Displaying publications 1 - 20 of 192 in total

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  1. Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, et al.
    Autophagy, 2016;12(1):1-222.
    PMID: 26799652 DOI: 10.1080/15548627.2015.1100356
  2. CMS Collaboration, Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Bergauer T, et al.
    Eur Phys J C Part Fields, 2020;80(3):189.
    PMID: 32226948 DOI: 10.1140/epjc/s10052-020-7739-7
    A search is presented for τ slepton pairs produced in proton-proton collisions at a center-of-mass energy of 13 TeV . The search is carried out in events containing two τ leptons in the final state, on the assumption that each τ slepton decays primarily to a τ lepton and a neutralino. Events are considered in which each τ lepton decays to one or more hadrons and a neutrino, or in which one of the τ leptons decays instead to an electron or a muon and two neutrinos. The data, collected with the CMS detector in 2016 and 2017, correspond to an integrated luminosity of 77.2 fb - 1 . The observed data are consistent with the standard model background expectation. The results are used to set 95% confidence level upper limits on the cross section for τ slepton pair production in various models for τ slepton masses between 90 and 200 GeV and neutralino masses of 1, 10, and 20 GeV . In the case of purely left-handed τ slepton production and decay to a τ lepton and a neutralino with a mass of 1 GeV , the strongest limit is obtained for a τ slepton mass of 125 GeV at a factor of 1.14 larger than the theoretical cross section.
  3. CMS Collaboration, Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Bergauer T, et al.
    Eur Phys J C Part Fields, 2021;81(7):629.
    PMID: 34727144 DOI: 10.1140/epjc/s10052-021-09236-z
    Results of the Model Unspecific Search in CMS (MUSiC), using proton-proton collision data recorded at the LHC at a centre-of-mass energy of 13 TeV , corresponding to an integrated luminosity of 35.9 fb - 1 , are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches.
  4. Sirunyan AM, CMS Collaboration, Tumasyan A, Adam W, Bergauer T, Dragicevic M, et al.
    Eur Phys J C Part Fields, 2021;81(1):13.
    PMID: 33493254 DOI: 10.1140/epjc/s10052-020-08739-5
    A search for dark matter particles is performed using events with a Z boson candidate and large missing transverse momentum. The analysis is based on proton-proton collision data at a center-of-mass energy of 13 Te , collected by the CMS experiment at the LHC in 2016-2018, corresponding to an integrated luminosity of 137 fb - 1 . The search uses the decay channels Z → e e and Z → μ μ . No significant excess of events is observed over the background expected from the standard model. Limits are set on dark matter particle production in the context of simplified models with vector, axial-vector, scalar, and pseudoscalar mediators, as well as on a two-Higgs-doublet model with an additional pseudoscalar mediator. In addition, limits are provided for spin-dependent and spin-independent scattering cross sections and are compared to those from direct-detection experiments. The results are also interpreted in the context of models of invisible Higgs boson decays, unparticles, and large extra dimensions.
  5. CMS Collaboration, Sirunyan AM, Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, et al.
    Eur Phys J C Part Fields, 2021;81(6):488.
    PMID: 34727143 DOI: 10.1140/epjc/s10052-021-09200-x
    Production cross sections of the Higgs boson are measured in the H → Z Z → 4 ℓ ( ℓ = e , μ ) decay channel. A data sample of proton-proton collisions at a center-of-mass energy of 13 TeV , collected by the CMS detector at the LHC and corresponding to an integrated luminosity of 137 fb - 1 is used. The signal strength modifier μ , defined as the ratio of the Higgs boson production rate in the 4 ℓ channel to the standard model (SM) expectation, is measured to be μ = 0.94 ± 0.07 (stat) - 0.08 + 0.09 (syst) at a fixed value of m H = 125.38 GeV . The signal strength modifiers for the individual Higgs boson production modes are also reported. The inclusive fiducial cross section for the H → 4 ℓ process is measured to be 2 . 84 - 0.22 + 0.23 (stat) - 0.21 + 0.26 (syst) fb , which is compatible with the SM prediction of 2.84 ± 0.15 fb for the same fiducial region. Differential cross sections as a function of the transverse momentum and rapidity of the Higgs boson, the number of associated jets, and the transverse momentum of the leading associated jet are measured. A new set of cross section measurements in mutually exclusive categories targeted to identify production mechanisms and kinematical features of the events is presented. The results are in agreement with the SM predictions.
  6. Ishiura H, Shibata S, Yoshimura J, Suzuki Y, Qu W, Doi K, et al.
    Nat Genet, 2019 08;51(8):1222-1232.
    PMID: 31332380 DOI: 10.1038/s41588-019-0458-z
    Noncoding repeat expansions cause various neuromuscular diseases, including myotonic dystrophies, fragile X tremor/ataxia syndrome, some spinocerebellar ataxias, amyotrophic lateral sclerosis and benign adult familial myoclonic epilepsies. Inspired by the striking similarities in the clinical and neuroimaging findings between neuronal intranuclear inclusion disease (NIID) and fragile X tremor/ataxia syndrome caused by noncoding CGG repeat expansions in FMR1, we directly searched for repeat expansion mutations and identified noncoding CGG repeat expansions in NBPF19 (NOTCH2NLC) as the causative mutations for NIID. Further prompted by the similarities in the clinical and neuroimaging findings with NIID, we identified similar noncoding CGG repeat expansions in two other diseases: oculopharyngeal myopathy with leukoencephalopathy and oculopharyngodistal myopathy, in LOC642361/NUTM2B-AS1 and LRP12, respectively. These findings expand our knowledge of the clinical spectra of diseases caused by expansions of the same repeat motif, and further highlight how directly searching for expanded repeats can help identify mutations underlying diseases.
  7. Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, et al.
    Autophagy, 2021 Jan;17(1):1-382.
    PMID: 33634751 DOI: 10.1080/15548627.2020.1797280
    In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
  8. Murugesu S, Okayama K, Yamamoto Y, Terada K, Takahashi Y
    Epileptic Disord, 2020 Aug 01;22(4):455-461.
    PMID: 32782230 DOI: 10.1684/epd.2020.1182
    To evaluate changes in the pharmacokinetics of perampanel after discontinuation of carbamazepine. We enrolled 13 patients receiving perampanel who discontinued carbamazepine therapy between June 2016 and December 2018. Data on serum concentrations were obtained from the therapeutic drug monitoring database of the National Epilepsy Center (Shizuoka, Japan). To compare the pharmacokinetics of perampanel before and after discontinuation of carbamazepine, we determined the concentration/dose (CD) ratio of perampanel (serum level [ng/mL] divided by the dose [mg/kg]). The follow-up period was set to eight weeks following the discontinuation of carbamazepine therapy. The mean baseline CD ratio of perampanel was 1,247 ng/mL/mg/kg which increased markedly over time after discontinuation of carbamazepine, with a mean CD ratio at Weeks 1-2, Weeks 3-4, and Weeks 5-8 of 2,683, 3,914, and 4,220, respectively. At eight weeks, the mean CD ratio of perampanel had increased by 276%. Eleven patients developed adverse events, including dizziness, somnolence, irritability, and ataxia. Five of these 11 patients required perampanel dose reduction within eight weeks after discontinuation of carbamazepine. Two patients achieved seizure-free status at Weeks 5-8. The serum perampanel concentration began to increase from one week after discontinuation of carbamazepine, and continued to rise for eight weeks. Based on these findings, we recommend frequent monitoring of serum perampanel concentration for at least eight weeks after stopping carbamazepine therapy. Monitoring is required as a guide for dose adjustment in order to achieve a safe and effective therapeutic dose of perampanel.
  9. Yao K, Uedo N, Muto M, Ishikawa H, Cardona HJ, Filho ECC, et al.
    EBioMedicine, 2016 Jul;9:140-147.
    PMID: 27333048 DOI: 10.1016/j.ebiom.2016.05.016
    BACKGROUND: In many countries, gastric cancer is not diagnosed until an advanced stage. An Internet-based e-learning system to improve the ability of endoscopists to diagnose gastric cancer at an early stage was developed and was evaluated for its effectiveness.

    METHODS: The study was designed as a randomized controlled trial. After receiving a pre-test, participants were randomly allocated to either an e-learning or non-e-learning group. Only those in the e-learning group gained access to the e-learning system. Two months after the pre-test, both groups received a post-test. The primary endpoint was the difference between the two groups regarding the rate of improvement of their test results.

    FINDINGS: 515 endoscopists from 35 countries were assessed for eligibility, and 332 were enrolled in the study, with 166 allocated to each group. Of these, 151 participants in the e-learning group and 144 in the non-e-learning group were included in the analysis. The mean improvement rate (standard deviation) in the e-learning and non-e-learning groups was 1·24 (0·26) and 1·00 (0·16), respectively (P<0·001).

    INTERPRETATION: This global study clearly demonstrated the efficacy of an e-learning system to expand knowledge and provide invaluable experience regarding the endoscopic detection of early gastric cancer (R000012039).

  10. Yeong KY, Khaw KY, Takahashi Y, Itoh Y, Murugaiyah V, Suzuki T
    Bioorg Chem, 2020 01;94:103403.
    PMID: 31711765 DOI: 10.1016/j.bioorg.2019.103403
    Studies have suggested that sirtuin inhibition may have beneficial effects on several age-related diseases such as neurodegenerative disorders and cancer. Garcinia mangostana is a well-known tropical plant found mostly in South East Asia with several positive health effects. Some of its phytochemicals such as α-mangostin was found to be able to modulate sirtuin activity in mice and was implicated with inflammation, diabetes and obesity. However, comprehensive studies on sirtuin activity by the prenylated xanthones extracted from Garcinia mangostana have yet to be reported. The present study led to the discovery and identification of γ-mangostin as a potent and selective SIRT2 inhibitor. It was demonstrated that γ-mangostin was able to increase the α-tubulin acetylation in MDA-MD-231 and MCF-7 breast cancer cells. It was also found to possess potent antiproliferative activity against both cell lines. In addition, it was able to induce neurite outgrowth in the N2a cells.
  11. Ahmad MF, Sugishita Y, Suzuki-Takahashi Y, Sawada S, Iwahata H, Shiraishi E, et al.
    Front Med (Lausanne), 2021;8:670872.
    PMID: 34422852 DOI: 10.3389/fmed.2021.670872
    Breast cancer comprised at least 21.8% of the overall cancer among young adult (YA) women and became the leading cancer in this group in Japan, with 50% adolescent and YAs being diagnosed and 15-44-year-old women showing excellent 5-year survival. Surgical-chemoradiation therapy often results in excellent survivorship with an increased incidence of treatment-induced subfertility. Therefore, adding fertility preservation (FP) to the primary cancer treatment is necessary. Herein, we reported a series of cases of YA women with breast cancer who opted for FP, where their option was tailored accordingly. To date, the selection of oocytes, embryos and ovarian tissue is widely available as an FP treatment. PGT could reduce the risk of BRCA mutation transmission amongst BRCA carriers before pregnancy planning. Otherwise, gonadotropin-releasing hormone analog has no gonadoprotective effect and thus should not be considered as an FP option.
  12. Ahmad MF, Sugishita Y, Suzuki-Takahashi Y, Sawada S, Iwahata H, Shiraishi E, et al.
    J Adolesc Young Adult Oncol, 2020 08;9(4):496-501.
    PMID: 32283045 DOI: 10.1089/jayao.2019.0177
    Purpose:
    Our center is known as a pioneer center initiating oncofertility service since 2010 in Japan. We demonstrate our transition of this service in regional university hospitals ingenuously.
    Methods:
    We compared two phases of service: initial phase (2011 and 2012) and current phase (2019). The comparison included the number of women attending the oncofertility unit, diversity of breast cancer cases, the acceptability of preservation service, and the type of fertility preservation (FP) option offered in between these phases.
    Results:
    A total of 58 women were seen during the initial phase as compared with 41 women in the later phase. The mean age at diagnosis was not significantly different between the two periods. The majority of them were married and diagnosed with stage II luminar type. The current phase had a tendency to have a higher anti-Müllerian hormone level although not reaching significance. At least 50% of them declined FP and 84.5% never received ovarian control stimulation in the initial phase. Otherwise, 61% used aromatase inhibitor in the current phase. Only 15.5% in the initial phase received control ovarian stimulation whereas 63.4% in the current phase received it. The ovarian tissue cryopreservation was highly chosen during the initial phase (25.9%), whereas embryo cryopreservation (39%) was highly opted for during the current phase. All of our parameters are comparable between these two phases (p > 0.05).
    Conclusion:
    The significant changes of oncofertility practice were observed mainly due to the understanding of the oncofertility concept among reproductive physicians and the acceptance environment, including standard guidelines, supportive society, as well as advancements in cryobiology technique.
  13. Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Asilar E, Bergauer T, et al.
    Eur Phys J C Part Fields, 2018;78(11):965.
    PMID: 30881214 DOI: 10.1140/epjc/s10052-018-6373-0
    The production of a Z boson, decaying to two charged leptons, in association with jets in proton-proton collisions at a centre-of-mass energy of 13 TeV is measured. Data recorded with the CMS detector at the LHC are used that correspond to an integrated luminosity of 2.19 fb -1 . The cross section is measured as a function of the jet multiplicity and its dependence on the transverse momentum of the Z boson, the jet kinematic variables (transverse momentum and rapidity), the scalar sum of the jet momenta, which quantifies the hadronic activity, and the balance in transverse momentum between the reconstructed jet recoil and the Z boson. The measurements are compared with predictions from four different calculations. The first two merge matrix elements with different parton multiplicities in the final state and parton showering, one of which includes one-loop corrections. The third is a fixed-order calculation with next-to-next-to-leading order accuracy for the process with a Z boson and one parton in the final state. The fourth combines the fully differential next-to-next-to-leading order calculation of the process with no parton in the final state with next-to-next-to-leading logarithm resummation and parton showering.
  14. Nishina K, Melling L, Toyoda S, Itoh M, Terajima K, Waili JWB, et al.
    Sci Total Environ, 2023 May 10;872:162062.
    PMID: 36804973 DOI: 10.1016/j.scitotenv.2023.162062
    Oil palm plantations in Southeast Asia are the largest supplier of palm oil products and have been rapidly expanding in the last three decades even in peat-swamp areas. Oil palm plantations on peat ecosystems have a unique water management system that lowers the water table and, thus, may yield indirect N2O emissions from the peat drainage system. We conducted two seasons of spatial monitoring for the dissolved N2O concentrations in the drainage and adjacent rivers of palm oil plantations on peat swamps in Sarawak, Malaysia, to evaluate the magnitude of indirect N2O emissions from this ecosystem. In both the dry and wet seasons, the mean and median dissolved N2O concentrations exhibited over-saturation in the drainage water, i.e., the oil palm plantation drainage may be a source of N2O to the atmosphere. In the wet season, the spatial distribution of dissolved N2O showed bimodal peaks in both the unsaturated and over-saturated concentrations. The bulk δ15N of dissolved N2O was higher than the source of inorganic N in the oil palm plantation (i.e., N fertilizer and soil organic nitrogen) during both seasons. An isotopocule analysis of the dissolved N2O suggested that denitrification was a major source of N2O, followed by N2O reduction processes that occurred in the drainage water. The δ15N and site preference mapping analysis in dissolved N2O revealed that a significant proportion of the N2O produced in peat and drainage is reduced to N2 before being released into the atmosphere.
  15. Uchiyama Y, Yamaguchi D, Iwama K, Miyatake S, Hamanaka K, Tsuchida N, et al.
    Hum Mutat, 2021 01;42(1):50-65.
    PMID: 33131168 DOI: 10.1002/humu.24129
    Many algorithms to detect copy number variations (CNVs) using exome sequencing (ES) data have been reported and evaluated on their sensitivity and specificity, reproducibility, and precision. However, operational optimization of such algorithms for a better performance has not been fully addressed. ES of 1199 samples including 763 patients with different disease profiles was performed. ES data were analyzed to detect CNVs by both the eXome Hidden Markov Model (XHMM) and modified Nord's method. To efficiently detect rare CNVs, we aimed to decrease sequencing biases by analyzing, at the same time, the data of all unrelated samples sequenced in the same flow cell as a batch, and to eliminate sex effects of X-linked CNVs by analyzing female and male sequences separately. We also applied several filtering steps for more efficient CNV selection. The average number of CNVs detected in one sample was <5. This optimization together with targeted CNV analysis by Nord's method identified pathogenic/likely pathogenic CNVs in 34 patients (4.5%, 34/763). In particular, among 142 patients with epilepsy, the current protocol detected clinically relevant CNVs in 19 (13.4%) patients, whereas the previous protocol identified them in only 14 (9.9%) patients. Thus, this batch-based XHMM analysis efficiently selected rare pathogenic CNVs in genetic diseases.
  16. Chung WH, Chang WC, Lee YS, Wu YY, Yang CH, Ho HC, et al.
    JAMA, 2014 Aug 6;312(5):525-34.
    PMID: 25096692 DOI: 10.1001/jama.2014.7859
    The antiepileptic drug phenytoin can cause cutaneous adverse reactions, ranging from maculopapular exanthema to severe cutaneous adverse reactions, which include drug reactions with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The pharmacogenomic basis of phenytoin-related severe cutaneous adverse reactions remains unknown.
  17. Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Asilar E, Bergauer T, et al.
    Eur Phys J C Part Fields, 2019;79(5):421.
    PMID: 31178657 DOI: 10.1140/epjc/s10052-019-6909-y
    Combined measurements of the production and decay rates of the Higgs boson, as well as its couplings to vector bosons and fermions, are presented. The analysis uses the LHC proton-proton collision data set recorded with the CMS detector in 2016 at s = 13 Te , corresponding to an integrated luminosity of 35.9 fb - 1 . The combination is based on analyses targeting the five main Higgs boson production mechanisms (gluon fusion, vector boson fusion, and associated production with a W or Z boson, or a top quark-antiquark pair) and the following decay modes: H → γ γ , Z Z , W W , τ τ , b b , and μ μ . Searches for invisible Higgs boson decays are also considered. The best-fit ratio of the signal yield to the standard model expectation is measured to be μ = 1.17 ± 0.10 , assuming a Higgs boson mass of 125.09 Ge . Additional results are given for various assumptions on the scaling behavior of the production and decay modes, including generic parametrizations based on ratios of cross sections and branching fractions or couplings. The results are compatible with the standard model predictions in all parametrizations considered. In addition, constraints are placed on various two Higgs doublet models.
  18. Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, Dragicevic M, et al.
    Eur Phys J C Part Fields, 2015 10 29;75(10):511.
    PMID: 26549982
    Measurements of the [Formula: see text][Formula: see text] production cross sections in proton-proton collisions at center-of-mass energies of 7 and 8[Formula: see text] are presented. Candidate events for the leptonic decay mode [Formula: see text], where [Formula: see text] denotes an electron or a muon, are reconstructed and selected from data corresponding to an integrated luminosity of 5.1 (19.6)[Formula: see text] at 7 (8)[Formula: see text] collected with the CMS experiment. The measured cross sections, [Formula: see text] at 7[Formula: see text], and [Formula: see text] at 8[Formula: see text], are in good agreement with the standard model predictions with next-to-leading-order accuracy. The selected data are analyzed to search for anomalous triple gauge couplings involving the [Formula: see text][Formula: see text] final state. In the absence of any deviation from the standard model predictions, limits are set on the relevant parameters. These limits are then combined with the previously published CMS results for [Formula: see text][Formula: see text] in 4[Formula: see text] final states, yielding the most stringent constraints on the anomalous couplings.
  19. Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, et al.
    Eur Phys J C Part Fields, 2016;76(8):460.
    PMID: 28747851 DOI: 10.1140/epjc/s10052-016-4292-5
    Results are reported from a search for the pair production of top squarks, the supersymmetric partners of top quarks, in final states with jets and missing transverse momentum. The data sample used in this search was collected by the CMS detector and corresponds to an integrated luminosity of 18.9[Formula: see text] of proton-proton collisions at a centre-of-mass energy of 8[Formula: see text] produced by the LHC. The search features novel background suppression and prediction methods, including a dedicated top quark pair reconstruction algorithm. The data are found to be in agreement with the predicted backgrounds. Exclusion limits are set in simplified supersymmetry models with the top squark decaying to jets and an undetected neutralino, either through a top quark or through a bottom quark and chargino. Models with the top squark decaying via a top quark are excluded for top squark masses up to 755[Formula: see text] in the case of neutralino masses below 200[Formula: see text]. For decays via a chargino, top squark masses up to 620[Formula: see text] are excluded, depending on the masses of the chargino and neutralino.
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