Displaying publications 1 - 20 of 51 in total

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  1. Kong D, Abdul Halim S
    Cureus, 2023 Dec;15(12):e51420.
    PMID: 38299130 DOI: 10.7759/cureus.51420
    A 29-year-old female, with giant congenital melanocytic naevi (GCMN) presented with a-year history of symptoms and signs of intracranial hypertension. Investigations revealed raised cerebrospinal fluid (CSF) pressure and severe hypoglycorrhachia (low CSF glucose) without pleocytosis. Initial contrast-enhanced brain MRI was normal, but a repeat MRI after a year showed meningeal enhancement with mild communicating hydrocephalus. The raised intracranial pressure was treated with a lumbar-peritoneal shunt. Intraoperative CSF cytology revealed an abundance of squamous epithelia and degenerative cells, but no malignant cells. Her symptoms recovered with CSF diversion via shunt placement, but the hypoglycorrhachia remained. This case highlights the rare occurrence of a non-inflammatory cause of both intracranial hypertension and severe hypoglycorrhachia in a GCMN adult patient, with progressive radiological changes over time, consistent with a diagnosis of neurocutaneous melanosis.
  2. Jagadeeshan S, Prasad M, Badarni M, Ben-Lulu T, Liju VB, Mathukkada S, et al.
    Cancer Res, 2023 Apr 04;83(7):1031-1047.
    PMID: 36753744 DOI: 10.1158/0008-5472.CAN-22-2586
    The survival rate for patients with head and neck cancer (HNC) diagnosed with cervical lymph node (cLN) or distant metastasis is low. Genomic alterations in the HRAS oncogene are associated with advanced tumor stage and metastasis in HNC. Elucidation of the molecular mechanisms by which mutated HRAS (HRASmut) facilitates HNC metastasis could lead to improved treatment options for patients. Here, we examined metastasis driven by mutant HRAS in vitro and in vivo using HRASmut human HNC cell lines, patient-derived xenografts, and a novel HRASmut syngeneic model. Genetic and pharmacological manipulations indicated that HRASmut was sufficient to drive invasion in vitro and metastasis in vivo. Targeted proteomic analysis showed that HRASmut promoted AXL expression via suppressing the Hippo pathway and stabilizing YAP1 activity. Pharmacological blockade of HRAS signaling with the farnesyltransferase inhibitor tipifarnib activated the Hippo pathway and reduced the nuclear export of YAP1, thus suppressing YAP1-mediated AXL expression and metastasis. AXL was required for HRASmut cells to migrate and invade in vitro and to form regional cLN and lung metastases in vivo. In addition, AXL-depleted HRASmut tumors displayed reduced lymphatic and vascular angiogenesis in the primary tumor. Tipifarnib treatment also regulated AXL expression and attenuated VEGFA and VEGFC expression, thus regulating tumor-induced vascular formation and metastasis. Our results indicate that YAP1 and AXL are crucial factors for HRASmut-induced metastasis and that tipifarnib treatment can limit the metastasis of HNC tumors with HRAS mutations by enhancing YAP1 cytoplasmic sequestration and downregulating AXL expression.

    SIGNIFICANCE: Mutant HRAS drives metastasis of head and neck cancer by switching off the Hippo pathway to activate the YAP1-AXL axis and to stimulate lymphovascular angiogenesis.

  3. Zeimaran E, Pourshahrestani S, Kadri NA, Kong D, Shirazi SFS, Naveen SV, et al.
    Macromol Biosci, 2019 Oct;19(10):e1900176.
    PMID: 31441595 DOI: 10.1002/mabi.201900176
    Stretchable self-healing urethane-based biomaterials have always been crucial for biomedical applications; however, the strength is the main constraint of utilization of these healable materials. Here, a series of novel, healable, elastomeric, supramolecular polyester urethane nanocomposites of poly(1,8-octanediol citrate) and hexamethylene diisocyanate reinforced with cellulose nanocrystals (CNCs) are introduced. Nanocomposites with various amounts of CNCs from 10 to 50 wt% are prepared using solvent casting technique followed by the evaluation of their microstructural features, mechanical properties, healability, and biocompatibility. The synthesized nanocomposites indicate significantly higher tensile modulus (approximately 36-500-fold) in comparison to the supramolecular polymer alone. Upon exposure to heat, the materials can reheal, but nevertheless when the amount of CNC is greater than 10 wt%, the self-healing ability of nanocomposites is deteriorated. These materials are capable of rebonding ruptured parts and fully restoring their mechanical properties. In vitro cytotoxicity test of the nanocomposites using human dermal fibroblasts confirms their good cytocompatibility. The optimized structure, self-healing attributes, and noncytotoxicity make these nanocomposites highly promising for tissue engineering and other biomedical applications.
  4. Neoh CF, Senol E, Kara A, Dinleyici EC, Turner SJ, Kong DCM
    Eur J Clin Microbiol Infect Dis, 2018 Mar;37(3):537-544.
    PMID: 29185089 DOI: 10.1007/s10096-017-3147-9
    Micafungin was shown to be as efficacious as caspofungin in treating patients with candidaemia and invasive candidiasis (IC). However, it remains unknown if micafungin or caspofungin is a cost-effective definitive therapy for candidaemia and IC in Turkey. The present study aimed to determine the economic impact of using micafungin versus caspofungin for treatment of candidaemia and IC in the Turkish setting. A decision analytic model was constructed and was populated with data (i.e. transition probabilities, duration of initial antifungal treatment, reasons for treatment failure, percentage of patients who stepped down to oral fluconazole, and duration on oral fluconazole) obtained from a published randomised clinical trial. Cost inputs were derived from the latest Turkish resources while data that were not readily available in the literature were estimated by expert panels. One-way sensitivity analyses, threshold analyses, scenario analyses and probabilistic sensitivity analyses were conducted. Caspofungin (€2693) incurred a lower total cost than micafungin (€4422), with a net cost saving of €1729 per treated patient. Drug acquisition cost was the main cost driver for both study arms. The model outcome was robust over wide variations (of ±100.0% from the base case value) for all input parameters except for micafungin drug cost and the duration of initial treatment with micafungin. Caspofungin appears to be a cost-saving option in treating candidaemia and IC from the Turkish hospital perspective.
  5. Wu DBC, Chaiyakunapruk N, Pratoomsoot C, Lee KKC, Chong HY, Nelson RE, et al.
    Epidemiol Infect, 2018 03;146(4):496-507.
    PMID: 29446343 DOI: 10.1017/S0950268818000158
    Simulation models are used widely in pharmacology, epidemiology and health economics (HEs). However, there have been no attempts to incorporate models from these disciplines into a single integrated model. Accordingly, we explored this linkage to evaluate the epidemiological and economic impact of oseltamivir dose optimisation in supporting pandemic influenza planning in the USA. An HE decision analytic model was linked to a pharmacokinetic/pharmacodynamics (PK/PD) - dynamic transmission model simulating the impact of pandemic influenza with low virulence and low transmissibility and, high virulence and high transmissibility. The cost-utility analysis was from the payer and societal perspectives, comparing oseltamivir 75 and 150 mg twice daily (BID) to no treatment over a 1-year time horizon. Model parameters were derived from published studies. Outcomes were measured as cost per quality-adjusted life year (QALY) gained. Sensitivity analyses were performed to examine the integrated model's robustness. Under both pandemic scenarios, compared to no treatment, the use of oseltamivir 75 or 150 mg BID led to a significant reduction of influenza episodes and influenza-related deaths, translating to substantial savings of QALYs. Overall drug costs were offset by the reduction of both direct and indirect costs, making these two interventions cost-saving from both perspectives. The results were sensitive to the proportion of inpatient presentation at the emergency visit and patients' quality of life. Integrating PK/PD-EPI/HE models is achievable. Whilst further refinement of this novel linkage model to more closely mimic the reality is needed, the current study has generated useful insights to support influenza pandemic planning.
  6. Zeimaran E, Pourshahrestani S, Pingguan-Murphy B, Kong D, Naveen SV, Kamarul T, et al.
    Carbohydr Polym, 2017 Nov 01;175:618-627.
    PMID: 28917909 DOI: 10.1016/j.carbpol.2017.08.038
    Blends of poly (1, 8-octanediol citrate) (POC) and chitosan (CS) were prepared through solution casting technique. Films with different component fractions (POC/CS: 100/0, 90/10, 80/20, 70/30, 60/40, and 0/100) were successfully prepared and characterized for their mechanical, thermal, structural and morphological properties as well as biocompatibility. The incorporation of CS to POC significantly increased tensile strength and elastic modulus and presented limited influences on pH variation which is important to the biocompatibility of biomaterial implants. The assessment of surface topography indicated that blending could enhance and control the surface roughness of the pure films. POC/CS blends well-supported human dermal fibroblast cells attachment and proliferation, and thus can be used for a range of tissue engineering applications.
  7. Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, et al.
    Eur Phys J C Part Fields, 2017;77(11):751.
    PMID: 31999282 DOI: 10.1140/epjc/s10052-017-5140-y
    Measurements of the associated production of a
    Z
    boson with at least one jet originating from a b quark in proton-proton collisions at


    s

    =
    8

    TeV

    are presented. Differential cross sections are measured with data collected by the CMS experiment corresponding to an integrated luminosity of 19.8



    fb

    -
    1



    .
    Z
    bosons are reconstructed through their decays to electrons and muons. Cross sections are measured as a function of observables characterizing the kinematics of the
    b
    jet and the
    Z
    boson. Ratios of differential cross sections for the associated production with at least one
    b
    jet to the associated production with any jet are also presented. The production of a
    Z
    boson with at least two
    b
    jets is investigated, and differential cross sections are measured for the dijet system. Results are compared to theoretical predictions, testing two different flavour schemes for the choice of initial-state partons.
  8. Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, et al.
    Eur Phys J C Part Fields, 2017;77(1):15.
    PMID: 28260978 DOI: 10.1140/epjc/s10052-016-4504-z
    A measurement of the top quark pair production ([Formula: see text]) cross section in proton-proton collisions at the centre-of-mass energy of 8[Formula: see text] is presented using data collected with the CMS detector at the LHC, corresponding to an integrated luminosity of 19.6[Formula: see text]. This analysis is performed in the [Formula: see text] decay channels with one isolated, high transverse momentum electron or muon and at least four jets, at least one of which is required to be identified as originating from hadronization of a b quark. The calibration of the jet energy scale and the efficiency of b jet identification are determined from data. The measured [Formula: see text] cross section is [Formula: see text]. This measurement is compared with an analysis of 7[Formula: see text] data, corresponding to an integrated luminosity of 5.0[Formula: see text], to determine the ratio of 8[Formula: see text] to 7[Formula: see text] cross sections, which is found to be [Formula: see text]. The measurements are in agreement with QCD predictions up to next-to-next-to-leading order.
  9. Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, et al.
    Phys Rev Lett, 2016 Apr 29;116(17):172302.
    PMID: 27176516 DOI: 10.1103/PhysRevLett.116.172302
    Results on two-particle angular correlations for charged particles produced in pp collisions at a center-of-mass energy of 13 TeV are presented. The data were taken with the CMS detector at the LHC and correspond to an integrated luminosity of about 270  nb^{-1}. The correlations are studied over a broad range of pseudorapidity (|η|<2.4) and over the full azimuth (ϕ) as a function of charged particle multiplicity and transverse momentum (p_{T}). In high-multiplicity events, a long-range (|Δη|>2.0), near-side (Δϕ≈0) structure emerges in the two-particle Δη-Δϕ correlation functions. The magnitude of the correlation exhibits a pronounced maximum in the range 1.0
  10. Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, et al.
    Eur Phys J C Part Fields, 2016 03 17;76:155.
    PMID: 27471433
    New sets of parameters ("tunes") for the underlying-event (UE) modelling of the pythia8, pythia6 and herwig++ Monte Carlo event generators are constructed using different parton distribution functions. Combined fits to CMS UE proton-proton ([Formula: see text]) data at [Formula: see text] and to UE proton-antiproton ([Formula: see text]) data from the CDF experiment at lower [Formula: see text], are used to study the UE models and constrain their parameters, providing thereby improved predictions for proton-proton collisions at 13[Formula: see text]. In addition, it is investigated whether the values of the parameters obtained from fits to UE observables are consistent with the values determined from fitting observables sensitive to double-parton scattering processes. Finally, comparisons are presented of the UE tunes to "minimum bias" (MB) events, multijet, and Drell-Yan ([Formula: see text] lepton-antilepton+jets) observables at 7 and 8[Formula: see text], as well as predictions for MB and UE observables at 13[Formula: see text].
  11. Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, et al.
    Eur Phys J C Part Fields, 2016 03 08;76:128.
    PMID: 27471431
    The cross section for [Formula: see text] production in the all-jets final state is measured in pp collisions at a centre-of-mass energy of 8 [Formula: see text] at the LHC with the CMS detector, in data corresponding to an integrated luminosity of 18.4 [Formula: see text]. The inclusive cross section is found to be [Formula: see text] [Formula: see text]. The normalized differential cross sections are measured as a function of the top quark transverse momenta, [Formula: see text], and compared to predictions from quantum chromodynamics. The results are reported at detector, parton, and particle levels. In all cases, the measured top quark [Formula: see text] spectra are significantly softer than theoretical predictions.
  12. Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, et al.
    Phys Rev Lett, 2016 Feb 19;116(7):071801.
    PMID: 26943527 DOI: 10.1103/PhysRevLett.116.071801
    A search for narrow resonances in proton-proton collisions at sqrt[s]=13  TeV is presented. The invariant mass distribution of the two leading jets is measured with the CMS detector using a data set corresponding to an integrated luminosity of 2.4  fb^{-1}. The highest observed dijet mass is 6.1 TeV. The distribution is smooth and no evidence for resonant particles is observed. Upper limits at 95% confidence level are set on the production cross section for narrow resonances with masses above 1.5 TeV. When interpreted in the context of specific models, the limits exclude string resonances with masses below 7.0 TeV, scalar diquarks below 6.0 TeV, axigluons and colorons below 5.1 TeV, excited quarks below 5.0 TeV, color-octet scalars below 3.1 TeV, and W^{'} bosons below 2.6 TeV. These results significantly extend previously published limits.
  13. Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, et al.
    Phys Rev Lett, 2016 Jan 22;116(3):032301.
    PMID: 26849587 DOI: 10.1103/PhysRevLett.116.032301
    The production cross sections of the B^{+}, B^{0}, and B_{s}^{0} mesons, and of their charge conjugates, are measured via exclusive hadronic decays in p+Pb collisions at the center-of-mass energy sqrt[s_{NN}]=5.02  TeV with the CMS detector at the CERN LHC. The data set used for this analysis corresponds to an integrated luminosity of 34.6  nb^{-1}. The production cross sections are measured in the transverse momentum range between 10 and 60  GeV/c. No significant modification is observed compared to proton-proton perturbative QCD calculations scaled by the number of incoherent nucleon-nucleon collisions. These results provide a baseline for the study of in-medium b quark energy loss in Pb+Pb collisions.
  14. Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, et al.
    Eur Phys J C Part Fields, 2016 01 11;76:13.
    PMID: 26855607
    A measurement is presented of differential cross sections for Higgs boson (H) production in pp collisions at [Formula: see text][Formula: see text]. The analysis exploits the [Formula: see text] decay in data corresponding to an integrated luminosity of 19.7[Formula: see text] collected by the CMS experiment at the LHC. The cross section is measured as a function of the kinematic properties of the diphoton system and of the associated jets. Results corrected for detector effects are compared with predictions at next-to-leading order and next-to-next-to-leading order in perturbative quantum chromodynamics, as well as with predictions beyond the standard model. For isolated photons with pseudorapidities [Formula: see text], and with the photon of largest and next-to-largest transverse momentum ([Formula: see text]) divided by the diphoton mass [Formula: see text] satisfying the respective conditions of [Formula: see text] and [Formula: see text], the total fiducial cross section is [Formula: see text][Formula: see text].
  15. Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, et al.
    Eur Phys J C Part Fields, 2016;76(7):371.
    PMID: 28280444 DOI: 10.1140/epjc/s10052-016-4206-6
    A search is presented for narrow heavy resonances X decaying into pairs of Higgs bosons ([Formula: see text]) in proton-proton collisions collected by the CMS experiment at the LHC at [Formula: see text]. The data correspond to an integrated luminosity of 19.7[Formula: see text]. The search considers [Formula: see text] resonances with masses between 1 and 3[Formula: see text], having final states of two b quark pairs. Each Higgs boson is produced with large momentum, and the hadronization products of the pair of b quarks can usually be reconstructed as single large jets. The background from multijet and [Formula: see text] events is significantly reduced by applying requirements related to the flavor of the jet, its mass, and its substructure. The signal would be identified as a peak on top of the dijet invariant mass spectrum of the remaining background events. No evidence is observed for such a signal. Upper limits obtained at 95 % confidence level for the product of the production cross section and branching fraction [Formula: see text] range from 10 to 1.5[Formula: see text] for the mass of X from 1.15 to 2.0[Formula: see text], significantly extending previous searches. For a warped extra dimension theory with a mass scale [Formula: see text] [Formula: see text], the data exclude radion scalar masses between 1.15 and 1.55[Formula: see text].
  16. Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, et al.
    Eur Phys J C Part Fields, 2016;76(7):372.
    PMID: 28280445 DOI: 10.1140/epjc/s10052-016-4205-7
    Inclusive jet production in pPb collisions at a nucleon-nucleon (NN) center-of-mass energy of [Formula: see text] is studied with the CMS detector at the LHC. A data sample corresponding to an integrated luminosity of 30.1 nb[Formula: see text] is analyzed. The jet transverse momentum spectra are studied in seven pseudorapidity intervals covering the range [Formula: see text] in the NN center-of-mass frame. The jet production yields at forward and backward pseudorapidity are compared and no significant asymmetry about [Formula: see text] is observed in the measured kinematic range. The measurements in the pPb system are compared to reference jet spectra obtained by extrapolation from previous measurements in pp collisions at [Formula: see text]. In all pseudorapidity ranges, nuclear modifications in inclusive jet production are found to be small, as predicted by next-to-leading order perturbative QCD calculations that incorporate nuclear effects in the parton distribution functions.
  17. Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, et al.
    Eur Phys J C Part Fields, 2016;76(8):460.
    PMID: 28747851 DOI: 10.1140/epjc/s10052-016-4292-5
    Results are reported from a search for the pair production of top squarks, the supersymmetric partners of top quarks, in final states with jets and missing transverse momentum. The data sample used in this search was collected by the CMS detector and corresponds to an integrated luminosity of 18.9[Formula: see text] of proton-proton collisions at a centre-of-mass energy of 8[Formula: see text] produced by the LHC. The search features novel background suppression and prediction methods, including a dedicated top quark pair reconstruction algorithm. The data are found to be in agreement with the predicted backgrounds. Exclusion limits are set in simplified supersymmetry models with the top squark decaying to jets and an undetected neutralino, either through a top quark or through a bottom quark and chargino. Models with the top squark decaying via a top quark are excluded for top squark masses up to 755[Formula: see text] in the case of neutralino masses below 200[Formula: see text]. For decays via a chargino, top squark masses up to 620[Formula: see text] are excluded, depending on the masses of the chargino and neutralino.
  18. Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, et al.
    Eur Phys J C Part Fields, 2016;76(6):317.
    PMID: 28775662 DOI: 10.1140/epjc/s10052-016-4149-y
    A search for narrow resonances decaying to an electron and a muon is presented. The [Formula: see text] [Formula: see text] mass spectrum is also investigated for non-resonant contributions from the production of quantum black holes (QBHs). The analysis is performed using data corresponding to an integrated luminosity of 19.7[Formula: see text] collected in proton-proton collisions at a centre-of-mass energy of 8[Formula: see text] with the CMS detector at the LHC. With no evidence for physics beyond the standard model in the invariant mass spectrum of selected [Formula: see text] pairs, upper limits are set at 95 [Formula: see text] confidence level on the product of cross section and branching fraction for signals arising in theories with charged lepton flavour violation. In the search for narrow resonances, the resonant production of a [Formula: see text] sneutrino in R-parity violating supersymmetry is considered. The [Formula: see text] sneutrino is excluded for masses below 1.28[Formula: see text] for couplings [Formula: see text], and below 2.30[Formula: see text] for [Formula: see text] and [Formula: see text]. These are the most stringent limits to date from direct searches at high-energy colliders. In addition, the resonance searches are interpreted in terms of a model with heavy partners of the [Formula: see text] boson and the photon. In a framework of TeV-scale quantum gravity based on a renormalization of Newton's constant, the search for non-resonant contributions to the [Formula: see text] [Formula: see text] mass spectrum excludes QBH production below a threshold mass [Formula: see text] of 1.99[Formula: see text]. In models that invoke extra dimensions, the bounds range from 2.36[Formula: see text] for one extra dimension to 3.63[Formula: see text] for six extra dimensions. This is the first search for QBHs decaying into the [Formula: see text] [Formula: see text] final state.
  19. Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, et al.
    Eur Phys J C Part Fields, 2016;76(8):469.
    PMID: 28303084 DOI: 10.1140/epjc/s10052-016-4293-4
    The differential cross section and charge asymmetry for inclusive [Formula: see text] production at [Formula: see text] are measured as a function of muon pseudorapidity. The data sample corresponds to an integrated luminosity of 18.8[Formula: see text] recorded with the CMS detector at the LHC. These results provide important constraints on the parton distribution functions of the proton in the range of the Bjorken scaling variable x from [Formula: see text] to [Formula: see text].
  20. Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, et al.
    Eur Phys J C Part Fields, 2016;76(5):237.
    PMID: 28280427 DOI: 10.1140/epjc/s10052-016-4067-z
    A search for a massive resonance [Formula: see text]decaying into a W and a Higgs boson in the [Formula: see text] ([Formula: see text], [Formula: see text]) final state is presented. Results are based on data corresponding to an integrated luminosity of 19.7[Formula: see text] of proton-proton collisions at [Formula: see text] [Formula: see text], collected using the CMS detector at the LHC. For a high-mass ([Formula: see text]1[Formula: see text]) resonance, the two bottom quarks coming from the Higgs boson decay are reconstructed as a single jet, which can be tagged by placing requirements on its substructure and flavour. Exclusion limits at 95 % confidence level are set on the production cross section of a narrow resonance decaying into WH, as a function of its mass. In the context of a little Higgs model, a lower limit on the [Formula: see text] mass of 1.4[Formula: see text] is set. In a heavy vector triplet model that mimics the properties of composite Higgs models, a lower limit on the [Formula: see text] mass of 1.5[Formula: see text] is set. In the context of this model, the results are combined with related searches to obtain a lower limit on the [Formula: see text] mass of 1.8[Formula: see text], the most restrictive to date for decays to a pair of standard model bosons.
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