Transarterial Infusion of Epirubicin and Cisplatin Combined With Systemic Infusion of 5-Flurouracil Versus Sorafenib for Hepatocellular Carcinoma With Refractoriness of Transarterial Chemoembolization Using Doxorubicin.

Transarterial chemoembolization using doxorubicin (TACE-DOX) is an effective therapy for advanced hepatocellular carcinoma (HCC). However, there are limited options for patients with TACE refractoriness. We compared the effectiveness between sorafenib and transarterial chemolipiodolization using epirubicin and cisplatin combined with systemic infusion of 5-fluorouracil (5-FU; TACL-ECF) in patients with previous TACE-DOX refractoriness. We retrospectively analyzed 742 consecutively enrolled cohort patients who received TACE-DOX as the first-line therapy for HCC. Among the 94 patients who failed with TACE-DOX, 49 patients were treated with TACL-ECF and 45 patients were treated with sorafenib as a rescue therapy. The TACL-ECF regimen comprised transarterial infusion of epirubicin and cisplatin combined with systemic infusion of 5-FU. Of the 94 patients, 22 and 72 patients were in Barcelona Clinic Liver Cancer stages B and C, respectively; 66% patients were classified as having Child-Pugh class A (CPC A). Overall survival (OS) after rescue therapy did not differ between the sorafenib and TACL-ECF groups (4.1 months vs 6.4 months, P = .355). Progression-free survival (PFS) did not differ between the sorafenib and TACL-ECF groups (2.8 months vs 3.5 months, P = .629). Adverse events of CTC grade 3/4 occurred more frequently in the sorafenib group than in the TACL-ECF group (P = .024). The present study showed that the OS and PFS did not differ between patients given rescue TACL-ECF therapy and those given sorafenib therapy. The TACL-ECF treatment was better tolerated than sorafenib. The TACL-ECF might be considered as an alternative therapy for the patients with TACE-DOX refractoriness, especially CPC B and sorafenib-intolerant patients.

The ALBI grade provides objective hepatic reserve estimation across each BCLC stage of hepatocellular carcinoma.

BACKGROUND & AIMS: Overall survival (OS) is a composite clinical endpoint in hepatocellular carcinoma (HCC) due to the mutual influence of cirrhosis and active malignancy in dictating patient's mortality. The ALBI grade is a recently described index of liver dysfunction in hepatocellular carcinoma, based solely on albumin and bilirubin levels. Whilst accurate, this score lacks cross-validation, especially in intermediate stage HCC, where OS is highly heterogeneous. METHODS: We evaluated the prognostic accuracy of the ALBI grade in estimating OS in a large, multi-centre study of 2426 patients, including a large proportion of intermediate stage patients treated with chemoembolization (n=1461) accrued from Europe, the United States and Asia. RESULTS: Analysis of survival by primary treatment modality confirmed the ALBI grade as a significant predictor of patient OS after surgical resection (p<0.001), transarterial chemoembolization (p<0.001) and sorafenib (p<0.001). Stratification by Barcelona Clinic Liver Cancer stage confirmed the independent prognostic value of the ALBI across the diverse stages of the disease, geographical regions of origin and time of recruitment to the study (p<0.001). CONCLUSIONS: In this large, multi-centre retrospective study, the ALBI grade satisfied the criteria for accuracy and reproducibility following statistical validation in Eastern and Western HCC patients, including those treated with chemoembolization. Consideration should be given to the ALBI grade as a stratifying biomarker of liver reserve in routine clinical practice. LAY SUMMARY: Liver failure is a key determinant influencing the natural history of hepatocellular carcinoma (HCC). In this large multi-centre study we externally validate a novel biomarker of liver functional reserve, the ALBI grade, across all the stages of HCC.

A predictive model of the tensile strength of twisted carbon nanotube yarns.

Due to the outstanding mechanical properties of individual carbon nanotubes (CNTs) at the nanoscale, CNT yarns are expected to demonstrate high strength at the macroscale. In this study, a predictable model was developed to predict the tensile strength of twisted CNT yarns. First, the failure mechanism of twisted CNT yarns was investigated using in situ tensile tests and ex situ observations. It was revealed that CNT bundles, which are groups of CNTs that are tightly bound together, formed during tensile loading, leaving some voids around the bundles. Failure of the CNT yarns occurred as the CNT bundles were pulled out of the yarns. Two stresses that determined the tensile strength of the CNT yarns were identified: interfacial shear and frictional stresses originating from van der Waals interactions, and the lateral pressure generated by the twisted yarn structure. Molecular dynamics and yarn mechanics were used to calculate these two stresses. Finally, the tensile strength of CNT yarns was predicted and compared with experimental data, showing reasonable agreement.

Bond strength of individual carbon nanotubes grown directly on carbon fibers.

The performance of carbon nanotube (CNT)-based devices strongly depends on the adhesion of CNTs to the substrate on which they were directly grown. We report on the bond strength of CNTs grown on a carbon fiber (T700SC Toray), measured via in situ pulling of individual CNTs inside a transmission electron microscope. The bond strength of an individual CNT, obtained from the measured pulling force and CNT cross-section, was very high (∼200 MPa), 8-10 times higher than that of an adhesion model assuming only van der Waals interactions (25 MPa), presumably due to carbon-carbon interactions between the CNT (its bottom atoms) and the carbon substrate.

Validation of the hepatoma arterial embolization prognostic score in European and Asian populations and proposed modification.

BACKGROUND & AIMS: Transarterial chemoembolization (TACE) is used to treat hepatocellular carcinoma (HCC), but it is a challenge to predict patient survival. The hepatic arterial embolization prognostic (HAP) score has been shown to predict which patients will have shorter survival times and should not undergo TACE. We aimed to validate this scoring system in a prospective study of patients in Europe and Asia. METHODS: We evaluated the prognostic accuracy of the HAP score in estimating overall survival (OS) of 126 patients with HCC who received TACE in the United Kingdom or Italy (training set) from 2001 through 2013. We also analyzed data from 723 patients treated in Korea and Japan (validation set), including 79 with newly diagnosed HCC, who underwent TACE in Korea or Japan from 2004 through 2013. Response to TACE was determined based on computed tomography analysis. OS was calculated from the time of the first TACE until death or the last follow-up evaluation. RESULTS: OS was associated with hypoalbuminemia, α-fetoprotein level greater than 400 ng/mL, and tumor size greater than 7 cm at diagnosis (P < .01), but not a bilirubin level greater than 17 umol/L (P > .05), in both data sets. The lack of association between OS and bilirubin level was confirmed using receiver operating characteristic analysis. We developed a modified version of the HAP score, based on the level of albumin and α-fetoprotein and tumor size, which predicted OS with increased accuracy in the training and validation cohorts. CONCLUSIONS: In a multicenter validation study, we developed a modified version of the HAP that predicts survival of patients with HCC treated with TACE in Europe and Asia. This system might be used to identify patients with HCC most likely to benefit from TACE in clinical practice.

The usefulness of C-reactive protein and neutrophil-to-lymphocyte ratio for predicting the outcome in hospitalized patients with liver cirrhosis.

BACKGROUND: The role of clinical parameters such as systemic inflammatory response syndrome (SIRS) criteria in predicting the infection remains unclear in cirrhosis patients. The aim was to evaluate the usefulness of inflammatory markers including C-reactive protein (CRP) and the neutrophil-to-lymphocyte ratio (NLR) for diagnosis of infection and predicting the outcomes in hospitalized cirrhotic patients. METHODS: The study included 184 cirrhotic patients consecutively hospitalized from 2011 to 2012. The presence of overt infection and survival was evaluated. CRP concentration, NLR, Model for End-Stage Liver Disease (MELD) score and the presence of SIRS were assessed. RESULTS: The main cause of admission was uncontrolled ascites (36.4 %), followed by varix bleeding (23.9 %), and hepatic encephalopathy (13.6 %). Fifty-eight patients (31.5 %) had overt infection during hospitalization and thirty-two patients (17.4 %) expired during the follow up period (median 38 months). Ninety-two patients (52.2 %) fulfilled the SIRS criteria and among them, only 32 patients (38.5 %) had the overt infection. For diagnose of the infection, baseline CRP concentration was a significant factor compared to the presence of SIRS (odds ratio 1.202, P = 0.003). For predicting one-month short-term survival, MELD score, NLR and WBC count were significant factors but in Child-Pugh class C patients, NLR was only an independent factor. CONCLUSIONS: CRP was a significant indicator of infection in hospitalized cirrhotic patients and a NLR was a useful predictor of 1-month survival, particularly in Child-Pugh class C patients. This study suggests that the inflammatory markers such as CRP and NLR can help identify cirrhotic patients at risk of unfavorable outcomes.

Design and application of a novel in situ nano-manipulation stage for transmission electron microscopy.

A novel nano-scale manipulator capable of handling low-dimensional materials with three-dimensional linear motion, gripping action, and push-pull action of the gripper was developed for an in situ experiment in transmission electron microscopy. X-Y-Z positioning and push-pull action were accomplished by a piezotubing system, combined with a specially designed assembly stage that consisted of a lever-action gripping tip backed by a push-pull piezostack. The gripper tip consisted of tungsten wire fabricated by electrochemical etching followed by a focused ion beam process. Performance of the nano-scale manipulator was demonstrated in a grab-and-pick test of a single silver nanowire and in an in situ tensile test of a pearlitic steel sample with a specific orientation.

Self-assembled Fe3O4 nanoparticle clusters as high-performance anodes for lithium ion batteries via geometric confinement.

Although different kinds of metal oxide nanoparticles continue to be proposed as anode materials for lithium ion batteries (LIBs), their cycle life and power density are still not suitable for commercial applications. Metal oxide nanoparticles have a large storage capacity, but they suffer from the excessive generation of solid-electrolyte interphase (SEI) on the surface, low electrical conductivity, and mechanical degradation and pulverization resulted from severe volume expansion during cycling. Herein we present the preparation of mesoporous iron oxide nanoparticle clusters (MIONCs) by a bottom-up self-assembly approach and demonstrate that they exhibit excellent cyclic stability and rate capability derived from their three-dimensional mesoporous nanostructure. By controlling the geometric configuration, we can achieve stable interfaces between the electrolyte and active materials, resulting in SEI formation confined on the outer surface of the MIONCs.

Copper-indium-selenide quantum dot-sensitized solar cells.

We present a new synthetic process of near infrared (NIR)-absorbing copper-indium-selenide (CISe) quantum dots (QDs) and their applications to efficient and completely heavy-metal-free QD-sensitized solar cells (QDSCs). Lewis acid-base reaction of metal iodides and selenocarbamate enabled us to produce chalcopyrite-structured CISe QDs with controlled sizes and compositions. Furthermore, gram-scale production of CISe QDs was achieved with a high reaction yield of ~73%, which is important for the commercialization of low-cost photovoltaic (PV) devices. By changing the size and composition, electronic band alignment of CISe QDs could be finely tuned to optimize the energetics of the effective light absorption and injection of electrons into the TiO2 conduction band (CB). These energy-band-engineered QDs were applied to QDSCs, and the quantum-confinement effect on the PV performances was clearly demonstrated. Our best cell yielded a conversion efficiency of 4.30% under AM1.5G one sun illumination, which is comparable to the performance of the best solar cells based on toxic lead chalcogenide or cadmium chalcogenide QDs.

Deformation behavior of duplex austenite and ε-martensite high-Mn steel.

Deformation and work hardening behavior of Fe-17Mn-0.02C steel containing ε-martensite within the austenite matrix have been investigated by means of in situ microstructural observations and x-ray diffraction analysis. During deformation, the steel shows the deformation-induced transformation of austenite → ε-martensite → α'-martensite as well as the direct transformation of austenite → α'-martensite. Based on the calculation of changes in the fraction of each constituent phase, we found that the phase transformation of austenite → ε-martensite is more effective in work hardening than that of ε-martensite → α'-martensite. Moreover, reverse transformation of ε-martensite → austenite has also been observed during deformation. It originates from the formation of stacking faults within the deformed ε-martensite, resulting in the formation of 6H-long periodic ordered structure.

Correlation between the Surface Undulation and Luminescence Characteristics in Semi-Polar 112¯2 InGaN/GaN Multi-Quantum Wells.

Surface undulation was formed while growing InGaN/GaN multi-quantum wells on a semi-polar m-plane (1-100) sapphire substrate. Two distinct facets, parallel to 112¯2 and 011¯1, were formed in the embedded multi-quantum wells (MQWs). The structural and luminescence characteristics of the two facets were investigated using transmission electron microscopy equipped with cathodoluminescence. Those well-defined quantum wells, parallel and slanted to the growth plane, showed distinct differences in indium incorporation from both the X-ray yield and the contrast difference in annular darkfield images. Quantitative measurements of concentration in 011¯1 MQWs show an approximately 4 at% higher indium incorporation compared to the corresponding 112¯2 when the MQWs were formed under the same growth condition.

Multifunctional Fe3O4/TaO(x) core/shell nanoparticles for simultaneous magnetic resonance imaging and X-ray computed tomography.

Multimodal imaging is highly desirable for accurate diagnosis because it can provide complementary information from each imaging modality. In this study, a sol-gel reaction of tantalum(V) ethoxide in a microemulsion containing Fe(3)O(4) nanoparticles (NPs) was used to synthesize multifunctional Fe(3)O(4)/TaO(x) core/shell NPs, which were biocompatible and exhibited a prolonged circulation time. When the NPs were intravenously injected, the tumor-associated vessel was observed using computed tomography (CT), and magnetic resonance imaging (MRI) revealed the high and low vascular regions of the tumor.

One-step graphene coating of heteroepitaxial GaN films.

Today, state-of-the-art III-Ns technology has been focused on the growth of c-plane nitrides by metal-organic chemical vapor deposition (MOCVD) using a conventional two-step growth process. Here we show that the use of graphene as a coating layer allows the one-step growth of heteroepitaxial GaN films on sapphire in a MOCVD reactor, simplifying the GaN growth process. It is found that the graphene coating improves the wetting between GaN and sapphire, and, with as little as ~0.6 nm of graphene coating, the overgrown GaN layer on sapphire becomes continuous and flat. With increasing thickness of the graphene coating, the structural and optical properties of one-step grown GaN films gradually transition towards those of GaN films grown by a conventional two-step growth method. The InGaN/GaN multiple quantum well structure grown on a GaN/graphene/sapphire heterosystem shows a high internal quantum efficiency, allowing the use of one-step grown GaN films as 'pseudo-substrates' in optoelectronic devices. The introduction of graphene as a coating layer provides an atomic playground for metal adatoms and simplifies the III-Ns growth process, making it potentially very useful as a means to grow other heteroepitaxial films on arbitrary substrates with lattice and thermal mismatch.

In Situ TEM Study of Structural Changes in Na-ß″-Alumina Using Electron Beam Irradiation.

Real-time structural changes in Na-ß″-alumina were observed in situ using transmission electron microscopy (TEM) with electron beam irradiation. Na-ß″-alumina has been widely investigated as a solid electrolyte material for sodium-sulfur secondary batteries owing to its high ionic conductivity. This high conductivity is known to be due to the Na+ ions on the loosely packed conduction planes of Na-ß″-alumina. In the present study, we acquired real-time videos of the generation of spinel blocks caused by the conduction of Na+ ions. In addition, by observing Na extraction during electron beam irradiation, we experimentally confirmed that spinel block generation originates from the Na+ ion conduction, which has been a subject of recent debate.

Atomic Reconstruction and Oxygen Evolution Reaction of Mn3O4 Nanoparticles.

Understanding the chemical states of individual surface atoms and their arrangements is essential for addressing several current issues such as catalysis, energy stroage/conversion, and environmental protection. Here, we exploit a profile imaging technique to understand the correlation between surface atomic structures and the oxygen evolution reaction (OER) in Mn3O4 nanoparticles. We image surface structures of Mn3O4 nanoparticles and observe surface reconstructions in the (110) and (101) planes. Mn3+ ions at the surface, which are commonly considered as the active sites in OER, disappear from the reconstructed planes, whereas Mn3+ ions are still exposed at the edges of nanoparticles. Our observations suggest that surface reconstructions can deactivate low-index surfaces of Mn oxides in OER. These structural and chemical observations are further validated by density functional theory calculations. This work shows why atomic-scale characterization of surface structures is crucial for a molecular-level understanding of a chemical reaction in oxide nanoparticles.

Large-scale synthesis of uniform and extremely small-sized iron oxide nanoparticles for high-resolution T1 magnetic resonance imaging contrast agents.

Uniform and extremely small-sized iron oxide nanoparticles (ESIONs) of < 4 nm were synthesized via the thermal decomposition of iron-oleate complex in the presence of oleyl alcohol. Oleyl alcohol lowered the reaction temperature by reducing iron-oleate complex, resulting in the production of small-sized nanoparticles. XRD pattern of 3 nm-sized nanoparticles revealed maghemite crystal structure. These nanoparticles exhibited very low magnetization derived from the spin-canting effect. The hydrophobic nanoparticles can be easily transformed to water-dispersible and biocompatible nanoparticles by capping with the poly(ethylene glycol)-derivatized phosphine oxide (PO-PEG) ligands. Toxic response was not observed with Fe concentration up to 100 µg/mL in MTT cell proliferation assay of POPEG-capped 3 nm-sized iron oxide nanoparticles. The 3 nm-sized nanoparticles exhibited a high r(1) relaxivity of 4.78 mM(-1) s(-1) and low r(2)/r(1) ratio of 6.12, demonstrating that ESIONs can be efficient T(1) contrast agents. The high r(1) relaxivities of ESIONs can be attributed to the large number of surface Fe(3+) ions with 5 unpaired valence electrons. In the in vivo T(1)-weighted magnetic resonance imaging (MRI), ESIONs showed longer circulation time than the clinically used gadolinium complex-based contrast agent, enabling high-resolution imaging. High-resolution blood pool MR imaging using ESIONs enabled clear observation of various blood vessels with sizes down to 0.2 mm. These results demonstrate the potential of ESIONs as T(1) MRI contrast agents in clinical settings.

Giant Zeeman splitting in nucleation-controlled doped CdSe:Mn2+ quantum nanoribbons.

Doping of semiconductor nanocrystals by transition-metal ions has attracted tremendous attention owing to their nanoscale spintronic applications. Such doping is, however, difficult to achieve in low-dimensional strongly quantum confined nanostructures by conventional growth procedures. Here we demonstrate that the incorporation of manganese ions up to 10% into CdSe quantum nanoribbons can be readily achieved by a nucleation-controlled doping process. The cation-exchange reaction of (CdSe)(13) clusters with Mn(2+) ions governs the Mn(2+) incorporation during the nucleation stage. This highly efficient Mn(2+) doping of the CdSe quantum nanoribbons results in giant exciton Zeeman splitting with an effective g-factor of approximately 600, the largest value seen so far in diluted magnetic semiconductor nanocrystals. Furthermore, the sign of the s-d exchange is inverted to negative owing to the exceptionally strong quantum confinement in our nanoribbons. The nucleation-controlled doping strategy demonstrated here thus opens the possibility of doping various strongly quantum confined nanocrystals for diverse applications.

Soft-solution route to various ZnO nanoplate arrays.

Three different ZnO nanoplate arrays on Si-wafer were successfully synthesized at 95 °C from ZnO nanoparticles with modified surface by citrate anion. Shape, size, density, and orientation of the resulting nanoplates were dramatically changed by the nucleus seed concentration, which was controlled through different coating processes on the substrate.

Microstructural evolution of tantalum nitride thin films synthesized by inductively coupled plasma sputtering.

Tantalum nitride (TaNx) thin films were grown utilizing an inductively coupled plasma (ICP) assisted direct current (DC) sputtering, and 20-100% improved microhardness values were obtained. The detailed microstructural changes of the TaNx films were characterized utilizing transmission electron microscopy (TEM), as a function of nitrogen gas fraction and ICP power. As nitrogen gas fraction increases from 0.05 to 0.15, the TaNx phase evolves from body-centered-cubic (b.c.c.) TaN0.1, to face-centered-cubic (f.c.c.) δ-TaN, to hexagonal-close-packing (h.c.p.) ε-TaN phase. By increasing ICP power from 100 W to 400 W, the f.c.c. δ- TaN phase becomes the main phase in all nitrogen fractions investigated. The higher ICP power enhances the mobility of Ta and N ions, which stabilizes the δ-TaN phase like a high-temperature regime and removes the micro-voids between the columnar grains in the TaNx film. The dense δ-TaN structure with reduced columnar grains and micro-voids increases the strength of the TaNx film.

Sustained multiple organ ischaemia after transarterial chemoembolization with drug-eluting beads for hepatocellular carcinoma.

Transarterial chemoembolization (TACE) with drug-eluting beads (DC beads) may enhance drug delivery to tumours and reduce systemic toxicity. TACE with DC beads leads to significantly fewer serious side-effects compared with conventional TACE. A 66-year-old man with hepatocellular carcinoma (HCC) complained of continuous abdominal pain 1 month after TACE with DC beads. At the time of TACE, angiography revealed severe stenosis of both hepatic arteries. The diagnostic work up on admission suggested severe bile duct injury with regional bile duct dilatation, segmental liver and spleen infarction, necrotizing pancreatitis, as well as gastric and duodenal ulcers. The pathology specimens of the duodenum contained DC beads that had passed through small vessels in the connective tissue. The patient's condition appeared to improve after 2 weeks of antibiotic treatment and supportive care, but new multifocal liver and spleen infarction subsequently developed. After 2 months, he was well enough to be discharged. His HCC partially responded to the TACE with DC beads but eventually progressed and he died after 11 months. The present case report highlights unexpected ongoing multiple organ ischaemia in a 66-year-old man treated for HCC using TACE with DC beads. The use of TACE with DC beads should be carefully considered in patients with vascular strictures or aberrant blood supply.