Use of diffusion spectrum imaging in preliminary longitudinal evaluation of amyotrophic lateral sclerosis: Development of an imaging biomarker

Previous diffusion tensor imaging (DTI) studies have shown white matter pathology in amyotrophic lateral sclerosis (ALS), predominantly in the motor pathways. Further these studies have shown that DTI can be used longitudinally to track pathology over time, making white matter pathology a candidate as an outcome measure in future trials. DTI has demonstrated application in group studies, however its derived indices, for example fractional anisotropy, are susceptible to partial volume effects, making its role questionable in examining individual progression. We hypothesize that changes in the white matter are present in ALS beyond the motor tracts, and that the affected pathways and associated pattern of disease progression can be tracked longitudinally using automated diffusion connectometry analysis. Connectometry analysis is based on diffusion spectrum imaging and overcomes the limitations of a conventional tractography approach and DTI. The identified affected white matter tracts can then be assessed in a targeted fashion using High definition fiber tractography (a novel white matter MR imaging technique). Changes in quantitative and qualitative markers over time could then be correlated with clinical progression. We illustrate these principles toward developing an imaging biomarker for demonstrating individual progression, by presenting results for five ALS patients, including with longitudinal data in two. Preliminary analysis demonstrated a number of changes bilaterally and asymmetrically in motoric and extramotoric white matter pathways. Further the limbic system was also affected possibly explaining the cognitive symptoms in ALS. In the two longitudinal subjects, the white matter changes were less extensive at baseline, although there was evidence of disease progression in a frontal pattern with a relatively spared postcentral gyrus, consistent with the known pathology in ALS. © 2014 Abhinav, Yeh, El-Dokla, Ferrando, Chang, Lacomis, Friedlander and Fernandez-Miranda

AlCoNiFeCrTiVx High-Entropy Coatings Prepared by Electron-Beam Cladding

This is a post-peer-review, pre-copyedit version of an article published in "A. D. Pogrebnjak and O. Bondar (eds.), Microstructure and Properties of Micro- and Nanoscale Materials, Films, and Coatings (NAP 2019), Springer Proceedings in Physics 240". The final authenticated version is available online at: https://doi.org/10.1007/978-981-15-1742-6_16.This study reports the investigation of high-entropy coatings obtained by electron-beam cladding in a vacuum of Al-Co-Ni-Fe-Cr-Ti-Vx powder blend on a steel substrate. V was added to the Al-Co-Ni-Fe-Cr-Ti equiatomic system and the effects of this added element on structure, phase composition and microhardness of AlCoNiFeCrTiVx high entropy coatings resulted from electron beam cladding were studied. The AlCoNiFeCrTiV0 coatings consist of two solid solutions with BCC1 and BCC structure with different lattice parameters and a small volume fraction of σ-phase. It was shown that with an increase in V content from x = 0 to x = 1.5, the phase composition of the coatings transforms from two solid solutions to single BCC solid solution and σ-phases of different compositions. The σ-phase volume fraction increased with an increase in the V content. The addition of V to AlCoNiFeCrTi shows the strengthening effect of the AlCoNiFeCrTiV0.5–1.5 coatings and the Vickers hardness increased from 8.4 to 11 GPa. Microhardness of the coatings was affected by the sigma phase. The hardness enhancement can be likely attributed to the effect of solid solution strengthening and to the presence of σ-phase particles in the coating structure

Emergence of the rtA181T/sW172* mutant increased the risk of hepatoma occurrence in patients with lamivudine-resistant chronic hepatitis B

<p>Abstract</p> <p>Background</p> <p>Development of the hepatitis B virus (HBV) rtA181T/sW172* mutant could occur during prolonged lamivudine (LAM) therapy, conferring cross resistance to adefovir. Recent studies demonstrated an increased oncogenic potential of this mutant in NIH3T3 cells. In this study, we aimed to investigate the clinical significance of this finding.</p> <p>Methods</p> <p>Serum samples from 123 LAM-resistant chronic hepatitis B patients were submitted for virological assays. A highly sensitive amplification created restriction enzyme site (ACRES) method was devised to detect small amounts of the rtA181T mutant in the serum. Virological factors including HBV-DNA level, genotype, precore G1896A, BCP A1762T/G1764A, rtM204I/V, rtA181T and pre-S internal deletion mutations as well as clinical variables including subsequent use of rescue drugs were submitted for outcome analysis.</p> <p>Results</p> <p>By use of the highly sensitive ACRES method, the rtA181T mutant was detectable in 10 of the 123 LAM-resistant patients. During the mean follow-up period of 26.2 ± 16.4 months (range 2 to 108 months), 3 of the 10 (30.0%) rtA181T-positive patients and 2 of the 113 (1.8%) rtA181T-negative patients developed hepatocellular carcinoma (HCC). Kaplan-Meier analysis indicated that the presence of rtA181T mutation (P < 0.001), age > 50 years (P = 0.001), and liver cirrhosis (P < 0.001) were significantly associated with subsequent occurrence of HCC. All 5 HCC patients belonged to the older age and cirrhosis groups.</p> <p>Conclusions</p> <p>Emergence of the rtA181T/sW172* mutant in LAM-resistant patients increased the risk of HCC development in the subsequent courses of antiviral therapy.</p

Expression of ezrin is associated with invasion and dedifferentiation of hepatitis B related hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>Hepatocellular carcinoma (HCC) is the fifth most common malignancy in the world and constitutes the leading cause of cancer-related death among men, and second among women in Taiwan. Liver cirrhosis and HCC are relatively prevalent, and 80% to 85% of the patients with these conditions have positive results for hepatitis B surface antigen in Taiwan. Only 5% of the general population is seronegative for all hepatititis B virus (HBV) markers. This is the first study to determine the role of ezrin upon HBV HCC cell and patients with HBV HCC undergoing hepatectomy</p> <p>Methods</p> <p>Immunohistochemical study with ezrin in 104 human HBV-HCC cases were carried out to investigate its association with the clinicopathological features and the outcomes of 104 HBV-HCC patients undergoing hepatetomy. In addition, DNA constructs including the wild type ezrin (wt-ezrin) and mutant ezrin Tyr353 (Y353) were transfected into Hep3B cell to study its role in tumor invasion and differentiation.</p> <p>Results</p> <p>HBV HCC patients with ezrin over-expression independently have smaller tumor size, cirrhotic liver background, poor tumor differentiation, and more vascular invasion. Ezrin expression status has no impact on survival for HBV-HCC patients undergoing hepatectomy. The in vitro assay showed that wt-ezrin Hep3B cells have a significant higher level of AFP secretion and higher invasion ability as compared with the control and Y353- ezrin Hep3B cells.</p> <p>Conclusion</p> <p>Ezrin over-expression contributed to de-differentiation and invasion of HBV-HCC cell. HBV-HCC patients with ezrin over-expression were independently associated with tumor with smaller size, cirrhotic liver background, poor differentiation, and vascular invasion.</p

Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2008 update

Large amounts of new data on the natural history and treatment of chronic hepatitis B virus (HBV) infection have become available since 2005. These include long-term follow-up studies in large community-based cohorts or asymptomatic subjects with chronic HBV infection, further studies on the role of HBV genotype/naturally occurring HBV mutations, treatment of drug resistance and new therapies. In addition, Pegylated interferon α2a, entecavir and telbivudine have been approved globally. To update HBV management guidelines, relevant new data were reviewed and assessed by experts from the region, and the significance of the reported findings were discussed and debated. The earlier “Asian-Pacific consensus statement on the management of chronic hepatitis B” was revised accordingly. The key terms used in the statement were also defined. The new guidelines include general management, special indications for liver biopsy in patients with persistently normal alanine aminotransferase, time to start or stop drug therapy, choice of drug to initiate therapy, when and how to monitor the patients during and after stopping drug therapy. Recommendations on the therapy of patients in special circumstances, including women in childbearing age, patients with antiviral drug resistance, concurrent viral infection, hepatic decompensation, patients receiving immune-suppressive medications or chemotherapy and patients in the setting of liver transplantation, are also included

GLUT1 gene is a potential hypoxic marker in colorectal cancer patients

<p>Abstract</p> <p>Background</p> <p>Tumor hypoxia is an important factor related to tumor resistance to radiotherapy and chemotherapy. This study investigated molecules synthesized in colorectal cancer cells during hypoxia to explore the possibility of developing molecular probes capable of detecting cell death and/or the efficiency of radiotherapy and chemotherapy.</p> <p>Methods</p> <p>At first, we incubated two human colorectal adenocarcinoma cell lines SW480 (UICC stage II) and SW620 (UICC stage III) cells in hypoxic (≤2% O₂, 93% N₂, and 5% CO₂) and normoxic conditions (20% O₂, 75% N₂, and 5% CO₂) for 24 h and 48 h. The relative expression ratio of GLUT1 mRNA in hypoxic conditions was analyzed by RT-PCR. Ten cancerous tissues collected from human colorectal cancer patients were examined. HIF-1α and HIF-2α levels were measured to indicate the degree of hypoxia, and gene expression under hypoxic conditions was determined. As a comparison, HIF-1α, HIF-2α, and GLUT1 levels were measured in the peripheral blood of 100 CRC patients.</p> <p>Results</p> <p>Hypoxia-induced lactate was found to be elevated 3.24- to 3.36-fold in SW480 cells, and 3.06- to 3.17-fold in SW620 cells. The increased relative expression ratio of GLUT1 mRNA, under hypoxic conditions was higher in SW620 cells (1.39- to 1.72-fold elevation) than in SW480 cells (1.24- to 1.66-fold elevation). HIF-1α and HIF-2α levels were elevated and GLUT1 genes were significantly overexpressed in CRC tissue specimens. The elevated ratio of GLUT1 was higher in stage III and IV CRC tissue specimens than in the stage I and II (2.97–4.73 versus 1.44–2.11). GLUT1 mRNA was also increased in the peripheral blood of stage II and III CRC patients as compared to stage I patients, suggesting that GLUT1 may serve as a hypoxic indicator in CRC patients.</p> <p>Conclusion</p> <p>In conclusion, this study demonstrated that GLUT1 has the potential to be employed as a molecular marker to indicate the degree of hypoxia experienced by tumors circulating in the blood of cancer patients.</p

Enabling Universal Memory by Overcoming the Contradictory Speed and Stability Nature of Phase-Change Materials

The quest for universal memory is driving the rapid development of memories with superior all-round capabilities in non-volatility, high speed, high endurance and low power. Phase-change materials are highly promising in this respect. However, their contradictory speed and stability properties present a key challenge towards this ambition. We reveal that as the device size decreases, the phase-change mechanism changes from the material inherent crystallization mechanism (either nucleation- or growth-dominated), to the hetero-crystallization mechanism, which resulted in a significant increase in PCRAM speeds. Reducing the grain size can further increase the speed of phase-change. Such grain size effect on speed becomes increasingly significant at smaller device sizes. Together with the nano-thermal and electrical effects, fast phase-change, good stability and high endurance can be achieved. These findings lead to a feasible solution to achieve a universal memory

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Measurement of the Forward-Backward Asymmetry in the B -> K(*) mu+ mu- Decay and First Observation of the Bs -> phi mu+ mu- Decay

We reconstruct the rare decays $B^+ \to K^+\mu^+\mu^-$, $B^0 \to K^{*}(892)^0\mu^+\mu^-$, and $B^0_s \to \phi(1020)\mu^+\mu^-$ in a data sample corresponding to $4.4 {\rm fb^{-1}}$ collected in $p\bar{p}$ collisions at $\sqrt{s}=1.96 {\rm TeV}$ by the CDF II detector at the Fermilab Tevatron Collider. Using $121 \pm 16$ $B^+ \to K^+\mu^+\mu^-$ and $101 \pm 12$ $B^0 \to K^{*0}\mu^+\mu^-$ decays we report the branching ratios. In addition, we report the measurement of the differential branching ratio and the muon forward-backward asymmetry in the $B^+$ and $B^0$ decay modes, and the $K^{*0}$ longitudinal polarization in the $B^0$ decay mode with respect to the squared dimuon mass. These are consistent with the theoretical prediction from the standard model, and most recent determinations from other experiments and of comparable accuracy. We also report the first observation of the $B^0_s \to \phi\mu^+\mu^- decay and measure its branching ratio${\mathcal{B}}(B^0_s \to \phi\mu^+\mu^-) = [1.44 \pm 0.33 \pm 0.46] \times 10^{-6}$using$27 \pm 6$signal events. This is currently the most rare$B^0_s$ decay observed.Comment: 7 pages, 2 figures, 3 tables. Submitted to Phys. Rev. Let