Flow cytometry immunophenotyping for diagnostic orientation and classification of pediatric cancer based on the euroflow solid tumor orientation tube (Stot)

© 2021 by the authors.Early diagnosis of pediatric cancer is key for adequate patient management and improved outcome. Although multiparameter flow cytometry (MFC) has proven of great utility in the diagnosis and classification of hematologic malignancies, its application to non-hematopoietic pediatric tumors remains limited. Here we designed and prospectively validated a new single eight-color antibody combination—solid tumor orientation tube, STOT—for diagnostic screening of pediatric cancer by MFC. A total of 476 samples (139 tumor mass, 138 bone marrow, 86 lymph node, 58 peripheral blood, and 55 other body fluid samples) from 296 patients with diagnostic suspicion of pediatric cancer were analyzed by MFC vs. conventional diagnostic procedures. STOT was designed after several design–test–evaluate–redesign cycles based on a large panel of monoclonal antibody combinations tested on 301 samples. In its final version, STOT consists of a single 8-color/12-marker antibody combination (CD99-CD8/numyogenin/CD4-EpCAM/CD56/GD2/smCD3-CD19/cyCD3-CD271/CD45). Prospective validation of STOT in 149 samples showed concordant results with the patient WHO/ICCC-3 diagnosis in 138/149 cases (92.6%). These included: 63/63 (100%) reactive/disease-free samples, 43/44 (98%) malignant and 4/4 (100%) benign non-hematopoietic tumors together with 28/38 (74%) leukemia/lymphoma cases; the only exception was Hodgkin lymphoma that required additional markers to be stained. In addition, STOT allowed accurate discrimination among the four most common subtypes of malignant CD45− CD56++ non-hematopoietic solid tumors: 13/13 (GD2++ numyogenin− CD271−/+ nuMyoD1− CD99− EpCAM−) neuroblastoma samples, 5/5 (GD2− numyogenin++ CD271++ nuMyoD1++ CD99−/+ EpCAM−) rhabdomyosarcomas, 2/2 (GD2−/+ numyogenin− CD271+ nuMyoD1− CD99+ EpCAM−) Ewing sarcoma family of tumors, and 7/7 (GD2− numyogenin− CD271+ nuMyoD1− CD99− EpCAM+) Wilms tumors. In summary, here we designed and validated a new standardized antibody combination and MFC assay for diagnostic screening of pediatric solid tumors that might contribute to fast and accurate diagnostic orientation and classification of pediatric cancer in routine clinical practice.This research was funded by the EuroFlow Consortium; Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro, Brazil (FAPERJ), numbers: E26/110.105/2014, E-26/010.101259/2018, and E26/102.191/2013; grant from Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brasília, Brazil (CNPQ), Brasília, Brazil, numbers: 303765/2018-6, 409440/2016-7, and 400194/2014-7; and Instituto Desiderata/Chevron, Rio de Janeiro, Brazil, grant “Actions to improve pediatric cancer assistance in RJ”; the EuroFlow Consortium (grant LSHB-CT-2006-018708); Centro de Investigación Biomédica en Red de Cáncer (CIBER-ONC; Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain and FONDOS FEDER), numbers: CB16/12/00400, CB16/12/00233, CB16/12/00369, CB16/12/00489 and CB16/12/00480; grant from Bilateral Cooperation Program between Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-CAPES (Brasília/Brazil) and Dirección General de Políticas Universitárias (DGPU)-Ministério de Educación, Cultura y Deportes (Madrid/Spain) number DGPU 311/15

Giant liver cyst in a newborn with pseudoprune-belly syndrome - A case report

Introduction: Pseudoprune-belly syndrome is a rare anomaly, an incomplete form of Prune-belly syndrome. The etiology is not clear, and though this syndrome may present associated with other malformations, the association with a liver cyst is extremely rare. Case presentation: We report the case of a male newborn who was referred to our hospital with an antenatal ultrasound that suggested a gastric duplication. Clinical examination revealed lax abdominal wall, unilateral undescended testis and a palpable mass on the right upper quadrant with fuzzy boundaries. On laparotomy we found a giant hepatic cyst displacing the bowel to the left. The baby underwent a partial ressection and marsupialization of the cyst as total resection was infeasible. The patient's recovery was uneventful. Conclusion: Although rarely, the Pseudoprune-belly syndrome can present with a liver cyst. Large liver cysts should be partially or totally ressected as soon as possible

The CMS Statistical Analysis and Combination Tool: COMBINE

International audienceThis paper describes the COMBINE software package used for statistical analyses by the CMS Collaboration. The package, originally designed to perform searches for a Higgs boson and the combined analysis of those searches, has evolved to become the statistical analysis tool presently used in the majority of measurements and searches performed by the CMS Collaboration. It is not specific to the CMS experiment, and this paper is intended to serve as a reference for users outside of the CMS Collaboration, providing an outline of the most salient features and capabilities. Readers are provided with the possibility to run COMBINE and reproduce examples provided in this paper using a publicly available container image. Since the package is constantly evolving to meet the demands of ever-increasing data sets and analysis sophistication, this paper cannot cover all details of COMBINE. However, the online documentation referenced within this paper provides an up-to-date and complete user guide

Search for long-lived heavy neutrinos in the decays of B mesons produced in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceA search for long-lived heavy neutrinos (N) in the decays of \PB mesons produced in proton-proton collisions at $\sqrt{s}$ = 13 TeV is presented. The data sample corresponds to an integrated luminosity of 41.6 fb$^{-1}$ collected in 2018 by the CMS experiment at the CERN LHC, using a dedicated data stream that enhances the number of recorded events containing B mesons. The search probes heavy neutrinos with masses in the range 1 $\lt$$m_\mathrm{N}$$\lt$ 3 GeV and decay lengths in the range 10$^{-2}$$\lt$$c\tau$$\lt$ 10$^{4}$ mm, where $\tau_\mathrm{N}$ is the N proper mean lifetime. Signal events are defined by the signature B $\to$$\ell_\mathrm{B}$NX; N $\to$$\ell^{\pm} \pi^{\mp}$, where the leptons $\ell_\mathrm{B}$ and $\ell$ can be either a muon or an electron, provided that at least one of them is a muon. The hadronic recoil system, X, is treated inclusively and is not reconstructed. No significant excess of events over the standard model background is observed in any of the $\ell^{\pm}\pi^{\mp}$ invariant mass distributions. Limits at 95% confidence level on the sum of the squares of the mixing amplitudes between heavy and light neutrinos, $\vert V_\mathrm{N}\vert^2$, and on $c\tau$ are obtained in different mixing scenarios for both Majorana and Dirac-like N particles. The most stringent upper limit $\vert V_\mathrm{N}\vert^2$ $\lt$ 2.0$\times$10$^{-5}$ is obtained at $m_\mathrm{N}$ = 1.95 GeV for the Majorana case where N mixes exclusively with muon neutrinos. The limits on $\vert V_\mathrm{N}\vert^2$ for masses 1 $\lt$ $m_\mathrm{N}$ $\lt$ 1.7 GeV are the most stringent from a collider experiment to date

Dark sector searches with the CMS experiment

Astrophysical observations provide compelling evidence for gravitationally interacting dark matter in the universe that cannot be explained by the standard model of particle physics. The extraordinary amount of data from the CERN LHC presents a unique opportunity to shed light on the nature of dark matter at unprecedented collision energies. This Report comprehensively reviews the most recent searches with the CMS experiment for particles and interactions belonging to a dark sector and for dark-sector mediators. Models with invisible massive particles are probed by searches for signatures of missing transverse momentum recoiling against visible standard model particles. Searches for mediators are also conducted via fully visible final states. The results of these searches are compared with those obtained from direct-detection experiments. Searches for alternative scenarios predicting more complex dark sectors with multiple new particles and new forces are also presented. Many of these models include long-lived particles, which could manifest themselves with striking unconventional signatures with relatively small amounts of background. Searches for such particles are discussed and their impact on dark-sector scenarios is evaluated. Many results and interpretations have been newly obtained for this Report.Astrophysical observations provide compelling evidence for gravitationally interacting dark matter in the universe that cannot be explained by the standard model of particle physics. The extraordinary amount of data from the CERN LHC presents a unique opportunity to shed light on the nature of dark matter at unprecedented collision energies. This Report comprehensively reviews the most recent searches with the CMS experiment for particles and interactions belonging to a dark sector and for dark-sector mediators. Models with invisible massive particles are probed by searches for signatures of missing transverse momentum recoiling against visible standard model particles. Searches for mediators are also conducted via fully visible final states. The results of these searches are compared with those obtained from direct-detection experiments. Searches for alternative scenarios predicting more complex dark sectors with multiple new particles and new forces are also presented. Many of these models include long-lived particles, which could manifest themselves with striking unconventional signatures with relatively small amounts of background. Searches for such particles are discussed and their impact on dark-sector scenarios is evaluated. Many results and interpretations have been newly obtained for this Report

Observation of double J/ψ\psi meson production in pPb collisions at sNN\sqrt{s_\mathrm{NN}} = 8.16 TeV

International audienceThe first observation of the concurrent production of two J/$\psi$ mesons in proton-nucleus collisions is presented. The analysis is based on a proton-lead (pPb) data sample recorded at a nucleon-nucleon center-of-mass energy of 8.16 TeV by the CMS experiment at the CERN LHC and corresponding to an integrated luminosity of 174.6 nb$^{-1}$. The two J/$\psi$ mesons are reconstructed in their $\mu^+\mu^-$ decay channels with transverse momenta $p_\mathrm{T}$$\gt$ 6.5 GeV and rapidity $\lvert y \rvert$$\lt$ 2.4. Events where one of the J/$\psi$ mesons is reconstructed in the dielectron channel are also considered in the search. The pPb $\to$ J/$\psi$J/$\psi$+X process is observed with a significance of 5.3 standard deviations. The measured inclusive fiducial cross section, using the four-muon channel alone, is $\sigma$(pPb$\to$ J/$\psi$J/$\psi$+X)= 22.0 $\pm$ 8.9 (stat) $\pm$ 1.5 (syst) nb. A fit of the data to the expected rapidity separation for pairs of J/$\psi$ mesons produced in single (SPS) and double (DPS) parton scatterings yields $\sigma^{\mathrm{pPb}\to\mathrm{J}/\psi\mathrm{J}/\psi+\mathrm{X}}_\text{SPS}$ = 16.5 $\pm$ 10.8 (stat) $\pm$ 0.1 (syst) nb and $\sigma^{\mathrm{pPb}\to \mathrm{J}/\psi\mathrm{J}/\psi+\mathrm{X}}_\text{DPS}$ = 5.4 $\pm$ 6.2 (stat) $\pm$ 0.4 (syst) nb, respectively. This latter result can be transformed into a lower bound on the effective DPS cross section, closely related to the squared average interparton transverse separation in the collision, of $\sigma_\text{eff}$$\gt$ 1.0 mb at 95% confidence level

Search for new resonances decaying to pairs of merged diphotons in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceA search is presented for an extended Higgs sector with two new particles, X and $\phi$, in the process X $\to$$\phi\phi$$\to$$(\gamma\gamma)(\gamma\gamma)$. Novel neural networks classify events with diphotons that are merged and determine the diphoton masses. The search uses LHC proton-proton collision data at $\sqrt{s}$ = 13 TeV collected with the CMS detector, corresponding to an integrated luminosity of 138 fb$^{-1}$. No evidence of such resonances is seen. Upper limits are set on the production cross section versus the resonance masses, representing the most sensitive search in this channel

Search for CPCP violation in D0^0→\to KS0^0_\mathrm{S}KS0^0_\mathrm{S} decays in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceA search is reported for charge-parity D$^0$$\to$ K$^0_\mathrm{S}$K$^0_\mathrm{S}$$CP$ violation in D$^0$$\to$ K$^0_\mathrm{S}$K$^0_\mathrm{S}$ decays, using data collected in proton-proton collisions at $\sqrt{s}$ = 13 TeV recorded by the CMS experiment in 2018. The analysis uses a dedicated data set that corresponds to an integrated luminosity of 41.6 fb$^{-1}$, which consists of about 10 billion events containing a pair of ẖadrons, nearly all of which decay to charm hadrons. The flavor of the neutral D meson is determined by the pion charge in the reconstructed decays D$^{*+}$$\to$ D$^0\pi^+$ and D$^{*-}$$\to$ D$^0\pi^-$. The D$^0$$\to$ K$^0_\mathrm{S}$K$^0_\mathrm{S}$$CP$ asymmetry in D$^0$$\to$ K$^0_\mathrm{S}$K$^0_\mathrm{S}$ is measured to be $A_{CP}$( K$^0_\mathrm{S}$K$^0_\mathrm{S}$) = (6.2 $\pm$ 3.0 $\pm$ 0.2 $\pm$ 0.8)%, where the three uncertainties represent the statistical uncertainty, the systematic uncertainty, and the uncertainty in the measurement of the D$^0$ $\to$ K$^0_\mathrm{S}$K$^0_\mathrm{S}$ $CP$ asymmetry in the D$^0$ $\to$ K$^0_\mathrm{S}\pi^+\pi^-$ decay. This is the first D$^0$ $\to$ K$^0_\mathrm{S}$K$^0_\mathrm{S}$ $CP$ asymmetry measurement by CMS in the charm sector as well as the first to utilize a fully hadronic final state

Search for heavy neutral leptons in final states with electrons, muons, and hadronically decaying tau leptons in proton-proton collisions at s\sqrt{s} =13 TeV

International audienceA search for heavy neutral leptons (HNLs) of Majorana or Dirac type using proton-proton collision data at $\sqrt{s}$ =13 TeV is presented. The data were collected by the CMS experiment at the CERN LHC and correspond to an integrated luminosity of 138 fb$^{-1}$. Events with three charged leptons (electrons, muons, and hadronically decaying tau leptons) are selected, corresponding to HNL production in association with a charged lepton and decay of the HNL to two charged leptons and a standard model (SM) neutrino. The search is performed for HNL masses between 10 GeV and 1.5 TeV. No evidence for an HNL signal is observed in data. Upper limits at 95% confidence level are found for the squared coupling strength of the HNL to SM neutrinos, considering exclusive coupling of the HNL to a single SM neutrino generation, for both Majorana and Dirac HNLs. The limits exceed previously achieved experimental constraints for a wide range of HNL masses, and the limits on tau neutrino coupling scenarios with HNL masses above the W boson mass are presented for the first time

Search for the Z boson decay to ττμμ\tau\tau\mu\mu in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceThe first search for the Z boson decay to $\tau\tau\mu\mu$ at the CERN LHC is presented, based on data collected by the CMS experiment at the LHC in proton-proton collisions at a center-of-mass energy of 13 TeV and corresponding to an integrated luminosity of 138 fb$^{-1}$. The data are compatible with the predicted background. For the first time, an upper limit at the 95% confidence level of 6.9 times the standard model expectation is placed on the ratio of the Z $\to$ $\tau\tau\mu\mu$ to Z $\to$ 4$\mu$ branching fractions. Limits are also placed on the six flavor-conserving four-lepton effective-field-theory operators involving two muons and two tau leptons, for the first time testing all such operators