Hepatocellular carcinoma (HCC) versus non-HCC: accuracy and reliability of Liver Imaging Reporting and Data System v2018

PurposeThe Liver Imaging Reporting and Data System (LI-RADS) was created to standardize the diagnostic criteria for hepatocellular carcinoma (HCC) and has undergone multiple revisions including a recent update in 2018 (v2018). The primary aim of this study was to determine the diagnostic performance and interrater reliability (IRR) of LI-RADS v2018 for distinguishing HCC from non-HCC primary hepatic malignancy in patients at-risk' for HCC. A secondary aim was to assess the impact of changes introduced in the v2018 diagnostic algorithm.MethodsThis retrospective study combined a 10-year experience of pathologically proven primary liver malignancies from two large liver transplant centers. Two blinded readers independently evaluated each lesion and assigned a LI-RADS diagnostic category, additionally scoring all relevant imaging features. Changes in category based on the reader-provided features and the new v2018 criteria were assessed by a study coordinator.ResultsThe final study cohort comprised 105 HCCs and 73 non-HCC primarily liver malignancies. LI-RADS had a high specificity for distinguishing HCC from non-HCC (89% and 90% for reader 1 and reader 2, respectively), and IRR was moderate to substantial for final LI-RADS category and most features. Revision of the LI-RADS v2018 diagnostic algorithm resulted in very few changes [5 (2.8%) and 3 (1.7%) for reader 1 and reader 2, respectively] in overall lesion classification.ConclusionLI-RADS diagnostic categories and features had moderate to substantial IRR and high specificity for distinguishing HCC from non-HCC primary liver malignancy. Revision of LI-RADS v2018 diagnostic algorithm resulted in reclassification of very few lesions

Effect of cube texture on local softening of friction stir welded joints for nanostructured AA2024 processed by accumulative roll bonding

Copyright © 2023 The Authors. The current research provides an insight into the correlation between the crystallographic textures, microstructure, and hardness of friction stir welded joints in nanostructured AA2024 alloys processed through accumulative roll bonding (ARB). Utilizing varying rotational speeds (250, 500, 750, and 1000 rpm) at a constant traverse tool (150 mm/min) during friction stir welding (FSW), microstructural analyses reveal distinct grain structures and texture components in the nugget zone. The fully recrystallized Cube {001}⟨100⟩ texture-oriented grains appear at the rotational speed of 750 rpm. The hardness profiles of ARB-processed strips after FSW at different rotational speeds show local softening in the nugget zones. There might be a hypothesis concerning the dissolution of stable and metastable precipitates based on generated heat input, providing insights into the mechanisms influencing hardness variations. Notably, the examination of Cube {001}⟨100⟩ texture and its correlation with local softening adds a valuable dimension to the understanding of microstructural changes in FSW of nanostructured AA2024 alloys processed by accumulative roll bonding process

Expanding the Liver Imaging Reporting and Data System (LI-RADS) v2018 diagnostic population: performance and reliability of LI-RADS for distinguishing hepatocellular carcinoma (HCC) from non-HCC primary liver carcinoma in patients who do not meet strict LI-RADS high-risk criteria

Background: Hepatocellular carcinoma (HCC) can be diagnosed using imaging criteria in patients at high-risk for HCC, according to Liver Imaging Reporting and Data System (LI-RADS) guidelines. The aim of this study was to determine the diagnostic performance and inter-rater reliability (IRR) of LI-RADS v2018 for differentiating HCC from non-HCC primary liver carcinoma (PLC), in patients who are at increased risk for HCC but not included in the LI-RADS 'high-risk' population.Methods: This retrospective HIPAA-compliant study included a 10-year experience of pathologicallyproven PLC at two liver transplant centers, and included patients with non-cirrhotic hepatitis C infection, non-cirrhotic non-alcoholic fatty liver disease, and fibrosis. Two readers evaluated each lesion and assigned an overall LI-RADS diagnostic category, additionally scoring all major, LR-M, and ancillary features.Results: The final study cohort consisted of 27 HCCs and 104 non-HCC PLC in 131 patients. The specificity of a 'definite HCC' designation was 97% for reader 1 and 100% for reader 2. The IRR was fair for overall LI-RADS category and substantial for most major features.Conclusion: In a population at increased risk for HCC but not currently included in the LI-RADS 'high-risk' population, LI-RADS v2018 demonstrated very high specificity for distinguishing pathologicallyproven HCC from non-HCC PLC

Improving strength-ductility synergy of nano/ultrafine-structured Al/Brass composite by cross accumulative roll bonding process

Copyright © 2023 The Author(s). Increasing the strength of metallic multilayered composites fabricated through accumulative roll bonding (ARB) is typically accompanied by a sacrifice in ductility. In the current work, we propose a strategy to achieve microstructural refinement and outstanding strength-ductility synergy in Al/Brass composites. Here, the aluminum matrix exhibits a bimodal grain distribution, consisting of fine equiaxed grains with an average size of ∼100 nm and ultrafine-elongated grains, in which the brass fragments were distributed uniformly. These microstructural features, introduced through cross accumulative roll bonding (CARB), provide synergistic strengthening effects. The CARB processed composite exhibits a mean misorientation angle of 43.16° and a fraction of high angle grain boundaries of 87%, compared to values of 38.02° and 79% for ARB processed specimen. The CARB processed composite demonstrates a major texture characterized by prominent Rotated Brass {110}, Rotated Goss {011}, and Rotated Cube {001} components. In contrast, the ARB processed specimen revealed strong Goss {011}, Rotated Goss {011}, Brass {011}, and S {123} components. The Copper {112} and S {123} components were nearly absent in the CARB processed composite, because both of them were unstable under the CARB regime. The CARB processed composite shows a tensile strength of 405 MPa and a remarkable elongation of 12.4% at ambient temperature, outperforming ARB processed specimen with a tensile strength of 335 MPa and elongation of 9.5%. These unique mechanical properties in the CARB processed composite are ascribed to the dislocation strengthening, bimodal grain size distribution, uniformity of the brass fragments, and quality of bonding at the interfaces.Ministry of Science and Higher Education of the Russian Federation (FENU-2023-0013).; Seoul National University, Seoul, South Korea (Brain Korea 21 (BK21) Postdoctoral Fellowship to MN).

Cancer treatment-related neuropathic pain:proof of concept study with menthol—a TRPM8 agonist

PURPOSE: Effective treatment of neuropathic pain without unacceptable side effects is challenging. Cancer sufferers increasingly live with long-term treatment-related neuropathic pain, resulting from chemotherapy-induced peripheral neuropathy (CIPN) or surgical scars. This proof-of-concept study aimed to determine whether preclinical evidence for TRPM8 ion channels in sensory neurons as a novel analgesic target could be translated to clinical benefit in patients with neuropathic pain, using the TRPM8 activator menthol. PATIENTS AND METHODS: Patients with problematic treatment-related neuropathic pain underwent a baseline assessment using validated questionnaires, psychophysical testing, and objective functional measures. The painful area was treated with topical 1 % menthol cream twice daily. Assessments were repeated at 4–6 weeks. The primary outcome was the change in Brief Pain Inventory total scores at 4–6 weeks. Secondary outcomes included changes in function, mood and skin sensation. RESULTS: Fifty-one patients (female/male, 32/19) were recruited with a median age of 61 (ranging from 20 to 89). The commonest aetiology was CIPN (35/51), followed by scar pain (10/51). Thirty-eight were evaluable on the primary outcome. Eighty-two per cent (31/38) had an improvement in total Brief Pain Inventory scores (median, 47 (interquartile range, 30 to 64) to 34 (6 to 59), P < 0.001). Improvements in mood (P = 0.0004), catastrophising (P = 0.001), walking ability (P = 0.008) and sensation (P < 0.01) were also observed. CONCLUSION: This proof-of-concept study indicates that topical menthol has potential as a novel analgesic therapy for cancer treatment-related neuropathic pain. Improvements in patient-rated measures are supported by changes in objective measures of physical function and sensation. Further systematic evaluation of efficacy is required

Molecular pathway profiling of T lymphocyte signal transduction pathways; Th1 and Th2 genomic fingerprints are defined by TCR and CD28-mediated signaling

Contains fulltext : 108719.pdf (publisher's version ) (Open Access)BACKGROUND: T lymphocytes are orchestrators of adaptive immunity. Naive T cells may differentiate into Th1, Th2, Th17 or iTreg phenotypes, depending on environmental co-stimulatory signals. To identify genes and pathways involved in differentiation of Jurkat T cells towards Th1 and Th2 subtypes we performed comprehensive transcriptome analyses of Jurkat T cells stimulated with various stimuli and pathway inhibitors. Results from these experiments were validated in a human experimental setting using whole blood and purified CD4+ Tcells. RESULTS: Calcium-dependent activation of T cells using CD3/CD28 and PMA/CD3 stimulation induced a Th1 expression profile reflected by increased expression of T-bet, RUNX3, IL-2, and IFNgamma, whereas calcium-independent activation via PMA/CD28 induced a Th2 expression profile which included GATA3, RXRA, CCL1 and Itk. Knock down with siRNA and gene expression profiling in the presence of selective kinase inhibitors showed that proximal kinases Lck and PKCtheta are crucial signaling hubs during T helper cell activation, revealing a clear role for Lck in Th1 development and for PKCtheta in both Th1 and Th2 development. Medial signaling via MAPkinases appeared to be less important in these pathways, since specific inhibitors of these kinases displayed a minor effect on gene expression. Translation towards a primary, whole blood setting and purified human CD4+ T cells revealed that PMA/CD3 stimulation induced a more pronounced Th1 specific, Lck and PKCtheta dependent IFNgamma production, whereas PMA/CD28 induced Th2 specific IL-5 and IL-13 production, independent of Lck activation. PMA/CD3-mediated skewing towards a Th1 phenotype was also reflected in mRNA expression of the master transcription factor Tbet, whereas PMA/CD28-mediated stimulation enhanced GATA3 mRNA expression in primary human CD4+ Tcells. CONCLUSIONS: This study identifies stimulatory pathways and gene expression profiles for in vitro skewing of T helper cell activation. PMA/CD3 stimulation enhances a Th1-like response in an Lck and PKCtheta dependent fashion, whereas PMA/CD28 stimulation results in a Th2-like phenotype independent of the proximal TCR-tyrosine kinase Lck. This approach offers a robust and fast translational in vitro system for skewed T helper cell responses in Jurkat T cells, primary human CD4+ Tcells and in a more complex matrix such as human whole blood

Role of Lipids in Spheroidal High Density Lipoproteins

We study the structure and dynamics of spherical high density lipoprotein (HDL) particles through coarse-grained multi-microsecond molecular dynamics simulations. We simulate both a lipid droplet without the apolipoprotein A-I (apoA-I) and the full HDL particle including two apoA-I molecules surrounding the lipid compartment. The present models are the first ones among computational studies where the size and lipid composition of HDL are realistic, corresponding to human serum HDL. We focus on the role of lipids in HDL structure and dynamics. Particular attention is paid to the assembly of lipids and the influence of lipid-protein interactions on HDL properties. We find that the properties of lipids depend significantly on their location in the particle (core, intermediate region, surface). Unlike the hydrophobic core, the intermediate and surface regions are characterized by prominent conformational lipid order. Yet, not only the conformations but also the dynamics of lipids are found to be distinctly different in the different regions of HDL, highlighting the importance of dynamics in considering the functionalization of HDL. The structure of the lipid droplet close to the HDL-water interface is altered by the presence of apoA-Is, with most prominent changes being observed for cholesterol and polar lipids. For cholesterol, slow trafficking between the surface layer and the regimes underneath is observed. The lipid-protein interactions are strongest for cholesterol, in particular its interaction with hydrophobic residues of apoA-I. Our results reveal that not only hydrophobicity but also conformational entropy of the molecules are the driving forces in the formation of HDL structure. The results provide the first detailed structural model for HDL and its dynamics with and without apoA-I, and indicate how the interplay and competition between entropy and detailed interactions may be used in nanoparticle and drug design through self-assembly

Anomalous J/ψJ/\psi suppression in Pb-Pb interactions at 158 GeV per nucleon

The Drell-Yan and J/psi cross-sections measured in Pb-Pb collisions are compared with the values extrapolated from the results obtained in proton and light ion induced reactions. While the Drell-Yan production exhibits the normal expected behaviour, the yield of J/psi in Pb-Pb interactions is abnormally low, as it lies 9 standard deviations below the expected value. Moreover, the departure from the expected behaviour increases significantly from peripheral to central collisions. (C) 1997 Elsevier Science B.V