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  1. Drug Utilization Study On Indian Elderly Ambulatory Patients Using Who Prescribing Indicators
    Kashyap M, D Cruz S, Sachdev A, Tiwari P
    Value Health, 2015 Nov;18(7):A524.
    PMID: 26532939 DOI: 10.1016/j.jval.2015.09.1611
  2. Evidence-based information leads to reduction in inappropriate drug prescribing: Results from Indian older inpatients
    Kashyap M, D'Cruz S, Sachdev A, Tiwari P
    Int J Risk Saf Med, 2015;27(4):209-17.
    PMID: 26756894 DOI: 10.3233/JRS-150665
    Although several guidelines for appropriate prescribing are available, inappropriate drug prescription remains noteworthy problem among older adults. Indian older patients are also not spare from this issue and existing literature indicates a fair level of inappropriate drug use (IDU).
  3. Combination Therapy for the Treatment of Alzheimer's Disease: Recent Progress and Future Prospects
    Shirbhate E, Patel VK, Tiwari P, Kore R, Veerasamy R, Mishra A, et al.
    Curr Top Med Chem, 2022;22(22):1849-1867.
    PMID: 36082857 DOI: 10.2174/1568026622666220907114443
    BACKGROUND: The management of Alzheimer's disease is challenging due to its complexity. However, the currently approved and marketed treatments for this neurodegenerative disorder revolves around cholinesterase inhibitors, glutamate regulators, or the combination of these agents. Despite the prompt assurance of many new drugs, several agents were unsuccessful, especially in phase II or III trials, not meeting efficacy endpoints.

    OBJECTIVE: The execution of effective treatment approaches through further trials investigating a rational combination of agents is necessitude for Alzheimer's disease.

    METHODS: For this review, more than 248 relevant scientific papers were considered from a variety of databases (Scopus, Web of Science, Google Scholar, ScienceDirect, and PubMed) using the keywords Alzheimer's disease, amyloid-β, combination therapies, cholinesterase inhibitors, dementia, glutamate regulators, AD hypothesis.

    RESULT AND DISCUSSION: The researcher's intent is to either develop a disease-modifying therapeutic means for aiming in the early phases of dementia and/or optimize the available symptomatic treatments principally committed to the more advanced stages of Alzheimer's. Since Alzheimer's possesses multifactorial pathogenesis, designing a multimodal therapeutic intervention for targeting different pathological processes of dementia may appear to be the most practical method to alter the course of disease progression.

    CONCLUSION: The combination approach may even allow for providing individual agents in lower doses, with reducible costs and side effects. Numerous studies on combination therapy predicted better clinical efficacy than monotherapy. The literature review highlights the major clinical studies (both symptomatic and disease-modifying) conducted in the past decade on combination therapy to combat cognitive disorder.

  4. Multi-targeted HDAC Inhibitors as Anticancer Agents: Current Status and Future Prospective
    Patel VK, Shirbhate E, Tiwari P, Kore R, Veerasamy R, Mishra A, et al.
    Curr Med Chem, 2023;30(24):2762-2795.
    PMID: 36154583 DOI: 10.2174/0929867329666220922105615
    Multi-targeted agents can interact with multiple targets sequentially, resulting in synergistic and more effective therapies for several complicated disorders, including cancer, even with relatively modest activity. Histone deacetylase (HDAC) inhibitors are low molecular weight small compounds that increase the acetylation of histone and nonhistone proteins, altering gene expression and thereby impacting angiogenesis, metastasis, and apoptosis, among other processes. The HDAC inhibitors affect multiple cellular pathways thus producing adverse issues, causing therapeutic resistance, and they have poor pharmacokinetic properties. The designing of HDAC-based dual/multi-target inhibitor is an important strategy to overcome adverse effects, drug resistance and increase the effectiveness in controlling cancer. The selection of target combinations to design multitarget HDAC inhibitor is generally accomplished on the basis of systematic highthroughput screening (HTS), network pharmacology analysis methods. The identification of the pharmacophore against individual targets is performed using rational or computation methods. The identified pharmacophore can combine with merged, fused, or linked with the cleavable or non-cleavable linker to retain the interaction with the original target while being compatible with the other target. The objective of this review is to elucidate the potential targets' design strategies, biological activity, and the recent development of dual/multi-targeting HDAC inhibitors as potential anticancer agents. This review elucidates the designing strategies of the potential target along with biological activity and the recent development of dual/multi-targeting HDAC inhibitors as potential anticancer agents. The development of HDAC-based dual/multi-target inhibitors is important for overcoming side effects, drug resistance, and effective cancer control.
  5. Fulltext Development of chemically synthesized hydroxyapatite composite with reduced graphene oxide for enhanced mechanical properties
    Flora B, Kumar R, Tiwari P, Kumar A, Ruokolainen J, Narasimhan AK, et al.
    J Mech Behav Biomed Mater, 2023 Jun;142:105845.
    PMID: 37060714 DOI: 10.1016/j.jmbbm.2023.105845
    A successful attempt has been made to improve the mechanical properties of Hydroxyapatite (HAp) and reduced graphene oxide (rGO) composite nanoparticles (NPs). Various proportions of HAp and rGO were synthesized to improve the mechanical properties. HAp NPs were prepared using the wet precipitation method and further calcined to form crystalline particles. The physicochemical characterization of the HAp NPs revealed that the crystalline size and percentage of crystallinity were calculated to be 42.49 ± 1.2 nm and 44% post calcination. Furthermore, the rGO-HA composites were prepared using ball milling and obtained in the shape of pellets with different ratios of rGO (10, 20, 30, 40, 50% wt.). The mechanical properties have been evaluated through a Universal testing machine. Compared to calcined HAp (cHAp), the strength of variants significantly enhanced with the increased concentration of rGO. The compressive strength of HA-rGO with the ratio of the concentration of 60:40% by weight is a maximum of about 10.39 ± 0.43 MPa. However, the porosity has also been bolstered by increasing the concentration of rGO, which has been evaluated through the liquid displacement method. The mean surface roughness of the composites has also been evaluated from the images through Image J (an image analysis program).
  6. Fulltext Exploring the efficacy of 1-amino-cyclopropane-1-carboxylic acid (ACCA) as a natural compound in strengthening maize resistance against biotic and abiotic stressors: an empirical computational study
    Debnath S, Elgorban AM, Bahkali AH, Eswaramoorthy R, Verma M, Tiwari P, et al.
    Front Microbiol, 2023;14:1232086.
    PMID: 37637126 DOI: 10.3389/fmicb.2023.1232086
    OBJECTIVE: This study aims to understand plant-bacteria interactions that enhance plant resistance to environmental stressors, with a focus on maize (Zea mays L.) and its vulnerability to various pathogenic organisms. We examine the potential of 1-amino-cyclopropane-1-carboxylic acid (ACCA) as a compound to boost maize's resilience against stressors and pathogens.

    BACKGROUND: With the growing global population and increased food demand, the study of endophytes, comprising bacteria and fungi, becomes crucial. They reside within plant tissues, affecting their hosts either beneficially or detrimentally. Agrobacteria are of specific interest due to their potential to contribute to developing strategies for plant resistance enhancement.

    METHODS: We conducted exhaustive research on the defense-related proteins and mechanisms involved in maize-pathogen interactions. The efficacy of ACCA as a natural-compound that could enhance maize's resistance was examined.

    RESULTS: Our research indicates that ACCA, having a binding energy of -9.98 kcal/mol, successfully strengthens maize resistance against pathogenic assaults and drought stress. It plays a crucial protective role in maize plants as they mature, outperforming other ligands in its effectiveness to improve productivity and increase yield.

    CONCLUSION: Applying ACCA to maize plants has considerable potential in enhancing their resilience and tolerance to stress, proving to be an effective strategy to boost crop yield and productivity. This could help address the increasing global food demand. However, more research is needed to optimize ACCA application methods and to gain a comprehensive understanding of its long-term effects on maize cultivations and the environment.

  7. Studies of Charm Quark Diffusion inside Jets Using Pb-Pb and pp Collisions at sqrt[s_{NN}]=5.02  TeV
    Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Asilar E, Bergauer T, et al.
    Phys Rev Lett, 2020 Sep 04;125(10):102001.
    PMID: 32955327 DOI: 10.1103/PhysRevLett.125.102001
    The first study of charm quark diffusion with respect to the jet axis in heavy ion collisions is presented. The measurement is performed using jets with p_{T}^{jet}>60  GeV/c and D^{0} mesons with p_{T}^{D}>4  GeV/c in lead-lead (Pb-Pb) and proton-proton (pp) collisions at a nucleon-nucleon center-of-mass energy of sqrt[s_{NN}]=5.02  TeV, recorded by the CMS detector at the LHC. The radial distribution of D^{0} mesons with respect to the jet axis is sensitive to the production mechanisms of the meson, as well as to the energy loss and diffusion processes undergone by its parent parton inside the strongly interacting medium produced in Pb-Pb collisions. When compared to Monte Carlo event generators, the radial distribution in pp collisions is found to be well described by pythia, while the slope of the distribution predicted by sherpa is steeper than that of the data. In Pb-Pb collisions, compared to the pp results, the D^{0} meson distribution for 4
  8. Observation of the B_{s}^{0}→X(3872)ϕ Decay
    Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Bergauer T, Dragicevic M, et al.
    Phys Rev Lett, 2020 Oct 09;125(15):152001.
    PMID: 33095627 DOI: 10.1103/PhysRevLett.125.152001
    Using a data sample of proton-proton collisions at sqrt[s]=13  TeV, corresponding to an integrated luminosity of 140  fb^{-1} collected by the CMS experiment in 2016-2018, the B_{s}^{0}→X(3872)ϕ decay is observed. Decays into J/ψπ^{+}π^{-} and K^{+}K^{-} are used to reconstruct, respectively, the X(3872) and ϕ. The ratio of the product of branching fractions B[B_{s}^{0}→X(3872)ϕ]B[X(3872)→J/ψπ^{+}π^{-}] to the product B[B_{s}^{0}→ψ(2S)ϕ]B[ψ(2S)→J/ψπ^{+}π^{-}] is measured to be [2.21±0.29(stat)±0.17(syst)]%. The ratio B[B_{s}^{0}→X(3872)ϕ]/B[B^{0}→X(3872)K^{0}] is found to be consistent with one, while the ratio B[B_{s}^{0}→X(3872)ϕ]/B[B^{+}→X(3872)K^{+}] is two times smaller. This suggests a difference in the production dynamics of the X(3872) in B^{0} and B_{s}^{0} meson decays compared to B^{+}. The reported observation may shed new light on the nature of the X(3872) particle.
  9. Search for Leptoquarks Coupled to Third-Generation Quarks 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, 2018 Dec 14;121(24):241802.
    PMID: 30608761 DOI: 10.1103/PhysRevLett.121.241802
    Three of the most significant measured deviations from standard model predictions, the enhanced decay rate for B→D^{(*)}τν, hints of lepton universality violation in B→K^{(*)}ℓℓ decays, and the anomalous magnetic moment of the muon, can be explained by the existence of leptoquarks (LQs) with large couplings to third-generation quarks and masses at the TeV scale. The existence of these states can be probed at the LHC in high energy proton-proton collisions. A novel search is presented for pair production of LQs coupled to a top quark and a muon using data at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 35.9  fb^{-1}, recorded by the CMS experiment. No deviation from the standard model prediction has been observed and scalar LQs decaying exclusively into tμ are excluded up to masses of 1420 GeV. The results of this search are combined with those from previous searches for LQ decays into tτ and bν, which excluded scalar LQs below masses of 900 and 1080 GeV. Vector LQs are excluded up to masses of 1190 GeV for all possible combinations of branching fractions to tμ, tτ and bν. With this analysis, all relevant couplings of LQs with an electric charge of -1/3 to third-generation quarks are probed for the first time.
  10. Evidence for the Associated Production of a Single Top Quark and a Photon 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, 2018 Nov 30;121(22):221802.
    PMID: 30547617 DOI: 10.1103/PhysRevLett.121.221802
    The first evidence of events consistent with the production of a single top quark in association with a photon is reported. The analysis is based on proton-proton collisions at sqrt[s]=13  TeV and recorded by the CMS experiment in 2016, corresponding to an integrated luminosity of 35.9  fb^{-1}. Events are selected by requiring the presence of a muon (μ), a photon (γ), an imbalance in transverse momentum from an undetected neutrino (ν), and at least two jets (j) of which exactly one is identified as associated with the hadronization of a b quark. A multivariate discriminant based on topological and kinematic event properties is employed to separate signal from background processes. An excess above the background-only hypothesis is observed, with a significance of 4.4 standard deviations. A fiducial cross section is measured for isolated photons with transverse momentum greater than 25 GeV in the central region of the detector. The measured product of the cross section and branching fraction is σ(pp→tγj)B(t→μνb)=115±17(stat)±30(syst)  fb, which is consistent with the standard model prediction.
  11. Studies of Beauty Suppression via Nonprompt D^{0} Mesons in Pb-Pb Collisions at sqrt[s_{NN}]=5.02  TeV
    Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Asilar E, Bergauer T, et al.
    Phys Rev Lett, 2019 Jul 12;123(2):022001.
    PMID: 31386524 DOI: 10.1103/PhysRevLett.123.022001
    The transverse momentum spectra of D^{0} mesons from b hadron decays are measured at midrapidity (|y|<1) in pp and Pb-Pb collisions at a nucleon-nucleon center of mass energy of 5.02 TeV with the CMS detector at the LHC. The D^{0} mesons from b hadron decays are distinguished from prompt D^{0} mesons by their decay topologies. In Pb-Pb collisions, the B→D^{0} yield is found to be suppressed in the measured p_{T} range from 2 to 100  GeV/c as compared to pp collisions. The suppression is weaker than that of prompt D^{0} mesons and charged hadrons for p_{T} around 10  GeV/c. While theoretical calculations incorporating partonic energy loss in the quark-gluon plasma can successfully describe the measured B→D^{0} suppression at higher p_{T}, the data show an indication of larger suppression than the model predictions in the range of 2
  12. Observation of the Production of Three Massive Gauge Bosons at sqrt[s]=13  TeV
    Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Bergauer T, Dragicevic M, et al.
    Phys Rev Lett, 2020 Oct 09;125(15):151802.
    PMID: 33095594 DOI: 10.1103/PhysRevLett.125.151802
    The first observation is reported of the combined production of three massive gauge bosons (VVV with V=W, Z) in proton-proton collisions at a center-of-mass energy of 13 TeV. The analysis is based on a data sample recorded by the CMS experiment at the CERN LHC corresponding to an integrated luminosity of 137  fb^{-1}. The searches for individual WWW, WWZ, WZZ, and ZZZ production are performed in final states with three, four, five, and six leptons (electrons or muons), or with two same-sign leptons plus one or two jets. The observed (expected) significance of the combined VVV production signal is 5.7 (5.9) standard deviations and the corresponding measured cross section relative to the standard model prediction is 1.02_{-0.23}^{+0.26}. The significances of the individual WWW and WWZ production are 3.3 and 3.4 standard deviations, respectively. Measured production cross sections for the individual triboson processes are also reported.
  13. Evidence for Top Quark Production in Nucleus-Nucleus Collisions
    Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Bergauer T, Dragicevic M, et al.
    Phys Rev Lett, 2020 Nov 27;125(22):222001.
    PMID: 33315428 DOI: 10.1103/PhysRevLett.125.222001
    Ultrarelativistic heavy ion collisions recreate in the laboratory the thermodynamical conditions prevailing in the early universe up to 10^{-6}  sec, thereby allowing the study of the quark-gluon plasma (QGP), a state of quantum chromodynamics (QCD) matter with deconfined partons. The top quark, the heaviest elementary particle known, is accessible in nucleus-nucleus collisions at the CERN LHC, and constitutes a novel probe of the QGP. Here, we report the first evidence for the production of top quarks in nucleus-nucleus collisions, using lead-lead collision data at a nucleon-nucleon center-of-mass energy of 5.02 TeV recorded by the CMS experiment. Two methods are used to measure the cross section for top quark pair production (σ_{tt[over ¯]}) via the selection of charged leptons (electrons or muons) and bottom quarks. One method relies on the leptonic information alone, and the second one exploits, in addition, the presence of bottom quarks. The measured cross sections, σ_{tt[over ¯]}=2.54_{-0.74}^{+0.84} and 2.03_{-0.64}^{+0.71}  μb, respectively, are compatible with expectations from scaled proton-proton data and QCD predictions.
  14. 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.
  15. Jet Shapes of Isolated Photon-Tagged Jets in Pb-Pb and pp Collisions at sqrt[s_{NN}]=5.02  TeV
    Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Asilar E, Bergauer T, et al.
    Phys Rev Lett, 2019 Apr 19;122(15):152001.
    PMID: 31050516 DOI: 10.1103/PhysRevLett.122.152001
    The modification of jet shapes in Pb-Pb collisions, relative to those in pp collisions, is studied for jets associated with an isolated photon. The data were collected with the CMS detector at the LHC at a nucleon-nucleon center-of-mass energy of 5.02 TeV. Jet shapes are constructed from charged particles with track transverse momenta (p_{T}) above 1  GeV/c in annuli around the axes of jets with p_{T}^{jet}>30  GeV/c associated with an isolated photon with p_{T}^{γ}>60  GeV/c. The jet shape distributions are consistent between peripheral Pb-Pb and pp collisions, but are modified for more central Pb-Pb collisions. In these central Pb-Pb events, a larger fraction of the jet momentum is observed at larger distances from the jet axis compared to pp, reflecting the interaction between the partonic medium created in heavy ion collisions and the traversing partons.
  16. Search for W Boson Decays to Three Charged Pions
    Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Asilar E, Bergauer T, et al.
    Phys Rev Lett, 2019 Apr 19;122(15):151802.
    PMID: 31050519 DOI: 10.1103/PhysRevLett.122.151802
    For the first time, a search for the rare decay of the W boson to three charged pions has been performed. Proton-proton collision data recorded by the CMS experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 77.3  fb^{-1}, have been analyzed. No significant excess is observed above the background expectation. An upper limit of 1.01×10^{-6} is set at 95% confidence level on the branching fraction of the W boson to three charged pions. This provides a strong motivation for theoretical calculations of this branching fraction.
  17. Search for Narrow Hγ Resonances 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 01;122(8):081804.
    PMID: 30932612 DOI: 10.1103/PhysRevLett.122.081804
    A search for heavy, narrow resonances decaying to a Higgs boson and a photon (Hγ) has been performed in proton-proton collision data at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 35.9  fb^{-1} collected with the CMS detector at the LHC in 2016. Events containing a photon and a Lorentz-boosted hadronically decaying Higgs boson reconstructed as a single, large-radius jet are considered, and the γ+jet invariant mass spectrum is analyzed for the presence of narrow resonances. To increase the sensitivity of the search, events are categorized depending on whether or not the large-radius jet can be identified as a result of the merging of two jets originating from b quarks. Results in both categories are found to agree with the predictions of the standard model. Upper limits on the production rate of Hγ resonances are set as a function of their mass in the range of 720-3250 GeV, representing the most stringent constraints to date.
  18. Search for Dark Matter Particles Produced in Association with a Top Quark Pair at sqrt[s]=13  TeV
    Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Asilar E, Bergauer T, et al.
    Phys Rev Lett, 2019 Jan 11;122(1):011803.
    PMID: 31012697 DOI: 10.1103/PhysRevLett.122.011803
    A search is performed for dark matter particles produced in association with a top quark pair in proton-proton collisions at sqrt[s]=13  TeV. The data correspond to an integrated luminosity of 35.9  fb^{-1} recorded by the CMS detector at the LHC. No significant excess over the standard model expectation is observed. The results are interpreted using simplified models of dark matter production via spin-0 mediators that couple to dark matter particles and to standard model quarks, providing constraints on the coupling strength between the mediator and the quarks. These are the most stringent collider limits to date for scalar mediators, and the most stringent for pseudoscalar mediators at low masses.
  19. Observation of Two Excited B_{c}^{+} States and Measurement of the B_{c}^{+}(2S) Mass in pp Collisions at sqrt[s]=13  TeV
    Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Bergauer T, Brandstetter J, et al.
    Phys Rev Lett, 2019 Apr 05;122(13):132001.
    PMID: 31012626 DOI: 10.1103/PhysRevLett.122.132001
    Signals consistent with the B_{c}^{+}(2S) and B_{c}^{*+}(2S) states are observed in proton-proton collisions at sqrt[s]=13  TeV, in an event sample corresponding to an integrated luminosity of 143  fb^{-1}, collected by the CMS experiment during the 2015-2018 LHC running periods. These excited b[over ¯]c states are observed in the B_{c}^{+}π^{+}π^{-} invariant mass spectrum, with the ground state B_{c}^{+} reconstructed through its decay to J/ψπ^{+}. The two states are reconstructed as two well-resolved peaks, separated in mass by 29.1±1.5(stat)±0.7(syst)  MeV. The observation of two peaks, rather than one, is established with a significance exceeding five standard deviations. The mass of the B_{c}^{+}(2S) meson is measured to be 6871.0±1.2(stat)±0.8(syst)±0.8(B_{c}^{+})  MeV, where the last term corresponds to the uncertainty in the world-average B_{c}^{+} mass.
  20. Observation of Single Top Quark Production in Association with a Z Boson 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 Apr 05;122(13):132003.
    PMID: 31012605 DOI: 10.1103/PhysRevLett.122.132003
    The observation of single top quark production in association with a Z boson and a quark (tZq) is reported. Events from proton-proton collisions at a center-of-mass energy of 13 TeV containing three charged leptons (either electrons or muons) and at least two jets are analyzed. The data were collected with the CMS detector in 2016 and 2017 and correspond to an integrated luminosity of 77.4fb^{-1}. The increased integrated luminosity, a multivariate lepton identification, and a redesigned analysis strategy improve significantly the sensitivity of the analysis compared to previous searches for tZq production. The tZq signal is observed with a significance well over 5 standard deviations. The measured tZq production cross section is σ(pp→tZq→tℓ^{+}ℓ^{-}q)=111±13(stat)_{-9}^{+11}(syst)  fb, for dilepton invariant masses above 30 GeV, in agreement with the standard model expectation.
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