Displaying publications 21 - 40 of 88 in total

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  1. Vithana EN, Khor CC, Qiao C, Nongpiur ME, George R, Chen LJ, et al.
    Nat Genet, 2012 Oct;44(10):1142-1146.
    PMID: 22922875 DOI: 10.1038/ng.2390
    Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study including 1,854 PACG cases and 9,608 controls across 5 sample collections in Asia. Replication experiments were conducted in 1,917 PACG cases and 8,943 controls collected from a further 6 sample collections. We report significant associations at three new loci: rs11024102 in PLEKHA7 (per-allele odds ratio (OR)=1.22; P=5.33×10(-12)), rs3753841 in COL11A1 (per-allele OR=1.20; P=9.22×10(-10)) and rs1015213 located between PCMTD1 and ST18 on chromosome 8q (per-allele OR=1.50; P=3.29×10(-9)). Our findings, accumulated across these independent worldwide collections, suggest possible mechanisms explaining the pathogenesis of PACG.
  2. Khor CC, Do T, Jia H, Nakano M, George R, Abu-Amero K, et al.
    Nat Genet, 2016 May;48(5):556-62.
    PMID: 27064256 DOI: 10.1038/ng.3540
    Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study (GWAS) followed by replication in a combined total of 10,503 PACG cases and 29,567 controls drawn from 24 countries across Asia, Australia, Europe, North America, and South America. We observed significant evidence of disease association at five new genetic loci upon meta-analysis of all patient collections. These loci are at EPDR1 rs3816415 (odds ratio (OR) = 1.24, P = 5.94 × 10(-15)), CHAT rs1258267 (OR = 1.22, P = 2.85 × 10(-16)), GLIS3 rs736893 (OR = 1.18, P = 1.43 × 10(-14)), FERMT2 rs7494379 (OR = 1.14, P = 3.43 × 10(-11)), and DPM2-FAM102A rs3739821 (OR = 1.15, P = 8.32 × 10(-12)). We also confirmed significant association at three previously described loci (P < 5 × 10(-8) for each sentinel SNP at PLEKHA7, COL11A1, and PCMTD1-ST18), providing new insights into the biology of PACG.
  3. Yin T, Xu L, Gil B, Merali N, Sokolikova MS, Gaboriau DCA, et al.
    ACS Nano, 2023 Aug 08;17(15):14619-14631.
    PMID: 37470391 DOI: 10.1021/acsnano.3c01812
    Biosensors based on graphene field effect transistors (GFETs) have the potential to enable the development of point-of-care diagnostic tools for early stage disease detection. However, issues with reproducibility and manufacturing yields of graphene sensors, but also with Debye screening and unwanted detection of nonspecific species, have prevented the wider clinical use of graphene technology. Here, we demonstrate that our wafer-scalable GFETs array platform enables meaningful clinical results. As a case study of high clinical relevance, we demonstrate an accurate and robust portable GFET array biosensor platform for the detection of pancreatic ductal adenocarcinoma (PDAC) in patients' plasma through specific exosomes (GPC-1 expression) within 45 min. In order to facilitate reproducible detection in blood plasma, we optimized the analytical performance of GFET biosensors via the application of an internal control channel and the development of an optimized test protocol. Based on samples from 18 PDAC patients and 8 healthy controls, the GFET biosensor arrays could accurately discriminate between the two groups while being able to detect early cancer stages including stages 1 and 2. Furthermore, we confirmed the higher expression of GPC-1 and found that the concentration in PDAC plasma was on average more than 1 order of magnitude higher than in healthy samples. We found that these characteristics of GPC-1 cancerous exosomes are responsible for an increase in the number of target exosomes on the surface of graphene, leading to an improved signal response of the GFET biosensors. This GFET biosensor platform holds great promise for the development of an accurate tool for the rapid diagnosis of pancreatic cancer.
  4. 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
  5. 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.
  6. Aljunid SM, Srithamrongsawat S, Chen W, Bae SJ, Pwu RF, Ikeda S, et al.
    Value Health, 2012 2 1;15(1 Suppl):S132-8.
    PMID: 22265060 DOI: 10.1016/j.jval.2011.11.004
    This article sought to describe the health-care data situation in six selected economies in the Asia-Pacific region. Authors from Thailand, China mainland, South Korea, Taiwan, Japan, and Malaysia present their analyses in three parts. The first part of the article describes the data-collection process and the sources of data. The second part of the article presents issues around policies of data sharing with the stakeholders. The third and final part of the article focuses on the extent of health-care data use for policy reform in these different economies. Even though these economies differ in their economic structure and population size, they share some similarities on issues related to health-care data. There are two main institutions that collect and manage the health-care data in these economies. In Thailand, China mainland, Taiwan, and Malaysia, the Ministry of Health is responsible through its various agencies for collecting and managing the health-care data. On the other hand, health insurance is the main institution that collects and stores health-care data in South Korea and Japan. In all economies, sharing of and access to data is an issue. The reasons for limited access to some data are privacy protection, fragmented health-care system, poor quality of routinely collected data, unclear policies and procedures to access the data, and control on the freedom on publication. The primary objective of collecting health-care data in these economies is to aid the policymakers and researchers in policy decision making as well as create an awareness on health-care issues for the general public. The usage of data in monitoring the performance of the heath system is still in the process of development. In conclusion, for the region under discussion, health-care data collection is under the responsibility of the Ministry of Health and health insurance agencies. Data are collected from health-care providers mainly from the public sector. Routinely collected data are supplemented by national surveys. Accessibility to the data is a major issue in most of the economies under discussion. Accurate health-care data are required mainly to support policy making and evidence-based decisions.
  7. Zhang H, Rios RS, Boursier J, Anty R, Chan WK, George J, et al.
    Chin Med J (Engl), 2023 Feb 05;136(3):341-350.
    PMID: 36848175 DOI: 10.1097/CM9.0000000000002603
    BACKGROUND: Liver biopsy for the diagnosis of non-alcoholic steatohepatitis (NASH) is limited by its inherent invasiveness and possible sampling errors. Some studies have shown that cytokeratin-18 (CK-18) concentrations may be useful in diagnosing NASH, but results across studies have been inconsistent. We aimed to identify the utility of CK-18 M30 concentrations as an alternative to liver biopsy for non-invasive identification of NASH.

    METHODS: Individual data were collected from 14 registry centers on patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD), and in all patients, circulating CK-18 M30 levels were measured. Individuals with a NAFLD activity score (NAS) ≥5 with a score of ≥1 for each of steatosis, ballooning, and lobular inflammation were diagnosed as having definite NASH; individuals with a NAS ≤2 and no fibrosis were diagnosed as having non-alcoholic fatty liver (NAFL).

    RESULTS: A total of 2571 participants were screened, and 1008 (153 with NAFL and 855 with NASH) were finally enrolled. Median CK-18 M30 levels were higher in patients with NASH than in those with NAFL (mean difference 177 U/L; standardized mean difference [SMD]: 0.87 [0.69-1.04]). There was an interaction between CK-18 M30 levels and serum alanine aminotransferase, body mass index (BMI), and hypertension ( P  L. Both sensitivity (55% [52%-59%]) and positive predictive value (59%) were not ideal.

    CONCLUSION: This large multicenter registry study shows that CK-18 M30 measurement in isolation is of limited value for non-invasively diagnosing NASH.

  8. Leon AJ, Borisevich V, Boroumand N, Seymour R, Nusbaum R, Escaffre O, et al.
    PLoS Negl Trop Dis, 2018 03;12(3):e0006343.
    PMID: 29538374 DOI: 10.1371/journal.pntd.0006343
    Henipavirus infection causes severe respiratory and neurological disease in humans that can be fatal. To characterize the pathogenic mechanisms of henipavirus infection in vivo, we performed experimental infections in ferrets followed by genome-wide gene expression analysis of lung and brain tissues. The Hendra, Nipah-Bangladesh, and Nipah-Malaysia strains caused severe respiratory and neurological disease with animals succumbing around 7 days post infection. Despite the presence of abundant viral shedding, animal-to-animal transmission did not occur. The host gene expression profiles of the lung tissue showed early activation of interferon responses and subsequent expression of inflammation-related genes that coincided with the clinical deterioration. Additionally, the lung tissue showed unchanged levels of lymphocyte markers and progressive downregulation of cell cycle genes and extracellular matrix components. Infection in the brain resulted in a limited breadth of the host responses, which is in accordance with the immunoprivileged status of this organ. Finally, we propose a model of the pathogenic mechanisms of henipavirus infection that integrates multiple components of the host responses.
  9. Duan M, Xu L, Gu T, Sun Y, Xia Q, He J, et al.
    Food Chem X, 2023 Dec 30;20:100899.
    PMID: 38144818 DOI: 10.1016/j.fochx.2023.100899
    In order to explore the characteristic aroma flavor and its formation mechanism of old ducks, two ages (30 days and 60 days) of young ducks and three ages of old ducks (300 days, 900 days, and 1500 days) were selected and studied. An electronic nose was applied to evaluate the overall aroma flavor, and the result showed significant differences between the five duck samples. By gas chromatography-mass spectrometry (GC-MS), forty-eight volatile flavor compounds were detected, including seven aldehydes, six esters, five alcohols, five nitrogen compounds, twenty-one hydrocarbons, and four others. Among these compounds, twelve components, such as hexanal and dimethyl anthranilate, were considered as the characteristic flavor compounds along with duck aging. Furthermore, correlation analysis indicated that meat's unsaturated free fatty acids, especially linoleic acid (C18:2), were responsible for the duck's characteristic flavor formation. These data contribute to the flavor research and identification of old ducks.
  10. Muller L, Goh BS, Cordovés AP, Sargsyan G, Sikka K, Singh S, et al.
    Int J Pediatr Otorhinolaryngol, 2023 Jul;170:111583.
    PMID: 37245391 DOI: 10.1016/j.ijporl.2023.111583
    OBJECTIVES: The aim of this study was to report on the educational placement, quality of life and speech reception changes in a prospectively recruited group of children after they received a cochlear implant (CI).

    METHOD: Data was collected on 1085 CI recipients of as part of a prospective, longitudinal, observational, international, multi-centre, paediatric registry, initiated by Cochlear Ltd (Sydney, NSW, Australia). Outcome data from children (≤10 years old) implanted in routine practice was voluntarily entered into a central, externally hosted, e-platform. Collection occurred prior to initial device activation (baseline) and at six monthly follow-up intervals up to 24 months and then at 3 years post activation. Clinician reported baseline and follow up questionnaires and Categories of Auditory Performance version II (CAP-II) outcomes were collated. Self-reported evaluation forms and patient information were provided by the parent/caregiver/patient via the implant recipient baseline and follow up, Children Using Hearing Implants Quality of Life (CuHIQoL) and Speech Spatial Qualities (SSQ-P) Parents Version questionnaires.

    RESULTS: Children were mainly bilaterally profoundly deaf, unilaterally implanted and used a contralateral hearing aid. Prior to implant 60% used signing or total communication as their main mode of communication. Mean age at implant was 3.2 ± 2.2 years (range 0-10 years). At baseline 8.6% were in mainstream education with no additional support and 82% had not yet entered school. After three years of implant use, 52% had entered mainstream education with no additional support and 38% had not yet entered school. In the sub-group of 141 children who were implanted at or after three years of age and were thus old enough to be in mainstream school at the three-year follow up, an even higher proportion (73%) were in mainstream education with no support. Quality of life scores for the child improved statistically significantly post implant compared to baseline and continued to improve significantly at each interval up to 3 years (p 

  11. Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, et al.
    Phys Rev Lett, 2016 Apr 29;116(17):172302.
    PMID: 27176516 DOI: 10.1103/PhysRevLett.116.172302
    Results on two-particle angular correlations for charged particles produced in pp collisions at a center-of-mass energy of 13 TeV are presented. The data were taken with the CMS detector at the LHC and correspond to an integrated luminosity of about 270  nb^{-1}. The correlations are studied over a broad range of pseudorapidity (|η|<2.4) and over the full azimuth (ϕ) as a function of charged particle multiplicity and transverse momentum (p_{T}). In high-multiplicity events, a long-range (|Δη|>2.0), near-side (Δϕ≈0) structure emerges in the two-particle Δη-Δϕ correlation functions. The magnitude of the correlation exhibits a pronounced maximum in the range 1.0
  12. CMS Collaboration, Chatrchyan S, Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, et al.
    Eur Phys J C Part Fields, 2014 08 07;74(8):2973.
    PMID: 25814904
    Measurements are reported of the WZ and ZZ production cross sections in proton-proton collisions at [Formula: see text][Formula: see text] in final states where one Z boson decays to b-tagged jets. The other gauge boson, either W or Z, is detected through its leptonic decay (either [Formula: see text], [Formula: see text] or [Formula: see text], [Formula: see text], or [Formula: see text]). The results are based on data corresponding to an integrated luminosity of 18.9 fb[Formula: see text] collected with the CMS detector at the Large Hadron Collider. The measured cross sections, [Formula: see text] and [Formula: see text], are consistent with next-to-leading order quantum chromodynamics calculations.
  13. Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, et al.
    Eur Phys J C Part Fields, 2016;76(7):379.
    PMID: 28280447 DOI: 10.1140/epjc/s10052-016-4105-x
    Jet multiplicity distributions in top quark pair ([Formula: see text]) events are measured in pp collisions at a centre-of-mass energy of 8 TeV with the CMS detector at the LHC using a data set corresponding to an integrated luminosity of 19.7[Formula: see text]. The measurement is performed in the dilepton decay channels ([Formula: see text], [Formula: see text], and [Formula: see text]). The absolute and normalized differential cross sections for [Formula: see text] production are measured as a function of the jet multiplicity in the event for different jet transverse momentum thresholds and the kinematic properties of the leading additional jets. The differential [Formula: see text] and [Formula: see text] cross sections are presented for the first time as a function of the kinematic properties of the leading additional [Formula: see text] jets. Furthermore, the fraction of events without additional jets above a threshold is measured as a function of the transverse momenta of the leading additional jets and the scalar sum of the transverse momenta of all additional jets. The data are compared and found to be consistent with predictions from several perturbative quantum chromodynamics event generators and a next-to-leading order calculation.
  14. Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, et al.
    Eur Phys J C Part Fields, 2016 01 11;76:13.
    PMID: 26855607
    A measurement is presented of differential cross sections for Higgs boson (H) production in pp collisions at [Formula: see text][Formula: see text]. The analysis exploits the [Formula: see text] decay in data corresponding to an integrated luminosity of 19.7[Formula: see text] collected by the CMS experiment at the LHC. The cross section is measured as a function of the kinematic properties of the diphoton system and of the associated jets. Results corrected for detector effects are compared with predictions at next-to-leading order and next-to-next-to-leading order in perturbative quantum chromodynamics, as well as with predictions beyond the standard model. For isolated photons with pseudorapidities [Formula: see text], and with the photon of largest and next-to-largest transverse momentum ([Formula: see text]) divided by the diphoton mass [Formula: see text] satisfying the respective conditions of [Formula: see text] and [Formula: see text], the total fiducial cross section is [Formula: see text][Formula: see text].
  15. CMS Collaboration, Chatrchyan S, Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, et al.
    Eur Phys J C Part Fields, 2014 11 12;74(11):3129.
    PMID: 25814874
    A measurement of differential cross sections for the production of a pair of isolated photons in proton-proton collisions at [Formula: see text] is presented. The data sample corresponds to an integrated luminosity of 5.0[Formula: see text] collected with the CMS detector. A data-driven isolation template method is used to extract the prompt diphoton yield. The measured cross section for two isolated photons, with transverse energy above 40 and 25[Formula: see text] respectively, in the pseudorapidity range [Formula: see text], [Formula: see text] and with an angular separation [Formula: see text], is [Formula: see text][Formula: see text]. Differential cross sections are measured as a function of the diphoton invariant mass, the diphoton transverse momentum, the azimuthal angle difference between the two photons, and the cosine of the polar angle in the Collins-Soper reference frame of the diphoton system. The results are compared to theoretical predictions at leading, next-to-leading, and next-to-next-to-leading order in quantum chromodynamics.
  16. Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, et al.
    Eur Phys J C Part Fields, 2016;76(10):536.
    PMID: 28316485 DOI: 10.1140/epjc/s10052-016-4346-8
    A measurement of the decorrelation of azimuthal angles between the two jets with the largest transverse momenta is presented for seven regions of leading jet transverse momentum up to 2.2[Formula: see text]. The analysis is based on the proton-proton collision data collected with the CMS experiment at a centre-of-mass energy of 8[Formula: see text] corresponding to an integrated luminosity of 19.7[Formula: see text]. The dijet azimuthal decorrelation is caused by the radiation of additional jets and probes the dynamics of multijet production. The results are compared to fixed-order predictions of perturbative quantum chromodynamics (QCD), and to simulations using Monte Carlo event generators that include parton showers, hadronization, and multiparton interactions. Event generators with only two outgoing high transverse momentum partons fail to describe the measurement, even when supplemented with next-to-leading-order QCD corrections and parton showers. Much better agreement is achieved when at least three outgoing partons are complemented through either next-to-leading-order predictions or parton showers. This observation emphasizes the need to improve predictions for multijet production.
  17. Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, Dragicevic M, et al.
    Eur Phys J C Part Fields, 2015 02 10;75(2):66.
    PMID: 25838791
    The purely electroweak (EW) cross section for the production of two jets in association with a Z boson, in proton-proton collisions at [Formula: see text], is measured using data recorded by the CMS experiment at the CERN LHC, corresponding to an integrated luminosity of 19.7[Formula: see text]. The electroweak cross section for the [Formula: see text] final state (with [Formula: see text] or [Formula: see text] and j representing the quarks produced in the hard interaction) in the kinematic region defined by [Formula: see text][Formula: see text], [Formula: see text][Formula: see text], transverse momentum [Formula: see text][Formula: see text], and pseudorapidity [Formula: see text], is found to be [Formula: see text], in agreement with the standard model prediction. The associated jet activity of the selected events is studied, in particular in a signal-enriched region of phase space, and the measurements are found to be in agreement with QCD predictions.
  18. Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, et al.
    Eur Phys J C Part Fields, 2016;76(7):372.
    PMID: 28280445 DOI: 10.1140/epjc/s10052-016-4205-7
    Inclusive jet production in pPb collisions at a nucleon-nucleon (NN) center-of-mass energy of [Formula: see text] is studied with the CMS detector at the LHC. A data sample corresponding to an integrated luminosity of 30.1 nb[Formula: see text] is analyzed. The jet transverse momentum spectra are studied in seven pseudorapidity intervals covering the range [Formula: see text] in the NN center-of-mass frame. The jet production yields at forward and backward pseudorapidity are compared and no significant asymmetry about [Formula: see text] is observed in the measured kinematic range. The measurements in the pPb system are compared to reference jet spectra obtained by extrapolation from previous measurements in pp collisions at [Formula: see text]. In all pseudorapidity ranges, nuclear modifications in inclusive jet production are found to be small, as predicted by next-to-leading order perturbative QCD calculations that incorporate nuclear effects in the parton distribution functions.
  19. CMS Collaboration, Chatrchyan S, Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, et al.
    Eur Phys J C Part Fields, 2014 08 20;74(8):3014.
    PMID: 25814909
    The normalised differential top quark-antiquark production cross section is measured as a function of the jet multiplicity in proton-proton collisions at a centre-of-mass energy of 7[Formula: see text] at the LHC with the CMS detector. The measurement is performed in both the dilepton and lepton+jets decay channels using data corresponding to an integrated luminosity of 5.0[Formula: see text]. Using a procedure to associate jets to decay products of the top quarks, the differential cross section of the [Formula: see text] production is determined as a function of the additional jet multiplicity in the lepton+jets channel. Furthermore, the fraction of events with no additional jets is measured in the dilepton channel, as a function of the threshold on the jet transverse momentum. The measurements are compared with predictions from perturbative quantum chromodynamics and no significant deviations are observed.
  20. Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, et al.
    Eur Phys J C Part Fields, 2017;77(4):236.
    PMID: 28515665 DOI: 10.1140/epjc/s10052-017-4730-z
    The WZ production cross section is measured by the CMS experiment at the CERN LHC in proton-proton collision data samples corresponding to integrated luminosities of 4.9[Formula: see text] collected at [Formula: see text], and 19.6[Formula: see text] at [Formula: see text]. The measurements are performed using the fully-leptonic WZ decay modes with electrons and muons in the final state. The measured cross sections for [Formula: see text] are [Formula: see text] [Formula: see text] and [Formula: see text] [Formula: see text]. Differential cross sections with respect to the [Formula: see text] boson [Formula: see text], the leading jet [Formula: see text], and the number of jets are obtained using the [Formula: see text] data. The results are consistent with standard model predictions and constraints on anomalous triple gauge couplings are obtained.
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