Angiogenic output in viral hepatitis, C and B, and HCV-associated hepatocellular carcinoma

Introduction: Angiogenesis is known to play a pivotal role in most of malignancy, including HCC, and in chronic inflammation.Aim: To investigate the angiogenic output in HCV and HBV infection and its implication in the development of HCV associated HCC.Materials and methods: Blood samples were collected and grouped as; HS healthy subjects control group; HCC–HCV; chronic HCV infected patient group (HCV+ve) who are positive for serum anti-HCV antibodies and HCV–RNA; anti-HCV antibody positive and HCV–RNA negative patient group (HCVve); patients with positive HBsAg and HBV-DNA group (HBV+ve); and HBsAg positive and HBV-DNA negative patient group (HBVve). Serum levels of vascular endothelial growth factor, angiopoietin-2, endostatin and angiostatin were assessed in different studied groups.Results: The level of sVEGF was insignificantly elevated in both HCV+ve and HCVve groups when compared with controls, while Ang-2, sES and sAS were significantly elevated in both groups as compared with healthy controls. The studied parameters were significantly elevated in HBV-+ve patients when compared with the control. However, HBVve patients showed significantly elevated levels in sAng-2, sES and sAS when compared with the control while the level of sVEGF was equal to that of controls. In patients with HCC, the studied parameters showed a significant elevation when compared with healthy controls and patients either with HBV or HCV infection except for sAS in the case of HCV-+ve patients and VEGF for HBV-+ve patients who were also higher but not significant.Conclusion: The increased hepatic angiogenesis in chronic HCV and HBV could provide the molecular basis for liver carcinogenesis and contribute to the increased risk of HCC in patients with cirrhosis due to HCV and/or HBV.KEYWORDS Angiogenesis; HCC; HCV; HB

Analysis of IL28B Variants in an Egyptian Population Defines the 20 Kilobases Minimal Region Involved in Spontaneous Clearance of Hepatitis C Virus

Spontaneous clearance of hepatitis C virus (HCV) occurs in ∼30% of acute infections. Host genetics play a major role in HCV clearance, with a strong effect of single nucleotide polymorphisms (SNPs) of the IL28B gene already found in different populations, mostly infected with viral genotypes 1 and 3. Egypt has the highest prevalence of HCV infection in the world, which is mostly due to viral genotype 4. We investigated the role of several IL28B SNPs in HCV spontaneous clearance in an Egyptian population. We selected nine SNPs within the IL28B genomic region covering the linkage disequilibrium (LD) block known to be associated with HCV clearance in European populations. These SNPs were genotyped in 261 HCV-infected Egyptian subjects (130 with spontaneous clearance and 131 with chronic infection). The most associated SNPs were rs12979860 (P = 1.6×10−7) and the non-synonymous IL28B SNP, rs8103142 (P = 1.6×10−7). Interestingly, three SNPs at the two bounds of the region were monomorphic, reducing the size of the LD block in which the causal variants are potentially located to ∼20 kilobases. HCV clearance in Egypt was associated with a region of IL28B smaller than that identified in European populations, and involved the non-synonymous IL28B SNP, rs8103142

Risk Factors for Anthroponotic Cutaneous Leishmaniasis at the Household Level in Kabul, Afghanistan

Cutaneous leishmaniasis is a vector-borne protozoan disease that is characterized by cutaneous lesions which develop at the site of the insect bite. Lesions can vary in severity, clinical appearance, and time to cure; in a proportion of patients lesions can become chronic, leading to disfiguring mucosal leishmaniasis or leishmaniasis recidvans. Albeit not fatal, cutaneous leishmaniasis can have a significant social impact as it may lead to severe stigmatisation of affected individuals when lesions or scars occur on the face and exposed extremeties. Over the last 10–20 years there has been an increase in the number of leishmaniasis cases reported in South Asia, particularly in Afghanistan. Little is known about the household-level risk factors for infection and disease. Here we confirm previous reports that had shown the association of cutaneous leishmaniasis with age and clustering of cases at the household-level. Additionally, we show that risk of cutaneous leishmaniasis is associated with household construction (i.e. brick walls) and design (i.e. proportion of windows with screens)

Life-Course Genome-wide Association Study Meta-analysis of Total Body BMD and Assessment of Age-Specific Effects.

Bone mineral density (BMD) assessed by DXA is used to evaluate bone health. In children, total body (TB) measurements are commonly used; in older individuals, BMD at the lumbar spine (LS) and femoral neck (FN) is used to diagnose osteoporosis. To date, genetic variants in more than 60 loci have been identified as associated with BMD. To investigate the genetic determinants of TB-BMD variation along the life course and test for age-specific effects, we performed a meta-analysis of 30 genome-wide association studies (GWASs) of TB-BMD including 66,628 individuals overall and divided across five age strata, each spanning 15 years. We identified variants associated with TB-BMD at 80 loci, of which 36 have not been previously identified; overall, they explain approximately 10% of the TB-BMD variance when combining all age groups and influence the risk of fracture. Pathway and enrichment analysis of the association signals showed clustering within gene sets implicated in the regulation of cell growth and SMAD proteins, overexpressed in the musculoskeletal system, and enriched in enhancer and promoter regions. These findings reveal TB-BMD as a relevant trait for genetic studies of osteoporosis, enabling the identification of variants and pathways influencing different bone compartments. Only variants in ESR1 and close proximity to RANKL showed a clear effect dependency on age. This most likely indicates that the majority of genetic variants identified influence BMD early in life and that their effect can be captured throughout the life course

MUSiC : a model-unspecific search for new physics in proton-proton collisions at root s=13TeV

Results of the Model Unspecific Search in CMS (MUSiC), using proton-proton collision data recorded at the LHC at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1), are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches.Peer reviewe

Measurement of the W gamma Production Cross Section in Proton-Proton Collisions at root s=13 TeV and Constraints on Effective Field Theory Coefficients

A fiducial cross section for W gamma production in proton-proton collisions is measured at a center-of-mass energy of 13 TeV in 137 fb(-1) of data collected using the CMS detector at the LHC. The W -> e nu and mu nu decay modes are used in a maximum-likelihood fit to the lepton-photon invariant mass distribution to extract the combined cross section. The measured cross section is compared with theoretical expectations at next-to-leading order in quantum chromodynamics. In addition, 95% confidence level intervals are reported for anomalous triple-gauge couplings within the framework of effective field theory.Peer reviewe

Measurement of the top quark mass using events with a single reconstructed top quark in pp collisions at root s=13 TeV

Abstract:A measurement of the top quark mass is performed using a data sample en-riched with single top quark events produced in thetchannel. The study is based on proton-proton collision data, corresponding to an integrated luminosity of 35.9 fb−1, recorded at√s= 13TeV by the CMS experiment at the LHC in 2016. Candidate events are selectedby requiring an isolated high-momentum lepton (muon or electron) and exactly two jets,of which one is identified as originating from a bottom quark. Multivariate discriminantsare designed to separate the signal from the background. Optimized thresholds are placedon the discriminant outputs to obtain an event sample with high signal purity. The topquark mass is found to be172.13+0.76−0.77GeV, where the uncertainty includes both the sta-tistical and systematic components, reaching sub-GeV precision for the first time in thisevent topology. The masses of the top quark and antiquark are also determined separatelyusing the lepton charge in the final state, from which the mass ratio and difference aredetermined to be0.9952+0.0079−0.0104and0.83+1.79−1.35GeV, respectively. The results are consistentwithCPTinvariance

4E assessment of power generation systems for a mobile house in emergency condition using solar energy: a case study

In this study, a solar parabolic trough concentrator (PTC) was evaluated as a heat source of a power generation system based on energy (E1), exergy (E2), environmental (E3), and economic (E4) analyses. Various configurations of power generation systems were investigated, including the solar SRC (SRC) and solar ORC (ORC). Water and R113 were used as heat transfer fluids of SRC and ORC system, respectively. It should be mentioned that the proposed solar systems were evaluated for providing the required power of a mobile house in an emergency condition such as an earthquake that was happened in Kermanshah, Iran, in 2016 with many homeless people. The PTC system was optically and thermally investigated based on sensitivity analysis. The optimized PTC system was assumed as a heat source of the RC with two various configurations for power generation. Then, the solar RC systems were investigated based on 4E analyses for providing the power of the mobile house based on various numbers of solar RC units. It was concluded that the solar SRC system could be recommended for achieving the highest 4E performance. The highest value of its energy efficiency was found at 24.60% and of his exergy at 26.37%. On the other hand, the ORC system has energy and exergy efficiencies at 17.64% and 18.91%, respectively, which are significantly lower than the efficiencies of the SRC system. The optimum heat source temperature for the SRC system is found at 650 K, while for the ORC system at 499 K. Moreover, the best economic performance was found with the SRC system with a payback period of 7.47 years. Finally, the CO2 mitigated per annum (φCO2) was estimated at 5.29 (tones year−1), and the carbon credit (ZCO2) was calculated equal to 76.71 ($ year−1)

Measurements of production cross sections of the Higgs boson in the four-lepton final state in proton–proton collisions at √s=13Te

Production cross sections of the Higgs boson are measured in the H → Z Z → 4 ℓ (ℓ=e,μ) decay channel. A data sample of proton–proton collisions at a center-of-mass energy of 13Te, collected by the CMS detector at the LHC and corresponding to an integrated luminosity of 137fb-1 is used. The signal strength modifier μ, defined as the ratio of the Higgs boson production rate in the 4 ℓ channel to the standard model (SM) expectation, is measured to be μ=0.94±0.07(stat)-0.08+0.09(syst) at a fixed value of mH=125.38Ge. The signal strength modifiers for the individual Higgs boson production modes are also reported. The inclusive fiducial cross section for the H → 4 ℓ process is measured to be 2.84-0.22+0.23(stat)-0.21+0.26(syst)fb, which is compatible with the SM prediction of 2.84±0.15fb for the same fiducial region. Differential cross sections as a function of the transverse momentum and rapidity of the Higgs boson, the number of associated jets, and the transverse momentum of the leading associated jet are measured. A new set of cross section measurements in mutually exclusive categories targeted to identify production mechanisms and kinematical features of the events is presented. The results are in agreement with the SM predictions.STFC, Marie-Curie program and the European Research Council and Horizon 2020 Gran