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Let |$X$| be a Calabi–Yau variety of Picard number two with infinite birational automorphism group. We show that the numerical dimension |$\kappa ^{\mathbb{R}}_{\sigma }$| of the extremal rays of the closed movable cone of |$X$| is |$\dim X/2$|⁠. More generally, we investigate the relation between the two numerical dimensions |$\kappa ^{\mathbb{R}}_{\sigma }$| and |$\kappa ^{\mathbb{R}}_{\textrm{vol}}$| for Calabi–Yau varieties. We also compute |$\kappa ^{\mathbb{R}}_{\sigma }$| for non-big divisors in the closed movable cone of a projective hyperkähler manifold. [ABSTRACT FROM AUTHOR]

Dried red chilies are widely used globally and are susceptible to contamination by fungi and fungal toxins. Roasting is a common way of processing dried red chilies. This study explored the effects of Aspergillus niger and ochratoxin A (OTA) contamination on the quality of roasted chilies, and the fate of OTA during the roasting process. Three optimum roasting conditions (140 °C×8 min, 160 °C×6 min, and 180 °C×4 min) were screened out by a combination of instrumental and manual sensory evaluations. Under these roasting conditions, A. niger and OTA contamination diminished the quality and taste of roasted chilies. With increasing roasting temperature and time duration, OTA content and mold counts gradually decreased, together with the DNA degradation of OTA biosynthesis-related genes of A. niger in roasted chilies. The roasting condition at 180 °C×4 min showed the greatest decomposition effect on OTA, while also maintaining good sensory quality of roasted chilies. This study shed light on the fate of OTA during the chili roasting process. [ABSTRACT FROM AUTHOR]

Aims The clinical correlates and outcomes of asymptomatic atrial fibrillation (AF) in hospitalized patients are largely unknown. We aimed to investigate the clinical correlates and in-hospital outcomes of asymptomatic AF in hospitalized Chinese patients. Methods and results We conducted a cross-sectional registry study of inpatients with AF enrolled in the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation Project between February 2015 and December 2019. We investigated the clinical characteristics of asymptomatic AF and the association between the clinical correlates and the in-hospital outcomes of asymptomatic AF. Asymptomatic and symptomatic AF were defined according to the European Heart Rhythm Association score. Asymptomatic patients were more commonly males (56.3%) and had more comorbidities such as hypertension (57.4%), diabetes mellitus (18.6%), peripheral artery disease (PAD; 2.3%), coronary artery disease (55.5%), previous history of stroke/transient ischaemic attack (TIA; 17.9%), and myocardial infarction (MI; 5.4%); however, they had less prevalent heart failure (9.6%) or left ventricular ejection fractions ≤40% (7.3%). Asymptomatic patients were more often hospitalized with a non-AF diagnosis as the main diagnosis and were more commonly first diagnosed with AF (23.9%) and long-standing persistent/permanent AF (17.0%). The independent determinants of asymptomatic presentation were male sex, long-standing persistent AF/permanent AF, previous history of stroke/TIA, MI, PAD, and previous treatment with anti-platelet drugs. The incidence of in-hospital clinical events such as all-cause death, ischaemic stroke/TIA, and acute coronary syndrome (ACS) was higher in asymptomatic patients than in symptomatic patients, and asymptomatic clinical status was an independent risk factor for in-hospital all-cause death, ischaemic stroke/TIA, and ACS. Conclusion Asymptomatic AF is common among hospitalized patients with AF. Asymptomatic clinical status is associated with male sex, comorbidities, and a higher risk of in-hospital outcomes. The adoption of effective management strategies for patients with AF should not be solely based on clinical symptoms. [ABSTRACT FROM AUTHOR]

Activation of inflammasomes—immune system receptor sensor complexes that selectively activate inflammatory responses—has been associated with diverse human diseases, and many nanomedicine studies have reported that structurally and chemically diverse inorganic nanomaterials cause excessive inflammasome activation. Here, in stark contrast to reports of other inorganic nanomaterials, we find that nickel-cobalt alloy magnetic nanocrystals (NiCo NCs) actually inhibit activation of NLRP3, NLRC4 and AIM2 inflammasomes. We show that NiCo NCs disrupt the canonical inflammasome ASC speck formation process by downregulating the lncRNA Neat1 , and experimentally confirm that the entry of NiCo NCs into cells is required for the observed inhibition of inflammasome activation. Furthermore, we find that NiCo NCs inhibit neutrophil recruitment in an acute peritonitis mouse model and relieve symptoms in a colitis mouse model, again by inhibiting inflammasome activation. Beyond demonstrating a highly surprising and apparently therapeutic impact for an inorganic nanomaterial on inflammatory responses, our work suggests that nickel- and cobalt-containing nanomaterials may offer an opportunity to design anti-inflammatory nanomedicines for the therapeutics of macrophage-mediated diseases. [ABSTRACT FROM AUTHOR]

We show that the anti-canonical volume of a canonical weak |${\mathbb {Q}}$| -Fano three-fold is at most |$324$|⁠. [ABSTRACT FROM AUTHOR]

Context: Some studies have reported the early miscarriage rate is higher in polycystic ovary syndrome (PCOS) women. However, there is a lack of evidence as to whether the risk of embryo abnormalities increases in PCOS women. Objective: This work aimed to evaluate the association between PCOS and embryo ploidy. Methods: A secondary analysis of a multicenter, randomized controlled trial was conducted from July 2017 to June 2018. The original intent was to identify whether preimplantation genetic test for aneuploidy (PGT-A) improves the live birth rate as compared with in vitro fertilization (IVF). From 14 reproductive centers, 190 patients diagnosed with PCOS and 1:1 age-matched non-PCOS patients were chosen from a PGT-A group. A total of 380 patients with 1118 embryos were included in our study. Intervention included women diagnosed with PCOS, and the main outcome measures were embryonic aneuploidy and embryonic mosaic. Results: After adjusting for potential confounders, the rate of embryonic aneuploidy and embryonic mosaic in the PCOS group were comparable with the control group (embryonic aneuploid rate PCOS group: 14.0% vs control group: 18.3%, adjusted OR [95% CI]: 0.78 [0.54, 1.12]; P=.19; embryonic mosaic rate 10.9% vs 10.1%, adjusted OR [95% CI]: 0.91 [0.59, 1.40]; P=.66). We further stratified PCOS women into 4 groups according to phenotype. The rate of aneuploid and mosaic embryos was comparable between each PCOS phenotype and control group. There was still no significant difference of embryonic aneuploid and embryo mosaic rates among the 4 phenotypes. Conclusion: The risk of aneuploid and mosaic embryos did not increase in PCOS women. Thus, we suggest that the miscarriage rate arising from abnormal embryonic chromosomes could be similar between PCOS and non-PCOS women. [ABSTRACT FROM AUTHOR]

Aims Fascicular ventricle tachycardia (FVT) arising from the proximal aspect of left His-Purkinje system (HPS) has not been specially addressed. Current study was to investigate its clinical, electrocardiographic, and electrophysiological characteristics. Methods and results Eighteen patients who were identified as this rare FVT were consecutively enrolled, and their scalar electrocardiogram and electrophysiological data were collected and analysed. The ventricular tachycardia (VT) morphology was similar to sinus rhythm (SR) in eight patients, left bundle branch block type in one patient, right bundle branch block type in seven patients, and both narrow and wide QRS type in two patients. During VT, right-sided His potential preceded the QRS with His-ventricle (H-V) interval of 36.3 ± 12.4 ms, which was shorter than that during SR (−51.4 ± 8.6 ms) (P = 0.002). The earliest Purkinje potentials (PPs) were recorded within 7 ± 3 mm of left-side His and preceded the QRS by 49.1 ± 14.0 ms. Mapping along the left anterior fascicle and left posterior fascicle revealed an antegrade activation sequence in all with no P1 potentials recorded. In the two patients with two VT morphologies, the earliest PP was documented at the same site, and the activation sequence of HPS remained antegrade. Ablation at the earliest PP successfully eliminated the tachycardia, except one patient who developed complete atrial-ventricular block and two patients who abandoned ablations. After at least 12 months follow-up, 15 patients were free from any recurrences. Conclusions Fascicular ventricle tachycardia arising from the proximal aspect of left HPS was featured by recording slightly shorter H-V interval and absence of P1 potentials. Termination of VT requires ablation at the left-sided His or its adjacent region. [ABSTRACT FROM AUTHOR]

Antibodies are essential to life, and knowing their structures can facilitate the understanding of antibody–antigen recognition mechanisms. Precise antibody structure prediction has been a core challenge for a prolonged period, especially the accuracy of H3 loop prediction. Despite recent progress, existing methods cannot achieve atomic accuracy, especially when the homologous structures required for these methods are not available. Recently, RoseTTAFold, a deep learning-based algorithm, has shown remarkable breakthroughs in predicting the 3D structures of proteins. To assess the antibody modeling ability of RoseTTAFold, we first retrieved the sequences of 30 antibodies as the test set and used RoseTTAFold to model their 3D structures. We then compared the models constructed by RoseTTAFold with those of SWISS-MODEL in a different way, in which we stratified Global Model Quality Estimate (GMQE) into three different ranges. The results indicated that RoseTTAFold could achieve results similar to SWISS-MODEL in modeling most CDR loops, especially the templates with a GMQE score under 0.8. In addition, we also compared the structures modeled by RoseTTAFold, SWISS-MODEL and ABodyBuilder. In brief, RoseTTAFold could accurately predict 3D structures of antibodies, but its accuracy was not as good as the other two methods. However, RoseTTAFold exhibited better accuracy for modeling H3 loop than ABodyBuilder and was comparable to SWISS-MODEL. Finally, we discussed the limitations and potential improvements of the current RoseTTAFold, which may help to further the accuracy of RoseTTAFold's antibody modeling. [ABSTRACT FROM AUTHOR]

This article discusses a case study of a 65-year-old man who was hospitalized after experiencing a transient syncope. The patient had abnormal Q-waves and ST-segment elevation on an electrocardiogram, and coronary angiography revealed an occlusive stenosis in the first obtuse marginal artery. Transthoracic echocardiography and cardiovascular magnetic resonance imaging confirmed the presence of an intramyocardial dissecting hematoma (IDH) in the lateral wall of the left ventricle. The patient was treated with medications due to the high risk of operation during acute myocardial infarction, and the IDH was monitored and eventually operated on. The patient recovered during the 6-month follow-up. The article emphasizes that IDH is a rare but potentially deadly complication of acute myocardial infarction, reperfusion procedures, or trauma, and individualized management is crucial for improving patient outcomes. [Extracted from the article]

The purpose of this study was to determine whether circular RNA hsa_circ_0002874 could serve as a novel biomarker for the diagnosis of gastric cancer (GC). The expression level of hsa_circ_0002874 mean (interquartile range [IQR]) in the plasma of patients with GC, patients with benign gastric lesions, and healthy individuals was 3.482 (IQR, 1.524–9.048), 1.261 (IQR, 0.817–2.000), and 1.00 (IQR, 0.726–1.382), respectively, whereas there was no significant difference between the latter 2 groups. The plasma expression level of hsa_circ_0002874 was significantly correlated with tumor stage (U  = 234.0; P < .001) and lymph node metastasis (U  = 240.0; P < .001). The receiver operating characteristic (ROC) curve showed that the sensitivity of the combined determination of hsa_circ_0002874 and the serum markers CEA and CA19-9 was 95.8% in patients with GC compared with that of the healthy group and 93.0% compared with that of patients with benign gastric tumor lesions. The specificity of hsa_circ_0002874 in differentiating GC from benign lesions was 98.3%. The results showed that plasma hsa_circ_0002874 may prove to be a useful biomarker for auxiliary diagnosis, the grading of malignant neoplasms, and the prognostic prediction of GC. [ABSTRACT FROM AUTHOR]

Theory suggests that the orbits of a large fraction of binary systems, including planet–star binary systems, shrink by a few orders of magnitude after formation. But so far, only one hot Jupiter with tidally driven orbital decay has been found by transit timing variations. We propose to search for orbital decay companions in heartbeat star systems because the orbital angular momentum is effectively transferred to the host star, causing tidal dissipation. KIC 3766353 is one of the heartbeat stars with tidally excited oscillations. We acquired the primary and the secondary eclipse time variations from the Kepler photometric light curves. Timing analysis shows that KIC 3766353 is a hierarchical triple system with a hidden third body and a red dwarf (mass 0.35 M⊙, radius 0.34  R ⊙) in its inner orbit. The minimum mass of the third body is ∼0.26 M⊙, and the distance from the inner orbital is ∼111.4  R ⊙. The period decay rate of the red dwarf is approximately 358 ms yr−1. The combined effects of the light-traveltime and the orbital decay lead to the observed timing variations. Future monitoring with long-time baseline observations is required to delve into the contributions of these two effects. [ABSTRACT FROM AUTHOR]

Context: Previous work has demonstrated the role of the circadian clock in ovarian steroid hormone synthesis and attributed embryo implantation failure associated with arrhythmic circadian clock genes to insufficient ovarian-derived progesterone synthesis. Research on expression of core circadian clock genes in the endometrium itself and possible roles in compromised endometrial receptivity and recurrent implantation failure (RIF) are limited.Objective: We aimed to assess the core circadian clock gene profiling in human endometrium across the menstrual cycle and the possible gene interaction networks in the endometrial receptivity of window of implantation (WOI) as well as RIF.Methods: The study was initially an in silico study, with confirmatory lab-based data from primary human endometrial stromal cells (hESCs) as well as endometrial biopsies obtained from 60 women undergoing gynecological surgery in a clinical research center. The study included 30 RIF women and 30 age-matched and body mass index-matched controls.Results: Initial data mining and bioinformatics analysis of human endometrial microarray datasets across the menstrual cycle and between RIF women versus controls demonstrated the varied expression of core circadian clock genes across menstrual cycle, including the key role of PER2 in WOI and RIF. A PER2-centered network was investigated in the regulation of endometrial receptivity. We also confirmed the evidently increased mRNA expression of SHTN1, RXFP1, KLF5, and STEAP4 in the endometrium of RIF women, displaying the same trend as PER2 did, without any changes in MT1E and FKBP5. Treatment of PER2 siRNA in hESCs verified the positive regulation of PER2 to SHTN1, KLF5, and STEAP4.Conclusion: Aberrant expression of endometrial PER2 might contribute to impaired endometrial receptivity and development of RIF via regulating SHTN1, KLF5, and STEAP4. [ABSTRACT FROM AUTHOR]

Macrophages are a double-edged sword with potential cancer-promoting and anticancer effects. Controversy remains regarding the effect of macrophages, especially M1 macrophages, on tumor promotion and suppression. We aimed to investigate the role of M1 macrophages in the occurrence and progression of esophageal squamous cell carcinoma (ESCC). Analyzing the data in Gene Expression Omnibus database by the CIBERSORT algorithm found that M1 macrophages were one of the important components of many immune cells in ESCCs, and the increase in their number was obviously negatively correlated with tumor T staging. This result was verified by our experimental data: the density of CD68/HLA-DR double-stained M1 macrophages in ESCC tumor nest and tumor stroma was significantly higher than that in cancer-adjacent normal (CAN) tissues. The density of M1 macrophages in ESCC tumor nest was negatively correlated with the patient's lymph node metastasis and clinical stage (P < 0.05), and the negative tendency was more obvious for M1 macrophages in ESCC tumor stroma (P < 0.001). Exposure to M1 macrophage-conditioned medium inhibited ESCC cell migration and invasion ability significantly (P < 0.05). Moreover, the increased M1 macrophage density in ESCC tumor stroma correlated positively with good prognosis of ESCC. M1 macrophages were involved in inhibiting ESCC cell migration and invasion, which could serve as a good prognostic factor in patients with ESCC. [ABSTRACT FROM AUTHOR]

Detailed understanding of stellar physics is essential towards a robust determination of stellar properties (e.g. radius, mass, and age). Among the vital input physics used in the modelling of solar-type stars which remain poorly constrained, is the initial helium abundance. To this end, when constructing stellar model grids, the initial helium abundance is estimated either (i) by using the semi-empirical helium-to-heavy element enrichment ratio, (Δ Y /Δ Z), anchored to the standard big bang nucleosynthesis value, or (ii) by setting the initial helium abundance as a free variable. Adopting 35 low-mass, solar-type stars with multiyear Kepler photometry from the asteroseismic 'LEGACY' sample, we explore the systematic uncertainties on the inferred stellar parameters (i.e. radius, mass, and age) arising from the treatment of the initial helium abundance in stellar model grids. The stellar masses and radii derived from grids with free initial helium abundance are lower compared to those from grids based on a fixed Δ Y /Δ Z ratio. We find the systematic uncertainties on mean density, radius, mass, and age arising from grids which employ a fixed value of Δ Y /Δ Z and those with free initial helium abundance to be ∼ 0.9 per cent, ∼ 2 per cent, ∼ 5 per cent, and ∼ 29 per cent, respectively. We report that the systematic uncertainties on the inferred masses and radii arising from the treatment of initial helium abundance in stellar grids lie within the expected accuracy limits of ESA's PLATO, although this is not the case for the age. [ABSTRACT FROM AUTHOR]

Context: Dysregulated immune hemostasis occurs in unexplained recurrent spontaneous abortion (URSA). Synthesized by cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE), hydrogen sulfide (H2S) promotes regulatory T-cell differentiation and regulates immune hemostasis; yet, its role in URSA is elusive.Objective: To determine if H2S plays a role in early pregnancy and if dysregulated H2S signaling results in recurrent spontaneous abortion.Design: First trimester placenta villi and decidua were collected from normal and URSA pregnancies. Protein expression was examined by immunohistochemistry and immunoblotting. Human trophoblast HTR8/SVneo and JEG3 cells were treated with H2S donors; HTR8/SVneo cells were transfected with CBS ribonucleic acid interference (RNAi) or complementary deoxyribonucleic acid. Cell migration and invasion were determined by transwell assays; trophoblast transcriptomes were determined by RNA sequencing (RNA-seq). Wild-type, CBS-deficient, and CBA/J × DBA/2 mice were treated with CBS and CSE inhibitors or H2S donors to determine the role of H2S in early pregnancy in vivo.Results: CBS and CSE proteins showed cell-specific expressions, but only CBS decreased in the villous cytotrophoblast in URSA versus normal participants. H2S donors promoted migration and invasion and MMP-2 and VEGF expression in human placenta trophoblast cells that contain SV40 viral deoxyribonucleic acid sequences (HTR8/SVneo) and human placenta trophoblast cells (JEG3 cells), similar to forced CBS expression in HTR8/SVneo cells. The CBS-responsive transcriptomes in HTR8/SVneo cells contained differentially regulated genes (ie, interleukin-1 receptor and prostaglandin-endoperoxide synthase 2) that are associated with nuclear factor-κB-mediated inflammatory response. In vivo, dysregulated CBS/H2S signaling significantly increased embryonic resorption and decidual T-helper 1/T-helper 2 imbalance in mice, which was partially rescued by H2S donors.Conclusion: CBS/H2S signaling maintains early pregnancy, possibly via regulating maternal-fetal interface immune hemostasis, offering opportunities for H2S-based immunotherapies for URSA. [ABSTRACT FROM AUTHOR]

Aims: Accessory pathways (APs) successfully ablated at the aortomitral continuity (AMC) were sporadically reported but relevant data are very limited. We aimed to describe the electrophysiological characteristics of AMC-AP and the related anatomy.Methods and Results: This study involved eight (male/female = 3/5, mean age 42.6 ± 10.5 years) patients with left-sided AP successfully ablated in the AMC region. The retrograde atrial activation sequence was analysed and compared via recordings at the His-bundle (HB), coronary sinus (CS), and roving catheter during tachycardia, and the peak of QRS from the same cardiac circle used as time reference. Of the eight patients, two received prior ablations. During tachycardia, the activation time at the proximal CS (CSp), lateral CS (CSl), and HB region averaged 120 ± 26 ms, 124 ± 29 ms, and 117 ± 21 ms following the reference, respectively (P = 0.86). The latest atrial activation was recorded in the posterior CS which averaged 135 ± 25 ms following the reference. Placing the ablation catheter to AMC via retrograde approach was attempted in all cases but stable positioning achieved in none. Via transseptal approach, the ablation catheter could be easily placed at the AMC and recorded the earliest retrograde atrial activations with 60 ± 27 ms earlier than the relatively 'earliest' CS/HB recordings, and ablation at this site successfully eliminated AP conduction. No patients had recovered AP conduction after at least 12-month follow-up.Conclusion: AMC-AP is featured by recording comparable retrograde atrial activation times at CSp, CSl, and HB with the latest recordings at the posterior CS. Stable placement and successful ablation in the AMC via retrograde aortic approach was difficult but can be achieved via transseptal approach. [ABSTRACT FROM AUTHOR]

Context: Premature ovarian insufficiency (POI) is characterized by cessation of menstruation before 40 years of age and elevated serum level of FSH (>25 IU/L). Recent studies have found a few causative genes responsible for POI enriched in meiotic recombination and DNA damage repair pathways.Objective: To investigate the role of variations in homologous recombination genes played in POI pathogenesis.Methods: The whole exome sequencing was performed in 50 POI patients with primary amenorrhea. Functional characterizations of the novel variants were carried out in budding yeast and human cell line.Results: We identified 8 missense variants in 7 homologous recombination genes, including EXO1, RAD51, RMI1, MSH5, MSH2, MSH6, and MLH1. The mutation p.Thr52Ser in EXO1 impaired the meiotic process of budding yeast and p.Glu68Gly in RAD51-altered protein localization in human cells, both of them impaired the efficiency of homologous recombination repair for DNA double-stranded breaks in human cells.Conclusions: Our study first linked the variants of EXO1 and RAD51 with POI and further highlighted the role of DNA repair genes in ovarian dysgenesis. [ABSTRACT FROM AUTHOR]

Tea is one of the most popular nonalcoholic beverages due to its characteristic secondary metabolites with numerous health benefits. Although two draft genomes of tea plant (Camellia sinensis) have been published recently, the lack of chromosome-scale assembly hampers the understanding of the fundamental genomic architecture of tea plant and potential improvement. Here, we performed a genome-wide chromosome conformation capture technique (Hi-C) to obtain a chromosome-scale assembly based on the draft genome of C. sinensis var. sinensis and successfully ordered 2984.7 Mb (94.7%) scaffolds into 15 chromosomes. The scaffold N50 of the improved genome was 218.1 Mb, ~157-fold higher than that of the draft genome. Collinearity comparison of genome sequences and two genetic maps validated the high contiguity and accuracy of the chromosome-scale assembly. We clarified that only one Camellia recent tetraploidization event (CRT, 58.9–61.7 million years ago (Mya)) occurred after the core-eudicot common hexaploidization event (146.6–152.7 Mya). Meanwhile, 9243 genes (28.6%) occurred in tandem duplication, and most of these expanded after the CRT event. These gene duplicates increased functionally divergent genes that play important roles in tea-specific biosynthesis or stress response. Sixty-four catechin- and caffeine-related quantitative trait loci (QTLs) were anchored to chromosome assembly. Of these, two catechin-related QTL hotspots were derived from the CRT event, which illustrated that polyploidy has played a dramatic role in the diversification of tea germplasms. The availability of a chromosome-scale genome of tea plant holds great promise for the understanding of genome evolution and the discovery of novel genes contributing to agronomically beneficial traits in future breeding programs. [ABSTRACT FROM AUTHOR]

Catechins are the predominant products in tea plants and have essential functions for both plants and humans. Several genes encoding the enzymes regulating catechin biosynthesis have been identified, and the identification of single nucleotide polymorphisms (SNPs) resulting in nonsynonymous mutations within these genes can be used to establish a functional link to catechin content. Therefore, the transcriptomes of two parents and four filial offspring were sequenced using next-generation sequencing technology and aligned to the reference genome to enable SNP mining. Subsequently, 176 tea plant accessions were genotyped based on candidate SNPs using kompetitive allele-specific polymerase chain reaction (KASP). The catechin contents of these samples were characterized by high-performance liquid chromatography (HPLC), and analysis of variance (ANOVA) was subsequently performed to determine the relationship between genotypes and catechin content. As a result of these efforts, a SNP within the chalcone synthase (CHS) gene was shown to be functionally associated with catechin content. Furthermore, the geographical and interspecific distribution of this SNP was investigated. Collectively, these results will contribute to the early evaluation of tea plants and serve as a rapid tool for accelerating targeted efforts in tea breeding. [ABSTRACT FROM AUTHOR]

Aims: We aimed to investigate the safety of discontinuing oral anticoagulation (OAC) therapy after apparently successful atrial fibrillation (AF) ablation, using data from the Chinese Atrial Fibrillation Registry study.Methods and Results: We identified 4512 consecutive patients who underwent successful AF ablation between August 2011 and December 2017. Of them, 3149 discontinued OAC 3 months post-ablation (Off-OAC group) and 1363 continued OAC beyond this period (On-OAC group). Regular follow-up examinations were undertaken to detect AF recurrence, monitor OAC therapy, and measure clinical outcomes. Primary outcomes included thromboembolic and major bleeding (MB) events experienced beyond 3 months after ablation. Low thromboembolic and MB event rates were noted in the on-treatment analysis. The incidence rates for thromboembolism were 0.54 [95% confidence interval (CI) 0.39-0.76] and 0.86 (95% CI 0.56-1.30) per 100 patient-years, and that for MB events were 0.19 (95% CI 0.11-0.34) and 0.35 (95% CI 0.18-0.67) per 100 patient-years, for the Off-OAC and On-OAC groups over mean follow-up periods of 24.2 ± 14.7 and 23.0 ± 13.6 months, respectively. Similar results were observed in the intention-to-treat analysis. Previous history of ischaemic stroke (IS)/transient ischaemic attack (TIA)/systemic embolism (SE) [hazard ratio (HR) 3.40, 95% CI 1.92-6.02; P < 0.01] and diabetes mellitus (HR 2.06, 95% CI 1.20-3.55, P = 0.01) were independently associated with thromboembolic events, while OAC discontinuation (HR 0.71, 95% CI 0.41-1.23, P = 0.21) remained insignificant in multivariable analysis.Conclusions: This study suggests that it may be safe to discontinue OAC in post-ablation patients under diligent monitoring, in the absence of AF recurrence, history of IS/TIA/SE, and diabetes mellitus. However, further large-scale randomized trials are required to confirm this.Trial Registration: Chinese Clinical Trial Registry ChiCTR-OCH-13003729. URL: http://www.chictr.org.cn/showproj.aspx?proj=5831. [ABSTRACT FROM AUTHOR]

Objective: To describe psychotropic medications prescription patterns among adolescents in Taiwan; focusing on age, gender, duration of treatments and various classes of psychotropic medications.Design: A retrospective description analysis.Setting: Taiwan National Health Insurance Database.Participants: Twelve to seventeen years' patients treated with psychotropic medications.Intervention: None.Main Outcome Measure(s): Percentage and duration of treatment with psychotropic medications during the study periods by medication classes and age groups were calculated. In addition, top three prescribed psychotropic medications were also determined.Results: A total of 3,120 patients were prescribed psychotropic drugs. The percentage of adolescent patients that received anxiolytics and antidepressants in 2002-2012 were 2.89% and 2.15%, respectively. Also, 851 patients (1.21%) were prescribed hypnotics and 638 (0.91%) were given sedatives. The prevalence rate of the prescription of psychotropic drugs increased steadily with age and females were more treated than males except antipsychotic. Among psychotropic drugs, antidepressants (mean: 8.6 times) were refilled more but antipsychotics (mean 188 days) were the long-term treatment drugs. Additionally, the trend of hospital visits fluctuated over the year while May and December showed a higher rate of visits.Conclusions: These findings show that the prevalence of psychotropic drug prescriptions in Taiwanese adolescents is even low but increasing trends in the prescription of these medications raises some concern. As the evidence of psychotropic drug safety and effectiveness in adolescents is still inadequate; we recommend that healthcare providers should consider psychotropic drugs therapy, continuously monitor for outcomes and empower their patients to improve their knowledge, therapeutic outcomes and quality of life. [ABSTRACT FROM AUTHOR]

Aims: Catheter ablation is underutilized in atrial septal defect (ASD) patients who have undergone implantation of an atrial septal occluder (ASO). This study evaluates the feasibility and safety of catheter ablation of atrial fibrillation (AF) in this subset of patients.Methods and results: Sixteen patients (age 56 ± 12 years, 10 men) with drug-refractory AF (10 paroxysmal and 6 persistent) and previously implanted ASO were enrolled. Balloon dilatation of the closure device was performed if the native septum passage could not be achieved. For paroxysmal AF, the ablation strategy was circumferential pulmonary vein isolation (CPVI), and for persistent AF, additional linear ablation was performed. Transseptal access was achieved through the native septum in 11 patients (Group A) and through the ASO using balloon dilatation in 5 patients (Group B). Circumferential pulmonary vein isolation was achieved in all 16 patients, and linear block was achieved in all persistent patients except for 1 patient who did not achieve mitral isthmus block. The transseptal, total fluoroscopy, and procedural durations were 5 ± 3 vs. 38 ± 8 min, 31 ± 11 vs. 54 ± 15 min, and 165 ± 35 vs. 224 ± 36 min, respectively, in Group A vs. Group B, respectively (all P < 0.05). No shunt at atrial level was detected by transthoracic echocardiography at 3-month follow-up. During a follow-up of 16 ± 6 months, sinus rhythm was maintained in 12 of 16 patients. No severe complications were observed.Conclusion: In ASD patients with ASO, catheter ablation of AF is feasible, safe, and effective. The balloon dilatation technique can facilitate transseptal access through the ASO. [ABSTRACT FROM AUTHOR]

Aims: To assess the association and the predictive value of plasma homocysteine (Hcy) levels with LA/LAA thrombus in non-valvular Atrial fibrillation (AF) patients with low CHA2DS2-VASc score.Methods and results: Eight hundred and eighty-eight consecutive patients in non-valvular AF with CHA2DS2-VASc score of 0 and 1 were enrolled. All patients routinely underwent transthoracic echocardiography and transoesophageal echocardiography. A total of thirty-two patients had LA/LAA thrombus. Compared with patients without LA/LAA thrombus, plasma Hcy levels were significantly higher in patients with LA/LAA thrombus (16.5 ± 4.8 mmol/L vs. 13.4 ± 4.1 mmol/L, P = 0.009). In multivariate analysis, Hcy was independently associated with LA/LAA thrombus (OR 1.048, 95% CI 1.007-1.090, P = 0.022). Hcy demonstrated a significant predictive value with area under the curve of 0.722 (95% CI 0.662-0.781, P < 0.001). The optimal cut-off point for Hcy predicting LA/LAA thrombus was 13.5 mmol/L (sensitivity 67%, specificity 65%). Patients with Hcy ≥13.5 mmol/L had higher prevalence of LA/LAA thrombus compared with those with Hcy <13.5 mmol/L (6.1% vs. 2.1%, P < 0.001). Elevated Hcy significantly increased the risk of LA/LAA thrombus in patients with CHA2DS2-VASc score of 0 and 1 (OR 11.789, 95% CI 1.437-96.746, P = 0.022; OR 2.256, 95% CI 1.007-5.155, P = 0.048, respectively).Conclusion: Elevated plasma Hcy increases the risk of LA/LAA thrombus in non-valvular AF patients with low CHA2DS2-VASc score, thus it should be taken into account in prediction of thromboembolism. [ABSTRACT FROM AUTHOR]

* Background and Aims To understand the link between species diversity and phenotype developmental evolution is an important issue in evolutionary biology. Yarrows in the genus Achillea (Asteraceae) show a great diversity in leaf serrate or pinnate dissection patterns. In Arabidopsis thaliana, the development of leaf serration requires the activity of the transcription factor CUC2. Does this regulator also work for leaf dissections of the Asteraceae plants? If so, how do the conserved regulatory 'tools' work differently to produce diverse leaf forms? * Methods Seedling leaf morphology was observed, and morphogenesis of leaf serration or lobes was examined by scanning electron microscopy (SEM). NAM genes, orthologues of arabidopsis CUC2, were isolated from A. acuminata with serrate leaves and A. asiatica with three-pinnatisect leaves, respectively. By means of wholemount in situ mRNA hybridization and two quantitative gene expression assays, the droplet digital PCR (ddPCR) and quantitative real-time PCR (qPCR), expression patterns of the NAM genes during leaf dissection development were checked in both species for comparison. * Key Results For both species, the development of leaf dissection initiated when a leaf blade was about 300-400 µm long. In A. acuminata, in situ hybridization showed NAM expression signals at leaf margins where teeth are growing, or later on, in the sinuses of the teeth, whilst in A. asiatica, hybridization signals appear not only on leaf margins but further on the margins of leaf lobes. Both ddPCR and qPCR revealed a continuous decline of AacNAM expression from the early to the late developmental stages of a single leaf of A. acuminata, whereas a relatively long maintenance and fluctuation of AasNAM expression was seen in a leaf of A. asiatica. * Conclusions Differential spatiotemporal patterns of NAM expression were found between the two yarrow species during development of leaf dissection. This study provides the first evidence for NAM activity in the development of leaf dissection of the Asteraceae plants, and demonstrates that leaf form diversity is correlated to the altered NAM expression dynamic. [ABSTRACT FROM AUTHOR]

Study Question: Do oral contraceptives (OCs) and progestins impact live birth rate of IVF when used for cycle scheduling in women with polycystic ovary syndrome (PCOS)?Summary Answer: OCs used for scheduling IVF cycle were associated with lowered rates of pregnancy and live birth after fresh embryo transfer, whereas progestins used for this purpose yield higher rates of pregnancy and live birth than OCs.What Is Known Already: Due to oligo-menorrhea in PCOS, OCs and progestin are extensively used to schedule the start of an IVF cycle in women with PCOS. Little is known about the effect of such pretreatments on outcomes, especially, the rate of live birth.Study Design, Size, Duration: This was a nested cohort study and secondary analysis of a multicenter randomized trial, which was designed to compare live birth rate after fresh embryo transfer vs frozen embryo transfer (FET) in women with PCOS (Frefro-PCOS). A total of 1508 women were enrolled from 14 centers between June 2013 and May 2014.Participants/materials, Setting, Methods: At the discretion of local investigators, subjects were instructed to wait for spontaneous menses (Control group, n = 323), or were prescribed progestins (P group, n = 283) or OCs (OCs group, n = 902) to induce menstruation prior to the start of ovarian stimulation. GnRH antagonist protocol was initiated at Day 2 or 3 of induced or spontaneous menses cycle. The rates of pregnancy, pregnancy loss and live birth after either fresh embryo transfer or FET were compared among these three groups.Main Results and the Role Of Chance: With fresh embryo transfer, women with OC-induced menses had lower rates of clinical pregnancy (48.8% vs 63.6%, relative rate (RR): 0.77, 95% CI: 0.66-0.89) and live birth (36.1% vs 48.1%, RR: 0.75, 95% CI: 0.61-0.92) than women with spontaneous menses. With freeze-all and deferred FET, women with OC-induced menses had a similar pregnancy rate but a higher pregnancy loss rate (27.7% vs 13.0%, RR: 2.13, 95% CI: 1.28-3.52) after FET than women with spontaneous menses. The live birth rate after FET in women with OC-induced menses, progestin-induced menses and spontaneous menses was 49.4%, 50.7% and 60.2%, respectively (P = 0.06). Progestin-induced menses was associated with similar rates of pregnancy, pregnancy loss and live birth after transfer of either fresh or frozen embryos compared with spontaneous menses. Multivariate logistic regression analysis showed that OCs used for menses induction was associated with lower rate of live birth.Limitations, Reasons For Caution: The methods for menses induction were not assigned randomly, thus selection bias was highly likely because of the study design and significant differences that were observed in the baseline characteristics of the women in the different groups. The mean BMI in this study population was relatively normal; the applicability of this result to obese PCOS women needs to be evaluated in further study.Wider Implications Of the Findings: Our results suggest that either waiting for a spontaneous menses or using progestin is a better option than using OCs to induce menses in women with PCOS prior to ovarian stimulation using GnRH antagonist protocol for IVF. Further randomized controlled studies are needed to confirm our findings.Study Funding/competing Interests: This study was funded by National Basic Research Program of China (973 Program) (2012CB944700), the State Key Program of National Natural Science Foundation of China (81430029), National Natural Science Foundation of China (81471428) and Thousand Talents Program (Drs Legro and Zhang H). Dr Legro reports receiving consulting fees from Euroscreen, Kindex, Bayer and Millendo Pharmaceuticals and research funding from Ferring. Others report no disclosures.Trial Registration Number: Frefro-PCOS was registered at Clinicaltrials.gov: NCT01841528. [ABSTRACT FROM AUTHOR]

STUDY QUESTION: Are telomere length and telomerase activity associated with biochemical primary ovarian insufficiency (POI)? SUMMARY ANSWER: Shortened telomere length and diminished telomerase activity were associated with biochemical POI. WHAT IS KNOWN ALREADY: POI is a result of pathological reproductive aging and encompasses occult, biochemical and overt stages. Studies have indicated telomere length as a biomarker for biological aging. STUDY DESIGN, SIZE, DURATION: A total of 120 patients with biochemical POI and 279 control women were recruited by the Center for Reproductive Medicine of Shandong University. PARTICIPANTS/MATERIALS, SETTING, METHODS: Telomere length in peripheral blood leukocytes (LTL) and granulosa cells (GTL) was measured using a modified Quantitative Polymerase Chain Reaction technique. The relative telomerase activity (RTA) in granulosa cells was detected using a modified quantitative-telomeric repeat amplification protocol assay. MAIN RESULTS AND THE ROLE OF CHANCE: After adjusting for age, patients with biochemical POI (n = 120) exhibited significantly shorter LTLs (0.75 ± 0.09 vs 1.79 ± 0.12, P < 0.001; OR = 0.54, 95% CI = 0.43-0.68) and GTLs (0.78 ± 0.09 vs 1.90 ± 0.23, P < 0.001; OR = 0.54, 95% CI = 0.41-0.70) than the controls (n = 279 for LTLs; n = 90 for GTLs). Significantly diminished RTAs in granulosa cells were detected in patients with biochemical POI (n = 31) compared with the controls (n = 38) (1.57 ± 0.59 vs 4.63 ± 0.93, P = 0.025; OR = 0.84, 95% CI = 0.72-0.98). LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: The cross-sectional nature of this study might have its limit in telomere length as well as telomerase activity along with the progressing decline in ovarian function. WIDER IMPLICATIONS OF THE FINDINGS: These findings suggest that telomere length and telomerase activity may be considered as indicators for progression of ovarian decline. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by the National Basic Research Program of China (973 Program) (2012CB944700), Science research foundation item of no-earnings health vocation (201402004) and the National Natural Science Foundation of China (31471352, 81270662, 81471509, 81300461, 81522018). [ABSTRACT FROM AUTHOR]

Starch synthesis is a key process that influences crop yield and quality, though little is known about the regulation of this complex metabolic pathway. Here, we present the identification of ZmbZIP91 as a candidate regulator of starch synthesis via co-expression analysis in maize (Zea mays L.). ZmbZIP91 was strongly associated with the expression of starch synthesis genes. Reverse tanscription-PCR (RT-PCR) and RNA in situ hybridization indicated that ZmbZIP91 is highly expressed in maize endosperm, with less expression in leaves. Particle bombardment-mediated transient expression in maize endosperm and leaf protoplasts demonstrated that ZmbZIP91 could positively regulate the expression of starch synthesis genes in both leaves and endosperm. Additionally, the Arabidopsis mutant vip1 carried a mutation in a gene (VIP1) that is homologous to ZmbZIP91, displayed altered growth with less starch in leaves, and ZmbZIP91 was able to complement this phenotype, resulting in normal starch synthesis. A yeast one-hybrid experiment and EMSAs showed that ZmbZIP91 could directly bind to ACTCAT elements in the promoters of starch synthesis genes (pAGPS1, pSSI, pSSIIIa, and pISA1). These results demonstrate that ZmbZIP91 acts as a core regulatory factor in starch synthesis by binding to ACTCAT elements in the promoters of starch synthesis genes. [ABSTRACT FROM AUTHOR]

Aims: This prospective clinical trial was designed to evaluate the efficacy of an ablation strategy, namely '2C3L', in the treatment of persistent atrial fibrillation (AF); and to compare its efficacy with that of the 'stepwise' approach, which has been acknowledged as a promising ablation technique for persistent AF.Methods and Results: The '2C3L' technique is a fixed ablation approach consisting of bilateral circumferential pulmonary vein antrum isolation (PVAI) and three linear ablation lesion sets across the mitral isthmus, left atrial roof, and cavo-tricuspid isthmus. One hundred and forty-six patients with persistent AF were randomized to undergo ablation by using the '2C3L' or the 'stepwise' technique (n = 73, respectively). The primary endpoint was freedom from any atrial tachyarrhythmia off antiarrhythmic drug (AAD) after a single procedure at follow-up. Twelve months after a single procedure, there was no difference in sinus rhythm (SR) maintenance rate between the two groups (67% for '2C3L' vs. 60% for 'stepwise', P = 0.394; 95% confidence interval of between-group difference -8.7 to 22.4%). The procedure (222 ± 42 vs. 263 ± 41 min), fluoroscopy (41 ± 9 vs. 55 ± 8 min), and radiofrequency (RF) (107 ± 32 vs. 128 ± 38 min) time were significantly shorter in the '2C3L' group (all P < 0.001). At 25 ± 5 months after the first procedure, 57.5 and 52.1% of patients from the '2C3L' group and the 'stepwise' group were in SR off AAD (P = 0.494), respectively.Conclusions: For catheter ablation of persistent AF, the '2C3L' strategy is a fixed approach associated with clinical efficacy similar to that of the 'stepwise' approach but with less RF delivery, fewer X-ray exposure, and shorter procedural time. [ABSTRACT FROM AUTHOR]

Background: Primary ovarian insufficiency (POI) is characterized by marked heterogeneity, but with a significant genetic contribution. Identifying exact causative genes has been challenging, with many discoveries not replicated. It is timely to take stock of the field, outlining the progress made, framing the controversies and anticipating future directions in elucidating the genetics of POI.Methods: A search for original articles published up to May 2015 was performed using PubMed and Google Scholar, identifying studies on the genetic etiology of POI. Studies were included if chromosomal analysis, candidate gene screening and a genome-wide study were conducted. Articles identified were restricted to English language full-text papers.Results: Chromosomal abnormalities have long been recognized as a frequent cause of POI, with a currently estimated prevalence of 10-13%. Using the traditional karyotype methodology, monosomy X, mosaicism, X chromosome deletions and rearrangements, X-autosome translocations, and isochromosomes have been detected. Based on candidate gene studies, single gene perturbations unequivocally having a deleterious effect in at least one population include Bone morphogenetic protein 15 (BMP15), Progesterone receptor membrane component 1 (PGRMC1), and Fragile X mental retardation 1 (FMR1) premutation on the X chromosome; Growth differentiation factor 9 (GDF9), Folliculogenesis specific bHLH transcription factor (FIGLA), Newborn ovary homeobox gene (NOBOX), Nuclear receptor subfamily 5, group A, member 1 (NR5A1) and Nanos homolog 3 (NANOS3) seem likely as well, but mostly being found in no more than 1-2% of a single population studied. Whole genome approaches have utilized genome-wide association studies (GWAS) to reveal loci not predicted on the basis of a candidate gene, but it remains difficult to locate causative genes and susceptible loci were not always replicated. Cytogenomic methods (array CGH) have identified other regions of interest but studies have not shown consistent results, the resolution of arrays has varied and replication is uncommon. Whole-exome sequencing in non-syndromic POI kindreds has only recently begun, revealing mutations in the Stromal antigen 3 (STAG3), Synaptonemal complex central element 1 (SYCE1), minichromosome maintenance complex component 8 and 9 (MCM8, MCM9) and ATP-dependent DNA helicase homolog (HFM1) genes. Given the slow progress in candidate-gene analysis and relatively small sample sizes available for GWAS, family-based whole exome and whole genome sequencing appear to be the most promising approaches for detecting potential genes responsible for POI.Conclusion: Taken together, the cytogenetic, cytogenomic (array CGH) and exome sequencing approaches have revealed a genetic causation in ∼20-25% of POI cases. Uncovering the remainder of the causative genes will be facilitated not only by whole genome approaches involving larger cohorts in multiple populations but also incorporating environmental exposures and exploring signaling pathways in intragenic and intergenic regions that point to perturbations in regulatory genes and networks. [ABSTRACT FROM AUTHOR]

STUDY QUESTION: Do mutations and/or polymorphisms in coding sequences in Wingless-Type MMTV Integration Site Family, Member 6 (WNT6) play a role in unexplained recurrent miscarriage (unexplained RM) in Chinese couples? SUMMARY ANSWER: We found four mutations in the coding sequences of WNT6 which appear to exist in a small proportion of Chinese women with unexplained RM. WHAT is known already: WNT6 has been proved to be essential forstromal cell proliferation during decidualization in mice, but in humans WNT6 has not been studied in recurrent miscarriage populations. STUDY DESIGN, SIZE, DURATION: For this study, 100 couples with unexplained RM (at least three or more unexplained spontaneous miscarriages), and 100 ethnically matched fertile couples (at least one live birth and no history of pregnancy pathologies) were recruited. All the participants were chosen over a 7-year period from the National Research Center for Assisted Reproductive Technology and Reproductive Genetics at Shandong University, Jinan, China. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients were recruited following extensive clinical studies. GenomicDNA was isolated from peripheral blood. Mutation analysis in the coding regions of WNT6 was performed by PCR amplification and DNA sequences testing in all participants. Functional effects of missense variants were predicted using Polyphen-2 and sorting intolerant from tolerant (SIFT). MAIN RESULTS AND THE ROLE OF CHANCE: Four rare novel mutations, including one missense mutation, were found in intron 1,exon 3 and the 3' untranslated region of WNT6 in four women with unexplained RM. Gene software predictions showed that the missense mutation in exon 3 could alterthe function of WNT6. No mutations or polymorphisms were detected in the male partners of the unexplained RM patients or in the fertile controls. To further validate the findings, we continued to screen this missense mutation site in another 100 peripheral blood samples of normal fertile females, and there was still no positive result. LIMITATIONS, REASONS FOR CAUTION: There is no direct evidence to validate whether these novel mutations discovered in the present research are related to unexplained RM. Further studies are warranted to investigate the role of WNT6 in unexplained RM, including larger studies in an independent group. WIDER IMPLICATIONS OF THE FINDINGS: These results provide evidence to suggest the importance of WNT6 in reproductive failure and may support the hypothesis that WNT6 is essential forstromal cell proliferation during decidualization. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by Science and Technology Development Planning of Shandong (2013GGE27001), the National Natural Science Foundation of China (81300459), the Science Projection of Bureau of Public Health in Weifang (2012044) and the Science Research Foundation Item of No-earnings Health Vocation. The authors have no competing interests to declare. [ABSTRACT FROM AUTHOR]

Aims This study sought to explore the predictors of recurrence in patients with paroxysmal atrial fibrillation (AF) undergoing repeat catheter ablation, especially the impact of left atrial (LA) remodelling after the original procedure on the outcome of repeat procedure. Methods and results Ninety-five patients undergoing repeat ablation were enroled in this study. Repeat procedure endpoints were pulmonary vein isolation, linear block when linear ablation is performed, and non-inducibility of atrial tachyarrhythmia by burst pacing. Patients with LA enlargement between the pre-original procedure and pre-repeat procedure were categorized as Group 1 (35 patients), while individuals with no change or decrease of LA diameter were categorized as Group 2 (60 patients). The mean duration from the original procedure to the repeat procedure was 12 months (1–40 months). After 29.6 ± 20.5 (3–73) months follow-up from the repeat procedure, 33 patients experienced recurrence (34.7%). The recurrence rate was significantly higher in Group 1 than in Group 2 (51.4 VS. 25.0%, P = 0.017). In univariate analysis, LA remodelling was the only predictor of recurrence. In multivariate analysis, after adjustment for age and LA diameter, Group 1 had a greater risk of recurrence after the repeat procedure (hazard ratio = 2.22, 95% confidence interval: 1.02–4.81, P = 0.043). Conclusions Left atrial enlargement after undergoing the original catheter ablation of paroxysmal AF was an independent risk factor of recurrence after repeat ablation. [ABSTRACT FROM PUBLISHER]