of the thermal stress conditions with 125°C high temperature operating life test over 1K hours.

BackgroundSecondary prevention therapy for patients with coronary artery disease using an antiplatelet agent, β-blocker, renin-angiotensin system blocker (RASB), or statin plays an important role in the reduction of coronary events after coronary artery bypass grafting (CABG) surgery or percutaneous coronary intervention (PCI). We analyzed the status and effects of secondary prevention after coronary revascularization in Taiwan.MethodsThis national population-based cohort study was conducted by analyzing the Longitudinal Health Insurance Database 2000 from the National Health Insurance Research Database of Taiwan. Patients who underwent CABG or PCI from 2004 to 2009 were included in the analysis. The baseline characteristics of the patients and ACC/AHA class I medication use at 12 months were analyzed. The primary endpoints were a composite of major adverse cardiac and cerebrovascular events.ResultsA total of 5544 patients comprising 895 CABG and 4649 PCI patients were evaluated. CABG patients had more comorbidities and a higher rate of major adverse event during the follow-up period. However, use of antiplatelet agents and RASB at 12 months was significantly lower in CABG patients than in PCI patients (44.2% vs. 50.9% and 38.6% vs. 48.9%, both p < 0.01). Age, diabetes, and chronic kidney disease were independent risk factors while statin use was a protective factor for the primary endpoints in both PCI and CABG groups.ConclusionThere is still much room to improve class I medication use in secondary prevention for patients after revascularization in Taiwan. Statin could be an effective treatment to improve the outcomes.

Oral squamous cell carcinoma (OSCC) is one of the most common cancer types worldwide and can be divided into three major subsites: buccal mucosal SCC (BMSCC), tongue SCC (TSCC), and lip SCC (LSCC). The autophagy marker microtubule-associated protein light chain 3B (MAP1LC3B) and adaptor sequestosome 1(SQSTM1) are widely used proteins to evaluate autophagy in tumor tissues. However, the role of MAP1LC3B and SQSTM1 in OSCC is not fully understood, particularly in certain subsites. With a tissue microarray comprised of 498 OSCC patients, including 181 BMSCC, 244 TSCC, and 73 LSCC patients, we found that the expression levels of MAP1LC3B and cytoplasmic SQSTM1 were elevated in the tumor tissues of three subsites compared with those in adjacent normal tissues. MAP1LC3B was associated with a poor prognosis only in TSCC. SQSTM1 was associated with poor differentiation in three subsites, while the association with lymph node invasion was only observed in BMSCC. Interestingly, MAP1LC3B was positively correlated with SQSTM1 in the tumor tissues of BMSCC, whereas it showed no correlation with SQSTM1 in adjacent normal tissue. The coexpression of higher MAP1LC3B and SQSTM1 demonstrated a significantly worse disease-specific survival (DSS) and disease-free survival (DFS) in patients with BMSCC and LSCC, but not TSCC. The knockdown of MAP1LC3B and SQSTM1 reduced autophagy, cell proliferation, invasion and tumorspheres of BMSCC cells. Additionally, silencing both MAP1LC3B and SQSTM1 enhanced the cytotoxic effects of paclitaxel in the tumorspheres of BMSCC cells. Taken together, MAP1LC3B and SQSTM1 might modulate autophagy to facilitate tumorigenesis and chemoresistance in OSCC, particularly in BMSCC.

OBJECTIVE To evaluate whether home or ambulatory blood pressure (BP) monitoring was associated with preclinical hypertensive cardiovascular target organ damage (TOD). METHODS We enrolled participants with prehypertension and stage 1 hypertension from 11 medical centers within the Taiwan hypertension-associated cardiac disease consortium. Recordings of clinical BP measurement, ambulatory BP monitoring for 24 hours, and home BP monitoring during morning and evening were made. The measured parameters of target organ damage included left ventricular mass index (LVMI), left atrial volume index (LAVI), and carotid-femoral pulse wave velocity (PWV). RESULTS Data were collected from 561 study participants (mean age, 65.0 ± 10.8 years; men, 61.3%). Morning and evening home BP values were slightly higher than the daytime and nighttime ABP values (difference for systolic morning-daytime/evening-nighttime, 7.3 ± 14.2/11.3 ± 18.5 mm Hg, P < .001; for diastolic, 5.4 ± 9.4/7.3 ± 12.1, P < .001). Daytime ambulatory (r = 0.114), nighttime ambulatory (r = 0.130), morning home (r = 0.310), and evening home (r = 0.220) systolic BPs (SBPs) were all associated with LVMI (all P < .05). The correlation coefficient was significantly greater for the relationship between daytime home SBP and LVMI than for the relationship between ambulatory SBP and LVMI (P < .01). The goodness of fit of the association between SBP and LVMI improved by adding home daytime SBP to the other SBPs (P < .001). Similar findings were observed for LAVI, but not for PWV. CONCLUSION These findings indicate that morning SBP assessed by home monitoring appears to be a better predictor than other BP measures to determine preclinical hypertensive cardiovascular damage in patients with early-stage hypertension.

Background Several randomized control trials have established that drugs can decrease the heart failure (HF) rehospitalization in patients with HF. However, limited studies have investigated the duration of medicine use to decrease the rehospitalization period in the real world. Hence, this study aims to investigate whether the evidence-based medicine decreases the HF rehospitalization in different treatment intervals in the clinical practice. Method We examined patients admitted with acute HF from the National Health Insurance Research Database in Taiwan. In addition, the major adverse cardiovascular events (MACE) were the composite endpoints of the in-hospital mortality and rehospitalization after 1 year. Furthermore, we analyzed the medicine use to decrease 14 days and 1, 6, and 12 months' HF rehospitalization. Results Overall, we examined 11,012 patients. The use of the renin–angiotensin system (RAS) blockers [hazard ratio (HR), 0.58; P < 0.01], β-blocker (HR, 0.67; P < 0.01), spironolactone (HR, 0.63; P < 0.01), and digitalis (HR, 0.67; P < 0.01) associated with the lower in-hospital mortality rate. The Cox regression analysis revealed that RAS blocker (HR, 0.86; P < 0.01) and β-blocker (HR, 0.71; P < 0.01) were independent predictors for MACE. Although RAS blockers declined rehospitalization to 6 months, β-blocker decreased the rehospitalization rate after 1 month use and the benefit persisted till 12 months. Furthermore, digitalis only lowered rehospitalization to 14 days. Conclusion This study suggests that the use of evidence-based medicine is associated with lower MACE for patients with HF, and these drugs could play vital roles in different periods to decrease the rehospitalization in the clinical setting.

In association studies, the combined effects of single nucleotide polymorphism (SNP)-SNP interactions and the problem of imbalanced data between cases and controls are frequently ignored. In the present study, we used an improved multifactor dimensionality reduction (MDR) approach namely MDR-ER to detect the high order SNP‑SNP interaction in an imbalanced breast cancer data set containing seven SNPs of chemokine CXCL12/CXCR4 pathway genes. Most individual SNPs were not significantly associated with breast cancer. After MDR‑ER analysis, six significant SNP‑SNP interaction models with seven genes (highest cross‑validation consistency, 10; classification error rates, 41.3‑21.0; and prediction error rates, 47.4‑55.3) were identified. CD4 and VEGFA genes were associated in a 2‑loci interaction model (classification error rate, 41.3; prediction error rate, 47.5; odds ratio (OR), 2.069; 95% bootstrap CI, 1.40‑2.90; P=1.71E‑04) and it also appeared in all the best 2‑7‑loci models. When the loci number increased, the classification error rates and P‑values decreased. The powers in 2‑7‑loci in all models were >0.9. The minimum classification error rate of the MDR‑ER‑generated model was shown with the 7‑loci interaction model (classification error rate, 21.0; OR=15.282; 95% bootstrap CI, 9.54‑23.87; P=4.03E‑31). In the epistasis network analysis, the overall effect with breast cancer susceptibility was identified and the SNP order of impact on breast cancer was identified as follows: CD4 = VEGFA > KITLG > CXCL12 > CCR7 = MMP2 > CXCR4. In conclusion, the MDR‑ER can effectively and correctly identify the best SNP‑SNP interaction models in an imbalanced data set for breast cancer cases.

Stromal vascular fraction (SVF) cells were used to increase the efficacy of a newly formed adipose tissue in a collagen gel in vitro. However, the outcome of the seeded cells in the collagen gel in vivo remains unknown. We traced the SVF cells in the host tissue and evaluated the efficacy of SVF for fat tissue engineering.The aggregates implanted in the experimental and control groups were prepared by mixing SVF with the collagen gel and Dulbecco's modified Eagle medium with the collagen gel, respectively. The aggregates were implanted using a subcutaneous injection into the backs of immunodeficient mice. The aggregates were harvested 1, 2, 4, and 6 months after implantation; and 9 mice were euthanized each time. Macroscopic changes in the volume and wet weight of the aggregates were assessed. The formation of adipose tissue was studied using hematoxylin and eosin and Nile red staining. The origin and survival of adipocytes in the aggregates were examined through the immunostaining of leptin antibodies, DNA assay, and tracing of SVF cells by 1,1'-dioctadecyl-3,3,3',3'- tetramethylindocarbocyanine perchlorate labeling.The formation of adipose tissue was observed in all of the aggregates. Implanted human SVF cells remained in the experimental aggregates harvested after 1, 2, and 4 months but not after 6 months. At 6 months, viable adipocytes in both groups were of murine origin. Furthermore, at 6 months, the mean volume of the aggregate (P0.001) and the mean percentage of adipocytes (P0.001) were significantly higher in the experimental group than in the control group.Implanted SVF cells could not be traced in the aggregates harvested at 6 months but promoted the recruitment of host adipocytes to generate more adipose tissue in the experimental group than in the control group.

Upstroke time (UT), measured from the foot-to-peak peripheral pulse wave, is a merged parameter used to assess arterial stiffness and target vascular injuries. In this study, we aimed to investigate UT for the prediction of cardiovascular and all-cause mortality in patients with chronic kidney disease (CKD). This longitudinal study enrolled 472 patients with CKD. Blood pressure, brachial pulse wave velocity (baPWV), and UT were automatically measured by a Colin VP-1000 instrument. During a median follow-up of 91 months, 73 cardiovascular and 183 all-cause mortality instances were recorded. Multivariable Cox analyses indicated that UT was significantly associated with cardiovascular mortality (hazard ratio (HR) = 1.010, p = 0.007) and all-cause mortality (HR = 1.009, p < 0.001). The addition of UT into the clinical models including traditional risk factors and baPWV further increased the value in predicting cardiovascular and all-cause mortality (both p < 0.001). In the Kaplan–Meier analyses, UT ≥ 180 ms could predict cardiovascular and all-cause mortality (both log-rank p < 0.001). Our study found that UT was a useful parameter in predicting cardiovascular and all-cause mortality in CKD patients. Additional consideration of the UT might provide an extra benefit in predicting cardiovascular and all-cause mortality beyond the traditional risk factors and baPWV.

Atherosclerotic cardiovascular disease (ASCVD) including cerebrovascular disease (CVD), coronary artery disease (CAD), and peripheral arterial disease (PAD), contributes to the major causes of death in the world. Although several studies have evaluated the association between gender and major adverse cardiovascular outcomes in old ASCVD patients, the result is not consistent. Hence, we need a large-scale study to address this issue.This retrospective cohort study included aged over 60 year-old patients with a diagnosis of ASCVD, including CVD, CAD, or PAD, from the database contained in the Taiwan National Health Insurance Bureau during 2001 to 2004. The matched cohort was matched by age, comorbidities, and medical therapies at a 1:1 ratio. A total of 9696 patients were enrolled in this study, that is, there were 4848 and 4848 patients in the matched male and female groups, respectively. The study endpoints included acute myocardial infarction, hemorrhagic stroke, ischemic stroke, vascular procedures, in-hospital mortality, and so on. In multivariate Cox regression analysis in matched cohort, the adjusted hazard ratios (HRs) for female group in predicting acute myocardial infarction, hemorrhagic stroke, ischemic stroke, vascular procedures, and in-hospital mortality were 0.67 (P < .001), 0.73 (P = .0015), 0.78 (P < .001), 0.59 (P < .001), and 0.77 (P = .0007), respectively.In this population-based propensity matched cohort study, age over 60 year-old female patients with ASCVD were associated with lower rates of acute myocardial infarction, hemorrhagic stroke, ischemic stroke, vascular procedures, and in-hospital mortality than male patients. Further prospective studies may be investigated in Taiwan.

Molecular mechanisms and pathological features of p-Cresyl sulfate (PCS)-induced uremic lung injury (ULI) in chronic kidney disease (CKD) remain unclear. We analyzed pleural effusions (PE) from CKD and non-CKD patients for uremic toxins, reactive oxygen species (ROS), and chemotactic cytokines. Correlations between PE biomarkers and serum creatinine were also studied. Cell viability and inflammatory signaling pathways were investigated in PCS-treated human alveolar cell model. To mimic human diseases, CKD-ULI mouse model was developed with quantitative comparison of immunostaining and morphometric approach. PE from CKD patients enhance expressions of uremic toxins, hydroxyl radicals, and IL-5/IL-6/IL-8/IL-10/IL-13/ENA-78/GRO &alpha, /MDC/thrombopoietin/VEGF. PE concentrations of ENA-78/VEGF/IL-8/MDC/PCS/indoxyl sulphate correlate with serum creatinine concentrations. In vitro, PCS promotes alveolar cell death, cPLA2/COX-2/aquaporin-4 expression, and NADPH oxidase/mitochondria activation-related ROS. Intracellular ROS is abrogated by non-specific ROS scavenger N-acetyl cysteine (NAC), inhibitors of NADPH oxidase and mitochondria-targeted superoxide scavenger. However, only NAC protects against PCS-induced cell death. In vivo, expressions of cPLA2/COX2/8-OHdG, resident alveolar macrophages, recruited leukocytes, alveolar space, interstitial edema and capillary leakage increase in lung tissues of CKD-ULI mice, and NAC pretreatment ameliorates alveolar&ndash, capillary injury. PCS causes alveolar&ndash, capillary injury through triggering intracellular ROS, downstream prostaglandin pathways, cell death, and activating leukocytes to release multiplex chemoattractants and extracellular ROS. Thus PCS and nonspecific ROS serve as potential therapeutic targets.

Background The function of a protein is determined by its native protein structure. Among many protein prediction methods, the Hydrophobic-Polar (HP) model, an ab initio method, simplifies the protein folding prediction process in order to reduce the prediction complexity. Results In this study, the ions motion optimization (IMO) algorithm was combined with the greedy algorithm (namely IMOG) and implemented to the HP model for the protein folding prediction based on the 2D-triangular-lattice model. Prediction results showed that the integration method IMOG provided a better prediction efficiency in a HP model. Compared to others, our proposed method turned out as superior in its prediction ability and resilience for most of the test sequences. The efficiency of the proposed method was verified by the prediction results. The global search capability and the ability to escape from the local best solution of IMO combined with a local search (greedy algorithm) to the new algorithm IMOG greatly improve the search for the best solution with reliable protein folding prediction. Conclusion Overall, the HP model integrated with IMO and a greedy algorithm as IMOG provides an improved way of protein structure prediction of high stability, high efficiency, and outstanding performance.

Background Visfatin has been reported to be associated with breast cancer progression, but the interaction between the visfatin and clinicopathologic factors in breast cancer progression status requires further investigation. To address this problem, it is better to simultaneously consider multiple factors in sensitivity and specificity assays. Methods In this study, a dataset for 105 breast cancer patients (84 disease-free and 21 progressing) were chosen. Individual and cumulative receiver operating characteristics (ROC) were used to analyze the impact of each factor along with interaction effects. Results In individual ROC analysis, only 3 of 13 factors showed better performance for area under curve (AUC), i.e., AUC > 7 for hormone therapy (HT), tissue visfatin, and lymph node (LN) metastasis. Under our proposed scoring system, the cumulative ROC analysis provides higher AUC performance (0.746–0.886) than individual ROC analysis in predicting breast cancer progression. Considering the interaction between these factors, a minimum of six factors, including HT, tissue visfatin, LN metastasis, tumor stage, age, and tumor size, were identified as being highly interactive and associated with breast cancer progression, providing potential and optimal discriminators for predicting breast cancer progression. Conclusion Taken together, the cumulative ROC analysis provides better prediction for breast cancer progression than individual ROC analysis. Electronic supplementary material The online version of this article (10.1186/s12935-018-0517-z) contains supplementary material, which is available to authorized users.

Background The relationship of epicardial fat and cardiac arrhythmias has been described in many studies. The association of the amounts of epicardial fat and the characteristics of electrocardiogram (ECG) remains unclear. The purpose of this study was to elucidate the association between the amounts of epicardial fat and the characteristics of ECG. Methods A total of 100 consecutive patients who received multi-detector computer tomography (MDCT) were enrolled. The amounts of epicardial fat, including total heart, total atria, total ventricles, right atrium (RA), right ventricle (RV), left atrium (LA), and left ventricle (LV) regions, were measured. The PR interval in lead II, the P wave duration in lead I, the characteristics of inter-atrial conduction block manifested in ECG, the corrected QT interval (QTc) and the QT dispersion of a 12‑lead ECG were measured manually by a computer caliper. Results The PR interval was correlated with the amounts of epicardial fat including total heart, total atria, total ventricles, RA, RV, LA, and LV ( R = 0.295, p = 0.003; R = 0.379, p R = 0.284, p = 0.003; R = 0.415, p R = 0.287, p R = 0.33, p R = 0.244, p = 0.014). The P wave duration of lead I was also correlated with the amounts of epicardial fat ( R = 0.202, p = 0.043; R = 0.283, p = 0.004; R = 0.225, p = 0.024; R = 0.365, p R = 0.256, p = 0.001; R = 0.20, p = 0.046; R = 0.199, p = 0.048) but the QTc interval and the QT dispersion were not. Inter-atrial conduction block was also associated with the amounts of epicardial fat, including total atria, RA and LA in univariate analysis (odds ratio (OR): 1.04, 95% of confidence interval (CI): 1.01–1.06, p = 0.015; OR: 1.08, 95% CI: 1.02–1.15, p = 0.011; OR: 1.05, 95% CI: 1.01–1.10, p = 0.031). In multivariate analysis of linear regression, the amounts of RA epicardial fat was most significantly associated with the PR interval, and the P wave duration (β value: 1.30, 95% CI: 0.59–2.02, p p = 0.001). In multivariate analysis of logistic regression, inter-atrial conduction block was also significantly associated with the amounts of RA epicardial fat (odds ratio (OR): 1.08, 95% CI: 1.02–1.15, p = 0.011). Conclusions The PR interval, P wave duration and inter-atrial conduction block were associated with the amounts of epicardial fat, which might imply an effect for arrhythmogenesis.

Aims: The renal systolic time intervals (STIs), including renal pre-ejection period (PEP), renal ejection time (ET), and renal PEP/renal ET measured by renal Doppler ultrasound, were associated with poor cardiac function and adverse cardiac outcomes. However, the relationship between renal hemodynamic parameters and arterial stiffness in terms of brachial-ankle pulse wave velocity (baPWV) has never been evaluated. The aim of this study was to assess the relationship between renal STIs and baPWV. Methods: This cross-sectional study enrolled 230 patients. The renal hemodynamics was measured from Doppler ultrasonography and baPWV was measured from ABI-form device by an oscillometric method. Results: Patients with baPWV ≧ 1672 cm/s had a higher value of renal resistive index (RI) and lower values of renal PEP and renal PEP/ET (all P< 0.001). In univariable analysis, baPWV was significantly associated with renal RI, renal PEP, and renal PEP/renal ET (all P< 0.001). In multivariable analysis, renal PEP (unstandardized coefficient β = -3.185; 95% confidence interval = -5.169 to -1.201; P = 0.002) and renal PEP/renal ET (unstandardized coefficient β = -5.605; 95% CI = -10.217 to -0.992; P = 0.018), but not renal RI, were still the independent determinants of baPWV. Conclusion: Our results found that renal PEP and renal PEP/renal ET were independently associated with baPWV. Hence, renal STIs measured from renal echo may have a significant correlation with arterial stiffness.

Background: Anemia and echocardiographic systolic and diastolic parameters are useful predictors of cardiovascular outcomes in patients with atrial fibrillation (AF). However, no studies have evaluated the use of anemia for predicting cardiovascular outcome in AF patients when the important echocardiographic parameters are known. Therefore, this study was designed to evaluate whether low hemoglobin is a useful parameter for predicting poor cardiac outcome after adjustment for important echocardiographic parameters in AF patients. Methods: Index beat method was used to measure echocardiographic parameters in 166 patients with persistent AF. Cardiac events were defined as death and hospitalization for heart failure. The association of hemoglobin with adverse cardiac events was assessed by Cox proportional hazards model. Results: The 49 cardiac events identified in this population included 21 deaths and 28 hospitalizations for heart failure during an average follow-up of 20 months (25th-75th percentile: 14-32 months). Multivariable analysis showed that increased left ventricular mass index (LVMI) and decreased body mass index, estimated glomerular filtration rate, and hemoglobin (hazard ratio 0.827; P = 0.015) were independently associated with increased cardiac events. Additionally, tests of a Cox model that included important clinic variables, LVMI, left ventricular ejection fraction, and the ratio of transmitral E-wave velocity to early diastolic mitral annulus velocity showed that including hemoglobin significantly increased value in predicting adverse cardiac events (P = 0.010). Conclusions: Hemoglobin is a useful parameter for predicting adverse cardiac events, and including hemoglobin may improve the prognostic prediction of conventional clinical and echocardiographic parameters in patients with AF.

PurposeThe pre-ejection period-derived myocardial performance index measured from tissue Doppler echocardiography (PEPa-derived MPI) was reported to be associated with left ventricular systolic and diastolic function in atrial fibrillation (AF). However, its relationship with cardiovascular outcomes in AF has never been evaluated. This study sought to examine the ability of PEPa-derived MPI in predicting adverse cardiovascular events in AF patients.MethodsIn 196 persistent AF patients, we performed comprehensive echocardiography with measurement of PEPa-derived MPI using index beat method. The index beat was defined as the beat following the nearly equal preceding (RR1) and pre-preceding (RR2) intervals. The cycle length of index beat and RR1 and RR2 must be >500ms and the difference between RR1 and RR2 must be

The step count is an important information for developing services for smartphone users. Most existing step counting solutions restrict that: 1) the phone has to be fixed to the user and 2) the user cannot use the phone naturally while walking. We can see that these restrictions are inconvenient for users. In this paper, we propose a step calculation algorithm, which can relieve the above restrictions and can count users’ steps precisely. The proposed algorithm is composed of two phases. The first phase collects linear acceleration and gravity values from the smartphone’s accelerometer. Then, this phase derives the horizontal components of the perceived linear acceleration values and identifies possible start points of periodical regular fluctuations (of linear acceleration measurements). The second phase adopts the concept of correlation coefficients to identify whether the collected sensing measurements exhibit similar tendencies and calculates step counts. In this paper, we implement the proposed method on the android platform. The experiment results indicate that the proposed scheme can analyze gaits accurately and count steps effectively.

Oral cancer is the sixth most common cancer worldwide with a high mortality rate. Biomarkers that anticipate susceptibility, prognosis, or response to treatments are much needed. Oral cancer is a polygenic disease involving complex interactions among genetic and environmental factors, which require multifaceted analyses. Here, we examined in a dataset of 103 oral cancer cases and 98 controls from Taiwan the association between oral cancer risk and the DNA repair genes X-ray repair cross-complementing group (XRCCs) 1-4, and the environmental factors of smoking, alcohol drinking, and betel quid (BQ) chewing. We employed logistic regression, multifactor dimensionality reduction (MDR), and hierarchical interaction graphs for analyzing gene-gene (G×G) and gene-environment (G×E) interactions. We identified a significantly elevated risk of the XRCC2 rs2040639 heterozygous variant among smokers [adjusted odds ratio (OR) 3.7, 95% confidence interval (CI)=1.1-12.1] and alcohol drinkers [adjusted OR=5.7, 95% CI=1.4-23.2]. The best two-factor based G×G interaction of oral cancer included the XRCC1 rs1799782 and XRCC2 rs2040639 [OR=3.13, 95% CI=1.66-6.13]. For the G×E interaction, the estimated OR of oral cancer for two (drinking-BQ chewing), three (XRCC1-XRCC2-BQ chewing), four (XRCC1-XRCC2-age-BQ chewing), and five factors (XRCC1-XRCC2-age-drinking-BQ chewing) were 32.9 [95% CI=14.1-76.9], 31.0 [95% CI=14.0-64.7], 49.8 [95% CI=21.0-117.7] and 82.9 [95% CI=31.0-221.5], respectively. Taken together, the genotypes of XRCC1 rs1799782 and XRCC2 rs2040639 DNA repair genes appear to be significantly associated with oral cancer. These were enhanced by exposure to certain environmental factors. The observations presented here warrant further research in larger study samples to examine their relevance for routine clinical care in oncology.

Background Tricuspid regurgitation pressure gradient (TRPG) is reportedly a predictor of cardiovascular (CV) mortality in patients without atrial fibrillation (AF); its relationship with cardiac outcomes in patients with AF has never been evaluated. This study aimed to examine the ability of TRPG to predict CV events and all-cause mortality in patients with AF. Materials and Methods Comprehensive echocardiography was performed in 155 patients with persistent AF. Combined CV events were defined as CV mortality, stroke and hospitalization for heart failure. Results During an average follow-up period of 27 months, 57 CV events and 31 all-cause deaths occurred. According to multivariate analysis, predictors of CV events included diuretic use, decreased left ventricular ejection fraction (LVEF), increased ratio of transmitral E velocity (E) to early diastolic mitral annular velocity (E′) and TRPG. Predictors of all-cause mortality included old age, decreased LVEF, increased E/E′ and TRPG. Notably, the addition of TRPG to a model containing clinical significant parameters, LVEF and E/E′ significantly improved the values in predicting adverse CV events and all-cause mortality. Conclusions The TRPG is not only a useful predictor of adverse CV events and all-cause mortality in patients with AF, it may also provide additional prognostic values for CV outcome and all-cause mortality over conventional parameters in such patients.

The hydrophobic-polar (HP) model is commonly used for predicting protein folding structures and hydrophobic interactions. This study developed a particle swarm optimization (PSO)-based algorithm combined with local search algorithms; specifically, the high exploration PSO (HEPSO) algorithm (which can execute global search processes) was combined with three local search algorithms (hill-climbing algorithm, greedy algorithm, and Tabu table), yielding the proposed HE-L-PSO algorithm. By using 20 known protein structures, we evaluated the performance of the HE-L-PSO algorithm in predicting protein folding in the HP model. The proposed HE-L-PSO algorithm exhibited favorable performance in predicting both short and long amino acid sequences with high reproducibility and stability, compared with seven reported algorithms. The HE-L-PSO algorithm yielded optimal solutions for all predicted protein folding structures. All HE-L-PSO-predicted protein folding structures possessed a hydrophobic core that is similar to normal protein folding.

The aim of this study was to evaluate the use of renal systolic time intervals measured by electrocardiographic gated Doppler ultrasonography for predicting adverse cardiac events. This longitudinal observation study enrolled 205 patients. Renal systolic time intervals, including pre-ejection period (PEP) and ejection time (ET), and ratio of renal PEP to ET, were measured by electrocardiographic gated Doppler ultrasound. The 14 adverse cardiac events identified in this population included 9 cardiac deaths and 5 hospitalizations for heart failure during an average follow up of 30.9 months (25th–75th percentile: 30–33 months). Renal PEP (hazard ratio = 1.023, P = 0.001), renal ET (hazard ratio = 0.975, P = 0.001) and renal PEP/ET (per 0.01 unit increase, hazard ratio = 1.060, P

The interaction between the meiotic recombination 11 homolog A (MRE11) oncoprotein and breast cancer recurrence status remains unclear. The aim of this study was to assess the interaction between MRE11 and clinicopathologic variables in breast cancer. A dataset for 254 subjects with breast cancer (220 nonrecurrent and 34 recurrent) was used in individual and cumulated receiver operating characteristic (ROC) analyses of MRE11 and 12 clinicopathologic variables for predicting breast cancer recurrence. In individual ROC analysis, the area under curve (AUC) for each predictor of breast cancer recurrence was smaller than 0.7. In cumulated ROC analysis, however, the AUC value for each predictor improved. Ten relevant variables in breast cancer recurrence were used to find the optimal prognostic indicators. The presence of any six of the following ten variables had a high (79%) sensitivity and a high (70%) specificity for predicting breast cancer recurrence: tumor size ≥ 2.4 cm, tumor stage II/III, therapy other than hormone therapy, age ≥ 52 years, MRE11 positive cells > 50%, body mass index ≥ 24, lymph node metastasis, positivity for progesterone receptor, positivity for epidermal growth factor receptor, and negativity for estrogen receptor. In conclusion, this study revealed that these 10 clinicopathologic variables are the minimum discriminators needed for optimal discriminant effectiveness in predicting breast cancer recurrence.

A Micro-Grid (MG) is an energy community having various Distributed Energy Resources (DERs) such as diesel engines, micro turbines, solar power, wind power, fuel cells and energy storage devices. The multi-agent architecture offers a hierarchical structure is very suitable for managing multi-individual and heterogeneous DERs in the MG environment. This paper proposes a Agent-based Demand and Supply Control Framework (AD-SCF) which merges with the existing MG Energy Management System (EMS). Moreover, the AD-SCF adopts the embedding of sensors that can provide environmental and DERs information to EMS. It enhances the exchanges information EMS with the other key elements to determine the best optimal controls on power flow, load dispatch and scheduling in MG.

Patient Initials or Identifier Number Lee ### Relevant Clinical History and Physical Exam A 46-year-old male with a history of diabetes mellitus and hyperlipidemia was admitted to our cardiac centre due to intermittent chest discomfort in the recent months. His physical exam was unremarkable

BACKGROUND: Patients with chronic kidney disease (CKD) often have poor vascular compliance and poor left ventricular diastolic dysfunction (LVDD). The pulse pressure index (PPI) defined as ((systolic blood pressure - diastolic blood pressure)/systolic blood pressure) reflects vascular compliance. Vascular compliance is reportedly associated with left ventricular diastolic function. This study of CKD patients investigated whether PPI correlates with the ratio of transmitral E wave velocity (E) to early diastole mitral annulus velocity (Ea) or with LVDD. METHODS: This study enrolled 511 CKD patients who had been referred for echocardiographic examination. Blood pressure was automatically measured with an ABI-form device. The LVDD was defined as E-to-transmitral A wave velocity ratio of ≥0.9, Ea

Background. Atrial fibrillation (AF) and vascular disease share several risk factors and the two diseases often coexist. Heart rate (HR) is reported to be a major determinant of arterial stiffness. AF patients often have a transiently or persistently rapid HR. Hence, this study was to assess whether AF was significantly associated with arterial stiffness and HR could significantly influence the relationship between AF and arterial stiffness. Besides, we also determine the main correlates of arterial stiffness in AF patients and see whether HR was correlated with arterial stiffness in these patients. Methods. We included 166 AF and 1336 non-AF patients from subjects arranged for echocardiographic examinations. Arterial stiffness was assessed by brachial-ankle pulse wave velocity (baPWV). Results. Compared to non-AF patients, AF patients had a higher baPWV (p

The aim of this study was to examine the association of lead exposure with cardiac conduction disturbance among lead-exposed and nonexposed workers in Taiwan.The participants comprised 312 lead workers and 329 referents who had no known occupational lead exposure. During their annual health examination, they were invited to take part in the survey. Standard resting 12-lead electrocardiograms were obtained and the electrocardiographic features studied were related to blood lead levels (BLLs).The mean BLLs were 26.05 (SD = 13.98) and 2.62 (SD = 1.42) μg/dL in lead-exposed and reference groups, respectively. Compared with the referents, lead workers had significantly shorter PR interval and longer QTc interval. Especially, workers with BLL30 μg/dL had the highest risk after adjusting for age, sex, body mass index, and other potential confounders.The data suggest that lead exposure is positively associated with prolonged QTc interval.

This study computationally determines the contribution of clinicopathologic factors correlated with 5-year survival in oral squamous cell carcinoma (OSCC) patients primarily treated by surgical operation (OP) followed by other treatments. From 2004 to 2010, the program enrolled 493 OSCC patients at the Kaohsiung Medical Hospital University. The clinicopathologic records were retrospectively reviewed and compared for survival analysis. The Apriori algorithm was applied to mine the association rules between these factors and improved survival. Univariate analysis of demographic data showed that grade/differentiation, clinical tumor size, pathology tumor size, and OP grouping were associated with survival longer than 36 months. Using the Apriori algorithm, multivariate correlation analysis identified the factors that coexistently provide good survival rates with higher lift values, such as grade/differentiation = 2, clinical stage group = early, primary site = tongue, and group = OP. Without the OP, the lift values are lower. In conclusion, this hospital-based analysis suggests that early OP and other treatments starting from OP are the key to improving the survival of OSCC patients, especially for early stage tongue cancer with moderate differentiation, having a better survival (>36 months) with varied OP approaches.

Objectives: The amount of fat tissue is associated with an increasing incidence of cardiac arrhythmias. The purpose of this study was to investigate effects of adipocytokines from different body fat on delayed rectifier K+ outward currents (IK). Methods: H9c2 cells were treated with adipocytokine-free medium (the Adipo-free group) and with adipocytokines from epicardial (central fat group) and limb (peripheral fat group) rat fat tissues. IK, as well as expressions of Kv2.1 and Kv2.1 mRNA in H9c2 cells, were measured and compared between different groups. Results: IK measured in H9c2 cells immediately after treatment with adipocytokines were not significantly different from those treated with adipocytokine-free medium. After H9c2 cells were treated with adipocytokines for 18 h, IK were significantly decreased in the peripheral and central fat groups in comparison with the Adipo-free group. Compared with the peripheral fat group, IK were more significantly decreased in the central fat group. Expressions of Kv2.1 and Kv2.1 mRNA in H9c2 cells were not significantly different among the three groups. Conclusions: Adipocytokines significantly decreased IK in H9c2 cells, and IK was more prominently decreased by adipocytokines from epicardial fat than from limb fat tissues. The decrease in IK by adipocytokines may partially contribute to the mechanisms of arrhythmogenesis by fat tissues.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor. It has come to our attention that there is substantial duplication of some figures between this Kaohsiung Journal of Medical Science article and an earlier paper by the same authors, Chao-Neng Tseng et al, A method to identify RNA A-to-I editing targets using I-specific cleavage and exon array analysis, Molecular and Cellular Probes, Vol 27, 38-45 (2013), http://dx.doi.org/10.1016/j.mcp.2012.08.008. One of the conditions of submission of a paper for publication is that authors declare explicitly that their work is original and has not appeared in a publication elsewhere. Re-use of any data should be appropriately cited. As such this article represents a severe abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process.

BACKGROUND Visible oral and oropharyngeal premalignant lesions may be used to monitor for a second primary oral cancer. To control for bias, we focused on the visible oral and oropharyngeal premalignant lesions of patients with oral cancer with a positive betel-nut chewing habit. Visible oral and oropharyngeal premalignant lesions that can predict second primary oral cancers were studied. METHODS Nine hundred ninety-seven patients with positive betel-nut chewing habits and oral cancer were enrolled in this retrospective cohort study. We analyzed the relevance of their visible oral and oropharyngeal premalignant lesion incidence and relative clinicopathological variables to the development of a second primary oral cancer. RESULTS Second primary oral cancer risk was significantly higher in patients with positive visible oral and oropharyngeal premalignant lesions (P < .0001), especially in younger patients (P = .0023; ≤40 years: adjusted odds ratio [OR] 2.66; 40-60 years: adjusted OR 2.61). The heterogeneous leukoplakia was (adjusted OR 2.17) higher than homogeneous leukoplakia. CONCLUSION The predictive value and practicality of visible oral and oropharyngeal premalignant lesions make it a potentially valuable marker in follow-ups of patients with a positive betel-nut chewing habit with oral cancer, especially young patients with heterogeneous leukoplakia.

The aims of this study were to investigate the correlation between renal and cardiac STIs, including pre-ejection period (PEP), ejection time (ET), and PEP/ET, and to assess the diagnostic values of renal STIs in predicting left ventricular ejection fraction (LVEF) 0.46 in prediction of LVEF

The thickness of epicardial adipose tissue (EAT) was reported to be highly associated with the incidence and severity of atrial fibrillation (AF). This study was conducted to analyze the ability of EAT thickness in predicting adverse cardiovascular (CV) events in AF. In 190 persistent AF patients, we performed a comprehensive transthoracic echocardiographic examination with assessment of EAT thickness. The definition of CV events included CV mortality, hospitalization for heart failure, myocardial infarction, and stroke. There were 69 CV events including 19 CV deaths, 32 hospitalizations for heart failure, 3 myocardial infarctions, and 15 strokes during a mean follow-up of 29 (25th–75th percentile: 17–36) months. The multivariable analysis demonstrates that chronic heart failure, increased left ventricular (LV) mass index and the ratio of transmitral E-wave velocity to early diastolic mitral annulus velocity, decreased body mass index, and increased EAT thickness (per 1-mm increase, odds ratio 1.224, 95% confidence interval [CI] 1.096–1.368, P

Aims Some guidelines or studies consider haematuria an indication for renal biopsy or a potential cause of albuminuria that precludes accurate assessment of urinary albumin excretion. This study examined the justification of excluding haematuria in interpreting urinary albumin excretion in patients with Type 2 diabetes and its associations with other diabetes-related variables. Methods Between May and November 2008, patients with Type 2 diabetes at a single centre with data on urinary albumin excretion and urinalysis in the same urine sample were recruited. Urinary albumin excretion was determined by urine albumin/creatinine ratio in spot urine. Diagnosis of haematuria was made by positive urine occult blood from 1+ to 4+ and/or presence of more than nine red blood cells/ml in urinalysis. Demographic, anthropometric, clinical and laboratory variables and diabetes-associated complications were analysed. Results In total, 743 patients were enrolled. Prevalence of haematuria among patients with normoalbuminuria, microalbuminuria, or macroalbuminuria was 8.7% (n = 13), 16.1% (n = 67) and 35.8% (n = 64), respectively. Urine albumin/creatinine ratio was significantly higher, while macroalbuminuria was more common in patients with haematuria (n = 144) than in those without (n = 599). Multiple regression analysis identified urine albumin/creatinine ratio (odds ratio 1.33, P = 0.01) and macroalbuminuria (odds ratio 2.66, P = 0.01) as the only independent predictors of haematuria. Moreover, urine albumin/creatinine ratio was an independent predictor of haematuria in the macroalbuminuria subgroup (odds ratio 1.30, P = 0.04). Conclusions Increased urine albumin/creatinine ratio and macroalbuminuria were the only independent predictors of haematuria in patients with Type 2 diabetes, raising questions on the justifications of excluding haematuria in interpreting urinary albumin excretion in patients with Type 2 diabetes and including haematuria as an indication for renal biopsy in those with macroalbuminuria.

Antrodia camphorata(AC) is well known in Taiwan as a traditional Chinese medicine. The aim of this study was to investigate whether a fermented culture broth of AC could inhibit melanoma proliferation and progressionviasuppression of the Wnt/β-catenin signaling pathway. In this study, we observed that AC treatment resulted in decreased cell viability and disturbed Wnt/β-catenin cascade in B16F10 and/or B16F1 melanoma cells. This result was accompanied by a decrease in the expression of Wnt/β-catenin transcriptional targets, including c-Myc and survivin. Furthermore, treatment of melanoma cells with AC resulted in a significant increase in apoptosis, which was associated with DNA fragmentation, cytochrome c release, caspase-9 and -3 activation, PARP degradation, Bcl-2/Bax dysregulation, and p53 expression. We also observed that AC caused G1phase arrest mediated by a downregulation of cyclin D1 and CDK4 and increased p21 and p27 expression. In addition, we demonstrated that non- and subcytotoxic concentrations of AC markedly inhibited migration and invasion of highly metastatic B16F10 cells. The antimetastatic effect of AC was further confirmed by reductions in the levels of MMP-2, MMP-9, and VEGF expression. These results suggest thatAntrodia camphoratamay exert antitumor activity by downregulating the Wnt/β-catenin pathways.