Molecular mechanisms of extracellular-ATP-mediated colorectal cancer progression: Implication of purinergic receptors-mediated nucleocytoplasmic shuttling of HuR.

One of the leading causes of cancer-related deaths worldwide is colorectal cancer (CRC). Extracellular ATP (e-ATP) and purinergic receptors (P2R) play a central role in CRC proliferation and progression. Human antigen R (HuR) is becoming more and more understood to be essential for the expression of genes linked to cancer. The current study demonstrates that ATP can mediate CRC (Caco-2 cells) progression via induction of HuR nucleocytoplasmic shuttling and subsequent expression of cancer-related genes, a consequence mostly mediated via the P2R receptor. It was also noted that suppression of HuR activity by using dihydrotanshinone I (DHTS) prevents cancer-related gene expression and subsequent CRC (Caco-2 cells) progression induced by ATP. The expression of cyclin A2/cyclin-dependent kinase 2 (CDK2), Bcl-2, ProT-α, hypoxia-inducible factor1-α (HIF1-α), vascular endothelial growth factor A (VEGF-A), transforming growth factor-ß (TGF-ß) and matrix metallopeptidase 9 (MMP-9) induced by ATP were highly reduced in the presence of either PPADS (non-selective P2R antagonist) or DHTS. In addition, e-ATP-induced Caco-2 cell proliferation as well as cell survival were highly reduced in the presence of either PPADS or DHTS or selective CDK-2 inhibitor (Roscovitine) or selective Bcl-2 inhibitor (ABT-263). Furthermore, it was found that MMP-9 is critical for Caco-2 cells migration induced by e-ATP as demonstrated by a clear reduction in cells migration in the presence of a selective MMP-9 inhibitor (Marimastat). Collectively, these data demonstrate that ATP through P2R activation can induce HuR nucleocytoplasmic shuttling that could be translated into an increase in cancer-related genes expression and subsequent, cell proliferation and progression.

Measurement of the J/ψ Polarization with Respect to the Event Plane in Pb-Pb Collisions at the LHC.

We study the polarization of inclusive J/ψ produced in Pb-Pb collisions at sqrt[s_{NN}]=5.02 TeV at the LHC in the dimuon channel, via the measurement of the angular distribution of its decay products. We perform the study in the rapidity region 2.5

First Measurement of Antideuteron Number Fluctuations at Energies Available at the Large Hadron Collider.

The first measurement of event-by-event antideuteron number fluctuations in high energy heavy-ion collisions is presented. The measurements are carried out at midrapidity (|η|<0.8) as a function of collision centrality in Pb-Pb collisions at sqrt[s_{NN}]=5.02 TeV using the ALICE detector. A significant negative correlation between the produced antiprotons and antideuterons is observed in all collision centralities. The results are compared with a state-of-the-art coalescence calculation. While it describes the ratio of higher order cumulants of the antideuteron multiplicity distribution, it fails to describe quantitatively the magnitude of the correlation between antiproton and antideuteron production. On the other hand, thermal-statistical model calculations describe all the measured observables within uncertainties only for correlation volumes that are different with respect to those describing proton yields and a similar measurement of net-proton number fluctuations.

Polarization of Λ and Λ[over ¯] Hyperons along the Beam Direction in Pb-Pb Collisions at sqrt[s]_{NN}=5.02 TeV.

The polarization of the Λ and Λ[over ¯] hyperons along the beam (z) direction, P_{z}, has been measured in Pb-Pb collisions at sqrt[s_{NN}]=5.02 TeV recorded with ALICE at the Large Hadron Collider (LHC). The main contribution to P_{z} comes from elliptic flow-induced vorticity and can be characterized by the second Fourier sine coefficient P_{z,s2}=⟨P_{z}sin(2φ-2Ψ_{2})⟩, where φ is the hyperon azimuthal emission angle and Ψ_{2} is the elliptic flow plane angle. We report the measurement of P_{z,s2} for different collision centralities and in the 30%-50% centrality interval as a function of the hyperon transverse momentum and rapidity. The P_{z,s2} is positive similarly as measured by the STAR Collaboration in Au-Au collisions at sqrt[s_{NN}]=200 GeV, with somewhat smaller amplitude in the semicentral collisions. This is the first experimental evidence of a nonzero hyperon P_{z} in Pb-Pb collisions at the LHC. The comparison of the measured P_{z,s2} with the hydrodynamic model calculations shows sensitivity to the competing contributions from thermal and the recently found shear-induced vorticity, as well as to whether the polarization is acquired at the quark-gluon plasma or the hadronic phase.

Hypertriton Production in p-Pb Collisions at sqrt[s_{NN}]=5.02 TeV.

The study of nuclei and antinuclei production has proven to be a powerful tool to investigate the formation mechanism of loosely bound states in high-energy hadronic collisions. The first measurement of the production of _{Λ}^{3}H in p-Pb collisions at sqrt[s_{NN}]=5.02 TeV is presented in this Letter. Its production yield measured in the rapidity interval -1

Measurement of Prompt D

The p_{T}-differential production cross sections of prompt D^{0}, Λ_{c}^{+}, and Σ_{c}^{0,++}(2455) charmed hadrons are measured at midrapidity (|y|<0.5) in pp collisions at sqrt[s]=13 TeV. This is the first measurement of Σ_{c}^{0,++} production in hadronic collisions. Assuming the same production yield for the three Σ_{c}^{0,+,++} isospin states, the baryon-to-meson cross section ratios Σ_{c}^{0,+,++}/D^{0} and Λ_{c}^{+}/D^{0} are calculated in the transverse momentum (p_{T}) intervals 2

Measurement of the Groomed Jet Radius and Momentum Splitting Fraction in pp and Pb-Pb Collisions at sqrt[s_{NN}]=5.02 TeV.

This article presents groomed jet substructure measurements in pp and Pb-Pb collisions at sqrt[s_{NN}]=5.02 TeV with the ALICE detector. The soft drop grooming algorithm provides access to the hard parton splittings inside a jet by removing soft wide-angle radiation. We report the groomed jet momentum splitting fraction, z_{g}, and the (scaled) groomed jet radius, θ_{g}. Charged-particle jets are reconstructed at midrapidity using the anti-k_{T} algorithm with resolution parameters R=0.2 and R=0.4. In heavy-ion collisions, the large underlying event poses a challenge for the reconstruction of groomed jet observables, since fluctuations in the background can cause groomed parton splittings to be misidentified. By using strong grooming conditions to reduce this background, we report these observables fully corrected for detector effects and background fluctuations for the first time. A narrowing of the θ_{g} distribution in Pb-Pb collisions compared to pp collisions is seen, which provides direct evidence of the modification of the angular structure of jets in the quark-gluon plasma. No significant modification of the z_{g} distribution in Pb-Pb collisions compared to pp collisions is observed. These results are compared with a variety of theoretical models of jet quenching, and provide constraints on jet energy-loss mechanisms and coherence effects in the quark-gluon plasma.

Experimental Evidence for an Attractive p-ϕ Interaction.

This Letter presents the first experimental evidence of the attractive strong interaction between a proton and a ϕ meson. The result is obtained from two-particle correlations of combined p-ϕ⊕ p[over ¯]-ϕ pairs measured in high-multiplicity pp collisions at sqrt[s]=13 TeV by the ALICE Collaboration. The spin-averaged scattering length and effective range of the p-ϕ interaction are extracted from the fully corrected correlation function employing the Lednický-Lyuboshits approach. In particular, the imaginary part of the scattering length vanishes within uncertainties, indicating that inelastic processes do not play a prominent role for the p-ϕ interaction. These data demonstrate that the interaction is dominated by elastic p-ϕ scattering. Furthermore, an analysis employing phenomenological Gaussian- and Yukawa-type potentials is conducted. Under the assumption of the latter, the N-ϕ coupling constant is found to be g_{N-ϕ}=0.14±0.03(stat)±0.02(syst). This work provides valuable experimental input to accomplish a self-consistent description of the N-ϕ interaction, which is particularly relevant for the more fundamental studies on partial restoration of chiral symmetry in nuclear medium.

Measurement of the Cross Sections of Ξ_{c}

The p_{T}-differential cross sections of prompt charm-strange baryons Ξ_{c}^{0} and Ξ_{c}^{+} were measured at midrapidity (|y|<0.5) in proton-proton (pp) collisions at a center-of-mass energy sqrt[s]=13 TeV with the ALICE detector at the LHC. The Ξ_{c}^{0} baryon was reconstructed via both the semileptonic decay (Ξ^{-}e^{+}ν_{e}) and the hadronic decay (Ξ^{-}π^{+}) channels. The Ξ_{c}^{+} baryon was reconstructed via the hadronic decay (Ξ^{-}π^{+}π^{+}) channel. The branching-fraction ratio BR(Ξ_{c}^{0}→Ξ^{-}e^{+}ν_{e})/BR(Ξ_{c}^{0}→Ξ^{-}π^{+})=1.38±0.14(stat)±0.22(syst) was measured with a total uncertainty reduced by a factor of about 3 with respect to the current world average reported by the Particle Data Group. The transverse momentum (p_{T}) dependence of the Ξ_{c}^{0}- and Ξ_{c}^{+}-baryon production relative to the D^{0} meson and to the Σ_{c}^{0,+,++}- and Λ_{c}^{+}-baryon production are reported. The baryon-to-meson ratio increases toward low p_{T} up to a value of approximately 0.3. The measurements are compared with various models that take different hadronization mechanisms into consideration. The results provide stringent constraints to these theoretical calculations and additional evidence that different processes are involved in charm hadronization in electron-positron (e^{+}e^{-}) and hadronic collisions.

Soft-Dielectron Excess in Proton-Proton Collisions at sqrt[s]=13 TeV.

A measurement of dielectron production in proton-proton (pp) collisions at sqrt[s]=13 TeV, recorded with the ALICE detector at the CERN LHC, is presented in this Letter. The data set was recorded with a reduced magnetic solenoid field. This enables the investigation of a kinematic domain at low dielectron (ee) invariant mass m_{ee} and pair transverse momentum p_{T,ee} that was previously inaccessible at the LHC. The cross section for dielectron production is studied as a function of m_{ee}, p_{T,ee}, and event multiplicity dN_{ch}/dη. The expected dielectron rate from hadron decays, called hadronic cocktail, utilizes a parametrization of the measured η/π^{0} ratio in pp and proton-nucleus collisions, assuming that this ratio shows no strong dependence on collision energy at low transverse momentum. Comparison of the measured dielectron yield to the hadronic cocktail at 0.15

Multiharmonic Correlations of Different Flow Amplitudes in Pb-Pb Collisions at sqrt[s_{NN}]=2.76 TeV.

The event-by-event correlations between three flow amplitudes are measured for the first time in Pb-Pb collisions, using higher-order symmetric cumulants. We find that different three-harmonic correlations develop during the collective evolution of the medium when compared to correlations that exist in the initial state. These new results cannot be interpreted in terms of previous lower-order flow measurements since contributions from two-harmonic correlations are explicitly removed in the new observables. A comparison to Monte Carlo simulations provides new and independent constraints for the initial conditions and system properties of nuclear matter created in heavy-ion collisions.

Λ_{c}

The prompt production of the charm baryon Λ_{c}^{+} and the Λ_{c}^{+}/D^{0} production ratios were measured at midrapidity with the ALICE detector in pp and p-Pb collisions at sqrt[s_{NN}]=5.02 TeV. These new measurements show a clear decrease of the Λ_{c}^{+}/D^{0} ratio with increasing transverse momentum (p_{T}) in both collision systems in the range 2

Elliptic Flow of Electrons from Beauty-Hadron Decays in Pb-Pb Collisions at sqrt[s_{NN}]=5.02 TeV.

The elliptic flow of electrons from beauty hadron decays at midrapidity (|y|<0.8) is measured in Pb-Pb collisions at sqrt[s_{NN}]=5.02 TeV with the ALICE detector at the LHC. The azimuthal distribution of the particles produced in the collisions can be parametrized with a Fourier expansion, in which the second harmonic coefficient represents the elliptic flow, v_{2}. The v_{2} coefficient of electrons from beauty hadron decays is measured for the first time in the transverse momentum (p_{T}) range 1.3-6 GeV/c in the centrality class 30%-50%. The measurement of electrons from beauty-hadron decays exploits their larger mean proper decay length cτ≈500 µm compared to that of charm hadrons and most of the other background sources. The v_{2} of electrons from beauty hadron decays at midrapidity is found to be positive with a significance of 3.75 σ. The results provide insights into the degree of thermalization of beauty quarks in the medium. A model assuming full thermalization of beauty quarks is strongly disfavored by the measurement at high p_{T}, but is in agreement with the results at low p_{T}. Transport models including substantial interactions of beauty quarks with an expanding strongly interacting medium describe the measurement within uncertainties.

Probing the Effects of Strong Electromagnetic Fields with Charge-Dependent Directed Flow in Pb-Pb Collisions at the LHC.

The first measurement at the LHC of charge-dependent directed flow (v_{1}) relative to the spectator plane is presented for Pb-Pb collisions at sqrt[s_{NN}]=5.02 TeV. Results are reported for charged hadrons and D^{0} mesons for the transverse momentum intervals p_{T}>0.2 GeV/c and 3

Evidence of Spin-Orbital Angular Momentum Interactions in Relativistic Heavy-Ion Collisions.

The first evidence of spin alignment of vector mesons (K^{*0} and ϕ) in heavy-ion collisions at the Large Hadron Collider (LHC) is reported. The spin density matrix element ρ_{00} is measured at midrapidity (|y|<0.5) in Pb-Pb collisions at a center-of-mass energy (sqrt[s_{NN}]) of 2.76 TeV with the ALICE detector. ρ_{00} values are found to be less than 1/3 (1/3 implies no spin alignment) at low transverse momentum (p_{T}<2 GeV/c) for K^{*0} and ϕ at a level of 3σ and 2σ, respectively. No significant spin alignment is observed for the K_{S}^{0} meson (spin=0) in Pb-Pb collisions and for the vector mesons in pp collisions. The measured spin alignment is unexpectedly large but qualitatively consistent with the expectation from models which attribute it to a polarization of quarks in the presence of angular momentum in heavy-ion collisions and a subsequent hadronization by the process of recombination.

Measurement of the Low-Energy Antideuteron Inelastic Cross Section.

In this Letter, we report the first measurement of the inelastic cross section for antideuteron-nucleus interactions at low particle momenta, covering a range of 0.3≤p<4 GeV/c. The measurement is carried out using p-Pb collisions at a center-of-mass energy per nucleon-nucleon pair of sqrt[s_{NN}]=5.02 TeV, recorded with the ALICE detector at the CERN LHC and utilizing the detector material as an absorber for antideuterons and antiprotons. The extracted raw primary antiparticle-to-particle ratios are compared to the results from detailed ALICE simulations based on the geant4 toolkit for the propagation of (anti)particles through the detector material. The analysis of the raw primary (anti)proton spectra serves as a benchmark for this study, since their hadronic interaction cross sections are well constrained experimentally. The first measurement of the inelastic cross section for antideuteron-nucleus interactions averaged over the ALICE detector material with atomic mass numbers ⟨A⟩=17.4 and 31.8 is obtained. The measured inelastic cross section points to a possible excess with respect to the Glauber model parametrization used in geant4 in the lowest momentum interval of 0.3≤p<0.47 GeV/c up to a factor 2.1. This result is relevant for the understanding of antimatter propagation and the contributions to antinuclei production from cosmic ray interactions within the interstellar medium. In addition, the momentum range covered by this measurement is of particular importance to evaluate signal predictions for indirect dark-matter searches.

Mixed phenotype acute leukaemia with t(9,22), BCR-ABL1: A case report.

INTRODUCTION: Mixed phenotype acute leukaemia (MPAL) is a rare entity of acute leukaemia. CASE REPORT: Here we report a case of a 39-year-old lady, with an incidental finding of hyperleukocytosis (white blood cells count: 139.2 x 109/L). Her peripheral blood film revealed 36% of blasts and a bone marrow aspiration showed 53% of blasts. Immunophenotyping showed a population of blasts exhibiting positivity of two lineages, myeloid lineage and B-lymphoid lineage with strong positivity of CD34 and terminal deoxynucleotidyl transferase (Tdt). A conventional karyotyping revealed the presence of Philadelphia chromosome. She was diagnosed with MPAL with t(9,22), BCR ABL1, which carried a poor prognosis. She was treated with acute lymphoblastic leukaemia (ALL) chemotherapy protocol coupled with a tyrosine kinase inhibitor and was planned for an allogeneic stem cells transplant. CONCLUSION: This MPAL case was diagnosed incidentally in an asymptomatic patient during medical check-up. We highlight this rare case report to raise the awareness about this rare disease. Understanding the pathogenesis of the disease with the underlying genes responsible for triggering the disease, uniform protocols for diagnosis and targeted treatment will help for proper management of these patients.

The effects of rectal cancer surgery on the anatomical localisation of ureters - a prospective observational study.

INTRODUCTION: Anatomical changes after surgery and fibrotic adhesions increase the organ laceration risk, including that of the ureter, in recurrent cases and secondary operations. The aim of this study was to investigate the changes in the anatomical localisations of the ureters via computed tomography urography in patients undergoing rectal cancer surgery. MATERIAL AND METHODS: The study involved prospectively collected data on the changes of ureteral location preoperatively and postoperatively in patients with operated rectal cancer. Distances (mm) of ureters determined midline in the computed tomography urogram phase. RESULTS: A total of 18 patients were included. The mean distances between the right (R1 ) and left (L1 ) ureters and the mid-vertebral line before the surgery were 30.9 ±5.4 mm and 34.5 ±9.9 mm, respectively. The postoperative distances between them (R2 and L2 ) were 26.4 ±9.1 mm and 29.5 ±9.9 mm, respectively. The R2 measurement showed that 83.3% (15/18) of the right ureters had deviated medially, whereas 16.7% (3/18) of them had deviated laterally. The L2 measurements showed that 88.8% (16/18) of the left ureters had deviated medially, whereas 11.2% (2/18) of them had deviated laterally. The differences between the preoperative and postoperative measurements of the right and left ureter positions were 4.5 ±9.2 mm and 4.9 ±4.6 mm, respectively, with the displacement in the left ureter being statistically significant (p ≤ 0.001). CONCLUSIONS: Rectal cancer surgery causes medially deviated changes in the positions of the ureters.

Impact of ICU Structure and Processes of Care on Outcomes After Severe Traumatic Brain Injury: A Multicenter Cohort Study.

OBJECTIVES: It is uncertain whether dedicated neurocritical care units are associated with improved outcomes for critically ill neurologically injured patients in the era of collaborative protocol-driven care. We examined the association between dedicated neurocritical care units and mortality and the effects of standardized management protocols for severe traumatic brain injury. DESIGN: We surveyed trauma medical directors from centers participating in the American College of Surgeons Trauma Quality Improvement Program to obtain information about ICU structure and processes of care. Survey data were then linked to the Trauma Quality Improvement Program registry, and random-intercept hierarchical multivariable modeling was used to evaluate the association between dedicated neurocritical care units, the presence of standardized management protocols and mortality. SETTING: Trauma centers in North America participating in Trauma Quality Improvement Program. PATIENTS: Data were analyzed from 9,773 adult patients with isolated severe traumatic brain injury admitted to 134 Trauma Quality Improvement Program centers between 2011 and 2013. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Only 50 ICUs (37%) were dedicated neurocritical care units, whereas 84 (63%) were general ICUs. Rates of standardized management protocols were similar comparing dedicated neurocritical care units and general ICUs. Among severe TBI patients admitted to trauma centers enrolled in Trauma Quality Improvement Program, care in a dedicated neurocritical care unit did not improve risk-adjusted in-hospital survival (odds ratio, 0.97; 95% CI, 0.80-1.19; p = 0.79). However, the presence of a standardized management protocol for these patients was associated with lower risk-adjusted in-hospital mortality (odds ratio, 0.77; 95% CI, 0.63-0.93; p = 0.009). CONCLUSIONS: Compared with dedicated neurocritical care models, standardized management protocols for severe traumatic brain injured patients are process-targeted intervention strategies that may improve clinical outcomes.

Differential expression of CYP2j2 gene and protein in Camelus dromedarius.

CYP2J2 is a member of the cytochrome P450 superfamily. It had been described in different mammalian species; however, no studies have described this gene in Camelus dromedarius. CYP2J2 is an epoxygenase enzyme which oxidizes various fatty acids, mainly arachidonic acid, via NADPH-dependent epoxidation to generate epoxyeicosatrienoic acids (EETs). It is a multi-functional enzyme that plays crucial roles in inflammation, cancer, drug metabolism, and embryo development. It controls the water re-absorption in the kidney and maintains the blood pressure and glucose homeostasis. This study is considered the first report investigating the differential expression profiles of the CYP2J2 mRNA and protein in the liver, heart, and kidney of Camelus dromedarius. A total of 30 samples were used to determine the expression of both CYP2J2 mRNA and protein using qRT-PCR and western blotting methods, respectively. The mRNA level of CYP2J2 was significantly elevated in the liver compared to that in the heart and kidney. The tissue distribution of the CYP2J2 protein was coherent to its transcript level in the kidney, but not in the liver and heart samples. The difference between the CYP2J2 mRNA and protein distributions in the three studied organs may be attributed to the mechanism by which the CYP2J2 might be involved in the adaptability of the camel to the arid environment.