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  1. Evidence for the Higgs Boson Decay to a Z Boson and a Photon at the LHC
    Aad G, Abbott B, Abeling K, Abicht NJ, Abidi SH, Aboulhorma A, et al.
    Phys Rev Lett, 2024 Jan 12;132(2):021803.
    PMID: 38277607 DOI: 10.1103/PhysRevLett.132.021803
    The first evidence for the Higgs boson decay to a Z boson and a photon is presented, with a statistical significance of 3.4 standard deviations. The result is derived from a combined analysis of the searches performed by the ATLAS and CMS Collaborations with proton-proton collision datasets collected at the CERN Large Hadron Collider (LHC) from 2015 to 2018. These correspond to integrated luminosities of around 140  fb^{-1} for each experiment, at a center-of-mass energy of 13 TeV. The measured signal yield is 2.2±0.7 times the standard model prediction, and agrees with the theoretical expectation within 1.9 standard deviations.
  2. Fulltext Medical record abstraction in a hospital with paper-based records: experience of early career psychiatrists in northern Borneo
    Ahmad Shahabuddin F, Wah KY, Buji RI, Zulkafli NS, Lee SW, Soon HL, et al.
    BJPsych Int, 2020 May;17(2):43-44.
    PMID: 32558818 DOI: 10.1192/bji.2019.29
    We used medical record abstraction to conduct research in a psychiatric hospital with paper-based medical records. The challenges we encountered included: the difficulty in retrieving files; the extensive effort and time needed to extract clinical information; the lack of a standardised documentation system of medical records; and the need for advanced computer literacy. To promote future research using electronic medical records, potential solutions include creating a registry of all patients receiving treatment, as well as equipping busy clinicians with computer skills.
  3. Fulltext Assessing generalisability of deep learning-based polyp detection and segmentation methods through a computer vision challenge
    Ali S, Ghatwary N, Jha D, Isik-Polat E, Polat G, Yang C, et al.
    Sci Rep, 2024 Jan 23;14(1):2032.
    PMID: 38263232 DOI: 10.1038/s41598-024-52063-x
    Polyps are well-known cancer precursors identified by colonoscopy. However, variability in their size, appearance, and location makes the detection of polyps challenging. Moreover, colonoscopy surveillance and removal of polyps are highly operator-dependent procedures and occur in a highly complex organ topology. There exists a high missed detection rate and incomplete removal of colonic polyps. To assist in clinical procedures and reduce missed rates, automated methods for detecting and segmenting polyps using machine learning have been achieved in past years. However, the major drawback in most of these methods is their ability to generalise to out-of-sample unseen datasets from different centres, populations, modalities, and acquisition systems. To test this hypothesis rigorously, we, together with expert gastroenterologists, curated a multi-centre and multi-population dataset acquired from six different colonoscopy systems and challenged the computational expert teams to develop robust automated detection and segmentation methods in a crowd-sourcing Endoscopic computer vision challenge. This work put forward rigorous generalisability tests and assesses the usability of devised deep learning methods in dynamic and actual clinical colonoscopy procedures. We analyse the results of four top performing teams for the detection task and five top performing teams for the segmentation task. Our analyses demonstrate that the top-ranking teams concentrated mainly on accuracy over the real-time performance required for clinical applicability. We further dissect the devised methods and provide an experiment-based hypothesis that reveals the need for improved generalisability to tackle diversity present in multi-centre datasets and routine clinical procedures.
  4. In-Hospital Coronary Revascularization Rates and Post-Discharge Mortality Risk in Non-ST-Segment Elevation Acute Coronary Syndrome
    Bueno H, Rossello X, Pocock SJ, Van de Werf F, Chin CT, Danchin N, et al.
    J Am Coll Cardiol, 2019 09 17;74(11):1454-1461.
    PMID: 31514947 DOI: 10.1016/j.jacc.2019.06.068
    BACKGROUND: The relationship between in-hospital coronary revascularization rate (CRR) and post-discharge mortality rates in survivors of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) at a system level is unclear.

    OBJECTIVES: The purpose of this study was to evaluate CRR and 2-year post-discharge mortality rate (2YMR) in NSTE-ACS.

    METHODS: CRR and 2YMR were analyzed by hospital rate of CRR (in deciles), by country, and by world region in 11,931 patients with NSTE-ACS who survived to discharge and were enrolled in the EPICOR (long-tErm follow uP of antithrombotic management patterns In acute CORonary syndrome patients) and EPICOR Asia: twin multinational, observational, prospective cohort studies.

    RESULTS: Significant differences in patient baseline characteristics, medical therapies, CRR, and 2YMR were found. Mean CRR ranged from 0.0% to 96.8% in the first and tenth decile, respectively (p 

  5. Searches for electroweak production of charginos, neutralinos, and sleptons decaying to leptons and W, Z, and Higgs bosons in pp collisions at 8 TeV
    CMS Collaboration, Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, et al.
    Eur Phys J C Part Fields, 2014 09 26;74(9):3036.
    PMID: 25814912
    Searches for the direct electroweak production of supersymmetric charginos, neutralinos, and sleptons in a variety of signatures with leptons and [Formula: see text], [Formula: see text], and Higgs bosons are presented. Results are based on a sample of proton-proton collision data collected at center-of-mass energy [Formula: see text] with the CMS detector in 2012, corresponding to an integrated luminosity of 19.5 [Formula: see text]. The observed event rates are in agreement with expectations from the standard model. These results probe charginos and neutralinos with masses up to 720 [Formula: see text], and sleptons up to 260 [Formula: see text], depending on the model details.
  6. Fulltext MUSiC: a model-unspecific search for new physics in proton-proton collisions at s = 13 TeV
    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.
  7. Measurement of top quark-antiquark pair production in association with a W or Z boson in pp collisions at [Formula: see text][Formula: see text]
    CMS Collaboration, Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, et al.
    Eur Phys J C Part Fields, 2014 09 17;74(9):3060.
    PMID: 25814914
    A measurement of the cross section for the production of top quark-antiquark pairs ([Formula: see text]) in association with a vector boson V (W or Z) in proton-proton collisions at [Formula: see text][Formula: see text] is presented. The results are based on a dataset corresponding to an integrated luminosity of 19.5 fb[Formula: see text] recorded with the CMS detector at the LHC. The measurement is performed in three leptonic (e and [Formula: see text]) channels: a same-sign dilepton analysis targeting [Formula: see text] events, and trilepton and four-lepton analyses designed for [Formula: see text] events. In the same-sign dilepton channel, the [Formula: see text] cross section is measured as [Formula: see text], corresponding to a significance of 1.6 standard deviations over the background-only hypothesis. Combining the trilepton and four-lepton channels, a direct measurement of the [Formula: see text] cross section, [Formula: see text], is obtained with a significance of 3.1 standard deviations. The measured cross sections are compatible with standard model predictions within their experimental uncertainties. The inclusive [Formula: see text] process is observed with a significance of 3.7 standard deviations from the combination of all three leptonic channels.
  8. Measurement of WZ and ZZ production in pp collisions at [Formula: see text] in final states with b-tagged jets
    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.
  9. Measurement of jet multiplicity distributions in [Formula: see text] production in pp collisions at [Formula: see text]
    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.
  10. Fulltext Measurements of production cross sections of the Higgs boson in the four-lepton final state in proton-proton collisions at s = 13 TeV
    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.
  11. Fulltext Search for direct pair production of supersymmetric partners to the τ lepton in proton-proton collisions at s = 13 TeV
    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.
  12. Measurement of differential cross sections for the production of a pair of isolated photons in pp collisions at [Formula: see text]
    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.
  13. Fulltext Search for heavy neutrinos and [Formula: see text] bosons with right-handed couplings in proton-proton collisions at [Formula: see text]
    CMS Collaboration, Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, et al.
    Eur Phys J C Part Fields, 2014;74(11):3149.
    PMID: 25814876 DOI: 10.1140/epjc/s10052-014-3149-z
    A search for heavy, right-handed neutrinos, [Formula: see text] ([Formula: see text]), and right-handed [Formula: see text] bosons, which arise in the left-right symmetric extensions of the standard model, has been performed by the CMS experiment. The search was based on a sample of two lepton plus two jet events collected in proton-proton collisions at a center-of-mass energy of 8[Formula: see text] corresponding to an integrated luminosity of 19.7 [Formula: see text]. For models with strict left-right symmetry, and assuming only one [Formula: see text] flavor contributes significantly to the [Formula: see text] decay width, the region in the two-dimensional [Formula: see text] mass plane excluded at a 95 % confidence level extends to approximately [Formula: see text] and covers a large range of neutrino masses below the [Formula: see text] boson mass, depending on the value of [Formula: see text]. This search significantly extends the [Formula: see text] exclusion region beyond previous results.
  14. Search for top squark and Higgsino production using diphoton Higgs boson decays
    Chatrchyan S, Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, et al.
    Phys Rev Lett, 2014 Apr 25;112(16):161802.
    PMID: 24815637
    Results are presented of a search for a "natural" supersymmetry scenario with gauge mediated symmetry breaking. It is assumed that only the supersymmetric partners of the top quark (the top squark) and the Higgs boson (Higgsino) are accessible. Events are examined in which there are two photons forming a Higgs boson candidate, and at least two b-quark jets. In 19.7  fb-1 of proton-proton collision data at s=8  TeV, recorded in the CMS experiment, no evidence of a signal is found and lower limits at the 95% confidence level are set, excluding the top squark mass below 360 to 410 GeV, depending on the Higgsino mass.
  15. Search for invisible decays of Higgs bosons in the vector boson fusion and associated ZH production modes
    Chatrchyan S, Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, et al.
    Eur Phys J C Part Fields, 2014;74(8):2980.
    PMID: 25814906
    A search for invisible decays of Higgs bosons is performed using the vector boson fusion and associated ZH production modes. In the ZH mode, the Z boson is required to decay to a pair of charged leptons or a [Formula: see text] quark pair. The searches use the 8 [Formula: see text] pp collision dataset collected by the CMS detector at the LHC, corresponding to an integrated luminosity of up to 19.7 [Formula: see text]. Certain channels include data from 7 [Formula: see text] collisions corresponding to an integrated luminosity of 4.9 [Formula: see text]. The searches are sensitive to non-standard-model invisible decays of the recently observed Higgs boson, as well as additional Higgs bosons with similar production modes and large invisible branching fractions. In all channels, the observed data are consistent with the expected standard model backgrounds. Limits are set on the production cross section times invisible branching fraction, as a function of the Higgs boson mass, for the vector boson fusion and ZH production modes. By combining all channels, and assuming standard model Higgs boson cross sections and acceptances, the observed (expected) upper limit on the invisible branching fraction at [Formula: see text] [Formula: see text] is found to be 0.58 (0.44) at 95 % confidence level. We interpret this limit in terms of a Higgs-portal model of dark matter interactions.
  16. Characteristics and outcomes of medically managed patients with non-ST-segment elevation acute coronary syndromes: Insights from the multinational EPICOR Asia study
    Chin CT, Ong TK, Krittayaphong R, Lee SW, Sawhney JPS, Kim HS, et al.
    Int J Cardiol, 2017 Sep 15;243:15-20.
    PMID: 28747021 DOI: 10.1016/j.ijcard.2017.04.059
    BACKGROUND: Many patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) are medically managed without coronary revascularization. The reasons vary and may impact prognosis.

    METHODS: EPICOR Asia (NCT01361386) is a prospective study of hospital survivors post-ACS enrolled in 218 hospitals from 8 countries/regions in Asia (06/2011-05/2012). All medically managed NSTE-ACS patients were classified into 3 groups: 1) no coronary angiography (CAG-); 2) non-significant coronary artery disease (CAD) on angiogram (CAG+ CAD-); and 3) significant CAD (CAG+ CAD+). We compared baseline differences between patients medically managed and patients undergoing revascularization, and also between the medically managed groups. Adverse events were reported and compared up to 2years.

    RESULTS: Of 6163 NSTE-ACS patients, 2272 (37%) were medically managed, with 1339 (59%), 254 (11%), and 679 (30%) in the CAG-, CAG+ CAD-, and CAG+ CAD+ groups, respectively. There were marked differences in the proportion of medically managed patients among the 8 countries/regions (13-81%). Medically managed patients had higher mortality at 2years compared with revascularization (8.7% vs. 3.0%, p<0.001). Among medically managed patients, CAG- patients were older, more likely to have pre-existing cardiovascular disease, and had the highest 2-year mortality (10.5% vs. 4.3% [CAG+ CAD-] and 6.6% [CAG+ CAD+], p<0.001). Mortality differences persisted after adjusting for other patient risk factors.

    CONCLUSIONS: Medically managed NSTE-ACS patients are a heterogeneous group with different risk stratification and variable prognosis. Identification of reasons underlying different management strategies, and key factors adversely influencing long-term prognosis, may improve outcomes.

  17. Clinical characteristics and outcomes of patients with mpox during the 2022 mpox outbreak compared with those before the outbreak: A systematic review and meta-analysis
    Cho W, Park S, Kim HJ, Lee M, Choi YS, Yeo SG, et al.
    Rev Med Virol, 2024 Jan;34(1):e2508.
    PMID: 38282393 DOI: 10.1002/rmv.2508
    On 23 July 2022, the World Health Organization declared the global mpox outbreak as a public health emergency of international significance. The mpox virus (MPXV) that caused the outbreak was classified as clade IIb, which belongs to the West African clade. However, the relationship between MPXV clades and symptoms, as well as the severity of mpox outcomes, is not fully understood. Thus, we aimed to investigate the global mpox prevalence and the differences in clinical manifestations and outcomes among patients with mpox between pre-outbreak (2003-2021) and the current mpox outbreak. In this systematic review and meta-analysis, PubMed/MEDLINE, Web of Science, Embase, Cumulative Index to Nursing and Allied Health Literature, and Google Scholar were searched using the keyword "monkeypox" and "mpox" up to 13 October 2022. A random effects model was used to obtain the pooled prevalence and 95% confidence intervals. This study included 27 articles, and 5698 patients with mpox with 19 distinctive features from 19 countries across five continents were assessed. Patients with mpox during the 2022 mpox outbreak showed mild clinical manifestations and outcomes compared with those before the 2022 mpox outbreak: mild rash (relative ratio [RR]: 5.09, 95% confidence interval [CI]: 1.52-17.08), fever (0.68, 0.49-0.94), pruritus (0.25, 0.19-0.32), myalgia (0.50, 0.31-0.81), headache (0.56, 0.35-0.88), skin ulcer (0.32, 0.17-0.59), abdominal symptom (0.29, 0.20-0.42), pharyngitis (0.32, 0.18-0.58), nausea or vomiting (0.15, 0.02-0.93), conjunctivitis (0.11, 0.03-0.38), concomitant infection with HIV (1.70, 0.95-3 0.04), and death (0.02, 0.001-0.31). MPXV clade IIb exhibited higher infectivity but may cause mild disease symptoms and low mortality rate. It is important to consider MPXV infection in patients with mpox-related features and/or a history of sexual transmission to prevent the spread of the disease and recognise the current pandemic threat.
  18. Fulltext Pharmaceutical care issues identified by pharmacists in patients with diabetes, hypertension or hyperlipidaemia in primary care settings
    Chua SS, Kok LC, Yusof FA, Tang GH, Lee SW, Efendie B, et al.
    BMC Health Serv Res, 2012;12:388.
    PMID: 23145922 DOI: 10.1186/1472-6963-12-388
    BACKGROUND: The roles of pharmacists have evolved from product oriented, dispensing of medications to more patient-focused services such as the provision of pharmaceutical care. Such pharmacy service is also becoming more widely practised in Malaysia but is not well documented. Therefore, this study is warranted to fill this information gap by identifying the types of pharmaceutical care issues (PCIs) encountered by primary care patients with diabetes mellitus, hypertension or hyperlipidaemia in Malaysia.
    METHODS: This study was part of a large controlled trial that evaluated the outcomes of multiprofessional collaboration which involved medical general practitioners, pharmacists, dietitians and nurses in managing diabetes mellitus, hypertension and hyperlipidaemia in primary care settings. A total of 477 patients were recruited by 44 general practitioners in the Klang Valley. These patients were counselled by the various healthcare professionals and followed-up for 6 months.
    RESULTS: Of the 477 participants, 53.7% had at least one PCI, with a total of 706 PCIs. These included drug-use problems (33.3%), insufficient awareness and knowledge about disease condition and medication (20.4%), adverse drug reactions (15.6%), therapeutic failure (13.9%), drug-choice problems (9.5%) and dosing problems (3.4%). Non-adherence to medications topped the list of drug-use problems, followed by incorrect administration of medications. More than half of the PCIs (52%) were classified as probably clinically insignificant, 38.9% with minimal clinical significance, 8.9% as definitely clinically significant and could cause patient harm while one issue (0.2%) was classified as life threatening. The main causes of PCIs were deterioration of disease state which led to failure of therapy, and also presentation of new symptoms or indications. Of the 338 PCIs where changes were recommended by the pharmacist, 87.3% were carried out as recommended.
    CONCLUSIONS: This study demonstrates the importance of pharmacists working in collaboration with other healthcare providers especially the medical doctors in identifying and resolving pharmaceutical care issues to provide optimal care for patients with chronic diseases.
    TRIAL REGISTRATION: ClinicalTrials.gov NCT00490672.
    Study name: Cardiovascular Risk Factors Intervention Strategies (CORFIS) trial
  19. Isoprenyl caffeate, a major compound in manuka propolis, is a quorum-sensing inhibitor in Chromobacterium violaceum
    Gemiarto AT, Ninyio NN, Lee SW, Logis J, Fatima A, Chan EW, et al.
    Antonie Van Leeuwenhoek, 2015 Aug;108(2):491-504.
    PMID: 26059863 DOI: 10.1007/s10482-015-0503-6
    The emergence of antibiotic-resistant bacterial pathogens, especially Gram-negative bacteria, has driven investigations into suppressing bacterial virulence via quorum sensing (QS) inhibition strategies instead of bactericidal and bacteriostatic approaches. Here, we investigated several bee products for potential compound(s) that exhibit significant QS inhibitory (QSI) properties at the phenotypic and molecular levels in Chromobacterium violaceum ATCC 12472 as a model organism. Manuka propolis produced the strongest violacein inhibition on C. violaceum lawn agar, while bee pollen had no detectable QSI activity and honey had bactericidal activity. Fractionated manuka propolis (pooled fraction 5 or PF5) exhibited the largest violacein inhibition zone (24.5 ± 2.5 mm) at 1 mg dry weight per disc. In C. violaceum liquid cultures, at least 450 µg/ml of manuka propolis PF5 completely inhibited violacein production. Gene expression studies of the vioABCDE operon, involved in violacein biosynthesis, showed significant (≥two-fold) down-regulation of vioA, vioD and vioE in response to manuka propolis PF5. A potential QSI compound identified in manuka propolis PF5 is a hydroxycinnamic acid-derivative, isoprenyl caffeate, with a [M-H] of 247. Complete violacein inhibition in C. violaceum liquid cultures was achieved with at least 50 µg/ml of commercial isoprenyl caffeate. In silico docking experiments suggest that isoprenyl caffeate may act as an inhibitor of the violacein biosynthetic pathway by acting as a competitor for the FAD-binding pockets of VioD and VioA. Further studies on these compounds are warranted toward the development of anti-pathogenic drugs as adjuvants to conventional antibiotic treatments, especially in antibiotic-resistant bacterial infections.
  20. Fulltext Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life Years for 29 Cancer Groups From 2010 to 2019: A Systematic Analysis for the Global Burden of Disease Study 2019
    Global Burden of Disease 2019 Cancer Collaboration, Kocarnik JM, Compton K, Dean FE, Fu W, Gaw BL, et al.
    JAMA Oncol, 2022 Mar 01;8(3):420-444.
    PMID: 34967848 DOI: 10.1001/jamaoncol.2021.6987
    IMPORTANCE: The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden.

    OBJECTIVE: To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019.

    EVIDENCE REVIEW: The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs).

    FINDINGS: In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3% (95% UI, 20.3%-32.3%) increase in new cases, a 20.9% (95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4% (1.1%-1.8%) in the low SDI quintile to 5.7% (4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and DALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles.

    CONCLUSIONS AND RELEVANCE: The results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world.

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