CYP2C8 gene polymorphism and bisphosphonate-related osteonecrosis of the jaw in patients with multiple myeloma

Osteonecrosis of the jaw is an uncommon but potentially serious complication of bisphosphonate therapy in multiple myeloma. Previous studies showed that the presence of one or two minor alleles of the cytochrome P450, subfamily 2C polypeptide 8 gene (CYP2C8) polymorphism rs1934951 was an independent prognostic marker associated with development of osteonecrosis of the jaw in multiple myeloma patients treated with bisphosphonates. The aim of this study was to validate the frequency of SNP rs193451 in 79 patients with multiple myeloma. In 9 (22%) patients developing osteonecrosis of the jaw, a heterozygous genotype was found, in contrast with those who did not develop osteonecrosis of the jaw (n=4, 11%) or healthy individuals (n=6, 13%). We found no differences in the cumulative risk of developing osteonecrosis of the jaw between patients homozygous and heterozygous for the major allele. We were unable to confirm a significant association between this polymorphism and the risk of developing osteonecrosis of the jaw

Genome-Wide Association Study of Metamizole-Induced Agranulocytosis in European Populations

Agranulocytosis is a rare yet severe idiosyncratic adverse drug reaction to metamizole, an analgesic widely used in countries such as Switzerland and Germany. Notably, an underlying mechanism has not yet been fully elucidated and no predictive factors are known to identify at-risk patients. With the aim to identify genetic susceptibility variants to metamizole-induced agranulocytosis (MIA) and neutropenia (MIN), we conducted a retrospective multi-center collaboration including cases and controls from three European populations. Association analyses were performed using genome-wide genotyping data from a Swiss cohort (45 cases, 191 controls) followed by replication in two independent European cohorts (41 cases, 273 controls) and a joint discovery meta-analysis. No genome-wide significant associations (p < 1 × 10−7) were observed in the Swiss cohort or in the joint meta-analysis, and no candidate genes suggesting an immune-mediated mechanism were identified. In the joint meta-analysis of MIA cases across all cohorts, two candidate loci on chromosome 9 were identified, rs55898176 (OR = 4.01, 95%CI: 2.41–6.68, p = 1.01 × 10−7) and rs4427239 (OR = 5.47, 95%CI: 2.81–10.65, p = 5.75 × 10−7), of which the latter is located in the SVEP1 gene previously implicated in hematopoiesis. This first genome-wide association study for MIA identified suggestive associations with biological plausibility that may be used as a stepping-stone for post-GWAS analyses to gain further insight into the mechanism underlying MIA.This research was funded by Swiss National Science Foundation, grant number 31003A_160206. The EuDAC study was funded by Carlos III Spanish Health Institute [FIS10/02632], the European Regional Development Fund FEDER, the Swedish Research Council [Medicine 521-2011-2440,521-2014-3370 and 2018-03307], the Swedish Heart and Lung Foundation [20120557,20140291 and 20170711] and a grant from the Federal Institute for Drugs and Medical Devices (Bonn, Germany). The EUDRAGENE collaboration has received support from the EC 5th Framework program [QLRI-CR-2002-02757] and the Serious Adverse Events Consortium, SAEC, a collaboration for academia and industry. M.M. is supported by the National Institute for Health Research Biomedical Research Center at Guy’s and St Thomas’ National Health Service Foundation Trust and King’s College London

Search for flavour-changing neutral tqH interactions with H -> gamma gamma in pp collisions at root s=13 TeV using the ATLAS detector

A search for flavour-changing neutral interactions involving the top quark, the Higgs boson and an up-type quark q ( q = c, u) is presented. The proton-proton collision data set used, with an integrated luminosity of 139 fb(-1), was collected at root s = 13TeV by the ATLAS experiment at the Large Hadron Collider. Both the decay process t -> qH in tt production and the production process pp. tH, with the Higgs boson decaying into two photons, are investigated. No significant excess is observed and upper limits are set on the t. cH and the t. uH branching ratios of 4.3x10(-4) and 3.8x10(-4), respectively, at the 95% confidence level, while the expected limits in the absence of signal are 4.7x10(-4) and 3.9x10(-4). Combining this search with ATLAS searches in the H. t+ t- and H. b b final states yields observed (expected) upper limits on the t -> cH branching ratio of 5.8 x 10(-4) (3.0 x 10(-4)) at the 95% confidence level. The corresponding observed (expected) upper limit on the t -> uH branching ratio is 4.0 x 10(-4) (2.4 x 10(-4))

Combined Measurement of the Higgs Boson Mass from the Formula Presented and Formula Presented Decay Channels with the ATLAS Detector Using Formula Presented, 8, and 13 TeV Formula Presented Collision Data

A measurement of the mass of the Higgs boson combining the Formula Presented and Formula Presented decay channels is presented. The result is based on Formula Presented of proton-proton collision data collected by the ATLAS detector during LHC run 2 at a center-of-mass energy of 13 TeV combined with the run 1 ATLAS mass measurement, performed at center-of-mass energies of 7 and 8 TeV, yielding a Higgs boson mass of Formula Presented. This corresponds to a 0.09% precision achieved on this fundamental parameter of the Standard Model of particle physics

Observation of an Excess of Dicharmonium Events in the Four-Muon Final State with the ATLAS Detector

A search is made for potential ccc[over ¯]c[over ¯] tetraquarks decaying into a pair of charmonium states in the four muon final state using proton-proton collision data at sqrt[s]=13  TeV, corresponding to an integrated luminosity of 140  fb^{-1} recorded by the ATLAS experiment at LHC. Two decay channels, J/ψ+J/ψ→4μ and J/ψ+ψ(2S)→4μ, are studied. Backgrounds are estimated based on a hybrid approach involving Monte Carlo simulations and data-driven methods. Statistically significant excesses with respect to backgrounds dominated by the single parton scattering are seen in the di-J/ψ channel consistent with a narrow resonance at 6.9 GeV and a broader structure at lower mass. A statistically significant excess is also seen in the J/ψ+ψ(2S) channel. The fitted masses and decay widths of the structures are reported

Search for nonresonant pair production of Higgs bosons in the Formula Presented final state in pp collisions at Formula Presented with the ATLAS detector

A search for nonresonant Higgs boson pair production in the Formula Presented final state is presented. The analysis uses Formula Presented of Formula Presented collision data at Formula Presented collected with the ATLAS detector at the Large Hadron Collider, and targets both the gluon-gluon fusion and vector-boson fusion production modes. No evidence of the signal is found and the observed (expected) upper limit on the cross section for nonresonant Higgs boson pair production is determined to be 5.4 (8.1) times the Standard Model predicted cross section at 95% confidence level. Constraints are placed on modifiers to the Formula Presented and Formula Presented couplings. The observed (expected) Formula Presented constraints on the Formula Presented coupling modifier, Formula Presented, are determined to be Formula Presented (Formula Presented), while the corresponding constraints for the Formula Presented coupling modifier, Formula Presented, are Formula Presented (Formula Presented). In addition, constraints on relevant coefficients are derived in the context of the Standard Model effective field theory and Higgs effective field theory, and upper limits on the Formula Presented production cross section are placed in seven Higgs effective field theory benchmark scenarios

Measurement of the Sensitivity of Two-Particle Correlations in pp Collisions to the Presence of Hard Scatterings

A key open question in the study of multiparticle production in high-energy pp collisions is the relationship between the "ridge"-i.e., the observed azimuthal correlations between particles in the underlying event that extend over all rapidities-and hard or semihard scattering processes. In particular, it is not known whether jets or their soft fragments are correlated with particles in the underlying event. To address this question, two-particle correlations are measured in pp collisions at sqrt[s]=13  TeV using data collected by the ATLAS experiment at the LHC, with an integrated luminosity of 15.8  pb^{-1}, in two different configurations. In the first case, charged particles associated with jets are excluded from the correlation analysis, while in the second case, correlations are measured between particles within jets and charged particles from the underlying event. Second-order flow coefficients, v_{2}, are presented as a function of event multiplicity and transverse momentum. These measurements show that excluding particles associated with jets does not affect the measured correlations. Moreover, particles associated with jets do not exhibit any significant azimuthal correlations with the underlying event, ruling out hard processes contributing to the ridge

Measurement of Suppression of Large-Radius Jets and Its Dependence on Substructure in Pb+Pb Collisions at Formula Presented with the ATLAS Detector

This letter presents a measurement of the nuclear modification factor of large-radius jets in Formula Presented Formula Presented collisions by the ATLAS experiment. The measurement is performed using Formula Presented and Formula Presented of Formula Presented and Formula Presented data, respectively. The large-radius jets are reconstructed with the anti-Formula Presented algorithm using a radius parameter of Formula Presented, by reclustering anti-Formula Presented Formula Presented jets, and are measured over the transverse momentum (Formula Presented) kinematic range of Formula Presented and absolute pseudorapidity Formula Presented. The large-radius jet constituents are further reclustered using the Formula Presented algorithm in order to obtain the splitting parameters, Formula Presented and Formula Presented, which characterize the transverse momentum scale and angular separation for the hardest splitting in the jet, respectively. The nuclear modification factor, Formula Presented, obtained by comparing the Formula Presented jet yields to those in Formula Presented collisions, is measured as a function of jet transverse momentum (Formula Presented) and Formula Presented or Formula Presented. A significant difference in the quenching of large-radius jets having single subjet and those with more complex substructure is observed. Systematic comparison of jet suppression in terms of Formula Presented for different jet definitions is also provided. Presented results support the hypothesis that jets with hard internal splittings lose more energy through quenching and provide a new perspective for understanding the role of jet structure in jet suppression

Correction: Liquori et al. Acute Promyelocytic Leukemia: A Constellation of Molecular Events around a Single PML-RARA Fusion Gene. Cancers 2020, 12, 624

The authors wish to make the following corrections to this paper [...