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Auto-inflammatory skin diseases place considerable symptomatic and emotional burden on the affected and put pressure on healthcare expenditures. Although most apparent symptoms manifest on the skin, the systemic inflammation merits a deeper analysis beyond the surface. We set out to identify systemic commonalities, as well as differences in the metabolome and lipidome when comparing between diseases and healthy controls. Lipidomic and metabolomic LC-MS profiling was applied, using plasma samples collected from patients suffering from atopic dermatitis, plaque-type psoriasis or hidradenitis suppurativa or healthy controls. Plasma profiles revealed a notable shift in the non-enzymatic anti-oxidant defense in all three inflammatory disorders, placing cysteine metabolism at the center of potential dysregulation. Lipid network enrichment additionally indicated the disease-specific provision of lipid mediators associated with key roles in inflammation signaling. These findings will help to disentangle the systemic components of autoimmune dermatological diseases, paving the way to individualized therapy and improved prognosis.
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Dermatite Atópica , Hidradenite Supurativa , Lipidômica , Metabolômica , Psoríase , Humanos , Dermatite Atópica/imunologia , Dermatite Atópica/sangue , Dermatite Atópica/metabolismo , Psoríase/metabolismo , Psoríase/imunologia , Psoríase/sangue , Hidradenite Supurativa/sangue , Hidradenite Supurativa/metabolismo , Hidradenite Supurativa/imunologia , Lipidômica/métodos , Feminino , Adulto , Masculino , Metabolômica/métodos , Pessoa de Meia-Idade , Metaboloma , Adulto Jovem , Inflamação/metabolismo , Inflamação/sangue , Metabolismo dos LipídeosRESUMO
BACKGROUND: Data on perioperative chemotherapy in resectable pancreatic ductal adenocarcinoma (rPDAC) are limited. NEONAX examined perioperative or adjuvant chemotherapy with gemcitabine plus nab-paclitaxel in rPDAC (National Comprehensive Cancer Network criteria). PATIENTS AND METHODS: NEONAX is a prospective, randomized phase II trial with two independent experimental arms. One hundred twenty-seven rPDAC patients in 22 German centers were randomized 1 : 1 to perioperative (two pre-operative and four post-operative cycles, arm A) or adjuvant (six cycles, arm B) gemcitabine (1000 mg/m2) and nab-paclitaxel (125 mg/m2) on days 1, 8 and 15 of a 28-day cycle. RESULTS: The primary endpoint was disease-free survival (DFS) at 18 months in the modified intention-to-treat (ITT) population [R0/R1-resected patients who started neoadjuvant chemotherapy (CTX) (A) or adjuvant CTX (B)]. The pre-defined DFS rate of 55% at 18 months was not reached in both arms [A: 33.3% (95% confidence interval [CI] 18.5% to 48.1%), B: 41.4% (95% CI 20.7% to 62.0%)]. Ninety percent of patients in arm A completed neoadjuvant treatment, and 42% of patients in arm B started adjuvant chemotherapy. R0 resection rate was 88% (arm A) and 67% (arm B), respectively. Median overall survival (mOS) (ITT population) as a secondary endpoint was 25.5 months (95% CI 19.7-29.7 months) in arm A and 16.7 months (95% CI 11.6-22.2 months) in the upfront surgery arm. This difference corresponds to a median DFS (mDFS) (ITT) of 11.5 months (95% CI 8.8-14.5 months) in arm A and 5.9 months (95% CI 3.6-11.5 months) in arm B. Treatment was safe and well tolerable in both arms. CONCLUSIONS: The primary endpoint, DFS rate of 55% at 18 months (mITT population), was not reached in either arm of the trial and numerically favored the upfront surgery arm B. mOS (ITT population), a secondary endpoint, numerically favored the neoadjuvant arm A [25.5 months (95% CI 19.7-29.7months); arm B 16.7 months (95% CI 11.6-22.2 months)]. There was a difference in chemotherapy exposure with 90% of patients in arm A completing pre-operative chemotherapy and 58% of patients starting adjuvant chemotherapy in arm B. Neoadjuvant/perioperative treatment is a novel option for patients with resectable PDAC. However, the optimal treatment regimen has yet to be defined. The trial is registered with ClinicalTrials.gov (NCT02047513) and the European Clinical Trials Database (EudraCT 2013-005559-34).
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Gencitabina , Neoplasias Pancreáticas , Humanos , Desoxicitidina , Estudos Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Albuminas , Paclitaxel , Terapia Neoadjuvante , Adjuvantes Imunológicos/uso terapêutico , Neoplasias PancreáticasRESUMO
BACKGROUND: Initial systemic therapy for patients with metastatic colorectal cancer (mCRC) is usually based on two- or three-drug chemotherapy regimens with fluoropyrimidine (5-fluorouracil (5-FU) or capecitabine), oxaliplatin and/or irinotecan, combined with either anti-VEGF (bevacizumab) or, for RAS wild-type (WT) tumors, anti-EGFR antibodies (panitumumab or cetuximab). Recommendations for patients who are not eligible for intensive combination therapies are limited and include fluoropyrimidine plus bevacizumab or single agent anti-EGFR antibody treatment. The use of a monochemotherapy concept of trifluridine/ tipiracil in combination with monoclonal antibodies is not approved for first-line therapy, yet. Results from the phase II TASCO trial evaluating trifluridine/ tipiracil plus bevacicumab in first-line treatment of mCRC patients and from the phase I/II APOLLON trial investigating trifluridine/ tipiracil plus panitumumab in pre-treated mCRC patients suggest favourable activity and tolerability of these new therapeutic approaches. METHODS: FIRE-8 ( NCT05007132 ) is a prospective, randomized, open-label, multicenter phase II study which aims to evaluate the efficacy of first-line treatment with trifluridine/tipiracil (35 mg/m2 body surface area (BSA), orally twice daily on days 1-5 and 8-12, q28 days) plus either the anti-EGFR antibody panitumumab (6 mg/kg body weight, intravenously on day 1 and 15, q28 days) [arm A] or (as control arm) the anti-VEGF antibody bevacizumab (5 mg/kg body weight, intravenously on day 1 and 15, q28 days) [arm B] in RAS WT mCRC patients. The primary objective is to demonstrate an improved objective response rate (ORR) according to RECIST 1.1 from 30% (control arm) to 55% with panitumumab. With a power of 80% and a two-sided significance level of 0.05, 138 evaluable patients are needed. Given an estimated drop-out rate of 10%, 153 patients will be enrolled. DISCUSSION: To the best of our knowledge, this is the first phase II trial to evaluate the efficacy of trifluridine/tipiracil plus panitumumab in first-line treatment of RAS WT mCRC patients. The administration of anti-EGFR antibodies rather than anti-VEGF antibodies in combination with trifluridine/tipiracil may result in an increased initial efficacy. TRIAL REGISTRATION: EU Clinical Trials Register (EudraCT) 2019-004223-20 . Registered October 22, 2019, ClinicalTrials.gov NCT05007132 . Registered on August 12, 2021.
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Neoplasias Colorretais , Trifluridina , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/efeitos adversos , Peso Corporal , Ensaios Clínicos Fase II como Assunto , Neoplasias Colorretais/patologia , Fluoruracila , Humanos , Estudos Multicêntricos como Assunto , Panitumumabe/uso terapêutico , Estudos Prospectivos , Pirrolidinas , Ensaios Clínicos Controlados Aleatórios como Assunto , Timina , Trifluridina/uso terapêuticoRESUMO
BACKGROUND: While several studies report on accuracy rates of pedicle screws, risk factors associated with inaccurate pedicle screw positioning in patients with thoracolumbar fractures are reported rarely. CT scan as a routine postoperative control is advocated by various authors, however its necessity remains unclear. METHODS: Two hundred forty-five patients were included in this retrospective study. Percutaneous dorsal instrumentation was most commonly performed (n = 201). Classification of Zdichavsky et al. and Rao et al. were used to classify screw misplacement and anterior perforation was further evaluated according to the extent of perforation (< 2 mm; > 2 mm). Multivariate analysis was performed to identify risk factors for misplacement of screws. RESULTS: One thousand sixty-eight pedicle screws were inserted in 245 patients. Misplacement was found in 51 screws (4.8%) in 42 patients (17.1%) according to the classification of Zdichavsky et al. and in 75 screws (7.0%) in 64 patients (26.1%) according to the classification of Rao et al.. An anterior perforation of the vertebral cortex was found in 56 screws (5.2%). Multivariate analysis showed fracture location in the upper thoracic (p = 0.048) and lumbar spine (p = 0.013) to be the only independent predictors for screw misplacement. In addition a significant correlation between pedicle diameter and the occurrence of screw malposition was found (p = 0.003). No consequences were drawn from postoperative routine CT in asymptomatic patients. CONCLUSION: An overall low rate of screw misplacement was found with fracture location in the upper thoracic and lumbar spine being the only factors independently associated with the risk of screw misplacement. No consequences were drawn from postoperative routine CT in asymptomatic patients. Therefore its use has to be discussed critically.
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Parafusos Pediculares , Fusão Vertebral , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Estudos Retrospectivos , Fusão Vertebral/efeitos adversos , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/cirurgia , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: Non-traumatic cardiac arrest (CA) and return of spontaneous circulation (ROSC) after cardiopulmonary resuscitation (CPR) are often associated with multiple pathologies. Expecting a high prevalence of important findings, a whole-body CT (WBCT) could be of relevance for therapy. The aim of this study is to investigate the feasibility and diagnostic yield of an early WBCT in this setting. METHODS: This single-center retrospective study included 100 consecutive patients (27 female; 73 male; mean age 68.5± 12.57 years) with non-traumatic, in- and out-of-hospital CA and ROSC following CPR, who underwent a contrast-enhanced WBCT within 6 h after ROSC over 12 months. CT findings were determined corresponding to anatomical region. RESULTS: Early WBCT was successfully carried out in 100% of the patients with CA and ROSC after CPR. Acute pathologies were found not only in the chest but also in the head (15%) and the abdomen (6%). Early global brain edema (n = 12), acute stroke (n = 3), pulmonary embolism (n = 10), pneumothorax (26%), acute abdominal pathologies (n = 6), iatrogenic bleeding (4%), and CPR-related injuries (93%) were detected by CT right from the beginning of the post-cardiac arrest care. CONCLUSIONS: An early WBCT is feasible and provides added diagnostic value for patients with ROSC after non-traumatic CA.
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Reanimação Cardiopulmonar , Parada Cardíaca/complicações , Parada Cardíaca/terapia , Tomografia Computadorizada por Raios X/métodos , Imagem Corporal Total , Idoso , Meios de Contraste , Feminino , Humanos , Masculino , Estudos RetrospectivosRESUMO
BACKGROUND: Malignant diseases lead to a decline in physical performance in a large number of patients. This includes a reduction of the musculoskeletal system, restrictions in cardiovascular fitness and psychogenically influenced syndromes such as fatigue and asthenia. It is not yet clear to what extent physical training can counteract these limitations or undesirable side effects and how this training needs to be designed in the individual situation. AIM OF THIS ARTICLE: The aim of this article is to find out whether physical training can be performed in cancer patients, how this training should be designed and which physical disorders can be influenced favorably. MATERIALS AND METHODS: In this review, the currently available work on this topic was evaluated and classified with regard to its feasibility and effects in cancer patients. RESULTS AND DISCUSSION: Physical training can be performed without complications in most patients even under treatment for the underlying malignant disease. It has a positive effect on physical performance, cardiovascular function, the perception of one's own cancer and overall well-being. Ideally, physical training for cancer patients should include a mixture of strength and endurance training. It should be carried out regularly and its intensity should be slowly increased. The type of physical activity should be adapted to the individual needs of the patient, take into account the particularities of the malignant disease and exclude any risk to the patient. CONCLUSION: In summary, a physical training program to accompany cancer therapy should be offered to virtually all patients with malignant disease.
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Antineoplásicos/efeitos adversos , Exercício Físico , Neoplasias/tratamento farmacológico , Aptidão Física , Esportes , Antineoplásicos/uso terapêutico , Sistema Cardiovascular , Humanos , Oncologia , Neoplasias/psicologia , Resistência Física/fisiologia , Qualidade de VidaRESUMO
Data from heavy ion collisions suggest that the evolution of a parton shower is modified by interactions with the color charges in the dense partonic medium created in these collisions, but it is not known where in the shower evolution the modifications occur. The momentum ratio of the two leading partons, resolved as subjets, provides information about the parton shower evolution. This substructure observable, known as the splitting function, reflects the process of a parton splitting into two other partons and has been measured for jets with transverse momentum between 140 and 500 GeV, in pp and PbPb collisions at a center-of-mass energy of 5.02 TeV per nucleon pair. In central PbPb collisions, the splitting function indicates a more unbalanced momentum ratio, compared to peripheral PbPb and pp collisions.. The measurements are compared to various predictions from event generators and analytical calculations.
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The relative yields of Ï mesons produced in pp and Pb-Pb collisions at sqrt[s_{NN}]=5.02 TeV and reconstructed via the dimuon decay channel are measured using data collected by the CMS experiment. Double ratios are formed by comparing the yields of the excited states, Ï(2S) and Ï(3S), to the ground state, Ï(1S), in both Pb-Pb and pp collisions at the same center-of-mass energy. The double ratios, [Ï(nS)/Ï(1S)]_{Pb-Pb}/[Ï(nS)/Ï(1S)]_{pp}, are measured to be 0.308±0.055(stat)±0.019(syst) for the Ï(2S) and less than 0.26 at 95% confidence level for the Ï(3S). No significant Ï(3S) signal is found in the Pb-Pb data. The double ratios are studied as a function of collision centrality, as well as Ï transverse momentum and rapidity. No significant dependencies are observed.
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A search for a heavy neutral lepton N of Majorana nature decaying into a W boson and a charged lepton is performed using the CMS detector at the LHC. The targeted signature consists of three prompt charged leptons in any flavor combination of electrons and muons. The data were collected in proton-proton collisions at a center-of-mass energy of 13 TeV, with an integrated luminosity of 35.9 fb^{-1}. The search is performed in the N mass range between 1 GeV and 1.2 TeV. The data are found to be consistent with the expected standard model background. Upper limits are set on the values of |V_{eN}|^{2} and |V_{µN}|^{2}, where V_{âN} is the matrix element describing the mixing of N with the standard model neutrino of flavor â. These are the first direct limits for N masses above 500 GeV and the first limits obtained at a hadron collider for N masses below 40 GeV.
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A search for resonancelike structures in the B_{s}^{0}π^{±} invariant mass spectrum is performed using proton-proton collision data collected by the CMS experiment at the LHC at sqrt[s]=8 TeV, corresponding to an integrated luminosity of 19.7 fb^{-1}. The B_{s}^{0} mesons are reconstructed in the decay chain B_{s}^{0}âJ/ψÏ, with J/ψâµ^{+}µ^{-} and ÏâK^{+}K^{-}. The B_{s}^{0}π^{±} invariant mass distribution shows no statistically significant peaks for different selection requirements on the reconstructed B_{s}^{0} and π^{±} candidates. Upper limits are set on the relative production rates of the X(5568) and B_{s}^{0} states times the branching fraction of the decay X(5568)^{±}âB_{s}^{0}π^{±}. In addition, upper limits are obtained as a function of the mass and the natural width of possible exotic states decaying into B_{s}^{0}π^{±}.
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The prompt D^{0} meson azimuthal anisotropy coefficients, v_{2} and v_{3}, are measured at midrapidity (|y|<1.0) in Pb-Pb collisions at a center-of-mass energy sqrt[s_{NN}]=5.02 TeV per nucleon pair with data collected by the CMS experiment. The measurement is performed in the transverse momentum (p_{T}) range of 1 to 40 GeV/c, for central and midcentral collisions. The v_{2} coefficient is found to be positive throughout the p_{T} range studied. The first measurement of the prompt D^{0} meson v_{3} coefficient is performed, and values up to 0.07 are observed for p_{T} around 4 GeV/c. Compared to measurements of charged particles, a similar p_{T} dependence, but smaller magnitude for p_{T}<6 GeV/c, is found for prompt D^{0} meson v_{2} and v_{3} coefficients. The results are consistent with the presence of collective motion of charm quarks at low p_{T} and a path length dependence of charm quark energy loss at high p_{T}, thereby providing new constraints on the theoretical description of the interactions between charm quarks and the quark-gluon plasma.
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A search for narrow resonances decaying to bottom quark-antiquark pairs is presented, using a data sample of proton-proton collisions at sqrt[s]=8 TeV corresponding to an integrated luminosity of 19.7 fb^{-1}. The search is extended to masses lower than those reached in typical searches for resonances decaying into jet pairs at the LHC, by taking advantage of triggers that identify jets originating from bottom quarks. No significant excess of events is observed above the background predictions. Limits are set on the product of cross section and branching fraction to bottom quarks for spin 0, 1, and 2 resonances in the mass range of 325-1200 GeV. These results improve on the limits for resonances decaying into jet pairs in the 325-500 GeV mass range.
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Measurements of fragmentation functions for jets associated with an isolated photon are presented for the first time in pp and Pb-Pb collisions. The analysis uses data collected with the CMS detector at the CERN LHC at a nucleon-nucleon center-of-mass energy of 5.02 TeV. Fragmentation functions are obtained for jets with p_{T}^{jet}>30 GeV/c in events containing an isolated photon with p_{T}^{γ}>60 GeV/c, using charged tracks with transverse momentum p_{T}^{trk}>1 GeV/c in a cone around the jet axis. The association with an isolated photon constrains the initial p_{T} and azimuthal angle of the parton whose shower produced the jet. For central Pb-Pb collisions, modifications of the jet fragmentation functions are observed when compared to those measured in pp collisions, while no significant differences are found in the 50% most peripheral collisions. Jets in central Pb-Pb events show an excess (depletion) of low (high) p_{T} particles, with a transition around 3 GeV/c. This measurement shows for the first time the in-medium shower modifications of partons (quark dominated) with well-defined initial kinematics. It constitutes a new well-controlled reference for testing theoretical models of the parton passage through the quark-gluon plasma.
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An inclusive search for the standard model Higgs boson (H) produced with large transverse momentum (p_{T}) and decaying to a bottom quark-antiquark pair (bb[over ¯]) is performed using a data set of pp collisions at sqrt[s]=13 TeV collected with the CMS experiment at the LHC. The data sample corresponds to an integrated luminosity of 35.9 fb^{-1}. A highly Lorentz-boosted Higgs boson decaying to bb[over ¯] is reconstructed as a single, large radius jet, and it is identified using jet substructure and dedicated b tagging techniques. The method is validated with Zâbb[over ¯] decays. The Zâbb[over ¯] process is observed for the first time in the single-jet topology with a local significance of 5.1 standard deviations (5.8 expected). For a Higgs boson mass of 125 GeV, an excess of events above the expected background is observed (expected) with a local significance of 1.5 (0.7) standard deviations. The measured cross section times branching fraction for production via gluon fusion of Hâbb[over ¯] with reconstructed p_{T}>450 GeV and in the pseudorapidity range -2.5<η<2.5 is 74±48(stat)_{-10}^{+17}(syst) fb, which is consistent within uncertainties with the standard model prediction.
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The first observation of electroweak production of same-sign W boson pairs in proton-proton collisions is reported. The data sample corresponds to an integrated luminosity of 35.9 fb^{-1} collected at a center-of-mass energy of 13 TeV with the CMS detector at the LHC. Events are selected by requiring exactly two leptons (electrons or muons) of the same charge, moderate missing transverse momentum, and two jets with a large rapidity separation and a large dijet mass. The observed significance of the signal is 5.5 standard deviations, where a significance of 5.7 standard deviations is expected based on the standard model. The ratio of measured event yields to that expected from the standard model at leading order is 0.90±0.22. A cross section measurement in a fiducial region is reported. Bounds are given on the structure of quartic vector boson interactions in the framework of dimension-8 effective field theory operators and on the production of doubly charged Higgs bosons.
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The azimuthal anisotropy Fourier coefficients (v_{n}) in 8.16 TeV p+Pb data are extracted via long-range two-particle correlations as a function of the event multiplicity and compared to corresponding results in pp and PbPb collisions. Using a four-particle cumulant technique, v_{n} correlations are measured for the first time in pp and p+Pb collisions. The v_{2} and v_{4} coefficients are found to be positively correlated in all collision systems. For high-multiplicity p+Pb collisions, an anticorrelation of v_{2} and v_{3} is observed, with a similar correlation strength as in PbPb data at the same multiplicity. The new correlation results strengthen the case for a common origin of the collectivity seen in p+Pb and PbPb collisions in the measured multiplicity range.
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A search for physics beyond the standard model in events with one or more high-momentum Higgs bosons, H, decaying to pairs of b quarks in association with missing transverse momentum is presented. The data, corresponding to an integrated luminosity of 35.9 fb^{-1}, were collected with the CMS detector at the LHC in proton-proton collisions at the center-of-mass energy sqrt[s]=13 TeV. The analysis utilizes a new b quark tagging technique based on jet substructure to identify jets from Hâbb[over ¯]. Events are categorized by the multiplicity of H-tagged jets, jet mass, and the missing transverse momentum. No significant deviation from standard model expectations is observed. In the context of supersymmetry (SUSY), limits on the cross sections of pair-produced gluinos are set, assuming that gluinos decay to quark pairs, H (or Z), and the lightest SUSY particle, LSP, through an intermediate next-to-lightest SUSY particle, NLSP. With large mass splitting between the NLSP and LSP, and 100% NLSP branching fraction to H, the lower limit on the gluino mass is found to be 2010 GeV.
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A search is reported for a narrow vector resonance decaying to quark-antiquark pairs in proton-proton collisions at sqrt[s]=13 TeV, collected with the CMS detector at the LHC. The data sample corresponds to an integrated luminosity of 2.7 fb^{-1}. The vector resonance is produced at large transverse momenta, with its decay products merged into a single jet. The resulting signature is a peak over background in the distribution of the invariant mass of the jet. The results are interpreted in the framework of a leptophobic vector resonance and no evidence is found for such particles in the mass range of 100-300 GeV. Upper limits at 95% confidence level on the production cross section are presented in a region of mass-coupling phase space previously unexplored at the LHC. The region below 140 GeV has not been explored by any previous experiments.
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The production of jets in association with Z bosons, reconstructed via the µ^{+}µ^{-} and e^{+}e^{-} decay channels, is studied in pp and, for the first time, in Pb-Pb collisions. Both data samples were collected by the CMS experiment at the LHC, at a nucleon-nucleon center-of-mass energy of 5.02 TeV. The Pb-Pb collisions were analyzed in the 0%-30% centrality range. The back-to-back azimuthal alignment was studied in both pp and Pb-Pb collisions for Z bosons with transverse momentum p_{T}^{Z}>60 GeV/c and a recoiling jet with p_{T}^{jet}>30 GeV/c. The p_{T} imbalance x_{jZ}=p_{T}^{jet}/p_{T}^{Z}, as well as the average number of jet partners per Z, R_{jZ}, was studied in intervals of p_{T}^{Z}. The R_{jZ} is found to be smaller in Pb-Pb than in pp collisions, which suggests that in Pb-Pb collisions a larger fraction of partons associated with the Z bosons fall below the 30 GeV/c p_{T}^{jet} threshold because they lose energy.
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Charge-dependent azimuthal particle correlations with respect to the second-order event plane in p-Pb and PbPb collisions at a nucleon-nucleon center-of-mass energy of 5.02 TeV have been studied with the CMS experiment at the LHC. The measurement is performed with a three-particle correlation technique, using two particles with the same or opposite charge within the pseudorapidity range |η|<2.4, and a third particle measured in the hadron forward calorimeters (4.4<|η|<5). The observed differences between the same and opposite sign correlations, as functions of multiplicity and η gap between the two charged particles, are of similar magnitude in p-Pb and PbPb collisions at the same multiplicities. These results pose a challenge for the interpretation of charge-dependent azimuthal correlations in heavy ion collisions in terms of the chiral magnetic effect.