Displaying publications 1 - 20 of 190 in total

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  1. Fulltext 5' isomiR variation is of functional and evolutionary importance
    Tan GC, Chan E, Molnar A, Sarkar R, Alexieva D, Isa IM, et al.
    Nucleic Acids Res, 2014 Aug;42(14):9424-35.
    PMID: 25056318 DOI: 10.1093/nar/gku656
    We have sequenced miRNA libraries from human embryonic, neural and foetal mesenchymal stem cells. We report that the majority of miRNA genes encode mature isomers that vary in size by one or more bases at the 3' and/or 5' end of the miRNA. Northern blotting for individual miRNAs showed that the proportions of isomiRs expressed by a single miRNA gene often differ between cell and tissue types. IsomiRs were readily co-immunoprecipitated with Argonaute proteins in vivo and were active in luciferase assays, indicating that they are functional. Bioinformatics analysis predicts substantial differences in targeting between miRNAs with minor 5' differences and in support of this we report that a 5' isomiR-9-1 gained the ability to inhibit the expression of DNMT3B and NCAM2 but lost the ability to inhibit CDH1 in vitro. This result was confirmed by the use of isomiR-specific sponges. Our analysis of the miRGator database indicates that a small percentage of human miRNA genes express isomiRs as the dominant transcript in certain cell types and analysis of miRBase shows that 5' isomiRs have replaced canonical miRNAs many times during evolution. This strongly indicates that isomiRs are of functional importance and have contributed to the evolution of miRNA genes.
  2. Fulltext A Deep Neural Network for Simultaneous Estimation of b Jet Energy and Resolution
    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 ¯ .
  3. A collective statement in support of saving pangolins
    Choo SW, Chong JL, Gaubert P, Hughes AC, O'Brien S, Chaber AL, et al.
    Sci Total Environ, 2022 Feb 14.
    PMID: 35176378 DOI: 10.1016/j.scitotenv.2022.153666
  4. Fulltext A leadless intracardiac transcatheter pacing system
    Reynolds D, Duray GZ, Omar R, Soejima K, Neuzil P, Zhang S, et al.
    N Engl J Med, 2016 Feb 11;374(6):533-41.
    PMID: 26551877 DOI: 10.1056/NEJMoa1511643
    BACKGROUND: A leadless intracardiac transcatheter pacing system has been designed to avoid the need for a pacemaker pocket and transvenous lead.
    METHODS: In a prospective multicenter study without controls, a transcatheter pacemaker was implanted in patients who had guideline-based indications for ventricular pacing. The analysis of the primary end points began when 300 patients reached 6 months of follow-up. The primary safety end point was freedom from system-related or procedure-related major complications. The primary efficacy end point was the percentage of patients with low and stable pacing capture thresholds at 6 months (≤2.0 V at a pulse width of 0.24 msec and an increase of ≤1.5 V from the time of implantation). The safety and efficacy end points were evaluated against performance goals (based on historical data) of 83% and 80%, respectively. We also performed a post hoc analysis in which the rates of major complications were compared with those in a control cohort of 2667 patients with transvenous pacemakers from six previously published studies.
    RESULTS: The device was successfully implanted in 719 of 725 patients (99.2%). The Kaplan-Meier estimate of the rate of the primary safety end point was 96.0% (95% confidence interval [CI], 93.9 to 97.3; P<0.001 for the comparison with the safety performance goal of 83%); there were 28 major complications in 25 of 725 patients, and no dislodgements. The rate of the primary efficacy end point was 98.3% (95% CI, 96.1 to 99.5; P<0.001 for the comparison with the efficacy performance goal of 80%) among 292 of 297 patients with paired 6-month data. Although there were 28 major complications in 25 patients, patients with transcatheter pacemakers had significantly fewer major complications than did the control patients (hazard ratio, 0.49; 95% CI, 0.33 to 0.75; P=0.001).
    CONCLUSIONS: In this historical comparison study, the transcatheter pacemaker met the prespecified safety and efficacy goals; it had a safety profile similar to that of a transvenous system while providing low and stable pacing thresholds. (Funded by Medtronic; Micra Transcatheter Pacing Study ClinicalTrials.gov number, NCT02004873.).
  5. Fulltext A multi-dimensional search for new heavy resonances decaying to boosted W W , W Z , or Z Z boson pairs in the dijet final state at 13  Te
    Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Bergauer T, Brandstetter J, et al.
    Eur Phys J C Part Fields, 2020;80(3):237.
    PMID: 32215380 DOI: 10.1140/epjc/s10052-020-7773-5
    A search in an all-jet final state for new massive resonances decaying to W W , W Z , or Z Z boson pairs using a novel analysis method is presented. The analysis is performed on data corresponding to an integrated luminosity of 77.3 fb - 1 recorded with the CMS experiment at the LHC at a centre-of-mass energy of 13  Te . The search is focussed on potential narrow-width resonances with masses above 1.2  Te , where the decay products of each W or Z boson are expected to be collimated into a single, large-radius jet. The signal is extracted using a three-dimensional maximum likelihood fit of the two jet masses and the dijet invariant mass, yielding an improvement in sensitivity of up to 30% relative to previous search methods. No excess is observed above the estimated standard model background. In a heavy vector triplet model, spin-1 Z ' and W ' resonances with masses below 3.5 and 3.8   Te , respectively, are excluded at 95% confidence level. In a bulk graviton model, upper limits on cross sections are set between 27 and 0.2 fb for resonance masses between 1.2 and 5.2   Te , respectively. The limits presented in this paper are the best to date in the dijet final state.
  6. Fulltext Acceptance and Perception of Artificial Intelligence Usability in Eye Care (APPRAISE) for Ophthalmologists: A Multinational Perspective
    Gunasekeran DV, Zheng F, Lim GYS, Chong CCY, Zhang S, Ng WY, et al.
    Front Med (Lausanne), 2022;9:875242.
    PMID: 36314006 DOI: 10.3389/fmed.2022.875242
    BACKGROUND: Many artificial intelligence (AI) studies have focused on development of AI models, novel techniques, and reporting guidelines. However, little is understood about clinicians' perspectives of AI applications in medical fields including ophthalmology, particularly in light of recent regulatory guidelines. The aim for this study was to evaluate the perspectives of ophthalmologists regarding AI in 4 major eye conditions: diabetic retinopathy (DR), glaucoma, age-related macular degeneration (AMD) and cataract.

    METHODS: This was a multi-national survey of ophthalmologists between March 1st, 2020 to February 29th, 2021 disseminated via the major global ophthalmology societies. The survey was designed based on microsystem, mesosystem and macrosystem questions, and the software as a medical device (SaMD) regulatory framework chaired by the Food and Drug Administration (FDA). Factors associated with AI adoption for ophthalmology analyzed with multivariable logistic regression random forest machine learning.

    RESULTS: One thousand one hundred seventy-six ophthalmologists from 70 countries participated with a response rate ranging from 78.8 to 85.8% per question. Ophthalmologists were more willing to use AI as clinical assistive tools (88.1%, n = 890/1,010) especially those with over 20 years' experience (OR 3.70, 95% CI: 1.10-12.5, p = 0.035), as compared to clinical decision support tools (78.8%, n = 796/1,010) or diagnostic tools (64.5%, n = 651). A majority of Ophthalmologists felt that AI is most relevant to DR (78.2%), followed by glaucoma (70.7%), AMD (66.8%), and cataract (51.4%) detection. Many participants were confident their roles will not be replaced (68.2%, n = 632/927), and felt COVID-19 catalyzed willingness to adopt AI (80.9%, n = 750/927). Common barriers to implementation include medical liability from errors (72.5%, n = 672/927) whereas enablers include improving access (94.5%, n = 876/927). Machine learning modeling predicted acceptance from participant demographics with moderate to high accuracy, and area under the receiver operating curves of 0.63-0.83.

    CONCLUSION: Ophthalmologists are receptive to adopting AI as assistive tools for DR, glaucoma, and AMD. Furthermore, ML is a useful method that can be applied to evaluate predictive factors on clinical qualitative questionnaires. This study outlines actionable insights for future research and facilitation interventions to drive adoption and operationalization of AI tools for Ophthalmology.

  7. Antithrombotic management and long-term outcomes following percutaneous coronary intervention for acute coronary syndrome in Asia
    Zhang S, Wang W, Sawhney JPS, Krittayaphong R, Kim HS, Nhan VT, et al.
    Int J Cardiol, 2020 07 01;310:16-22.
    PMID: 32192746 DOI: 10.1016/j.ijcard.2020.01.008
    BACKGROUND: Cardiovascular diseases account for approximately half of all deaths in Asia. The present analysis aimed to evaluate characteristics, antithrombotic management patterns (AMPs), and outcomes in patients with acute coronary syndrome (ACS) who underwent in-hospital percutaneous coronary intervention (PCI) and survived to hospital discharge, using data from the EPICOR Asia registry (NCT01361386).

    METHODS: Two-year post-discharge follow-up data were analyzed from 8757 ACS PCI patients from EPICOR Asia (218 centers, eight countries). Major adverse cardiovascular events (MACE; death, non-fatal myocardial infarction [MI], non-fatal ischemic stroke), PCI characteristics, and AMPs were recorded. For MACE, time - to - event was analyzed using Cox regression.

    RESULTS: Primary PCI was performed in 62.0% of ST-segment elevation MI (STEMI), 38.7% of non-STEMI (NSTEMI), and 24.2% of unstable angina (UA) patients. At 12 months, 88.1% of patients were on dual antiplatelet therapy (DAPT), with no differences by index event. Most (61.5%) still received DAPT at 2 years. Two-year incidences of mortality, composite MACE, and bleeding were 3.6%, 6.2%, and 6.6%, respectively. Risk of death and MACE was increased with STEMI and NSTEMI vs. UA. Patients from East Asia showed lower mortality and more bleeding vs. Southeast Asia/India.

    CONCLUSIONS: Many patients in EPICOR Asia underwent PCI and received DAPT up to 2 years post-discharge. These real-world findings improve our understanding of AMP impact on outcomes in Asian patients with ACS undergoing PCI.

  8. Antitumour effect of odoroside A and its derivative on human leukaemia cells through the ROS/JNK pathway
    Hu X, Chen T, Zhang S, Zhang Q, Li C, Wang X
    Basic Clin Pharmacol Toxicol, 2022 Jan;130(1):56-69.
    PMID: 34634178 DOI: 10.1111/bcpt.13673
    Oleandrigenin-3-O-β-D-diginoside (a derivative of odoroside A), isolated and purified by our group, has seldom been explored for its pharmacological activity. This study aimed at clarifying the mechanisms towards the leukaemia-suppressive role of odoroside A (compound #1) and its derivative, oleandrigenin-3-O-β-D-diginoside (compound #2) isolated from Nerium oleander. Viability and nuclear morphology change were assessed by CCK-8 assay and fluorescence microscope, respectively. Then, the cell apoptosis and autophagy induced by the compounds were detected by flow cytometry and Western blot. Xenograft model of nude mice was also applied to measure the leukaemia-suppressive effects of compound #2 in vivo. The result displayed that compound #1 and compound #2 inhibited the proliferation of HL60 and K562 cells and stronger effects were found in HL60 than K562 cells. Both of the compounds induced a dose-dependent apoptosis and autophagy in HL60 cells, where compound #2 was more potent than compound #1. Compound #2 also demonstrated a time-dependent apoptosis and autophagy in HL60 cells. Furthermore, ROS generation and JNK phosphorylation occurred in a dose-dependent manner in the cells treated with compound #2. Mitochondria also played critical role, proved by the decrease of Bcl-2, the release of cyto c to cytosol and the activation of caspase-3 and caspase-9. Moreover, the antitumour effects of compound #2 were validated in the nude mouse xenograft model in vivo. Odoroside A and its derivative inhibited the growth of leukaemia by inducing apoptosis and autophagy through the activation of ROS/JNK pathway. These results suggest that the compounds can serve as potential antitumour agents against leukaemia, especially acute myeloid leukaemia (AML).
  9. Fulltext Application of Biochar Derived From Pyrolysis of Waste Fiberboard on Tetracycline Adsorption in Aqueous Solution
    Xu D, Gao Y, Lin Z, Gao W, Zhang H, Karnowo K, et al.
    Front Chem, 2019;7:943.
    PMID: 32117859 DOI: 10.3389/fchem.2019.00943
    In this study, biochars derived from waste fiberboard biomass were applied in tetracycline (TC) removal in aqueous solution. Biochar samples were prepared by slow pyrolysis at 300, 500, and 800°C, and were characterized by ultimate analysis, Fourier transform infrared (FTIR), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), Brunauer-Emmett-Teller (BET), etc. The effects of ionic strength (0-1.0 mol/L of NaCl), initial TC concentration (2.5-60 ppm), biochar dosage (1.5-2.5 g/L), and initial pH (2-10) were systemically determined. The results present that biochar prepared at 800°C (BC800) generally possesses the highest aromatization degree and surface area with abundant pyridinic N (N-6) and accordingly shows a better removal efficiency (68.6%) than the other two biochar samples. Adsorption isotherm data were better fitted by the Freundlich model (R2 is 0.94) than the Langmuir model (R2 is 0.85). Thermodynamic study showed that the adsorption process is endothermic and mainly physical in nature with the values of ΔH0 being 48.0 kJ/mol, ΔS0 being 157.1 J/mol/K, and ΔG0 varying from 1.02 to -2.14 kJ/mol. The graphite-like structure in biochar enables the π-π interactions with a ring structure in the TC molecule, which, together with the N-6 acting as electron donor, is the main driving force of the adsorption process.
  10. Fulltext Asian Sudden Cardiac Death in Heart Failure (ASIAN-HF) registry
    Lam CS, Anand I, Zhang S, Shimizu W, Narasimhan C, Park SW, et al.
    Eur J Heart Fail, 2013 Aug;15(8):928-36.
    PMID: 23568645 DOI: 10.1093/eurjhf/hft045
    Our aim is to determine mortality and morbidity in Asian patients under clinical management for heart failure (HF). Specifically, we will define the incidence of, and risk factors for, sudden cardiac death, as well as the socio-cultural factors influencing therapeutic choices in these patients. Methods This is a prospective observational multinational Asian registry of 5000 patients with symptomatic HF (stage C) and LV systolic dysfunction (EF ≤ 40%) involving 44 centres across 11 Asian regions (China, Hong Kong, India, Indonesia, Japan, Korea, Malaysia, Philippines, Singapore, Taiwan and Thailand). Data collection includes demographic variables, clinical symptoms, functional status, date of HF diagnosis and prior cardiovascular investigations, clinical risk factors, lifestyle factors, socio-economic status, and survey of cultural beliefs, health practices, and attitudes towards device therapy. Centre-level characteristics (case load, referral pattern, specialization, and infrastructure) are also obtained. Patients uniformly undergo standard 12-lead ECG and transthoracic echocardiography at baseline, and are followed over 3 years for outcomes of death or hospitalization. The mode of death and cause of hospitalization are adjudicated by a central event adjudication committee using pre-specified criteria. Perspective By providing prospective data regarding the demographics, risk factors, and outcomes of Asian patients under treatment for HF, the ASIAN-HF registry is expected to advance fundamental understanding of the burden and predictors of death and hospitalization among these patients. The knowledge gained will be important for guiding resource allocation and planning preventive strategies to address the unmet and growing clinical needs of patients with cardiovascular disease in Asia. Trial registration NCT01633398.
  11. Azimuthal Correlations within Exclusive Dijets with Large Momentum Transfer in Photon-Lead Collisions
    Tumasyan A, Adam W, Bergauer T, Dragicevic M, Del Valle AE, Frühwirth R, et al.
    Phys Rev Lett, 2023 Aug 04;131(5):051901.
    PMID: 37595238 DOI: 10.1103/PhysRevLett.131.051901
    The structure of nucleons is multidimensional and depends on the transverse momenta, spatial geometry, and polarization of the constituent partons. Such a structure can be studied using high-energy photons produced in ultraperipheral heavy-ion collisions. The first measurement of the azimuthal angular correlations of exclusively produced events with two jets in photon-lead interactions at large momentum transfer is presented, a process that is considered to be sensitive to the underlying nuclear gluon polarization. This study uses a data sample of ultraperipheral lead-lead collisions at sqrt[s_{NN}]=5.02  TeV, corresponding to an integrated luminosity of 0.38  nb^{-1}, collected with the CMS experiment at the LHC. The measured second harmonic of the correlation between the sum and difference of the two jet transverse momentum vectors is found to be positive, and rising, as the dijet transverse momentum increases. A well-tuned model that has been successful at describing a wide range of proton scattering data from the HERA experiments fails to describe the observed correlations, suggesting the presence of gluon polarization effects.
  12. Fulltext Azimuthal separation in nearly back-to-back jet topologies in inclusive 2- and 3-jet events in pp collisions at s = 13 Te
    Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Asilar E, Bergauer T, et al.
    Eur Phys J C Part Fields, 2019;79(9):773.
    PMID: 31713548 DOI: 10.1140/epjc/s10052-019-7276-4
    A measurement for inclusive 2- and 3-jet events of the azimuthal correlation between the two jets with the largest transverse momenta, Δ ϕ 12 , is presented. The measurement considers events where the two leading jets are nearly collinear ("back-to-back") in the transverse plane and is performed for several ranges of the leading jet transverse momentum. Proton-proton collision data collected with the CMS experiment at a center-of-mass energy of 13 Te and corresponding to an integrated luminosity of 35.9 fb - 1 are used. Predictions based on calculations using matrix elements at leading-order and next-to-leading-order accuracy in perturbative quantum chromodynamics supplemented with leading-log parton showers and hadronization are generally in agreement with the measurements. Discrepancies between the measurement and theoretical predictions are as large as 15%, mainly in the region 177 ∘ < Δ ϕ 12 < 180 ∘ . The 2- and 3-jet measurements are not simultaneously described by any of models.
  13. Fulltext Best practices for managing malodorous and infected wounds in advanced cervical cancer
    Hamid HA, Lin X, Qin YK, Akim AM, Zhang L, Wang J, et al.
    Int Wound J, 2024 Feb;21(2):e14574.
    PMID: 38379231 DOI: 10.1111/iwj.14574
    This cross-sectional study was conducted to examine the most effective strategies for managing malodorous and infected wounds in patients who have been diagnosed with advanced cervical cancer. The research was conducted in Liupanshui, China. The study specifically examined demographic profiles, wound characteristics and effectiveness of wound management approaches. The study incorporated the heterogeneous sample of 289 participants who fulfilled the inclusion criteria. Data collection was conducted via structured questionnaires and medical record evaluations. Descriptive statistics and statistical analyses, such as regression analysis, were utilized to evaluate demographic attributes, wound profiles and effects of different approaches to wound management. The findings unveiled the heterogeneous demographic composition of patients, encompassing differences in socioeconomic standing, educational attainment and age. A wide range of wound characteristics were observed, as 65.7% of lesions during the acute phase with diameter between 2 and 5 centimetres, while 41.5% of lesions had this range. The most prevalent types of infections were those caused by fungi (48.4%), followed by bacterial infections lacking resistance (38.1%). A moderate degree of odour intensity was prevalent, affecting 45.0% of the cases. With maximal odour reduction of 80%, a mean healing time of 25 days and patient satisfaction rating of 4.5 out of 5, Negative Pressure Wound Therapy demonstrated itself to be the most efficacious treatment method. Additional approaches, such as photodynamic therapy and topical antibiotic therapy, demonstrated significant effectiveness, as evidenced by odour reductions of 70% and 75%, respectively, and patient satisfaction ratings of 4.3 and 4.2. Thus, the study determined challenges associated with management of malodorous and infected lesions among patients with advanced cervical cancer. The results underscored the significance of individualized care approaches, drew attention to efficacious wound management techniques and identified critical determinants that impacted patient recuperation. The findings of this study hold potential for advancing palliative care for individuals diagnosed with advanced cervical cancer.
  14. Fulltext Binding of Duck Tembusu Virus Nonstructural Protein 2A to Duck STING Disrupts Induction of Its Signal Transduction Cascade To Inhibit Beta Interferon Induction
    Zhang W, Jiang B, Zeng M, Duan Y, Wu Z, Wu Y, et al.
    J Virol, 2020 04 16;94(9).
    PMID: 32075929 DOI: 10.1128/JVI.01850-19
    Duck Tembusu virus (DTMUV), which is similar to other mosquito-borne flaviviruses that replicate well in most mammalian cells, is an emerging pathogenic flavivirus that has caused epidemics in egg-laying and breeding waterfowl. Immune organ defects and neurological dysfunction are the main clinical symptoms of DTMUV infection. Preinfection with DTMUV makes the virus impervious to later interferon (IFN) treatment, revealing that DTMUV has evolved some strategies to defend against host IFN-dependent antiviral responses. Immune inhibition was further confirmed by screening for DTMUV-encoded proteins, which suggested that NS2A significantly inhibited IFN-β and IFN-stimulated response element (ISRE) promoter activity in a dose-dependent manner and facilitated reinfection with duck plague virus (DPV). DTMUV NS2A was able to inhibit duck retinoic acid-inducible gene-I (RIG-I)-, and melanoma differentiation-associated gene 5 (MDA5)-, mitochondrial-localized adaptor molecules (MAVS)-, stimulator of interferon genes (STING)-, and TANK-binding kinase 1 (TBK1)-induced IFN-β transcription, but not duck TBK1- and interferon regulatory factor 7 (IRF7)-mediated effective phases of IFN response. Furthermore, we found that NS2A competed with duTBK1 in binding to duck STING (duSTING), impaired duSTING-duSTING binding, and reduced duTBK1 phosphorylation, leading to the subsequent inhibition of IFN production. Importantly, we first identified that the W164A, Y167A, and S361A mutations in duSTING significantly impaired the NS2A-duSTING interaction, which is important for NS2A-induced IFN-β inhibition. Hence, our data demonstrated that DTMUV NS2A disrupts duSTING-dependent antiviral cellular defenses by binding with duSTING, which provides a novel mechanism by which DTMUV subverts host innate immune responses. The potential interaction sites between NS2A and duSTING may be the targets of future novel antiviral therapies and vaccine development.IMPORTANCE Flavivirus infections are transmitted through mosquitos or ticks and lead to significant morbidity and mortality worldwide with a spectrum of manifestations. Infection with an emerging flavivirus, DTMUV, manifests with clinical symptoms that include lesions of the immune organs and neurological dysfunction, leading to heavy egg drop and causing serious harm to the duck industry in China, Thailand, Malaysia, and other Southeast Asian countries. Mosquito cells, bird cells, and mammalian cell lines are all susceptible to DTMUV infection. An in vivo study revealed that BALB/c mice and Kunming mice were susceptible to DTMUV after intracerebral inoculation. Moreover, there are no reports about DTMUV-related human disease, but antibodies against DTMUV and viral RNA were detected in serum samples of duck industry workers. This information implies that DTMUV has expanded its host range and may pose a threat to mammalian health. However, the pathogenesis of DTMUV is largely unclear. Our results show that NS2A strongly blocks the STING-induced signal transduction cascade by binding with STING, which subsequently blocks STING-STING binding and TBK1 phosphorylation. More importantly, the W164, Y167, or S361 residues in duSTING were identified as important interaction sites between STING and NS2A that are vital for NS2A-induced IFN production and effective phases of IFN response. Uncovering the mechanism by which DTMUV NS2A inhibits IFN in the cells of its natural hosts, ducks, will help us understand the role of NS2A in DTMUV pathogenicity.
  15. Fulltext Cardiovascular risk and events in 17 low-, middle-, and high-income countries
    Yusuf S, Rangarajan S, Teo K, Islam S, Li W, Liu L, et al.
    N Engl J Med, 2014 08 28;371(9):818-27.
    PMID: 25162888 DOI: 10.1056/NEJMoa1311890
    BACKGROUND: More than 80% of deaths from cardiovascular disease are estimated to occur in low-income and middle-income countries, but the reasons are unknown.
    METHODS: We enrolled 156,424 persons from 628 urban and rural communities in 17 countries (3 high-income, 10 middle-income, and 4 low-income countries) and assessed their cardiovascular risk using the INTERHEART Risk Score, a validated score for quantifying risk-factor burden without the use of laboratory testing (with higher scores indicating greater risk-factor burden). Participants were followed for incident cardiovascular disease and death for a mean of 4.1 years.
    RESULTS: The mean INTERHEART Risk Score was highest in high-income countries, intermediate in middle-income countries, and lowest in low-income countries (P<0.001). However, the rates of major cardiovascular events (death from cardiovascular causes, myocardial infarction, stroke, or heart failure) were lower in high-income countries than in middle- and low-income countries (3.99 events per 1000 person-years vs. 5.38 and 6.43 events per 1000 person-years, respectively; P<0.001). Case fatality rates were also lowest in high-income countries (6.5%, 15.9%, and 17.3% in high-, middle-, and low-income countries, respectively; P=0.01). Urban communities had a higher risk-factor burden than rural communities but lower rates of cardiovascular events (4.83 vs. 6.25 events per 1000 person-years, P<0.001) and case fatality rates (13.52% vs. 17.25%, P<0.001). The use of preventive medications and revascularization procedures was significantly more common in high-income countries than in middle- or low-income countries (P<0.001).
    CONCLUSIONS: Although the risk-factor burden was lowest in low-income countries, the rates of major cardiovascular disease and death were substantially higher in low-income countries than in high-income countries. The high burden of risk factors in high-income countries may have been mitigated by better control of risk factors and more frequent use of proven pharmacologic therapies and revascularization. (Funded by the Population Health Research Institute and others.).
    Note: Malaysia is a study site (Author: Yusoff K)
  16. Characteristics and mechanisms of phosphorous adsorption by rape straw-derived biochar functionalized with calcium from eggshell
    Cao H, Wu X, Syed-Hassan SSA, Zhang S, Mood SH, Milan YJ, et al.
    Bioresour Technol, 2020 Dec;318:124063.
    PMID: 32905948 DOI: 10.1016/j.biortech.2020.124063
    Biochar modified with calcium source is acted as an effective adsorbent for phosphorous recovery. In this research, eggshell is used as a low-cost and environmentally friendly calcium source to replace chemical reagents such as CaCO3, Ca(OH)2 and CaCl2 used in the modified biochar production. Biochar derived from rape straw and modified with eggshell shows prominent phosphorous adsorption performance (e.g., equilibrium adsorption amount, 109.7 mg/g). The kinetic and isotherm analysis demonstrate that chemical adsorption process is performed as the main controlled step for the modified biochar adsorption, and the phosphate adsorption process is composed of both monolayer adsorption and multi-layer adsorption. Moreover, it is found from the physicochemical structures comparison before and after phosphate adsorption that Ca-P precipitation, hydrogen bonding and electrostatic attraction are identified as main adsorption mechanisms. In addition, the adsorbed phosphates are mainly distributed inside the space with pore sizes of 15-50 nm.
  17. Chemotherapy impairs ovarian function through excessive ROS-induced ferroptosis
    Zhang S, Liu Q, Chang M, Pan Y, Yahaya BH, Liu Y, et al.
    Cell Death Dis, 2023 May 24;14(5):340.
    PMID: 37225709 DOI: 10.1038/s41419-023-05859-0
    Chemotherapy was conventionally applied to kill cancer cells, but regrettably, they also induce damage to normal cells with high-proliferative capacity resulting in cardiotoxicity, nephrotoxicity, peripheral nerve toxicity, and ovarian toxicity. Of these, chemotherapy-induced ovarian damages mainly include but are not limited to decreased ovarian reserve, infertility, and ovarian atrophy. Therefore, exploring the underlying mechanism of chemotherapeutic drug-induced ovarian damage will pave the way to develop fertility-protective adjuvants for female patients during conventional cancer treatment. Herein, we firstly confirmed the abnormal gonadal hormone levels in patients who received chemotherapy and further found that conventional chemotherapeutic drugs (cyclophosphamide, CTX; paclitaxel, Tax; doxorubicin, Dox and cisplatin, Cis) treatment significantly decreased both the ovarian volume of mice and the number of primordial and antral follicles and accompanied with the ovarian fibrosis and reduced ovarian reserve in animal models. Subsequently, Tax, Dox, and Cis treatment can induce the apoptosis of ovarian granulosa cells (GCs), likely resulting from excessive reactive oxygen species (ROS) production-induced oxidative damage and impaired cellular anti-oxidative capacity. Thirdly, the following experiments demonstrated that Cis treatment could induce mitochondrial dysfunction through overproducing superoxide in GCs and trigger lipid peroxidation leading to ferroptosis, first reported in chemotherapy-induced ovarian damage. In addition, N-acetylcysteine (NAC) treatment could alleviate the Cis-induced toxicity in GCs by downregulating cellular ROS levels and enhancing the anti-oxidative capacity (promoting the expression of glutathione peroxidase, GPX4; nuclear factor erythroid 2-related factor 2, Nrf2 and heme oxygenase-1, HO-1). Our study confirmed the chemotherapy-induced chaotic hormonal state and ovarian damage in preclinical and clinical examination and indicated that chemotherapeutic drugs initiated ferroptosis in ovarian cells through excessive ROS-induced lipid peroxidation and mitochondrial dysfunction, leading to ovarian cell death. Consequently, developing fertility protectants from the chemotherapy-induced oxidative stress and ferroptosis perspective will ameliorate ovarian damage and further improve the life quality of cancer patients.
  18. Combination of Searches for Higgs Boson Pair Production in Proton-Proton Collisions at sqrt[s]=13  TeV
    Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Asilar E, Bergauer T, et al.
    Phys Rev Lett, 2019 Mar 29;122(12):121803.
    PMID: 30978057 DOI: 10.1103/PhysRevLett.122.121803
    This Letter describes a search for Higgs boson pair production using the combined results from four final states: bbγγ, bbττ, bbbb, and bbVV, where V represents a W or Z boson. The search is performed using data collected in 2016 by the CMS experiment from LHC proton-proton collisions at sqrt[s]=13  TeV, corresponding to an integrated luminosity of 35.9  fb^{-1}. Limits are set on the Higgs boson pair production cross section. A 95% confidence level observed (expected) upper limit on the nonresonant production cross section is set at 22.2 (12.8) times the standard model value. A search for narrow resonances decaying to Higgs boson pairs is also performed in the mass range 250-3000 GeV. No evidence for a signal is observed, and upper limits are set on the resonance production cross section.
  19. Fulltext Combined measurements of Higgs boson couplings in proton-proton collisions at s = 13 Te
    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.
  20. Fulltext Combined searches for the production of supersymmetric top quark partners in proton-proton collisions at s = 13 Te
    Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, Chatterjee S, Dragicevic M, et al.
    Eur Phys J C Part Fields, 2021;81(11):970.
    PMID: 34793584 DOI: 10.1140/epjc/s10052-021-09721-5
    A combination of searches for top squark pair production using proton-proton collision data at a center-of-mass energy of 13 Te at the CERN LHC, corresponding to an integrated luminosity of 137 fb - 1 collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on the model, the combined result excludes a top squark mass up to 1325 Ge for a massless neutralino, and a neutralino mass up to 700 Ge for a top squark mass of 1150 Ge . Top squarks with masses from 145 to 295 Ge , for neutralino masses from 0 to 100 Ge , with a mass difference between the top squark and the neutralino in a window of 30 Ge around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420 Ge .
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