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Background The mechanisms underlying angiotensin receptor-neprilysin inhibitor (ARNi) suppression of ventricular arrhythmia (VA) are unclear. This study aimed to investigate the mechanism of ARNi-related suppression of VA in a heart failure (HF) model. Methods New Zealand white rabbits (n = 6 per group) were assigned to normal, HF [4 weeks of left ascending artery (LAD) ligation], angiotensin receptor blocker (ARB, valsartan at 27 mg/kg/day for 3 weeks after 1 week of LAD ligation), and ARNi (sacubitril at 34 mg/kg/day and valsartan at 27 mg/kg/day for 3 weeks after 1 week of LAD ligation) groups. Experiments involving echocardiogram, optical mapping, histological of trichrome stain and immunostain, and flow cytometry were performed. Results HF group had larger left ventricular (LV) internal dimensions in diastole and systole, and lower LV ejection fraction and fractional shortening than normal, ARB, and ARNi groups. HF group had a prolonged action potential duration (APD) and decreased conduction velocity (CV), which was mitigated in ARB and ARNi groups. HF group had a prolonged QRS duration, QT and QTc intervals, which was reversed in ARB and ARNi groups. HF group had a steeper maximum slope of APD restitutions, which was attenuated in normal, ARB, and ARNi groups. HF group had increased number of phase singularities (PSs) and VA inducibility than normal, ARB, and ARNi groups. A higher content of fibrosis was found in HF group than that in normal, ARB, and ARNi groups. Compared to ARB group, ARNi had a lower context of fibrosis. HF group had more peripheral blood CD4+ and CD8+ cells count than normal, ARB, and ARNi group. Conclusions In a rabbit model of ischemic HF, ventricular arrhythmogenesis could be suppressed by ARNi treatment. This appears to be mediated by reversing changes in the APD, CV, maximum slope of the APDR, PSs, fibrosis, and inflammation.

Germ cell-specific genes play an important role in establishing the reproductive system in sexual organisms and have been used as valuable markers for studying gametogenesis and sex differentiation. Previously, we isolated a vasa transcript as a germ cell marker to trace the origin and migration of germ cells in the oriental river prawn Macrobrachium nipponense. Here, we identified a new germ cell-specific marker MnTdrd RNA and assessed its temporal and spatial expression during oogenesis and embryogenesis. MnTdrd transcripts were expressed in high abundance in unfertilized eggs and embryos at cleavage stage and then dropped significantly during late embryogenesis, suggesting that MnTdrd mRNA is maternally inherited. In situ hybridization of ovarian tissue showed that MnTdrd mRNA was initially present in the cytoplasm of previtellogenic oocyte and localized to the perinuclear region as the accumulation of yolk in vitellogenic oocyte. Whole-mount in situ hybridization of embryos showed that MnTdrd-positive signals were only localized in one blastomere until 16-cell stage. In the blastula, there were approximately 16 MnTdrd-positive blastomeres. During embryonized-zoea stage, the MnTdrd-positive cells aggregated as a cluster and migrated to the genital rudiment which would develop into primordial germ cells (PGCs). The localized expression pattern of MnTdrd transcripts resembled that of the previously identified germ cell marker vasa, supporting the preformation mode of germ cell specification. Therefore, we concluded that MnTdrd, together with vasa, is a component of the germ plasm and might have critical roles in germ cell formation and differentiation in the prawn. Thus, MnTdrd can be used as a novel germ cell marker to trace the origin and migration of germ cells.

Hypoxia causes a series of responses supporting cells to survive in harsh environments. Substantial post-transcriptional and translational regulation during hypoxia has been observed. However, detailed regulatory mechanism in response to hypoxia is still far from complete. RNA m6A modification has been proven to govern the life cycle of RNAs. Here, we reported that total m6A level of mRNAs was decreased during hypoxia, which might be mediated by the induction of m6A eraser, ALKBH5. Meanwhile, expression levels of most YTH family members of m6A readers were systematically down-regulated. Transcriptome-wide analysis of m6A revealed a drastic reprogramming of m6A epitranscriptome during cellular hypoxia. Integration of m6A epitranscriptome with either RNA-seq based transcriptome analysis or mass spectrometry (LC-MS/MS) based proteome analysis of cells upon hypoxic stress revealed that reprogramming of m6A epitranscriptome reshaped the transcriptome and proteome, thereby supporting efficient generation of energy for adaption to hypoxia. Moreover, ATP production was blocked when silencing an m6A eraser, ALKBH5, under hypoxic condition, demonstrating that m6A pathway is an important regulator during hypoxic response. Collectively, our studies indicate that crosstalk between m6A and HIF1 pathway is essential for cellular response to hypoxia, providing insights into the underlying molecular mechanisms during hypoxia.

This study aimed to investigate the electromechanical function detected by acoustic cardiography before and after radiofrequency ablation therapy (RFA) in paroxysmal AF (PAF) patients with preserved left ventricular ejection fraction (LVEF). Seventy-five symptomatic PAF patients and 69 patients without arrhythmia were enrolled. Thirty-seven PAF patients received RFA therapy. Acoustic cardiographic exam was performed to check S3 and S4 heart sound, electromechanical activation time (EMAT), LV systolic time percentage (LVST), and systolic dysfunction index (SDI) in all participants. Furthermore, 37 PAF patients also received follow-up acoustic cardiography postRFA. PAF had impaired electromechanical systolic function compared with health participants (%EMAT 14.69 ± 3.62 vs. 10.84 ± 2.62; %LVST 40.83 ± 5.14 vs. 36.70 ± 3.87; SDI 4.75 ± 1.61 vs. 3.26 ± 0.96 all p

To develop a prognostic nomogram based on the albumin–bilirubin (ALBI) grade for prediction of the long-term survival of patients with intermediate-stage hepatocellular carcinoma (HCC) after transarterial chemoembolization combined with microwave ablation (TACE-MWA). We retrospectively studied 546 consecutive patients with intermediate-stage HCC according to the Barcelona Clinic Liver Cancer guidelines who underwent TACE-MWA between January 2000 and December 2016. Overall survival (OS) and progression-free survival (PFS) were analyzed. The predictive value of the ALBI grade was investigated. The prognostic nomogram was constructed using the independent predictors assessed by the multivariate Cox proportional hazards model. After a median follow-up of 35.0 months (range, 4.0–221.0 months), 380 patients had died. The median OS was 35.0 months (95% confidence interval (CI), 30.84–39.16 months), and the median PFS was 6.5 months (95% CI, 6.13–6.87 months). The ALBI grade was validated as an independent predictor of OS (p

The application of word associations has become increasingly widespread. However, the association norms produced by traditional free association tests tend not to exceed 10,000 stimulus words, making the number of associated words too small to be representative of the overall language. In this study we used text corpora totaling over 400 million Chinese words, along with a multitude of association measures, to automatically construct a Chinese Lexical Association Database (CLAD) comprising the lexical association of over 80,000 words. Comparison of the CLAD with a database of traditional Chinese word association norms shows that word associations extracted from large text corpora are similar in strength to those elicited from free association tests but contain a much greater number of associative word pairs. Additionally, the relatively small numbers of participants involved in the creation of traditional norms result in relatively coarse scales of association measurement, whereas the differentiation of association strengths is greatly enhanced in the CLAD. The CLAD provides researchers with a great supplement to traditional word association norms. A query website at www.chinesereadability.net/LexicalAssociation/CLAD/ affords access to the database.

Simple Summary In insects, the precise timing of metamorphosis and diapause is regulated by hormones. The Chinese oak silkworm, Antheraea pernyi, is a typical pupal diapause insect. Bivoltine species enter diapause in winter and terminate it under suitable environmental conditions in the following year; they produce 70% of total cocoons, whereas univoltine species in lower-latitude areas enter diapause in summer and contribute just one generation a year. A long photoperiod can trigger termination of pupal diapause. It is not clear how photoperiod influences hormone gene expression. Here, hormone-related genes were cloned, and their expression patterns were studied under different photoperiod treatments. The results will help us to understand the molecular changes during diapause termination under long photoperiods and improve breeding of multi-generation tussah pupae in areas where they are naturally univoltine. Abstract The Chinese oak silkworm is commonly used in pupal diapause research. In this study, a long photoperiod was used to trigger pupal diapause termination. Genes encoding three hormones, namely prothoracicotropic hormone (PTTH), ecdysis triggering hormone (ETH), and eclosion hormone (EH), were studied. Additionally, ecdysteroids (mainly 20-hydroxyecdysone, 20E) were quantified by HPLC. Pupal diapause stage was determined by measuring respiratory intensity. The pupae enter a low metabolic rate, which starts approximately 1 month after pupal emergence. ApPTTH expression showed a small increase at 14 days and then a larger increase from 35 days under the long photoperiod treatment. A similar pattern was observed for the titer of 20E in the hemolymph. However, ApETH expression later increased under the long photoperiod treatment (42 days) just before eclosion. Moreover, ApEH expression increased from 21 to 35 days, and then decreased before ecdysis. These results suggest that hormone-related gene expression is closely related to pupal development. Our study lays a foundation for future diapause studies in A. pernyi.

The reciprocal interactions between pathogens and hosts are complicated and profound. A comprehensive understanding of these interactions is essential for developing effective therapies against infectious diseases. Interferon responses induced upon virus infection are critical for establishing host antiviral innate immunity. Here, we provide a molecular mechanism wherein isoform switching of the host IKKε gene, an interferon-associated molecule, leads to alterations in IFN production during EV71 infection. We found that IKKε isoform 2 (IKKε v2) is upregulated while IKKε v1 is downregulated in EV71 infection. IKKε v2 interacts with IRF7 and promotes IRF7 activation through phosphorylation and translocation of IRF7 in the presence of ubiquitin, by which the expression of IFNβ and ISGs is elicited and virus propagation is attenuated. We also identified that IKKε v2 is activated via K63-linked ubiquitination. Our results suggest that host cells induce IKKε isoform switching and result in IFN production against EV71 infection. This finding highlights a gene regulatory mechanism in pathogen-host interactions and provides a potential strategy for establishing host first-line defense against pathogens., Chang et al. show that Enterovirus 71 (EV71) infection upregulates IKKε isoform 2 (IKKε v2), which in turn activates interferon regulatory factor 7 (IRF7). This study suggests that host cells trigger IKKε isoform switching to increase the production of interferon against EV71 infection, providing a potential strategy for boosting host’s antiviral defense.

Jia-Yan Ni,1–3 Hong-Liang Sun,1,2 Jiang-Hong Luo,1,2 Xiong-Ying Jiang,1,2 Dong Chen,1,2 Wei-Dong Wang,1,2 Yao-Ting Chen,1,2 Jin-Hua Huang,3 Lin-Feng Xu1,2 1Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province 510120, People’s Republic of China; 2Department of Interventional Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province 510120, People’s Republic of China; 3Department of Minimally Invasive Interventional Radiology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Cancer for Cancer Medicine, Guangzhou, Guangdong Province 510060, People’s Republic of ChinaCorrespondence: Jin-Hua HuangDepartment of Minimally Invasive Interventional Radiology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Cancer for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, Guangdong Province 510060, People’s Republic of ChinaTel +86-20-87343447Email huangjh_sysucc@163.comLin-Feng XuGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Interventional Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang Road West, Guangzhou, Guangdong Province 510120, People’s Republic of ChinaTel +86-20-34078680Email xu_lin_feng@163.comPurpose: The aim of this study was to investigate the safety and efficacy of transarterial chemoembolization and sorafenib (TACE-S) combined with microwave ablation (TACE-S-MWA) for the treatment of patients with advanced primary hepatocellular carcinoma (HCC).Methods: Between January 2015 and December 2018, 152 consecutive advanced HCC patients, who underwent TACE-S-MWA (MWA group, n=77) or TACE-S (Non-MWA group, n=75), were investigated. Overall survival (OS), time to progression (TTP) and safety were compared between the two groups. Prognostic factors were analyzed using the Cox proportional hazard regression model.Results: Baseline patient characteristics were balanced between the two groups. MWA group was associated with a higher OS (median, 19.0 vs 13.0 months; P

BACKGROUND The corrected QT interval (QTc) predicts prognosis for the general population and patients with coronary artery disease (CAD). Growth differentiation factor-15 (GDF-15) is a biomarker of myocardial fibrosis and left ventricular (LV) remodelling. The interaction between these two parameters is unknown. SUBJECTS AND METHODS This study included 487 patients with angiographically confirmed CAD. QTc was calculated using the Bazett formula. Multiple biochemistries and GDF-15 levels were measured. The primary endpoint was total mortality, and the secondary endpoints comprised the combination of total mortality, myocardial infarction and hospitalisation for heart failure and stroke. RESULTS The mean follow-up period was 1029 ± 343 days (5-1692 days), during which 21 patients died and 47 had secondary endpoints. ROC curve analysis for the optimal cut-off value of primary endpoint is 1.12 ng/mL for GDF-15 (AUC = 0.787, P = 9.0 × 10-6 ) and 438.5 msec for QTc (AUC = 0.698, P = .002). Utilising linear regression, QTc has a positive correlation with Log-GDF-15 (r = .216, P = 1.0 × 10-6 ). Utilising Kaplan-Meier analysis, both QTc interval and GDF-15 level are significant predictors for primary end point (P = .000194, P = 2.0 × 10-6 , respectively) and secondary endpoint (P = .00028, P = 6.15 × 10-8 , respectively). When combined these two parameters together, a significant synergistic predictive power was noted for primary and secondary endpoint (P = 2.31 × 10-7 , P = 1.26 × 10-8 , respectively). This combined strategy also showed significant correlation with the severity of CAD (P

Naja atra bites cause severe soft tissue injury and are prone to wound infections. The pathogens of Naja atra bite-wound infections are highly variable in different geographical regions. Here, we report the first coinfection with Shewanella algae and Morganella morganii from a Naja atra bite wound with resistome analysis using whole genome sequencing.

Nanopore sequencing has been widely used for the reconstruction of microbial genomes. Owing to higher error rates, errors on the genome are corrected via neural networks trained by Nanopore reads. However, the systematic errors usually remain uncorrected. This paper designs a model that is trained by homologous sequences for the correction of Nanopore systematic errors. The developed program, Homopolish, outperforms Medaka and HELEN in bacteria, viruses, fungi, and metagenomic datasets. When combined with Medaka/HELEN, the genome quality can exceed Q50 on R9.4 flow cells. We show that Nanopore-only sequencing can produce high-quality microbial genomes sufficient for downstream analysis. Supplementary Information The online version contains supplementary material available at (10.1186/s13059-021-02282-6).

Graphical abstract, Highlights • Emergence of carbapenem-resistant S. algae is a severe problem. • Re-sensitization of S. algae to carbapenem by CRISPR/Cas9 genome editing. • The blaOXA-55-like gene is essential for carbapenem resistance in S. algae. • One-plasmid genome editing system for CRISPR/Cas9 genome editing in S. algae. • CRISPR/Cas9 genome editing is a promising approach to validate the gene function., Antibiotic resistance in pathogens is a growing threat to human health. Of particular concern is resistance to carbapenem, which is an antimicrobial agent listed as critically important by the World Health Organization. With the global spread of carbapenem-resistant organisms, there is an urgent need for new treatment options. Shewanella algae is an emerging pathogen found in marine environments throughout the world that has increasing resistance to carbapenem. The organism is also a possible antibiotic resistance reservoir in humans and in its natural habitat. The development of CRISPR/Cas9-based methods has enabled precise genetic manipulation. A number of attempts have been made to knock out resistance genes in various organisms. The study used a single plasmid containing CRISPR/Cas9 and recE/recT recombinase to reverse an antibiotic-resistant phenotype in S. algae and showed blaOXA-55-like gene is essential for the carbapenem resistance. This result demonstrates a potential validation strategy for functional genome annotation in S. algae.

Background Premature ventricular contractions (PVCs) induced by subtle cardiac dysfunction are missed by echocardiography. We evaluated acoustic cardiography for detection of early electromechanical dysfunction in patients with idiopathic PVCs and normal left ventricular ejection fraction (LVEF), and investigated the impact of radiofrequency ablation (RFA) in reversing this adverse effect. Methods Eighty-six patients with PVCs and 33 normal controls having normal LVEF were studied. Fifty PVC patients were in the ablation group and 36 in the nonablation group. %Electromechanical activation time (%EMAT), %left ventricular systolic time (%LVST), third (S3) and fourth heart sound (S4), and systolic dysfunction index (SDI) during sinus rhythm (SR) were measured by acoustic cardiography (Audicor, Inovise Medical, Inc., Beaverton, OR, USA) pre- and postablation. In 28 patients, acoustic parameters were compared during SR without PVCs, and SR with single PVC, ≥ 2 PVCs, or ventricular tachycardia over 10-second Audicor recording in a single patient at different times. Twenty-four-hour acoustic cardiographic and acoustic cardiographic Holter recording were used to assess the impact of PVC burden on electromechanical function in 41 patients. Results %EMAT, S3, S4, and SDI showed significant worsening in the PVC versus control group. %EMAT and SDI were worsened with increasing PVC number in a 10-second strip. %EMAT showed significant linear increment with increasing PVC burden. There was a significant improvement in %EMAT, %LVST, S3, S4, and SDI postablation in patients with PVCs. Conclusion Acoustic cardiography can detect PVC-induced minor electromechanical dysfunction in patients with normal LVEF. RFA can reverse this adverse effect.

Shewanella xiamenensis is an emerging pathogen causing intra-abdominal infection and intestinal colonization. Epidemiologic clues suggest its role as a potential food-borne zoonotic agent. To date, four genome sequences of S. xiamenensis have been made publicly available. All of them were isolated from water samples. In this study, we characterized the genome of a S. xiamenensis strain isolated from a giant grouper in Taiwan. The genome of S. xiamenensis ZYW1 is 4,827,717 bp in length and encodes 4,239 open reading frames. Its genomic sequence shares high homology with other S. xiamenensis strains. blaOXA-416 was identified. This is the first detection of S. xiamenensis in Taiwan. These genomic data and analyses contribute to our understanding of S. xiamenensis and may help to elucidate disease-causing mechanisms in future studies.

We quantified cytomegalovirus (CMV) antiviral use and hospital length of stay (LOS) associated with CMV infection in a contemporary cohort of conventional (CONV) and CD34-selected (T cell–depleted) hematopoietic cell transplantation (HCT) recipients managed by preemptive therapy (PET) in a single US center. Adults who received first allogeneic HCT at Memorial Sloan Kettering Cancer Center from June 2010 through December 2014 were analyzed. Days on PET, number of readmissions, and readmission LOS by day 180 post-HCT were summarized. Estimated unit value (EUV) was defined as the expected number of PET days for a cohort of 100 HCT with characteristics as the analyzed cohort. Standardized incidence ratio was calculated as the ratio of observed outcomes of patients with CMV viremia over the outcomes of patients without CMV viremia. Of 318 patients, 88 received CONV and 230 CD34-selected HCT. Rates of CMV viremia were 26.3% for CONV and 41.9% for CD34-selected (P = .003). Among patients with viremia 68.2% CONV and 97.9% CD34-selected received PET. EUV for PET was 852 days and 2821 days for CONV and CD34-selected, respectively. The standardized incidence ratios for number of readmission and readmission LOS were 1.7 (95% confidence interval [CI], 1.4 to 2.1) and 1.2 (95% CI, 1.1 to 1.3), respectively, for CONV HCT and 1.7 (95% CI, 1.3 to 2.1) and 1.6 (95% CI, 1.5 to 1.7), respectively, for CD34-selected HCT. Overall survival was similar between patients with and without CMV viremia by HCT type. CMV end-organ disease was associated with lower overall survival only in CD34-selected HCT (P = .0007). CMV infection managed by PET requires substantial antiviral use and is associated with longer readmission LOS more, particularly among CD34-selected HCT.

In recent years, vancomycin-resistant Enterococcus (VRE) colonization is being increasingly encountered in transplant recipients, and VRE has become one of the leading causes of bacteremia early after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Data are sparse on the effect of empiric VRE therapy for febrile, neutropenic allo-HSCT recipients colonized with VRE. All allo-HSCT recipients aged ≥18years who developed VRE bacteremia (VREB) between 2005 and 2014 were identified and categorized as to whether they received empiric or directed VRE therapy. There were 434 (33%) VRE-colonized and 872 (67%) non-VRE-colonized patients during the study period, and 172 of the 434 (40%) VRE-colonized patients received empiric therapy. There was no significant difference in incidence of VREB among colonized patients who did or did not receive empiric therapy (28 of 172 [16%] vs 55 of 262 [21%]; P = .22). There were 95 patients with VREB, of which the majority (83 of 95; 87%) was known to be VRE-colonized. Of the 95 VREB episodes, 29 (31%) were treated with empiric VRE therapy, whereas 66 (69%) were treated with directed therapy. No significant differences in clinical outcomes, including median duration of bacteremia (2 days vs 2 days; P = .39), recurrent VREB (3 of 29 [10%] vs 5 of 66 [8%]; P = .65), 30-day all-cause mortality (1 of 29 [3%] vs 4 of 66 [6%]; P = .62), or VRE-attributable mortality (1 of 29 [3%] vs 1 of 66 [2%]; P = .55), were observed between the empiric therapy and directed therapy groups. Kaplan-Meier curve analysis showed no significant difference in survival at 30days in allo-HSCT recipients with VREB who received empiric therapy and those who received directed therapy (97% vs 94%; P = .62). Based on our data, we recommend against empiric use of VRE-active agents for fever and neutropenia in VRE-colonized patients undergoing allo-HSCT.

Summary Objectives To compare the effectiveness and tolerability of micafungin versus posaconazole during chemotherapy-induced neutropenia in acute leukemia (AL) and myelodysplastic syndrome (MDS). Methods Patients with AL or MDS undergoing chemotherapy were randomized to open-label micafungin 100 mg intravenously daily or posaconazole suspension 400 mg orally twice daily until neutrophil recovery, up to 28 days. Patients were followed for 12 weeks. The primary endpoint was prophylaxis failure (premature discontinuation due to infection, intolerance, adverse event, or death). Time to failure and survival were calculated by Kaplan–Meier analysis. Results From March 2011 to May 2016, 113 patients who received at least 2 doses of prophylaxis were analyzed (58 patients randomized to micafungin and 55 to posaconazole). Prophylaxis failure occurred in 34.5% and 52.7% of patients on micafungin and posaconazole, respectively (P = 0.0118). The median number of days on prophylaxis was 16 [interquartile range (IQR) 12–20] for micafungin and 13 [IQR 6–16] for posaconazole (P = 0.01). Micafungin failures were largely due to antifungal treatment; posaconazole failures were mostly due to gastrointestinal intolerance or adverse effects. IFI incidence and survival were similar between study arms. Conclusions Our data support micafungin as alternative antifungal prophylaxis in patients with AL and MDS.

Background Shewanella algae has been recognized as an emerging human pathogen. However, not much is known about the mechanism of its pathogenesis and its adaptation to a special niche such as the hepatobiliary tract. Results In this study, we isolated the S. algae ACCC strain from human bile and performed whole genome sequencing. S. algae ACCC consists of a circular 4,743,354-bp chromosome with a GC content of 53.08%, within 4080 protein coding sequences. The genome of strain ACCC contains a number of candidate genes which have been reported to be associated with bile adaption, including htpB, exbBD, wecA, galU, adeFGH and phoPQ regulon. Conclusions Our results highlight the association of S. algae with a rare disease profile. Further studies are needed to shed light on the evolution of pathogenesis and the niche adaptation of S. algae.

Background The occurrence and degree of suicidal ideation during the past month in adolescents should be regarded seriously. Several studies have noted that humor expression style and depressive emotion may influence adolescents’ suicidal ideation. However, there is insufficient evidence concerning whether positive emotion reduces such suicidal ideation in adolescents. In addition, the relationships among humor expression, depressive emotion, positive emotion and suicidal ideation remain to be confirmed. Therefore, in this study, we aimed to test the mediating roles of depressive emotion and positive emotion in the relationship between humor expression and recent adolescent’s suicidal ideation. Methods A total of 1551 students in junior high school completed questionnaires. The collected data were analyzed using structural equation modeling (SEM) with LISREL 8.80 and Monte Carlo resampling with R. Results The results indicate that suicidal ideation in adolescents during the past month was related not only to humor expression but also to depressive emotion and positive emotion. The stronger the depressive emotion felt, the stronger the suicidal ideation; in contrast, the stronger the positive emotion, the weaker the suicidal ideation. Moreover, depressive emotion and positive emotion were found to mediate the relationship between humor expression and suicidal ideation; additionally, positive emotion was found to mediate the relationship between depressive emotion and suicidal ideation. Conclusion These results highlight that depressive emotion and positive emotion may mediate the influence of humor expression on suicidal ideation among adolescents, and positive emotion may mediate the influence of depressive emotion on suicidal ideation. More attention should be paid to decreasing adolescents’ self-deprecating humor expression and depressive emotion, whereas more witty response humor expression and positive emotion should be encouraged to prevent their suicidal ideation.

Jia-Yan Ni,1,* Shan-Shan Liu,2,* Hong-Liang Sun,1 Wei-Dong Wang,1 Ze-Long Zhong,1 Si-Nan Hou,1 Yao-Ting Chen,1 Lin-Feng Xu1 1Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Interventional Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong Province, People’s Republic of China; 2Department of Public Health, Sushe Community Health Service Center, Guangzhou 510220, Guangdong Province, People’s Republic of China *These authors contributed equally tothiswork Objective: To compare the clinical efficacy and safety of transcatheter hepatic arterial infusion chemotherapy (HAIC) with those of sorafenib in the treatment of patients with hepatocellular carcinoma (HCC) of Barcelona Clinic Liver Cancer (BCLC) stage C. Methods: Potentially relevant studies comparing the clinical efficacy and safety of HAIC with those of sorafenib were searched using Medline, PubMed, Embase, Cochrane Library, and Chinese databases (Wanfang Data and China National Knowledge Infrastructure). Overall survival rate (OSR), tumor response rate, disease control rate (DCR), and serious adverse events (SAEs) were compared and analyzed. Pooled ORs with 95% CIs were calculated using either the fixed-effects model or the random-effects model. All statistical analyses were conducted using Review Manager (version 5.3) from the Cochrane Collaboration. Results: A total of 1,264 patients were included in this meta-analysis. The results of this study showed that HAIC was associated with significantly higher 1-, 2-, and 3-year OSRs than sorafenib (OR 1.88, 95% CI1-year: [1.27–2.78], P1-year=0.002; OR 2.15, 95% CI2-year: [1.06–4.37], P2-year=0.03; OR 7.90, 95% CI3-year: [2.12–29.42], P3-year=0.002). Compared to sorafenib, HAIC was associated with superior complete response (CR), partial response (PR), and objective response rate (ORR) (OR 3.90, 95% CICR: [1.89–8.03], PCR =0.0002; OR 3.47, 95% CIPR: [2.31–5.24], PPR

Cyclin B functions as a regulatory protein through association with its catalytic partner Cdc2 kinase forming M−phase promoting factor (MPF), which plays a central role in the meiotic maturation of oocyte. To gain insight into the molecular events, we here cloned a cyclin B cDNA from the ovary of the prawn Macrobrachium rosenbergii and compared its spatial–temporal expression patterns during oocyte maturation with those of crab Eriocheir sinensis. The prawn cyclin B cDNA encodes a 398 amino acid protein with predicted molecular weight of 45.16 kDa. Immunodetection of cyclin B protein by Western blot showed that a target band of approximately 53 kDa protein in the prawn ovaries at both late vitellogenesis (lVt) and germinal vesicle breakdown (GVBD) stages, whereas a 41 kDa band was present in the crab ovaries. Cyclin B protein expression changes indicating that the newly synthesis of cyclin B proteins could be required for GVBD in both prawn and crab. Immunohistochemical analysis revealed that both the prawn and crab cyclin B proteins, were localized in the ooplasm of previtellogenic oocytes, then relocated into germinal vesicle at vitellogenesis stage and localized on meiotic spindle at M phase. These similar behaviors suggested that the prawn and the crab cyclin B proteins associated with Cdc2 kinase have conserved roles in inducing GVBD and regulating the formation of meiotic spindle. The similar expression patterns of the cyclin B proteins during oocyte maturation implicated that the molecular mechanisms for MPF activation could be identical between the prawn and the crab.

Shewanella algae is not only the most commonly reported species in Shewanella human infections but also capable to inhabit a wide variety of habitats. Although there is evidence that quorum sensing is associated with bacterial adaptation to changing environmental conditions, little is known of the quorum sensing system in S. algae. In this study, we conducted the whole genome sequencing of S. algae strains and applied comparative genomics to reveal the core genome. Genes related to the quorum sensing system were identified by integrated bioinformatics analysis. S. algae harbor genes involved in all three main types of autoinducer systems. This study provides insights into the quorum sensing systems in S. algae, which might be valuable in the future study of cell behavior in S. algae.

Shewanella algae is an emerging marine zoonotic pathogen and accounts for considerable mortality and morbidity in compromised hosts. However, there is scarce literature related to the understanding of the genetic background of virulence determinants in S. algae. In this study, we aim to determine the occurrence of common virulence genes in S. algae using whole-genome sequence and comparative genomic analysis. Comparative genomics reveals putative-virulence genes related to bile resistance, chemotaxis, hemolysis, and motility. We detected the existence of hlyA, hlyD, and hlyIII involved in hemolysis. We also found chemotaxis gene cluster cheYZA operon and cheW gene. The results provide insights into the genetic basis underlying pathogenicity in S. algae.

Background Shewanella algae is a zoonotic pathogen that poses a serious health threat to immunocompromised hosts. Treatment of S. algae infections is challenging due to the pathogen's intrinsic resistance to a variety of β-lactam antibiotics. Therapeutic options have become further limited by the emergence of quinolone-resistant strains. Currently, there are few studies concerning the genetic and molecular mechanisms underlying acquired quinolones resistance in S. algae. qnrA was once proposed as the candidate gene related to quinolones resistance in S. algae. However, recent studies demonstrated qnrA are highly conservative and does not confer resistance to quinolones in S. algae. Methods A total of 27 non-duplicated isolates of S. algae strains were examined. MICs of ciprofloxacin were determined using Vitek 2. Whole genome sequencing was performed using MiSeq platform. Comprehensive Antibiotic Resistance Database and ResFinder were used for annotation of quinolones resistance genes. Multiple sequence alignment by EMBOSS Clustal Omega were used to identified mutation in quinolone resistance-determining regions. To investigation of the alteration of protein structure induced by mutation, in silico molecular docking studies was conducted using Accryl Discovery studio visualizer. Results All S. algae harbored the quinolone-resistance associated genes (qnrA, gyrA, gyrB, parC, and parE) regardless its resistance to ciprofloxacin. Comparison of these genomes identified a nonsynonymous mutation (S83V) in chromosome-encoded gyrase subunits (GyrA) in quinolone-resistant strain. We found this mutation disrupts the water-metal ion bridge, reduces the affinity of the quinolone-enzyme complex for the metal ions and therefore decrease the capability of quinolones to stabilize cleavage complexes. Conclusions The study provides insight into the quinolone resistance mechanisms in S. algae, which would be helpful for the evolution of antibiotic resistance in this bacterium.

Purpose: To compare the predictive value of albumin-bilirubin (ALBI) grade, platelet-ALBI (PALBI) grade and Child-Turcotte-Pugh (CTP) class in patients with large hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) combined with microwave ablation (TACE-MWA). Methods: A total of 349 consecutive HCC patients (89.1% male; mean [± SD] age 53.4 ± 12.27 years) from three medical centers, who underwent TACE-MWA for up to 3 HCCs with maximum diameters of 5.1–8.0 cm between January 2000 and June 2018, were investigated. Overall survival (OS) and progression-free survival (PFS) were analyzed. The prognostic performances of ALBI grade, PALBI grade and CTP class were compared. Results: TACE procedures were performed using lobaplatin (20–50 mg), epirubicin (30–60 mg), lipiodol (5–25 mL) and gelatin sponge particles (350–560 μm). The end point of the TACE procedure was stasis of blood flow in the feeder artery. The median follow-up duration was 28.0 months, the median OS was 28.0 months (95% confidence interval [CI] 23.55–32.45 months), and the median PFS was 4.8 months (95% CI 4.26–5.34 months). Patients with a ablation margin size of 11–15 mm experienced better PFS than those with a margin size of 6–10 or 0–5 mm (median, 6.5 versus [vs] 4.0 vs 2.3 months; p

There are few reports describing ventricular arrhythmias (VAs) from the crux and the corresponding endocardial site, i.e., the basal inferior segment of the interventricular septum (IVS). We aimed to investigate a distinct clinical group of VAs arising from the endocardium at this area in patients with structural heart diseases (SHD). We included 17 patients with SHD and clinically documented VAs. Thirteen patients underwent endocardial mapping only. Three patients underwent both epicardial and endocardial approaches and one had only epicardial mapping. Eighteen VAs were identified, 14 focal and 4 reentrant VAs, confirmed by entrainment. There were 2 VAs from the crux, 5 VAs from the corresponding endocardial site in the right ventricle (RV), and 11 from the site in the left ventricle (LV). Compared with the VAs from RV endocardium, VAs from LV endocardium had a higher R wave in V3 than V2 (V2R/V3R ratio, 1.83 ± 0.84 vs. 0.86 ± 0.38, P = 0.008) and a higher V3 transition ratio percentage (2.16 ± 2.07 vs. 0.58 ± 0.62, P = 0.008). Combining all 16 patients with endocardial mapping, there were also lower bipolar voltages (1.21 ± 1.05 vs. 3.10 ± 2.65 mv, P

Nonischemic cardiomyopathies (NICMs) are composed of variable disease entities, including primary and secondary cardiomyopathies. Determining the etiology of NICM provides pivotal roles of not only the understanding of the individual pathogenesis, but also the clinical management, such as risk stratification, pharmacological treatment, and intervention therapies. Despite the diverse causes of NICM, these cases mostly require clinical attention owing to progressive myocardial injury, resulting in ventricular dysfunction and heart failure. The interaction between the diseased ventricular substrates and systemic/neurophysiological factors contributes to the cornerstones responsible for ventricular arrhythmogenesis and sudden cardiac death (SCD). Prevention of SCD and diminishing ventricular tachyarrhythmias are the important mainstays for the management of NICM patients. Given the understanding of the abnormal ventricular substrates and advancement of navigation systems, radiofrequency catheter ablation (RFCA) has become an adjunctive or alternative strategy for NICM patients who experience drug‐refractory ventricular tachycardias (VTs). Successful ablation can frequently be achieved at the expense of an epicardial intervention. A recent study has proven the survival benefits for NICM patients who are free from recurrent VTs after a successful RFCA, regardless of the New York Heart Association (NYHA) functional class status or left ventricular ejection fraction. Additionally, recent evidence has highlighted the better delineation of a diseased myocardium through the incorporation of cardiovascular magnetic resonance imaging (CMRI) and 3D mapping systems, which can facilitate the identification of critical ventricular arrhythmogenic substrates in NICM patients.

Background For patients receiving palliative home care, the need to visit the emergency department is considered to be an indicator of poor quality care. The situation can be particularly distressing when it occurs outside of normal hours of palliative home care service. The aim of this study was to investigate the factors for emergency department use during out-of-hours periods of palliative home care service among advanced cancer patients in Taiwan. Methods This case-control study was based on a retrospective medical chart review (January 2010 to December 2012) of advanced cancer patients who were receiving palliative home care in a community hospital in south Taiwan. The use of emergency medical services by these patients was dichotomized into either normal hours (8 a.m. to midnight, Monday to Friday, excluding public holidays) of palliative home care or outside normal hours. Logistic regression analyses were performed to evaluate factors associated with emergency services use during out-of-hours period of palliative home care. Results: Of the 94 patients receiving palliative home care, 65 had used emergency services at least once during the 3-year study period. Of these 65 patients, 40% used emergency services during out-of-hours of palliative home care. Patients with distressing conditions (defined as the occurrence of any two conditions of dyspnea, change of consciousness, or gastrointestinal bleeding) were significantly more likely to use emergency services during out-of-hours of palliative home care. Conclusions Patients at risk of developing dyspnea, change of consciousness, or gastrointestinal bleeding should be provided with relevant information regarding these symptoms and signs.

Autophagy is a highly dynamic process characterized with the term of autophagic flux. In the present study, we developed a quantifiable luciferase reporter system to measure the capacity as well as the dynamics of autophagic flux. Briefly, a luciferase variant of Luc2p was fused with p62/SQSTM1 or its UBA domain deletion mutant (p62ΔU) and transfected into cells. The expressed Luc2p-p62 fusion protein was primarily degraded via autophagy, while Luc2p-p62ΔU was employed as a normalization control due to its resistance to autophagic degradation. The luciferase activity of the lysates from two parallel populations of glioma cells expressing either Luc2p-p62 or Luc2p-p62ΔU was determined and the ratio of Luc2p-p62ΔU/Luc2p-p62 was used to assay the autophagic flux. By this approach, the induction of autophagy was manifested as an increased Luc2p-p62ΔU/Luc2p-p62 ratio, which could be neutralized by autophagy inhibitors or knockdown of ATG5. The performance of our autophagic flux detection system was comparable to a recently reported GFP-LC3-RFP-LC3ΔG probe. We tested the system in TMZ treated glioma cells, and found that coadministration of chloroquine to attenuate cellular autophagic flux significantly improved the TMZ efficacy by triggering more early apoptosis. Collectively, our luciferase-based autophagic flux assay may serve as a useful alternative yet sensitive method for autophagic flux detection in tumor cells.

Background and Purpose— The risk of stroke in patients with short-run atrial tachyarrhythmia (AT) remains unclear. This study aimed to investigate the relationship between short-run AT and the stroke and the use of the CHA 2 DS 2 -VASc score for the risk stratification. Methods— From the registry of 24-hour Holter monitoring, 5342 subjects without known atrial fibrillation or stroke were enrolled. Short-run AT was defined as episodes of supraventricular ectopic beats Results— There were 1595 subjects (29.8%) with short-run AT. During the median follow-up period of 9.0 years, 494 subjects developed new-onset stroke. Patients with short-run AT had significantly higher stroke rates compared with patients without short-run AT (11.4% versus 8.3%; P 2 DS 2 -VASc score of 0 and 1 were 0.23 and 0.67, respectively. However, the number of them for patients with CHA 2 DS 2 -VASc score of 2, 3, 4, and ≥5 were 1.62, 1.89, 1.30, and 2.91, respectively. In patients with CHA 2 DS 2 -VASc score of 0 or 1, age (>61 years old) and burden of premature atrial contractions (>25 beats/d) independently predicted the risk of stroke. In subgroup analyses, short-run AT patients were divided into 3 groups based on their CHA 2 DS 2 -VASc scores: low score (score of 0 [men] or 1 [women]; n=324), intermediate score (score of 1 [men] or 2 [women]; n=275), and high score (score of ≥2 [men] or ≥3 [women]; n=996). When compared with low score, intermediate and high scores were independent predictors for stroke (hazard ratio, 6.165; P P Conclusions— Short-run AT increases the risk of stroke. Therefore, the CHA 2 DS 2 -VASc score could be used for the risk stratification. Age and burden of premature atrial contractions were independent predictors for stroke in patients with CHA 2 DS 2 -VASc score of 0 or 1.

This study aimed to examine the relationship between measurements related to heart sounds and the origin of ventricular arrhythmia. We retrospectively evaluated 45 patients undergoing catheter ablation with contemporaneous digital acoustic cardiography of the first heart sound (S1) and the second heart sound (S2). The patients with baseline wide QRS morphology (>120 ms or aberrant conduction), heart failure, valvular heart disease, chronic pulmonary disease, and obesity were excluded. Ventricular arrhythmias from the left ventricle had an increased S1 complexity score and S1 duration in comparison to adjacent sinus beats. On the other hand, ventricular arrhythmia from right ventricle had decreased S1 complexity score and S1 duration in comparison to adjacent sinus beats. The difference of S1 (ΔS1) parameters between premature ventricular complex and sinus beat was significantly smaller in right ventricular arrhythmia group compared with and left ventricular arrhythmia group. For predicting the origin of ventricular arrhythmia, the ΔS1 duration provide better predictive accuracy (sensitivity: 100%, specificity: 100%, cutoff value: −1.28 ms) in comparison to ΔS1 complexity score (sensitivity 71.4%, specificity 75.0%, cutoff value: −0.13). The change of S1 complexity and duration determined from acoustic cardiography could accurately predict the ventricular arrhythmia origin.

Background High-throughput sequencing offers higher throughput and lower cost for sequencing a genome. However, sequencing errors, including mismatches and indels, may be produced during sequencing. Because, errors may reduce the accuracy of subsequent de novo assembly, error correction is necessary prior to assembly. However, existing correction methods still face trade-offs among correction power, accuracy, and speed. Results We develop a novel overlap-based error correction algorithm using FM-index (called FMOE). FMOE first identifies overlapping reads by aligning a query read simultaneously against multiple reads compressed by FM-index. Subsequently, sequencing errors are corrected by k-mer voting from overlapping reads only. The experimental results indicate that FMOE has highest correction power with comparable accuracy and speed. Our algorithm performs better in long-read than short-read datasets when compared with others. The assembly results indicated different algorithms has its own strength and weakness, whereas FMOE is good for long or good-quality reads. Conclusions FMOE is freely available at https://github.com/ythuang0522/FMOC. Electronic supplementary material The online version of this article (doi:10.1186/s12859-017-1940-1) contains supplementary material, which is available to authorized users.

Background Alcohol consumption is known to increase the risk of atrial fibrillation (AF). Whether the genotypes of alcohol-metabolizing genes (alcohol dehydrogenase [ADH1B]) are associated with the risk of AF recurrence after catheter ablation remains unclear. Methods and results The ADH1B genotypes of 281 patients who received catheter ablation for AF were examined. We followed this group of patients to monitor their AF recurrence. Alcohol consumption levels of this cohort were evaluated before and after catheter ablation. There was no difference in the underlying diseases presented by the patients with different ADH1B genotypes. Regardless of the ADH1B genotypes, the amount of alcohol consumption was the only factor associated with left atrial dilatation. The ADH1B*2 alleles (hazard ratio: ADH1B*1/*2 vs *1/*1: 2.64; ADH1B*2/*2 vs *1/*1: 1.80, P = 0.02) and the levels of alcohol consumption were independently associated with AF recurrence in the patients with paroxysmal AF after catheter ablation. ADH1B polymorphisms were not associated with AF recurrence in the patients with nonparoxysmal AF. We also found that the association of increased AF recurrence with alcohol consumption and the ADH1B genotypes cannot be explained by mechanisms of systemic inflammation. Conclusions ADH1B*2/*2 genotype and amount of alcohol consumption increase the risk of AF recurrence after catheter ablation.

This study used a computer-based teaching system to investigate the effectiveness of stroke-order learning and writing exercises in promoting the ability of Chinese-as-a-foreign-language (CFL) learners to recognize and write Chinese characters. This study included a 2 (stroke-order and non-stroke-order) × 2 (writing exercise and non-writing exercise) × 2 (test point) mixed factorial design involving a total of 91 participants. We compared the difference in their Chinese character learning, including Chinese character recognition and handwriting, based on the learning conditions. We found that CFL learners who practiced writing the characters had improved accuracy in their Chinese writing assignments and meaning assignments compared with students who did not practice writing, indicating that writing exercises helped students to memorize the orthography and output of Chinese characters. Writing exercises also helped improve memorization of the meaning of Chinese characters. However, the traditional emphasis on the correct stroke order, which has been considered helpful for learning Chinese characters, demonstrated no significant impact on the effectiveness of recognizing and writing Chinese characters.

Author(s): Huang, Yao-Ting; Tang, Yu-Yu; Cheng, Jan-Fang; Wu, Zong-Yen; Mao, Yan-Chiao; Liu, Po-Yu

Background The changes of signal averaged ECG (SAECG) in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) undergoing radiofrequency catheter ablation (RFCA) of ventricular arrhythmias (VAs) remains unknown. Methods Between 2010 and 2014, a total of 81 ARVD/C patients underwent endocardial and/or epicardial RFCA for drug-refractory VAs. Seventy patients (mean age 46.2±14.1years, 37 males) achieving acute procedure success (negative inducibility) were enrolled. Baseline characteristics, non-invasive examinations and SAECG (before and 3months after RFCA) were collected retrospectively. Results After successful RFCA, the electrical parameters of SAECG changed in 39 patients (55.7%), including 28 patients (40%) with electrical regression (group 1), and 11 patients (15.7%) with electrical progression (group 3). Thirty-one patients (44.3%) showed no significant SAECG change (group 2). During a mean follow-up of 17.8±10.7months, 23 patients (32.9%) had VA recurrences, including 4 in group 1, 12 in group 2, and 7 in group 3. In comparisons with groups 2 and 3, group 1 patients had a significantly better VA recurrence-free survival ( P =0.02). In multivariable Cox regression analysis, electrical regression was found to be associated with fewer VA recurrences ( P =0.02, OR: 0.28, 95% CI: 0.10–0.83). Conclusions Electrical regression of SAECG after RFCA in ARVD/C was found to be associated with fewer VA recurrences.

Background Fever is associated with the manifestation of Brugada phenotype and ventricular tachycardia/ventricular fibrillation (VT/VF) in patients with Brugada syndrome (BrS). The thermal effect on the pathogenesis of functional substrates in BrS remains unknown. Objective This study aimed to elucidate the thermal effect on BrS phenotype, VT/VF, and electrophysiological characteristics of epicardial functional substrates in BrS. Methods We consecutively studied 15 patients with BrS receiving radiofrequency catheter ablation for drug-refractory ventricular tachyarrhythmias. Baseline characteristics, electrocardiographic features, and changes in epicardial functional substrates before and after epicardial warm water instillation (n = 6) were recorded and analyzed. Results A total of 15 male patients (mean age 41.3 ± 10.3 years) with type 1 BrS presenting with ventricular tachyarrhythmias were consecutively enrolled. Epicardial mapping in 11 patients demonstrated a significantly larger epicardial scar/low-voltage zone (LVZ) area within the right ventricular outflow tract and anterior right ventricular free wall than within the endocardium (6.32 ± 12.74 cm2 vs 52.91 ± 45.25 cm2; P = .007). Epicardial warm water instillation in 6 patients led to a significant enlargement of the functional scar/LVZ area (123.83 ± 35.26 cm2 vs 63.53 ± 40.57 cm2; P = .03), accelerated conduction velocity of the endocardium and epicardium without scar/LVZ area, and increased VT/VF inducibility (16.7% vs 100%; P = .02). Ablation by targeting premature ventricular complexes and/or epicardial abnormal substrates rendered noninducibility of VT/VF and prevented the recurrences of VT/VF. Conclusion Epicardial warm water instillation enhanced functional epicardial substrates, which contributed to the increased inducibility of ventricular tachyarrhythmias in BrS. Ablation by targeting the triggers and abnormal epicardial substrates provided an effective strategy for preventing ventricular tachyarrhythmia recurrences in BrS.

Objective Oral cancer (OC) is a leading cause of death from cancer in men between the ages of 25 and 44 years in Taiwan. The overall 5-year survival rates for the four OC stages (I–IV) in Taiwan are approximately 70%, 30%, 20%, and 10%, respectively, indicating the importance of the early diagnosis of oral potentially malignant disorders (OPMDs). Previous studies indicated an association between the OC incidence and certain environmental heavy metal concentrations. If these associations do exist for OC, they may also be observed for OPMD. The purpose of this study is to explore the association between the development of OPMD to OC and environmental heavy metals. Oral submucous fibrosis (OSF) and oral leukoplakia (OL) are two major types of OPMD in Taiwan. Materials and methods A retrospective cohort study was conducted by Changhua Christian Hospital, the sole medical center in Changhua County, where 2725 male adult patients diagnosed with either OSF or OL between 2000 and 2014 were recruited. Data were analyzed by Cox regression and adjusted for smoking and betel-quid chewing. Results and discussion OPMD patients who resided in areas with high nickel concentrations (polluted levels) exhibited hazard ratios of 1.8–2 for OC relative to those who lived in areas with low nickel levels ( P 0.01). Meanwhile, smokers with OPMDs had a hazard ratio of 2.8–2.9 relative to non-smokers. Betel-quid chewers had a 2.2–2.3 hazard ratio relative to non-chewers. Smoking, betel-quid chewing, and environmental nickel exposure are associated with an increased risk of OC development in OPMD patients. This study provides valuable findings on the environmental effects of heavy metals on human health. Enhanced surveillance of the condition of OPMD patients who have been exposed to high nickel concentrations may be crucial for OC prevention.

Aims Whether the distribution of scar in arrhythmogenic right ventricular cardiomyopathy (ARVC) plays a role in predicting different types of ventricular arrhythmias is unknown. This study aimed to investigate the prognostic value of scar distribution in patients with ARVC. Methods and results We studied 80 consecutive ARVC patients (46 men, mean age 47 ± 15 years) who underwent an electrophysiological study with ablation. Thirty-four patients receive both endocardial and epicardial mapping. Abnormal endocardial substrates and epicardial substrates were characterized. Three groups were defined according to the epicardial and endocardial scar gradient ( 20%: horizontal, as groups 1, 2, and 3, respectively). Sinus rhythm electrograms underwent a Hilbert-Huang spectral analysis and were displayed as 3D Simultaneous Amplitude Frequency Electrogram Transformation (SAFE-T) maps, which represented the arrhythmogenic potentials. The baseline characteristics were similar between the three groups. Group 3 patients had a higher incidence of fatal ventricular arrhythmias requiring defibrillation and cardiac arrest during the initial presentation despite having fewer premature ventricular complexes. A larger area of arrhythmogenic potentials in the epicardium was observed in patients with horizontal scar. The epicardial-endocardial scar gradient was independently associated with the occurrence of fatal ventricular arrhythmias after a multivariate adjustment. The total, ventricular tachycardia, and VF recurrent rates were higher in Group 3 during 38 ± 21 months of follow-up. Conclusion For ARVC, the epicardial substrate that extended in the horizontal plane rather than transmurally provided the arrhythmogenic substrate for a fatal ventricular arrhythmia circuit.

Background Gender differences in the penetrance and clinical expression of genetic mutations have been reported in patients with arrhythmogenic right ventricular (RV) dysplasia/cardiomyopathy (ARVD/C). Our study aimed at clarifying the impact of gender on ventricular substrates and clinical outcomes after radiofrequency catheter ablation (RFCA). Methods Patients with ARVD/C underwent RFCA for drug-refractory ventricular arrhythmias (VAs) were consecutively enrolled. Baseline characteristics, electrocardiograms, ventricular substrates, and VA recurrences after RFCA were extracted for comparison between genders. Results A total of 70 consecutive unselected patients with definite ARVD/C (36 men [51%], age 45±14years) were studied. Male patients had a higher incidence of sustained ventricular tachycardia and ventricular fibrillation or sudden cardiac arrest as initial manifestations. Electroanatomical mapping demonstrated that men with ARVD/C had a larger epicardial RV unipolar low-voltage zone, a larger endocardial and epicardial area with late potentials, and longer local abnormal ventricular activity. Cox regression analysis demonstrated that gender and late potential area predicted the recurrences of VAs. Conclusion Patients with ARVD/C displayed different characteristics of VAs and substrate properties between men and women. Male gender and the presence of larger area of abnormal electrograms independently predicted VA recurrences after RFCA.

Predictors of AF Progression After AblationIntroduction Although rare, some paroxysmal atrial fibrillations (AF) still progress despite radiofrequency (RF) ablation. In the study, we evaluated the long-term efficacy of RF ablation and the predictors of AF progression. Methods A total of 589 paroxysmal AF patients (404 men and 185 women; aged 54 ± 12 years) who received 3-dimensional mapping and ablation were enrolled. Their clinical parameters and electrophysiological characteristics were collected. They were divided into Group 1 (N = 13, with AF progression) and Group 2 (N = 576, no AF progression). AF progression was defined as recurrence of persistent AF. Results Group 1 patients had larger left atrial (LA) diameter, larger left ventricle (LV) end-systolic and end-diastolic diameters, poorer LV systolic function, and more amiodarone use at baseline. After 1.2 ± 0.5 procedures, 123 (21%) patients experienced recurrence during 56 ± 29 months’ follow-up. In the multivariate analysis, LA diameter (P = 0.018, HR = 1.12, 95% CI = 1.02–1.24) and LV end-systolic diameter (P = 0.005, HR = 1.10, 95% CI = 1.03–1.17) independently predicted AF progression. LA diameter >43 mm and LV end-systolic diameter >31 mm were the best cut-off values for predicting AF progression by ROC analysis. AF progression rate achieved 19% if they had both larger LA diameter (>43 mm) and LV end-systolic diameter (>31 mm). Conclusion RF ablation prevents the progression of paroxysmal AF effectively, except in patients with increased LA diameter and LV end-systolic diameter on echocardiogram, suggesting more aggressive rhythm control therapies should be considered in these patients.

The effectiveness of preemptive treatment (PET) for cytomegalovirus (CMV) in recipients of ex vivo T cell–depleted (TCD) hematopoietic cell transplantation (HCT) by CD34+ selection is not well defined. We analyzed 213 adults who received TCD-HCT at our institution from June 2010 through May 2014. Patients were monitored by a CMV quantitative PCR assay if recipient (R) or donor (D) were CMV seropositive. CMV viremia occurred early (median, 27 days after HCT) in 91 of 213 (42.7%) patients for a 180-day cumulative incidence of 84.5%, 61.8%, and 0 for R+/D+, R+/D−, and R−/D+ patients, respectively. CMV disease occurred in 5% of patients. In Cox regression analysis, R+/D+ status was associated with increased risk for CMV viremia compared with R+/D− (hazard ratio [HR], 1.79, 95% confidence interval [CI], 1.16 to 2.76, P = .01), whereas matched unrelated donor allograft was associated with decreased risk (HR, .62; 95% CI, .39 to .97, P = .04). Of 91 patients with CMV viremia, 52 (57%) had persistent viremia (>28 days duration). Time lag from detection of CMV viremia to PET was associated with incremental risk for persistent viremia (HR, 1.09; 95% CI, 1.01 to 1.18; P = .03). Overall, 166 of 213 (77.9%) patients were alive 1 year after HCT, with no difference between patients with and without CMV viremia or among the different CMV serostatus pairs (P = not significant). CMV viremia occurred in 70% of R + TCD-HCT. Delay in PET initiation was associated with persistent viremia. With PET, CMV R/D serostatus did not adversely impact survival in TCD-HCT on 1-year survival in the present cohort.

BACKGROUND Telomere length is a biologic aging marker. This study investigated leukocyte telomere length (LTL) as a new biomarker to predict recurrence after paroxysmal atrial fibrillation (PAF) ablation.Methods and Results:A total of 131 participants (26 healthy individuals and 105 symptomatic PAF patients) were enrolled. PAF patients (54.1±10.8 years) who received catheter ablation therapy were divided into 2 groups: recurrent AF (n=25) and no recurrent AF after catheter ablation (n=80). Peripheral blood mononuclear cells were collected from all subjects to measure LTL. Under 50 years old, LTL in healthy individuals (n=17) was longer than in PAF patients (n=31; 7.34±0.58 kbp vs. 6.44±0.91 kbp, P=0.01). In PAF patients, LTL was positively correlated with left atrial bipolar voltage (R=0.497, P

MicroRNA regulation is crucial for gene expression and cell functions. It has been linked to tumorigenesis, development and metastasis in colorectal cancer (CRC). Recently, the let-7 family has been identified as a tumor suppressor in different types of cancers. However, the function of the let-7 family in CRC metastasis has not been fully investigated. Here, we focused on analyzing the role of let-7g in CRC. The Cancer Genome Atlas (TCGA) genomic datasets of CRC and detailed data from a Taiwanese CRC cohort were applied to study the expression pattern of let-7g. In addition, in vitro as well as in vivo studies have been performed to uncover the effects of let-7g on CRC. We found that the expression of let-7g was significantly lower in CRC specimens. Our results further supported the inhibitory effects of let-7g on CRC cell migration, invasion and extracellular calcium influx through store-operated calcium channels. We report a critical role for let-7g in the pathogenesis of CRC and suggest let-7g as a potential therapeutic target for CRC treatment.

BackgroundSurgical cancer patients often have deteriorated physical activity (PA), which in turn, contributes to poor outcomes and early recurrence of cancer. Mobile health (mHealth) platforms are progressively used for monitoring clinical conditions in medical subjects. Despite prevalent enthusiasm for the use of mHealth, limited studies have applied these platforms to surgical patients who are in much need of care because of acutely significant loss of physical function during the postoperative period. ObjectiveThe aim of our study was to determine the feasibility and clinical value of using 1 wearable device connected with the mHealth platform to record PA among patients with gastric cancer (GC) who had undergone gastrectomy. MethodsWe enrolled surgical GC patients during their inpatient stay and trained them to use the app and wearable device, enabling them to automatically monitor their walking steps. The patients continued to transmit data until postoperative day 28. The primary aim of this study was to validate the feasibility of this system, which was defined as the proportion of participants using each element of the system (wearing the device and uploading step counts) for at least 70% of the 28-day study. “Definitely feasible,” “possibly feasible,” and “not feasible” were defined as ≥70%, 50%-69%, and 90%). Furthermore, we used a multivariable-adjusted model to predict early discharge, which demonstrated that every 1000-step increment of walking on postoperative day 5 was associated with early discharge (odds ratio 2.72, 95% CI 1.17-6.32; P=.02). ConclusionsIncorporating the use of mobile phone apps with wearable devices to record PA in patients of postoperative GC was feasible in patients undergoing gastrectomy in this study. With the support of the mHealth platform, this app offers seamless tracing of patients’ recovery with a little extra burden and turns subjective PA into an objective, measurable parameter.

Brain abscess is a severe infectious disease with high mortality and mobility. Although culture-based techniques have been widely used for the investigation of microbial composition of brain abscess, these approaches are inherent biased. Recent studies using 16S ribosomal sequencing approaches revealed high complexity of the bacterial community involved in brain abscess but fail to detect fungal and viral composition. In the study, both culture-independent nanopore metagenomic sequencing and culture-based whole-genome sequencing using both the Illumina and the Nanopore platforms were conducted to investigate the microbial composition and genomic characterization in brain abscess. Culture-independent metagenomic sequencing revealed not only a larger taxonomic diversity of bacteria but also the presence of fungi and virus communities. The culture-based whole-genome sequencing identified a novel species in Prevotella and reconstructs a Streptococcus constellatus with a high GC-skew genome. Antibiotic-resistance genes CfxA and ErmF associated with resistance to penicillin and clindamycin were also identified in culture-based and culture-free sequencing. This study implies current understanding of brain abscess need to consider the broader diversity of microorganisms.

Secondary metabolites are considered to be the major compounds in Cordyceps with anti-tumor, anti-aging and immunity-enhancing effects. The molecular structures of secondary metabolites form the basis for the development and utilization of Cordyceps. Metacordyceps neogunnii is an important Cordyceps resource, but less study has been made on the molecular structure of its secondary metabolites. In this study, gas chromatography-mass spectrometry (GC/MS) and ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) were used to analyze and identify the secondary metabolites from CH3OH/H2O extract of Metacordyceps neogunnii. The results show that a total of 22 compounds were identified by GC-MS, including 2 n-alkanes, 1 isoparaffin, 1 cycloalkane, 6 olefins and 13 esters. The predominant compounds were (E)-ocimene, (E)-β-ocimene, methyl oleate, dioctyl adipate, methyl palmitate and methyl linoleate, obtained by means of GC/MS. Five distince classes of secondary metabolites were speculated: 3 polypeptides, 2 esters, 1 isoflavone, 1 isoindrone and 3 amides, from which 10 compounds were detected using UPLC-Q-TOF/MS. (R)-N-((1-(((9H-fluorene-9-yl) methoxy) carbonyl) pyrrolidine-2-yl) methyl)-N-(2-(6-benzoylamino-9H-purin-9-yl) acetyl) glycine, benzyl (5-(2-((3-(2, 3-dihydrobenzo[b] [1, 4] dioxin-6-yl)-4-carbonyl-4H-chromene-7-yl) oxo) acetylamino) amyl) carbamate, 5, 5’-((propane-2, 2-diyl (4, 1-phenylene)) bis (oxo)) bis (2-(naphthalene-1-yl) isoindoline-1, 3-dione), 1-dodecylazepine-2-one and other compounds were the first detected in Metacordyceps neogunnii.

Background The objective of the current study was to examine whether the relation between aerobic fitness and academic achievement during adolescence is subject-dependent, and to investigate cumulative and recency effects. Methods This study made use of two nationwide datasets. The first was the aerobic fitness profile of junior high school students collected by the Ministry of Education in Taiwan. The second contained the scores on the Basic Competence Test for Junior High School Students (BCTJH). The sample consisted of 382,259 students who completed the BCTJH in the 5 years between 2009 and 2013. Data on each student’s aerobic fitness during their three years of junior high school were matched with their exam results at the end of this period. Results The results revealed that students classified as highly-fit during at least one of the three years had higher BCTJH scores than those who never achieved this level, with the size of effect increasing with the length of time that fitness was maintained. Additionally, aerobic fitness in the final year was more closely linked to BCTJH scores than that in the earlier two years. Fitness was also more strongly associated with exam performance in math, science and social science, relative to language-related subjects. Conclusions Our findings suggest that while aerobic fitness is positively related to academic achievement in Taiwanese junior high school students, the relationship depends on academic subject, as well as the length and time of being aerobically fit. Electronic supplementary material The online version of this article (10.1186/s12887-018-1384-4) contains supplementary material, which is available to authorized users.

Aim Cardiopulmonary resuscitation (CPR) quality affects survival after cardiac arrest. We aimed to investigate if a smartwatch with real-time feedback can improve CPR quality by healthcare professionals. Methods An app providing real-time audiovisual feedback was developed for a smartwatch. Emergency Department (ED) professionals were recruited and randomly allocated to either the intervention group wearing a smartwatch with the preinstalled app, or to a control group. All participants were asked to perform a two-minute CPR on a manikin at a 30:2 compression-ventilation ratio. Primary outcomes were the mean CCR and CCD measured on the manikin. A secondary outcome was the percentage of chest compressions meeting both the guideline-recommended rate (100–120 min−1) and depth (50–60 mm) of high-quality CPR during a 2-min period. Differences between groups were evaluated with t-test, Chi-Square test, or Mann–Whitney U test depending on the distribution. Results Eighty participants were recruited. 40 people were assigned to the intervention and 40 to the control group. The compression rates (mean ± SD, min−1) were significantly faster (but above the guideline recommendation, P Conclusion Without real-time feedback, chest compressions tend to be too fast and too shallow. CPR quality can be improved with the assistance of a smartwatch providing real-time feedback.