Displaying publications 1 - 20 of 190 in total

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  1. 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.
  2. 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
  3. 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.
  4. Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Bergauer T, Dragicevic M, et al.
    Comput Softw Big Sci, 2020;4(1):10.
    PMID: 33196702 DOI: 10.1007/s41781-020-00041-z
    We describe a method to obtain point and dispersion estimates for the energies of jets arising from b quarks produced in proton-proton collisions at an energy of s = 13 TeV at the CERN LHC. The algorithm is trained on a large sample of simulated b jets and validated on data recorded by the CMS detector in 2017 corresponding to an integrated luminosity of 41 fb - 1 . A multivariate regression algorithm based on a deep feed-forward neural network employs jet composition and shape information, and the properties of reconstructed secondary vertices associated with the jet. The results of the algorithm are used to improve the sensitivity of analyses that make use of b jets in the final state, such as the observation of Higgs boson decay to b b ¯ .
  5. 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).

  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, Dragicevic M, et al.
    Phys Rev Lett, 2015 Feb 13;114(6):061801.
    PMID: 25723204
    A search for new long-lived particles decaying to leptons is presented using proton-proton collisions produced by the LHC at √[s]=8  TeV. Data used for the analysis were collected by the CMS detector and correspond to an integrated luminosity of 19.7  fb(-1). Events are selected with an electron and muon with opposite charges that both have transverse impact parameter values between 0.02 and 2 cm. The search has been designed to be sensitive to a wide range of models with nonprompt e-μ final states. Limits are set on the "displaced supersymmetry" model, with pair production of top squarks decaying into an e-μ final state via R-parity-violating interactions. The results are the most restrictive to date on this model, with the most stringent limit being obtained for a top squark lifetime corresponding to cτ=2  cm, excluding masses below 790 GeV at 95% confidence level.
  13. Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, Dragicevic M, et al.
    Phys Rev Lett, 2015 Feb 6;114(5):051801.
    PMID: 25699433
    A study of vector boson scattering in pp collisions at a center-of-mass energy of 8 TeV is presented. The data sample corresponds to an integrated luminosity of 19.4  fb(-1) collected with the CMS detector. Candidate events are selected with exactly two leptons of the same charge, two jets with large rapidity separation and high dijet mass, and moderate missing transverse energy. The signal region is expected to be dominated by electroweak same-sign W-boson pair production. The observation agrees with the standard model prediction. The observed significance is 2.0 standard deviations, where a significance of 3.1 standard deviations is expected based on the standard model. Cross section measurements for W(±)W(±) and WZ processes in the fiducial region are reported. Bounds on the structure of quartic vector-boson interactions are given in the framework of dimension-eight effective field theory operators, as well as limits on the production of doubly charged Higgs bosons.
  14. Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, et al.
    Phys Rev Lett, 2016 Feb 19;116(7):071801.
    PMID: 26943527 DOI: 10.1103/PhysRevLett.116.071801
    A search for narrow resonances in proton-proton collisions at sqrt[s]=13  TeV is presented. The invariant mass distribution of the two leading jets is measured with the CMS detector using a data set corresponding to an integrated luminosity of 2.4  fb^{-1}. The highest observed dijet mass is 6.1 TeV. The distribution is smooth and no evidence for resonant particles is observed. Upper limits at 95% confidence level are set on the production cross section for narrow resonances with masses above 1.5 TeV. When interpreted in the context of specific models, the limits exclude string resonances with masses below 7.0 TeV, scalar diquarks below 6.0 TeV, axigluons and colorons below 5.1 TeV, excited quarks below 5.0 TeV, color-octet scalars below 3.1 TeV, and W^{'} bosons below 2.6 TeV. These results significantly extend previously published limits.
  15. Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, et al.
    Phys Rev Lett, 2016 Jan 22;116(3):032301.
    PMID: 26849587 DOI: 10.1103/PhysRevLett.116.032301
    The production cross sections of the B^{+}, B^{0}, and B_{s}^{0} mesons, and of their charge conjugates, are measured via exclusive hadronic decays in p+Pb collisions at the center-of-mass energy sqrt[s_{NN}]=5.02  TeV with the CMS detector at the CERN LHC. The data set used for this analysis corresponds to an integrated luminosity of 34.6  nb^{-1}. The production cross sections are measured in the transverse momentum range between 10 and 60  GeV/c. No significant modification is observed compared to proton-proton perturbative QCD calculations scaled by the number of incoherent nucleon-nucleon collisions. These results provide a baseline for the study of in-medium b quark energy loss in Pb+Pb collisions.
  16. Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, Dragicevic M, et al.
    Phys Rev Lett, 2015 Mar 13;114(10):101801.
    PMID: 25815923
    Results are presented from a search for new decaying massive particles whose presence is inferred from an imbalance in transverse momentum and which are produced in association with a single top quark that decays into a bottom quark and two light quarks. The measurement is performed using 19.7  fb^{-1} of data from proton-proton collisions at a center-of-mass energy of 8 TeV, collected with the CMS detector at the CERN LHC. No deviations from the standard model predictions are observed and lower limits are set on the masses of new invisible bosons. In particular, scalar and vector particles, with masses below 330 and 650 GeV, respectively, are excluded at 95% confidence level, thereby substantially extending a previous limit published by the CDF Collaboration.
  17. Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, Brandstetter J, et al.
    Phys Rev Lett, 2018 Apr 06;120(14):142301.
    PMID: 29694144 DOI: 10.1103/PhysRevLett.120.142301
    The relative yields of ϒ mesons produced in pp and Pb-Pb collisions at sqrt[s_{NN}]=5.02  TeV and reconstructed via the dimuon decay channel are measured using data collected by the CMS experiment. Double ratios are formed by comparing the yields of the excited states, ϒ(2S) and ϒ(3S), to the ground state, ϒ(1S), in both Pb-Pb and pp collisions at the same center-of-mass energy. The double ratios, [ϒ(nS)/ϒ(1S)]_{Pb-Pb}/[ϒ(nS)/ϒ(1S)]_{pp}, are measured to be 0.308±0.055(stat)±0.019(syst) for the ϒ(2S) and less than 0.26 at 95% confidence level for the ϒ(3S). No significant ϒ(3S) signal is found in the Pb-Pb data. The double ratios are studied as a function of collision centrality, as well as ϒ transverse momentum and rapidity. No significant dependencies are observed.
  18. Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Asilar E, Bergauer T, et al.
    Phys Rev Lett, 2020 Sep 04;125(10):102001.
    PMID: 32955327 DOI: 10.1103/PhysRevLett.125.102001
    The first study of charm quark diffusion with respect to the jet axis in heavy ion collisions is presented. The measurement is performed using jets with p_{T}^{jet}>60  GeV/c and D^{0} mesons with p_{T}^{D}>4  GeV/c in lead-lead (Pb-Pb) and proton-proton (pp) collisions at a nucleon-nucleon center-of-mass energy of sqrt[s_{NN}]=5.02  TeV, recorded by the CMS detector at the LHC. The radial distribution of D^{0} mesons with respect to the jet axis is sensitive to the production mechanisms of the meson, as well as to the energy loss and diffusion processes undergone by its parent parton inside the strongly interacting medium produced in Pb-Pb collisions. When compared to Monte Carlo event generators, the radial distribution in pp collisions is found to be well described by pythia, while the slope of the distribution predicted by sherpa is steeper than that of the data. In Pb-Pb collisions, compared to the pp results, the D^{0} meson distribution for 4
  19. Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Bergauer T, Dragicevic M, et al.
    Phys Rev Lett, 2020 Oct 09;125(15):152001.
    PMID: 33095627 DOI: 10.1103/PhysRevLett.125.152001
    Using a data sample of proton-proton collisions at sqrt[s]=13  TeV, corresponding to an integrated luminosity of 140  fb^{-1} collected by the CMS experiment in 2016-2018, the B_{s}^{0}→X(3872)ϕ decay is observed. Decays into J/ψπ^{+}π^{-} and K^{+}K^{-} are used to reconstruct, respectively, the X(3872) and ϕ. The ratio of the product of branching fractions B[B_{s}^{0}→X(3872)ϕ]B[X(3872)→J/ψπ^{+}π^{-}] to the product B[B_{s}^{0}→ψ(2S)ϕ]B[ψ(2S)→J/ψπ^{+}π^{-}] is measured to be [2.21±0.29(stat)±0.17(syst)]%. The ratio B[B_{s}^{0}→X(3872)ϕ]/B[B^{0}→X(3872)K^{0}] is found to be consistent with one, while the ratio B[B_{s}^{0}→X(3872)ϕ]/B[B^{+}→X(3872)K^{+}] is two times smaller. This suggests a difference in the production dynamics of the X(3872) in B^{0} and B_{s}^{0} meson decays compared to B^{+}. The reported observation may shed new light on the nature of the X(3872) particle.
  20. Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Asilar E, Bergauer T, et al.
    Phys Rev Lett, 2018 May 18;120(20):202005.
    PMID: 29864318 DOI: 10.1103/PhysRevLett.120.202005
    A search for resonancelike structures in the B_{s}^{0}π^{±} invariant mass spectrum is performed using proton-proton collision data collected by the CMS experiment at the LHC at sqrt[s]=8  TeV, corresponding to an integrated luminosity of 19.7  fb^{-1}. The B_{s}^{0} mesons are reconstructed in the decay chain B_{s}^{0}→J/ψϕ, with J/ψ→μ^{+}μ^{-} and ϕ→K^{+}K^{-}. The B_{s}^{0}π^{±} invariant mass distribution shows no statistically significant peaks for different selection requirements on the reconstructed B_{s}^{0} and π^{±} candidates. Upper limits are set on the relative production rates of the X(5568) and B_{s}^{0} states times the branching fraction of the decay X(5568)^{±}→B_{s}^{0}π^{±}. In addition, upper limits are obtained as a function of the mass and the natural width of possible exotic states decaying into B_{s}^{0}π^{±}.
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