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Funding Acknowledgements Type of funding sources: None. Background We previously showed that females were associated with a higher risk of arrhythmia recurrence after radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF). Whether age influences sex differences in terms of recurrence after CA of AF still remains unknown. Objective We sought to investigate the sex differences in the efficacy of RFCA of AF according to an advanced age. Methods We conducted a large-scale, prospective, multicenter, observational study (Kansai Plus Atrial Fibrillation Registry), enrolling 5010 consecutive patients who underwent an initial RFCA of AF at 26 centers (64±10 years; females, 27.3%; non-paroxysmal AF, 35.7%). The median follow-up duration was 2.9 years. Results The entire cohort was divided into either an age≥75 (n=790; females, 40.3%) and age < 75 years (n=4220; females, 24.9%). In the age≥75 group, the 3-year cumulative incidence of AF recurrences was identical between the sexes both after a single procedure (female vs. male, 38.1% vs. 40.7%, Log-rank P=0.39) and multiple procedures (22.3% vs. 21.6%, Log-rank P=0.96). On the other hand, in the age Conclusion While the incidence of an arrhythmia recurrence after radiofrequency catheter ablation of AF was similar between the sexes in patients with an age≥75, females had a higher incidence of recurrence than males in patients with an age

MAPK/ERK signaling inhibition repressed BRAFV600E-induced TLR4 expression at the plasma membrane.

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are essential players in the regulation of gene expression. The majority of the twenty different hnRNP proteins act through the modulation of pre-mRNA splicing. Most have been shown to regulate the expression of critical genes for the progression of tumorigenic processes and were also observed to be overexpressed in several types of cancer. Moreover, these proteins were described as essential components for the maturation of some microRNAs (miRNAs). In the human genome, over 70% of miRNAs are transcribed from introns; therefore, we hypothesized that regulatory proteins involved with splicing could be important for their maturation. Increased expression of the miR-17-92 cluster has already been shown to be related to the development of many cancers, such as thyroid, lung, and lymphoma. In this article, we show that overexpression of hnRNP A1 and hnRNP C in BCPAP thyroid cancer cells directly affects the expression of miR-17-92 miRNAs. Both proteins associate with the 5'-end of this cluster, strongly precipitate miRNAs miR-17 and miR-18a and upregulate the expression of miR-92a. Upon overexpression of these hnRNPs, BCPAP cells also show increased proliferation, migration, and invasion rates, suggesting upregulation of these proteins and miRNAs is related to an enhanced tumorigenic phenotype.

Introduction The electrical pulmonary vein (PV) isolation has been established as a curative therapy for paroxysmal atrial fibrillation (AF). Arctic Front™cryoballoon has been used worldwide for AF cryoablation. Recently, a new cryoballoon, POLARxTM CRYOABLATION system have been introduced, of which material of the balloon is softer and the N2O gas flow rate is higher. Purpose The aim was to investigate the procedural parameter and efficacy of POLARx comparing with Arctic Front. Methods This retrospective single center study included 101 consecutive patients who underwent paroxysmal AF ablation using cryoballoon at Keio University hospital from April 2021 to March 2022. The procedural data including the cryoballoon temperature and the number and duration of cryoablation were compared between POLARx (POLARx group) and ARCTIC FRONT ADVANCE PRO (AFA group). After the cryoablation, we added the radiofrequency application in order to maximize the isolated area when the voltage was remained inside PV (Figure 1). The necessities of the additional radiofrequency applications were also compared. Results In the present study, 64 patients in AFA group and 37 patients in POLARx group were analyzed. POLARx group included younger population and less females (62.8±9.9 vs 67.5±9.4 year of age, P=0.02; 13.5 vs 32.8%, P=0.04). There was no significant difference in comorbidities and examination data such as left atrium diameter or brain natriuretic peptide level. The minimal cryoballoon temperatures reached in POLARx group were lower than AFA group (−59.3±6.2 vs −47.7±7.5°C, P Conclusion The total number and duration of cryoablation were not significantly different between AFA and POLARx group, except for right superior PV. There was an advantage in largely isolating right inferior PV in POLARx group comparing with AFA group. Funding Acknowledgement Type of funding sources: None.

Background There are significant differences in the prevalence and prognosis of cardiovascular diseases between male and female. We previously reported that catheter ablation (CA) of atrial fibrillation (AF) was less effective in female than male, but whether their history of heart failure influence the recurrence after CA of AF remains still unknown. Purpose We sought to clarify sex differences in terms of AF recurrence after RFCA of AF according to the history of heart failure. Methods We conducted a large-scale, prospective, multicenter, observational study (Kansai Plus Atrial Fibrillation Registry). We enrolled 5010 consecutive patients who underwent an initial RFCA of AF at 26 centers (64±10 years; 1369 [27.3%] females; non-paroxysmal AF, 35.7%). The median follow-up duration was 2.9 years. Results Fourteen % of female had a history of heart failure prior to CA, while 12.8% of male had a history of heart failure at baseline (p=0.29). The 3-year cumulative incidence of AF recurrence after a single procedure was 43.3% in female and 39.0% in male (log rank P=0.0046). In patients with the history of heart failure, AF recurrence rates were 42.2% in female and 45.8% in male (log rank P=0.51). On the other hand, in patients without history of heart failure, more females experienced AF recurrence (female vs. male, 43.5% vs. 38.0%, log rank P=0.001). The rate of AF recurrence after multiple procedures was higher in female (24.2% vs. 19.6%, log rank P Conclusion The Kansai Plus Atrial Fibrillation Registry revealed a distinct sex difference in terms of the AF recurrence after CA of AF. Females had higher recurrence rates compared with males in patients without history of heart failure, while recurrence rates were similar between sexes in patients with history of heart failure. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Research Institute for Production Development in Kyoto, Japan.

Pericardial fat is appropriate tissue to cover the bronchial anastomotic site because its harvesting is minimally invasive. We investigated the changes in pericardial fat tissue around the anastomotic site after pulmonary resection with tracheobronchoplasty. The subjects of this study were 43 lung cancer patients who underwent pulmonary resection with tracheobronchoplasty. We measured the maximum cross-sectional area and average computed tomography (CT) values of the pedicle pericardial fat pad around the anastomotic site 1 week and then 6 months after the operation. The average volume of the residual pedicle pericardial fat pad 6 months postoperatively was 61%. A body mass index (BMI)

We undertook a DNA barcoding analysis on insect larvae occurring in bamboo galls from central Japan and showed that most of them were assigned to Cecidomyiidae.

A transparência é um dos requisitos fundamentais da democracia e é um aspecto crítico de processos como eleições e financiamento de campanhas eleitorais. Entretanto, frequentemente esses processos sofrem suspeitas de manipulação e exigem uma auditoria complexa para mitigá-las. Desse modo, esse artigo apresenta Logs Transparentes, um sistema que promove maior transparência e eficiência na auditabilidade através de uma arquitetura baseada em estruturas de dados verificáveis. O artigo aplica a solução especificamente para as eleições brasileiras e apresenta um protótipo com as principais operações necessárias para auditar uma eleição.

Background Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve endothelial dysfunction and reduce cardiovascular events in individuals with type 2 diabetes (T2D). Proprotein convertase subtilisin/kexin 9 (PCSK9i) inhibitors reduce cardiovascular events in high-risk patients. Whether the addition of PCSK9i to SGLT2i treatment adds benefits is not known. Objectives To assess the PCSK9-i effect on the endothelial function of T2D individuals under treatment with SGLT2-i. Methods Individuals with T2D were randomized in a 1:1 ratio to a 16-week treatment with either empagliflozin (E) or empagliflozin plus evolocumab (EE). The primary endpoint was post-treatment change from baseline in flow-mediated dilation (FMD) at 1-min. Secondary outcomes included changes in plasma levels of nitric oxide metabolites and isoprostane. Results A total of 110 patients were enrolled, the mean age was 58 years, and 71% were men. The median post-treatment change in FMD at 1-min was 2.7% (interquartile range [IQR]: 0.9%) and 0.4% (IQR: 0.9%) in the EE and E groups, respectively (p Conclusions In individuals with T2D, the addition of evolocumab on top of empagliflozin improves endothelial function.

In centrally-located lung cancer treatment, it is difficult to attain a sufficient resection margin. It is important to investigate recurrent styles in centrally-located lung cancer patients.Primary lung cancer located at the hilar area that requires pneumonectomy or sleeve lobectomy is defined as centrally-located lung cancer. Early recurrence was defined as that within 1 year after surgery.This study included 43 centrally-located lung cancer patients. Ten patients underwent pneumonectomy and 33 underwent sleeve lobectomy. Eleven patients experienced early recurrence. Non-squamous cell carcinoma (p=0.012), tumor size64 mm (p0.001) and pathological N2 (p=0.012) were significant predictors for early recurrence by univariate analysis. Also, tumor size64 mm (p=0.006) and pathological N2 (p=0.019) were independent predictors by multivariate analysis.Non-squamous cell carcinoma, tumor size and pathological N2 were significant predictors of early recurrence in centrally-located lung cancer. The type of surgical procedure did not affect recurrence development.

In Saccharomyces cerevisiae, Avt4 exports neutral and basic amino acids from vacuoles. Previous studies have suggested that the GATA transcription factors, Gln3 and Gat1, which are key regulators that adapt cells in response to changes in amino acid status, are involved in the AVT4 transcription. Here, we show that mutations in the putative GATA-binding sites of the AVT4 promoter reduced AVT4 expression. Consistently, a chromatin immunoprecipitation (ChIP) assay revealed that Gat1-Myc13 binds to the AVT4 promoter. Previous microarray results were confirmed that gln3∆gat1∆ cells showed a decrease in expression of AVT1 and AVT7, which also encode vacuolar amino acid transporters. Additionally, ChIP analysis revealed that the AVT6 encoding vacuolar acidic amino acid exporter represents a new direct target of the GATA transcription factor. The broad effect of the GATA transcription factors on the expression of AVT transporters suggests that vacuolar amino acid transport is integrated into cellular amino acid homeostasis.

Background/aim Identification of prognostic factors is helpful in selecting optimal treatment for centrally-located non-small cell lung cancer (NSCLC). This study aimed to detect prognostic factors in patients with centrally-located NSCLC. Patients and methods NSCLCs in the hilar area requiring pneumonectomy or sleeve lobectomy for complete removal are defined as centrally-located NSCLCs. We retrospectively investigated the clinical courses of 45 patients with such lesions. Results Sleeve lobectomies were performed on 33 patients and pneumonectomies on 12. Three and five-year survival rates were 72% and 62%, respectively. Presence of comorbidities (p=0.013), severe symptoms (p=0.001), high white cell count (p=0.001), and pathological T3-4 stage (p=0.004) were identified as independent predictors of poor prognosis. Operative procedures did not correlate with outcomes (p=0.722). Conclusion Presence of comorbidities, severe symptoms, high white cell counts, and pathological T stage are independent predictors of poor prognosis. These data can contribute in selecting appropriate treatments for such lesions.

Study question To evaluate the effectiveness of chlormadinone acetate (CMA) for preventing premature LH surge in patients with normal ovarian reserve compared to cetrorelix. Summary answer In progestin-primed ovarian stimulation (PPOS) than GnRH antagonist (GnRH-ant), the incidence of premature LH surge was significantly lower, without significant difference in oocyte maturation rate. What is known already The GnRH-ant protocol is one of the conventional protocols which has some disadvantages including increased premature LH surge rate and cancelation rate. In recent years, the PPOS protocol has attracted attention as a new ovarian stimulation using progestin as an alternative to GnRH analog for suppressing a premature LH surge, however its efficacy is still controversial. In addition, many studies have investigated the reproductive outcomes of PPOS using medroxy-progesterone acetate or dydrogesterone; however, there are few reports of CMA, an oral progestin, which is inexpensive and widely used in Japan. Study design, size, duration This retrospective cohort study was performed in a reproduction center between March 2018 and October 2020 which included 977 Japanese patients with normal ovarian reserve undergoing PPOS with CMA (n = 299), or GnRH antagonist (GnRH-ant) with cetrorelix (n = 608) in their first IVF cycle at the reproduction center. In subgroup analysis, pregnancy outcomes after frozen embryo transfers (FET) between PPOS (n = 284) and GnRH-ant (n = 579) were also compared. Participants/materials, setting, methods The inclusion criteria were patients aged < 40 years and AMH ≧ 1.1 ng/mL, who underwent autologous oocyte retrieval in their first IVF cycle with freeze-all strategy. The primary outcome was the incidence of premature LH surge, the secondary outcomes was oocyte maturation rate. To reduce the impact of treatment bias and potential confounding factors, we conducted logistic regression models with inverse-probability-of-treatment weighting (IPTW). Main results and the role of chance After IPTW, baseline clinical data were well-balanced between the two groups, including age, AMH, BMI, the duration, type, and cause of infertility, antral follicle count, the history of recurrent spontaneous abortion, and previous IVF attempts. The premature LH surge rate was significantly lower with PPOS (3.1%) compared to GnRH-ant (20.1%) (odds ratio, 0.21; 95% confidence interval, 0.11–0.36). No significant differences were found in total gonadotropin dose (2400IU for PPOS vs 2400IU for GnRH-ant, p = 0.136), the number of oocyte retrieval (n = 15 vs n = 15, p = 0.484), oocyte maturation rate (78.8% vs 77.8%, p = 0.275), fertilization rate (73.0% vs 72.0%, p = 0.412), viable embryo rate per oocyte retrieval (40% vs 40%, p = 0.890), and good quality blastocyst rate (72.0% vs 69.6%, p = 0.092). However, the good quality day-3 embryo rate was significantly lower with PPOS (37.2% vs 49.1%, p Limitations, reasons for caution This was a retrospective cohort study conducted in a single center. The participants in this study were limited to Japanese ethnicity. The results need to be validated across different centers and other ethnicities. Wider implications of the findings This is the first report assessing the reproductive outcomes on PPOS using CMA, widely used in Japan. The PPOS with CMA significantly suppressed the premature LH surge rate compared to GnRH-ant protocol, without decrease in oocyte maturation rate. Trial registration number N/A

Optical absorption spectra in the visible and near-infrared light were measured for magnetoelectric spin glass Ni_{0.4}Mn_{0.6}TiO_{3} under various field-cooled conditions. Despite the absence of long-range magnetic-dipole order, this spin-glass system exhibits nonreciprocal directional dichroism (NDD) at zero external field after a magnetoelectric field-cooled procedure. This result is distinct from previous studies on NDD in systems with magnetic toroidal moments induced either by long-range magnetic-dipole order or by applying crossed electric and magnetic fields. The present Letter conclusively demonstrates that the observed NDD originates from magnetoelectrically induced ferroic order of magnetic toroidal moments without conventional magnetic-dipole order.

To understand how ectomycorrhizal (ECM), wood-decomposing (WDC) and litter-decomposing (LDC) fungi differ in abundance and fruiting season, fruiting-body production was monitored by counting their number and/or measuring their biomass in deciduous broad-leaved and coniferous forests in Ishikawa (central Japan) and Hokkaido (northern Japan). ECM fungi were dominant in forests of both types in Ishikawa and a Larix kaempheri forest in Tomakomai (Hokkaido), whereas WDC fungi were dominant in a deciduous broad-leaved forest in Sapporo (Hokkaido). ECM and WDC fungi usually showed two abundance peaks in Kanazawa (Ishikawa), mid-summer and autumn for ECM fungi and spring or summer and autumn for WDC fungi, whereas LDC fungi usually showed one peak in autumn. In Tomakomai, the abundance peak appeared later in ECM fungi but earlier in LDC and WDC fungi in comparison with Kanazawa. The mode of resource acquisition is assumed as one of factors that affect the seasonal timing of fruiting-body production. On the other hand, highly positive correlations were often observed between precipitation in Jun or Aug and the fruiting-body production in summer and/or autumn in the survey in Kanazawa, suggesting that precipitation could affect the fruiting-body production a few months later.

Background/aim Hepatitis B core (HBc) antibody positivity indicates a history of hepatitis B virus (HBV) infection and latent infection. Patients and methods We conducted a retrospective case-control study of 512 and 495 head and neck cancer (HNC) and non-HNC patients treated at the Okayama University Hospital, Head and Neck Cancer Center from 2008-2017. Demographic data and risk factors that might affect HNC diagnosis were analyzed to assess their effects. Results Cancer diagnosis was found to correlate with HBc antibody positivity [odds ratio (OR)=1.50, 95% confidence interval (CI)=1.09-2.08], smoking (OR=3.03, 95%CI=2.16-4.25), and a previous history of cancer (OR=4.12, 95%CI=2.79-6.09). The HBs antigen positivity rate in both groups was very close to that observed in the general Japanese population. The HBc antibody positivity rate was very high only in the HNC group. Conclusion HBc antibody positivity and HNC are epidemiologically correlated.