On the possible secondary component of the order parameter observed in London penetration depth measurements

We discuss the effect of a secondary component of the superconducting order parameter on the superfluid density in the cuprates. If we assume a main $d_{x^2-y^2}$ gap, the most stable realization of a mixed order parameter has a time-reversal breaking $d_{x^2-y^2}+ \imath d_{xy}$ symmetry. In this state the nodes are removed and the temperature dependence of the superfluid density changes from the linear behavior of a pure d-wave to a more rounded shape at low temperature. The latter is compatible with the behavior experimentally observed in the in-plane magnetic field penetration depth of optimally doped $La_{2-x}Sr_xCuO_2$ and $YBa_2Cu_3O_{7-\delta}$.Comment: 4 pages, 2 figures, submitted to Phys. Rev.

Early diagnosis of liver cancer: an appraisal of international recommendations and future perspectives

AbstractAll Societies, AASLD, EASL, APASL and JSH, identify patients with cirrhosis as a target population for surveillance, with minor differences for additional categories of patients, such as chronic hepatitis B and hepatitis C patients with advanced fibrosis. According to AASLD, liver disease related to metabolic diseases including diabetes and obesity is a recognized target of screening, since those conditions have been causally related to HCC. All societies endorse radiological non‐invasive techniques as the mainstay for early diagnosis of HCC, but discrepancies exist between Societies on the utilization of contrast‐enhanced ultrasound and utilization of serum markers for surveillance and diagnosis of HCC. The diagnostic algorithm of the international societies differ substantially in the anatomic paradigm of EASL and APASL which identify 1 cm size as the starting point for radiological diagnosis of HCC compared to APASL algorithm based on the dynamic pattern of contrast imaging, independently on tumour size. While strengthening prediction in individual patients is expected to improve cost‐effectiveness ratios of screening, the benefits of pre‐treatment patient stratification by clinical, histological and genetic scores remain uncertain and exclusion of patients with severe co‐morbidities and advanced age is still debated

Kondo screening in Co adatoms with full Coulomb interaction

Using a numerically exact first-principles many-body approach, we revisit the "prototypical" Kondo case of a cobalt impurity on copper. Even though this is considered a well understood example of the Kondo effect, we reveal an unexpectedly strong dependence of the screening properties on the parametrization of the local Coulomb tensor. As a consequence, the Kondo temperature can vary by orders of magnitude depending on the complexity of the parametrization of the electron-electron interaction. Further, we challenge the established picture of a spin-$1$ moment involving two cobalt $d$-orbitals only, as orbital-mixing interaction terms boost the contribution of the remainder of the $d$-shell.Comment: 15 pages, 14 figures; final version with extended bibliography and appendi

Polydatin Induces Differentiation and Radiation Sensitivity in Human Osteosarcoma Cells and Parallel Secretion through Lipid Metabolite Secretion

Osteosarcoma is a bone cancer characterized by the production of osteoid tissue and immature bone from mesenchymal cells. Osteosarcoma mainly affects long bones (femur is most frequently site) and occur in children and young adults with greater incidence. Here, we investigated the role accomplished by polydatin, a natural antioxidative compound, in promoting osteogenic differentiation alone or after radiation therapy on osteosarcoma cells. In vitro, polydatin significantly induced cell cycle arrest in S-phase and enhanced bone alkaline phosphatase activity. Moreover, the differentiation process was paralleled by the activation of Wnt-β-catenin pathway. In combination with radiotherapy, the pretreatment with polydatin promoted a radiosensitizing effect on osteosarcoma cancer cells as demonstrated by the upregulation of osteogenic markers and reduced clonogenic survival of tumor cells. Additionally, we analyzed, by mass spectrometry, the secretion of sphingolipid, ceramides, and their metabolites in osteosarcoma cells treated with polydatin. Overall, our results demonstrate that polydatin, through the secretion of sphingolipids and ceramide, induced osteogenic differentiation, alone and in the presence of ionizing therapy. Future investigations are needed to validate the use of polydatin in clinical practice as a potentiating agent of radiotherapy-induced anticancer effects

Impact of Sarcopenia on the Survival of Patients with Hepatocellular Carcinoma Treated with Sorafenib

Background and aims: Sarcopenia has been associated with poor outcomes in patients with cirrhosis and hepatocellular carcinoma. We investigated the impact of sarcopenia on survival in patients with advanced hepatocellular carcinoma treated with Sorafenib. Methods: A total of 328 patients were retrospectively analyzed. All patients had an abdominal CT scan within 8 weeks prior to the start of treatment. Two cohorts of patients were analyzed: the "Training Group" (215 patients) and the "Validation Group" (113 patients). Sarcopenia was defined by reduced skeletal muscle index, calculated from an L3 section CT image. Results: Sarcopenia was present in 48% of the training group and 50% of the validation group. At multivariate analysis, sarcopenia (HR: 1.47, p = 0.026 in training; HR 1.99, p = 0.033 in validation) and MELD > 9 (HR: 1.37, p = 0.037 in training; HR 1.78, p = 0.035 in validation) emerged as independent prognostic factors in both groups. We assembled a prognostic indicator named "SARCO-MELD" based on the two independent prognostic factors, creating three groups: group 1 (0 prognostic factors), group 2 (1 factor) and group 3 (2 factors), the latter with significantly worse survival and shorter time receiving treatment

An atlas of the human liver diurnal transcriptome and its perturbation by hepatitis C virus infection

Chronic liver disease and cancer are global health challenges. The role of the circadian clock as a regulator of liver physiology and disease is well established in rodents, however, the identity and epigenetic regulation of rhythmically expressed genes in human disease is less well studied. Here we unravel the rhythmic transcriptome and epigenome of human hepatocytes using male human liver chimeric mice. We identify a large number of rhythmically expressed protein coding genes in human hepatocytes of male chimeric mice, which includes key transcription factors, chromatin modifiers, and critical enzymes. We show that hepatitis C virus (HCV) infection, a major cause of liver disease and cancer, perturbs the transcriptome by altering the rhythmicity of the expression of more than 1000 genes, and affects the epigenome, leading to an activation of critical pathways mediating metabolic alterations, fibrosis, and cancer. HCV-perturbed rhythmic pathways remain dysregulated in patients with advanced liver disease. Collectively, these data support a role for virus-induced perturbation of the hepatic rhythmic transcriptome and pathways in cancer development and may provide opportunities for cancer prevention and biomarkers to predict HCC risk

Characteristics and outcome of anti-hepatitis D virus positive patients with hepatocellular carcinoma

Background & aims: Chronic hepatitis D virus (HDV) often leads to end-stage liver disease and hepatocellular carcinoma (HCC). Comprehensive data pertaining to large populations with HDV and HCC are missing, therefore we sought to assess the characteristics, management, and outcome of these patients, comparing them to patients with hepatitis B virus (HBV) infection. Methods: We analysed the Italian Liver Cancer database focusing on patients with positivity for HBV surface antigen and anti-HDV antibodies (HBV/HDV, n = 107) and patients with HBV infection alone (n = 588). Clinical and oncological characteristics, treatment, and survival were compared in the two groups. Results: Patients with HBV/HDV had worse liver function [Model for End-stage Liver Disease score: 11 vs. 9, p < .0001; Child-Turcotte-Pugh score: 7 vs. 5, p < .0001] than patients with HBV. HCC was more frequently diagnosed during surveillance (72.9% vs. 52.4%, p = .0002), and the oncological stage was more frequently Milan-in (67.3% vs. 52.7%, p = .005) in patients with HBV/HDV. Liver transplantation was more frequently performed in HBV/HDV than in HBV patients (36.4% vs. 9.5%), while the opposite was observed for resection (8.4% vs. 20.1%, p < .0001), and in a competing risk analysis, HBV/HDV patients had a higher probability of receiving transplantation, independently of liver function and oncological stage. A trend towards longer survival was observed in patients with HBV/HDV (50.4 vs. 44.4 months, p = .106). Conclusions: In patients with HBV/HDV, HCC is diagnosed more frequently during surveillance, resulting in a less advanced cancer stage in patients with more deranged liver function than HBV alone. Patients with HBV/HDV have a heightened benefit from liver transplantation, positively influencing survival