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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.

The induction of artificial pneumothorax has many intraoperative advantages. However, few reports on the postoperative effects of artificial pneumothorax induction are available. In this study, we investigated the effect of artificial pneumothorax on postoperative clinical course in patients with mediastinal tumors. We retrospectively investigated the clinical courses of 89 patients who had undergone mediastinal tumor resection between January 2010 and December 2020. Sixty-five patients had undergone resection with artificial pneumothorax. The tumor location significantly varied across patients. The proportion of patients in whom artificial pneumothorax was induced was higher among those having anterior mediastinal tumors. The number of ports and the total skin incision length were significantly higher in patients without artificial pneumothorax. The C-reactive protein level elevation on postoperative day 2 and pleural effusion at 24 h after surgery were significantly higher in patients without artificial pneumothorax. Furthermore, the albumin level reduction and hospital stay after surgery were significantly lower in patients with artificial pneumothorax. Multiple regression analysis showed that the use of artificial pneumothorax was an independent predictive factor of the C-reactive protein level elevation on postoperative day 2 and pleural effusion at 24 h after surgery. In patients without artificial pneumothorax, the operation time positively correlated with the C-reactive protein level (r = 0.646, P

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.

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.

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.

Stricter control of risk factors has been pursued as a compelling strategy to mitigate cardiovascular events (CVE) in type 2 diabetes (T2D) individuals. However, the achievement rate of the recommended goals has remained low in clinical practice. This study investigated the 2019 ESC guideline recommendation attainment among T2D individuals enrolled in a national cohort held in Brazil. Data from 1030 individuals (mean age: 58 years old; 54% male; mean T2D duration: 9.7 years) were analyzed. The control rates were 30.6% for SBP, 18.8% for LDL-C, and 41% for A1c, and only 3.2% of the study participants met all three targets. Statins and high-intensity lipid-lowering therapy prescription rates were 45% and 8.2%, respectively. Longer T2D duration and those at higher CV risk were less likely to be controlled. Longer diabetes duration and higher CV risk were inversely related to the chance of achieving the recommended targets. Treatment escalation using conventional therapies would be sufficient to gain optimal control in most of the study sample. In conclusion, a minimal proportion of T2D individuals comply with guidelines-oriented CV prevention targets. Given the significant burden of the disease, and the substantial effect size predicted for these therapies, bridging this gap between guidelines and clinical practice should be considered an urgent call to public health managers.

The presence of a bidirectional risk for metachronous carcinomas among women with thyroid and breast cancer is well established. However, the underlying risk factors remain poorly understood. Two sisters developed papillary thyroid cancer (PTC) at age 32 and 34 years, followed by ductal carcinoma of the breast at 44 and 42 years. The 2 children of the younger sister developed ataxia-telangiectasia; the son also developed lymphoblastic lymphoma and his sister died secondary to acute lymphoblastic leukemia (ALL). They were found to be compound heterozygous for ataxia telangiectasia mutated (ATM) gene mutations (c.3848T>C, p.L1283P; and c.802C>T, p.Q268X). Exome sequencing of the 2 sisters (mother and aunt of the children with ataxia-telangiectasia) led to the detection of the pathogenic monoallelic ATM mutation in both of them (c.3848T>C; minor allele frequency [MAF] The findings suggest that monoallelic ATM mutations, presumably in conjunction with additional genetic and/or nongenetic factors, can confer a risk for developing PTC and breast cancer.

Full list of authors: Kawauchi, K.; Murgas, F.; Palle, E.; Narita, N.; Fukui, A.; Hirano, T.; Parviainen, H.; Ishikawa, H. T.; Watanabe, N.; Esparaza-Borges, E.; Kuzuhara, M.; Orell-Miquel, J.; Krishnamurthy, V; Mori, M.; Kagetani, T.; Zou, Y.; Isogai, K.; Livingston, J. H.; Howell, S. B.; Crouzet, N.; de Leon, J. P.; Kimura, T.; Kodama, T.; Korth, J.; Kurita, S.; Laza-Ramos, A.; Luque, R.; Madrigal-Aguado, A.; Miyakawa, K.; Morello, G.; Nishiumi, T.; Rodriguez, G. E. F.; Sanchez-Benavente, M.; Stangret, M.; Teng, H.; Terada, Y.; Gnilka, C. L.; Guerrero, N.; Harakawa, H.; Hodapp, K.; Hori, Y.; Ikoma, M.; Jacobson, S.; Konishi, M.; Kotani, T.; Kudo, T.; Kurokowa, T.; Kusakabe, N.; Nishikawa, J.; Omiya, M.; Serizawa, T.; Tamura, M.; Ueda, A.; Vievard, S.--This is an Open Access article, published by EDP Sciences, under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited., Context. The NASA space telescope TESS is currently in the extended mission of its all-sky search for new transiting planets. Of the thousands of candidates that TESS is expected to deliver, transiting planets orbiting nearby M dwarfs are particularly interesting targets since they provide a great opportunity to characterize their atmospheres by transmission spectroscopy. Aims. We aim to validate and characterize the new sub-Neptune-sized planet candidate TOI-2136.01 orbiting a nearby M dwarf (d = 33.36 ± 0.02pc, Teff = 3373 ± 108 K) with an orbital period of 7.852 days. Methods. We use TESS data, ground-based multicolor photometry, and radial velocity measurements with the InfraRed Doppler (IRD) instrument on the Subaru Telescope to validate the planetary nature of TOI-2136.01, and estimate the stellar and planetary parameters. We also conduct high-resolution transmission spectroscopy to search for helium in its atmosphere. Results. We confirm that TOI-2136.01 (now named TOI-2136b) is a bona fide planet with a planetary radius of Rp = 2.20 ± 0.07R⊕ and a mass of Mp = 4.7−2.6+3.1 M⊕. We also search for helium 10830 Å absorption lines and place an upper limit on the equivalent width of, The MEarth Project acknowledges funding from the David and Lucile Packard Fellowship for Science and Engineering, the National Science Foundation under grants AST-0807690, AST-1109468, AST-1616624 and AST-1004488 (Alan T. Waterman Award), the National Aeronautics and Space Administration under Grant No. 80NSSC18K0476 issued through the XRP Program, and the John Templeton Foundation. Based on observations obtained with the Samuel Oschin 48-inch Telescope at the Palomar Observatory as part of the Zwicky Transient Facility project. Z.T.F. is supported by the National Science Foundation under Grant No. AST-1440341 and a collaboration including Caltech, IPAC, the Weizmann Institute for Science, the Oskar Klein Center at Stockholm University, the University of Maryland, the University of Washington, Deutsches Elektronen-Synchrotron and Humboldt University, Los Alamos National Laboratories, the TANGO Consortium of Taiwan, the University of Wisconsin at Milwaukee, and Lawrence Berkeley National Laboratories. Operations are conducted by COO, IPAC, and UW. Our data reductions benefited from PyRAF and PyFITS that are the products of the Space Telescope Science Institute, which is operated by AURA for NASA. G.M. has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No. 895525. R.L. acknowledges financial support from the Spanish Ministerio de Ciencia e Innovación, through project PID2019-109522GB-C52, and the Centre of Excellence “Severo Ochoa” award to the Instituto de Astrofísica de Andalucía (SEV-2017-0709). J.K. gratefully acknowledge the support of the Swedish National Space Agency (SNSA; DNR 2020-00104). This work is partly supported by JSPS KAKENHI Grant Numbers JP21K20376, JP21K13975, JP21H00035, JP21K20388, JP20K14518, JP20K14521, JP19K14783, JP18H05439, JP17H04574, by Grant-in-Aid for JSPS Fellows Grant Number JP20J21872, by JST CREST Grant Number JPMJCR1761, by Astrobiology Center PROJECT Research AB031014, by Astrobiology Center SATELLITE Research project AB022006, and the Astrobiology Center of National Institutes of Natural Sciences (NINS) (Grant Number AB031010). M.T. is supported by MEXT/JSPS KAKENHI grant Nos. 18H05442, 15H02063, and 22000005. Some of the observations in the paper made use of the High-Resolution Imaging instrument Alopeke obtained under Gemini LLP Proposal Number: GN/S-2021A-LP-105. Alopeke was funded by the NASA Exoplanet Exploration Program and built at the NASA Ames Research Center by Steve B. Howell, Nic Scott, Elliott P. Horch, and Emmett Quigley. Alopeke was mounted on the Gemini North (and/or South) telescope of the international Gemini Observatory, a program of NSF’s OIR Lab, which is managed by the Association of Universities for Research in Astronomy (AURA) under a cooperative agreement with the National Science Foundation, on behalf of the Gemini partnership: the National Science Foundation (United States), National Research Council (Canada), Agencia Nacional de Investigación y Desarrollo (Chile), Mnisterio de Ciencia, Tecnología e Innovación (Argentina), Ministério da Ciência, Tecnologia, Inovações e Comunicações (Brazil), and Korea Astronomy and Space Science Institute (Republic of Korea).