Search

Mitochondrial N‐formylpeptides are released from damaged or dead cells to the extracellular spaces and cause inflammatory responses. The role of mitochondrial N‐formylpeptides in aseptic systemic inflammatory response syndromes induced by trauma or cardiac surgery has been well investigated. However, there are no reports regarding the role of mitochondrial N‐formylpeptides in cancer. In this study, we investigated the role of tumor cell‐derived mitochondrial N‐formylpeptides in anti‐tumor immunity using knockout murine tumor cells of mitochondrial methionyl‐tRNA formyltransferase (MTFMT), which catalyze N‐formylation of mitochondrial DNA‐encoded proteins. There was no apparent difference among the wild‐type and MTFMT‐knockout clones of E.G7‐OVA cells with respect to morphology, mitochondrial dynamics, glycolysis and oxidative phosphorylation, oxygen consumption rate, or in vitro cell growth. In contrast, in vivo tumor growth of MTFMT‐knockout cells was slower than that of wild‐type cells. A reduced number of myeloid‐derived suppressor cells and an increase of cytotoxic T‐lymphocytes in the tumor tissues were observed in the MTFMT‐knockout tumors. These results suggested that tumor cell‐derived mitochondrial N‐formylpeptides had a negative role in the host anti‐tumor immunity through modification of the tumor microenvironment. [ABSTRACT FROM AUTHOR]

Herein, the transparent conducting oxide (TCO) characteristics of the window layer as a factor in the decrease of conversion efficiency from lab‐scale cells to modules are focused on. Then, an optical model and a circuit model are constructed based on measured data, and TCO parameters are investigated to optimize Cu(In,Ga)Se2 (CIGS) module characteristics. Simulations assuming ZnO:Al and ZnO:B as the TCO, which are commonly used in CIGS modules with a substrate structure, show that the range of the TCO parameters to obtain high efficiency is limited. In particular, the optimum values of module characteristics are separated into high‐carrier density/thin‐film region with a smooth surface and low‐carrier density/thick‐film region with a textured surface for the TCO layer. In addition, simulations assuming a high‐mobility TCO and a wide‐gap CIGS absorber to boost conversion efficiency reveal that the wide‐gap CIGS absorber mitigates the effects of resistance losses and free carrier absorption due to the TCO, thereby expanding the design range of the carrier density in the TCO layer. [ABSTRACT FROM AUTHOR]

Introduction: Coronary computed tomography angiography (CCTA) is known to have a high negative predictive value (NPV) in identifying coronary artery disease (CAD). This study aimed to examine whether resting echocardiographic parameters could exclude significant CAD on CCTA. Methods: We recruited 142 patients who had undergone both CCTA and echocardiography within a 3‐month window. Based on the CCTA findings, patients were divided into two groups: Group A (non‐significant CAD, defined as all coronary segments having <50% stenosis) and Group B (significant CAD). Resting echocardiographic parameters were compared between the two groups to identify predictors of non‐significant CAD on CCTA. Results: A total 92 patients (mean age, 68 ± 13 years; males, 62%) were eligible for this study; 50 in Group A and 42 in Group B. Among the various echo parameters, left atrial volume index (LAVI) and left ventricular (LV) global longitudinal strain (GLS) were significantly lower in Group A (23.5 ± 7.6 vs. 33.6 ± 7.4 mL/m2, p <.001; −20.2 ± 1.8% vs. −16.8 ± 2.0%, p <.001, respectively). Analysis of the receiver operating characteristic curve revealed that the cutoff value to exclude significant CAD on CCTA was 29.0 mL/m2 for LAVI (NPV 80.8%) and −18.1% for GLS (NPV 80.7%). The NPV increased to 95.0% when these parameters were combined (LAVI < 29.0 mL/m2 and GLS < −18.1%). Conclusion: The combination of resting LAVI and GLS was clinically useful in excluding significant CAD via CCTA. [ABSTRACT FROM AUTHOR]

The behavior of carriers for an electron‐beam‐induced current (EBIC) evaluation is experimentally and theoretically analyzed for the polycrystalline Cu (In, Ga)Se2 (CIGS) thin‐film solar cells. The experimental EBIC signal in‐depth profiles of the CIGS layers show four features: peaks at grain boundaries (GBs), narrowed peaks near the surface, shifted peaks near the surface, and double peaks at the GBs and surface. Operating principles for CIGS solar cell devices under electron–hole pair excitation are systematically revealed utilizing a two‐dimensional theoretical EBIC simulation: (i) The EBIC peaks at the GBs are caused by a high hole barrier, including a valence band offset (ΔEV) and a band bending at the GBs; (ii) narrowing of EBIC peaks near the surface is caused by high defect densities at the GBs, grading of a conduction band minimum, and grading of acceptor concentration (Na) along with the CIGS depth direction; (iii) a shift in EBIC peaks near the surface is caused by high donor‐like defect densities at the surface; (iv) double peaks at the GBs and surface are caused by a thick surface layer (SL) with the ΔEV and the hole barrier at GBs. These findings of the EBIC analysis will help to comprehensively understand the complex polycrystalline CIGS carrier transport mechanism in realizing the highest‐efficiency CIGS solar cells. [ABSTRACT FROM AUTHOR]

Aim: Using classification tree analysis, we evaluated the most useful magnetic resonance (MR) image type in the differentiation between early and progressed hepatocellular carcinoma (eHCC and pHCC). Methods: We included pathologically proven 214 HCCs (28 eHCCs and 186 pHCCs) in 144 patients. The signal intensity of HCCs was assessed on in‐phase (T1in) and opposed‐phase T1‐weighted images (T1op), ultrafast T2‐weighted images (ufT2WI), fat‐saturated T2‐weighted images (fsT2WI), diffusion‐weighted images (DWI), contrast enhanced T1‐weighted images in the arterial phase (AP), portal venous phase (PVP), and the hepatobiliary phase. Fat content and washout were also evaluated. Fisher's exact test was performed to evaluate usefulness for the differentiation. Then, we chose MR images using binary logistic regression analysis and performed classification and regression tree analysis with them. Diagnostic performances of the classification tree were evaluated using a stratified 10‐fold cross‐validation method. Results: T1in, ufT2WI, fsT2WI, DWI, AP, PVP, fat content, and washout were all useful for the differentiation (p < 0.05), and AP and T1in were finally chosen for creating classification trees (p < 0.05). AP appeared in the first node in the tree. The area under the curve, sensitivity and specificity for eHCC, and balanced accuracy of the classification tree were 0.83 (95% CI 0.74–0.91), 0.64 (18/28, 95% CI 0.46–0.82), 0.94 (174/186, 95% CI 0.90–0.97), and 0.79 (95% CI 0.70–0.87), respectively. Conclusions: AP is the most useful MR image type and T1in the second in the differentiation between eHCC and pHCC. [ABSTRACT FROM AUTHOR]

The importance of positive band offset at the p–n interface of heterojunction thin‐film solar cells has been underlined in the authors' previous work on theoretical study of the role of n‐type layer in determining open‐circuit voltage – and experimental work by other research groups. An n‐type material with low electron affinity has the potential to fulfill the requirements for producing a high‐performance heterojunction thin‐film solar cell. In this current work, a new alternative transparent conductive oxide material for chalcopyrite heterojunction solar cells is investigated by alloying ZnO and GeO2 to grow a Zn‐Ge‐O thin‐film with low electron affinity. The film is grown by metal organic chemical vapor deposition with tetramethoxygermanium as the Ge source. Through film characterization, it is confirmed that higher concentrations of Ge in the film result in lower electron affinities and relatively constant valence band maximums. Different [Ge] / ([Zn] + [Ge]) also affects the film morphology, from polycrystalline at a lower concentration of Ge to aggregation of nanocrystals at a higher concentration of Ge. Electronic characterization and preliminary device application test show promising results for the future of the Zn‐Ge‐O thin‐film as an alternative n‐type layer for chalcopyrite solar cells. [ABSTRACT FROM AUTHOR]

Aims: Little is known about whether resting left ventricular global longitudinal strain (GLS) impairment is associated with myocardial perfusion abnormalities evaluated using 13N‐ammonia positron emission tomography (13N‐NH3‐PET)‐myocardial perfusion imaging (MPI). This study aimed to investigate the correlation between resting GLS and myocardial perfusion parameters in patients with a normal left ventricular ejection fraction (LVEF). We evaluated whether resting GLS can predict myocardial perfusion abnormalities in these patients. Methods and Results: We selected 157 patients with suspected stable angina pectoris who underwent both ATP‐stress NH3‐PET‐MPI and 2‐dimentional speckle tracing echocardiography. All subjects had a preserved LVEF and no known history of myocardial infarction. Patients were stratified into Group N (normal perfusion; summed stress score [SSS], 0–3; n = 101), Group M (mildly to moderately abnormal perfusion; SSS, 4–11; n = 41), or Group S (severely abnormal perfusion; SSS, 12+; n = 15). GLS was more impaired as myocardial perfusion abnormality severity increased (–17.9 ± 2.9% for Group N, –16.8 ± 3.1% for Group M, and –14.2 ± 3.5% for Group S; p <.001). GLS was weakly but significantly correlated with SSS (R =.32, p <.001), summed difference score (R =.32, p <.001), and myocardial blood flow during stress (R = –0.27, p <.001). Multivariate logistic regression analysis showed that male sex, diabetes mellitus, systolic blood pressure, and GLS were independent predictors of myocardial perfusion abnormality defined as Groups M and S. Additionally, the area under the curve for GLS for detecting myocardial perfusion abnormality was.65, and the optimal cutoff value for GLS was –16.5%, with sensitivity and specificity of 59% and 66%, respectively. Conclusion: In patients with suspected angina pectoris, resting GLS impairment despite a normal LVEF might aid the detection of hemodynamically significant coronary artery disease. [ABSTRACT FROM AUTHOR]

Accumulated clinical data of immune checkpoint blockades have suggested the importance of neoantigens in cancer immunity. Tumor antigens are released from dead cancer cells together with cellular components, such as damage‐associated molecular patterns (DAMPs), into the tumor microenvironment. We recently reported that high mobility group box 1 (HMGB1), a representative DAMP molecule, showed a negative impact on anti‐tumor immunity. However, a positive role of HMGB1 in the initiation of innate and subsequent adaptive immunity has also been demonstrated; thus, the effects of HMGB1 on anti‐tumor immunity have not been well understood. In this study, we identified nine immunogenic neoantigen epitopes of B16F10 murine melanoma cells and subsequently investigated the effects of suppression of HMGB1 on the induction of neoantigen‐specific immunity using HMGB1‐knockout tumors. Neoantigen‐reactive T cells were expanded in B16F10 tumor‐bearing mice, and T cell receptor repertoire analysis suggested that neoantigen‐reactive T cells were oligo‐clonally increased in B16F10 tumor bearers. An increase of neoantigen‐reactive T cells and oligoclonal expansion of the T cells were similarly detected in HMGB1‐knockout tumor‐bearing mice. The induction of neoantigen‐specific immunity under the suppression of HMGB1 in the tumor microenvironment shown in this study supports further development of combination therapy of HMGB1 suppression with neoantigen‐targeted cancer immunotherapies, including immune checkpoint blockade therapy. [ABSTRACT FROM AUTHOR]

The article titled "A new imaging classification for safer radial access visceral intervention of the liver and optimal case selection: A preliminary report" published in Hepatology Research discusses the use of the radial artery approach in abdominal arterial interventional procedures. The authors propose a simple and reproducible preoperative evaluation method, called TAC-F-R, to determine the indication for radial access visceral intervention (R.A.V.I.) and predict the difficulty of the procedure based on anatomical features of the aortic arch. The method uses oblique sagittal multiplanar reconstructed CT images and simple anatomical structures, making it practical for daily clinical practice. However, further validation and examination of other factors that influence the procedure are needed. [Extracted from the article]

Herein, Li‐doped NiO thin films are deposited on glass substrates using pressure‐gradient radiofrequency magnetron sputtering, with Ar and O2 as sputtering gases. Following film fabrication, their crystal structures, optical features, and electrical properties are investigated as functions of O2 flow rate to the total flow rate (O2/(O2 + Ar)) of 10 sccm. The deposited films are also annealed at 600 °C for 1 h in an oxygen atmosphere. Notably, the resistivity of the as‐deposited films decreases significantly by three orders of magnitude from 106 to 0.0232 Ω cm when the sputtering gas is changed from pure Ar to pure O2. However, the transmittance decreases with increasing oxygen flow rate. Investigations on the temperature dependence of conductivity reveal hole conduction in the range of ≈320–420 K owing to small polaron hopping. [ABSTRACT FROM AUTHOR]

We undertook an early phase II study of mixed 19‐peptide cancer vaccine monotherapy for 14 advanced metastatic triple‐negative breast cancer (mTNBC) patients refractory to systemic chemotherapy to develop a new type of cancer vaccine. The treatment protocol consisted of a weekly vaccination for 6 weeks, and there were no severe adverse events related to the vaccination throughout the trial. Increase of peptide‐specific IgG against the vaccinated human leukocyte antigen‐matched peptides, but not against the nonmatched peptides, was positively correlated with overall survival (OS) (P <.01). The median OS was 11.5 or 24.4 months in all 14 patients or the 10 patients who completed the vaccination. The patients with lower C‐reactive protein levels or 3 or fewer systemic chemotherapies were favorable candidates for this treatment. Advancement of this therapy to the next stage of study could be warranted based on the safety and immune boosting determined herein (clinical trial registration number: UMIN000014616). [ABSTRACT FROM AUTHOR]

The identification of useful biomarkers is an urgent issue in cancer treatment, particularly for immunotherapy, as only some patients experience benefits from this treatment. The early induction of the IgG response has been reported as a useful biomarker of favorable prognosis for cancer patients treated with a personalized peptide vaccination, but a portion of these patients (IgG nonresponders) fail to achieve an early induction of IgG response yet experience long‐term survival. It is thus necessary to identify other biomarkers of favorable prognosis among these patients. Here we report the usefulness of classical T‐cell markers (ie, the CD8 content and the CD4/CD8 ratio in peripheral blood) in IgG nonresponders among advanced or recurrent ovarian cancer patients treated with a personalized peptide vaccination. Among IgG nonresponders (n = 25), the overall survival (OS) of the increased‐CD8 group (n = 7) was significantly longer than that of the decreased‐CD8 group (n = 18; P =.018), and the OS of the patients with a decreased CD4/CD8 ratio (n = 10) was significantly longer than that of the patients with an increased ratio (n = 15; P =.0055). Thus, an increased content of CD8 and a decreased CD4/CD8 ratio are each favorable prognosis markers in IgG nonresponders treated with a personalized peptide vaccination. [ABSTRACT FROM AUTHOR]

Aim: In patients with chronic hepatitis C, hepatocellular carcinoma (HCC) occurs at a certain frequency, even if a sustained virologic response (SVR) is achieved by antiviral treatment. Old age, liver fibrosis, and high post‐treatment α‐fetoprotein (AFP) level are typical risk factors of post‐SVR HCC. We examined whether the frequencies and factors of HCC in patients with an SVR achieved from interferon treatment changed. Methods Among patients prospectively registered for pegylated interferon and ribavirin treatment, 2021 with an SVR without HCC development during the treatment period were followed up. The mean observation period was 49.5 ± 26.2 months. Results: The multivariable Cox regression analysis showed that older age, diabetes mellitus, advanced liver disease, and higher post‐treatment AFP level were the independent risk factors throughout the observation period. The annual occurrence rate of HCC was 0.74% in the third year, 0.54% in the fourth year, and 0.40% in the fifth year; it gradually decreased from the third year. Because the time course hazards for HCC changed at 48 months, we separately analyzed its risk factors before and after this change point. The multivariable Cox regression analysis showed that the four above‐mentioned factors were significantly related to HCC development within 4 years. Conversely, the univariable Cox regression analysis only identified diabetes mellitus as a significant factor for HCC development after 4 years. Conclusion: The frequency of HCC in hepatitis C patients who achieved an SVR from interferon treatment decreased during the observation period, and its risk factors changed between the early and late periods. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Although conventional microbiology cultures may be negative, polymerase chain reaction (PCR) can effectively identify both typical and atypical microorganisms. With careful interpretation, PCR could become the gold‐standard diagnostic test for culture‐negative bacterial pericarditis. Although conventional microbiology cultures may be negative, polymerase chain reaction (PCR) can effectively identify both typical and atypical microorganisms. With careful interpretation, PCR could become the gold‐standard diagnostic test for culture‐negative bacterial pericarditis. [ABSTRACT FROM AUTHOR]

The unintentional formation of a Cu depletion layer (CDL) on the surface of Cu(In,Ga)Se2 was observed in 1993, and CDLs have been expected to improve the performance of Cu(In,Ga)Se2 solar cells. However, methods of controlling CDLs have hitherto been unavailable. For the first time, we succeeded in controlling a uniform CDL on a Cu(In,Ga)Se2 surface by introducing irradiation with Se into the typical three‐stage growth process of Cu(In,Ga)Se2. We discuss the characterization and effects on device performance of CDLs. A uniform, smooth CDL with a thickness of 200 nm was formed at a Se irradiation time of 5 minutes, whereas the CDL formed at an irradiation time of 10 minutes was rough and non‐uniform. A maximum efficiency of 19.8% was achieved at an irradiation time of 5 minutes via the formation of a complete CDL. This simple, unique method may help to maximize efficiency of Cu(In,Ga)Se2 solar cells. We succeeded in controlling a uniform Cu depletion layer on a Cu(In,Ga)Se2 surface by introducing irradiation with Se into the typical three‐stage growth process of Cu(In,Ga)Se2. A uniform, smooth Cu depletion layer with a thickness of 200 nm was formed at a Se irradiation time of 5 minutes, whereas the Cu depletion layer formed at an irradiation time of 10 minutes was rough and nonuniform. A maximum efficiency of 19.8% was achieved at an irradiation time of 5 minutes via the formation of a complete Cu depletion layer. [ABSTRACT FROM AUTHOR]

Aim: To verify the utility of the 2‐in‐1‐out‐compartment model analysis (CMA) of intravenous contrast‐enhanced dynamic computed tomography (IV‐CT) for evaluating hepatic arterial and portal venous flow using intra‐arterial contrast‐enhanced CT (IA‐CT). Methods: We retrospectively evaluated 49 consecutive patients who underwent IV‐CT and were radiologically or histologically diagnosed as having hepatic malignant lesion (51 classical hepatocellular carcinomas [HCC], 4 early HCC, 3 cholangiolocellular carcinomas, 1 mixed HCC, 3 cholangiocellular carcinomas). As a gold standard for hepatic arterial and portal blood flows, we defined the normalized enhancement in CT values on CTAP (nCTAP) and CTHA (nCTHA). The hepatic arterial (k1a) and portal venous inflow velocity (k1p) constants in hepatic lesions and surrounding liver parenchyma were obtained from the CMA of IV‐CT with various outflow velocity constant (k2) limits using the nonlinear least square method. The correlation coefficient between the normalized enhancement in IA‐CT and CMA of IV‐CT was statistically evaluated according to various k2 limits. Results: The highest mean correlation coefficient between k1a and nCTHA (r = 0.65, P < 0.0001) was observed when k2 ≦0.035. The highest mean correlation coefficient between k1p and nCTAP (r = 0.69, P < 0.0001) was observed when k2≦0.045. The decrease in correlation coefficient was significant when the upper k2 limit was lower than 0.03 or higher than 0.07 compared to the best mean correlation coefficient (P < 0.05). Conclusion: Hepatic arterial and portal venous flows can be evaluated quantitatively to some extent with appropriate outflow velocity constant limits using the CMA of IV‐CT. [ABSTRACT FROM AUTHOR]

Peptide‐based cancer vaccines are able to induce strong immune responses, but their clinical results are unsatisfactory. To determine clinically correlated peptides, we analyzed survival data from urological cancer patients treated by personalized peptide vaccination (PPV), in which different multiple peptides were used for individual patients based on human leukocyte antigen (HLA) type and pre‐existing immunity. Survival data were obtained from a database of 265 urological cancer patients treated in 5 clinical PPV trials comprising 154 patients with castration‐resistant prostate cancer (CRPC) and 111 patients with advanced urothelial cancer (UC). Expression of tumor‐associated antigens (TAA) was evaluated in 10 prostate cancer tissues, 4 metastatic lymph nodes from prostate cancer, and 10 UC tissues using immunohistochemical staining. Clinical efficacy of individual peptides for overall survival was evaluated by the Cox proportional hazards regression model. All TAA coding candidate peptides used in PPV treatment were expressed in tumor cells from prostate cancer and UC samples except for p56Lck in both, and prostate‐specific antigen (PSA), prostatic acid phosphatase (PAP) and prostate‐specific membrane antigen (PSMA) in the UC samples. Patients with the following peptides had a significantly longer survival than patients without the peptides (hazard ratio <1.0, 95% confidence intervals <1.0 and P < .05): SART3‐109, PTHrP‐102, HNPRL‐140, SART3‐302 and Lck‐90 in CRPC patients, and EGF‐R‐800, Lck‐486, PSMA‐624, CypB‐129 and SART3‐734 in advanced UC patients, respectively. Correlated peptides selected using both survival data and pre‐existing immunity for PPV treatment may enhance the clinical benefits for urological cancer patients. [ABSTRACT FROM AUTHOR]

Aim: The purpose of this study was to determine whether the liver stiffness (LS) measured on magnetic resonance (MR) elastography can be estimated by a combination of gadoxetate disodium‐enhanced MR imaging (EOB‐MRI) and ordinary blood tests. Methods: We evaluated 33 consecutive patients with suspected liver disease who underwent EOB‐MRI using a Differential Subsampling with Cartesian Ordering MR sequence and MR elastography using a 1.5‐T MR system in this prospective study. A stepwise multiple linear regression model analysis of LS was performed using various predictive values obtained from two‐in‐one‐uptake, two‐compartment model analysis of EOB‐MRI (velocity constants of arterial inflow [K1a], portal venous inflow [K1p], hepatocellular uptake [Ki]), and ordinary blood test results (blood platelet count, serum albumin level [ALB], total serum bilirubin level [T‐BIL], and prothrombin time [PT%]). Results: Multiple linear regression model analysis revealed that hepatic perfusion‐uptake index (HPUI = –K1a + K1p + Ki) (P < 0.0001), albumin‐bilirubin linear predictor (ALBI‐LP = 0.66 × log10T‐BIL – 0.085 × ALB) (P = 0.034), and blood platelet count (P = 0.046) were significant independent predictors of LS (r = 0.863). The area under receiver operator characteristics curve of multiple linear regression model in prediction of the liver stiffness corresponding to higher (LS > 5.0 kPa) and lower (LS < 4.2 kPa) risk for developing hepatocellular carcinoma were 0.956 and 0.938, respectively. Conclusion: LS can be estimated quantitatively with the use of HPUI obtained from compartment model analysis of EOB‐MRI combined with ALBI‐LP and blood platelet count. [ABSTRACT FROM AUTHOR]

We recently succeeded in controlling a Cu‐deficient Cu(In,Ga)Se2 layer (CDL) on a Cu(In,Ga)Se2 (CIGS) surface by introducing an Se irradiation after the completion of the second stage in a three‐stage process during CIGS growth. The CDL on the surface causes the formation of a valence band offset (ΔEV) between the CDL and CIGS because the Cu vacancies decrease the valence band maximum of the CDL. Therefore, we can expect the suppression of recombination at the CdS/CIGS interface in CIGS solar cells due to the repelling of holes by ΔEV. The amount of knowledge regarding the properties of CDL/CIGS interfaces is observed to be quite small because a control technique for CDL has not been developed so far. In this study, the compositional and structural properties of an accurately controlled CDL/CIGS interface are investigated in detail. The composition of the interface between the CDL and CIGS is observed using an energy dispersive X‐ray spectroscopy with the help of a transmission electron microscope. Using nanobeam electron diffraction and Fourier transfer mapping analysis, it is confirmed that the ( 1 1 ¯ 2 ) plane in the CDL continuously grows on the ( 11 2 ¯ ) plane in CIGS. Further, these results indicate that a high‐quality interface is formed between the CDL and CIGS, which contains only a small amount of dangling bonds. Finally, a high conversion efficiency of 19.4% is achieved in the CIGS solar cell, which can be attributed to the formation of CDL and effect of ΔEV. [ABSTRACT FROM AUTHOR]

Abstract: Cu‐deficient layer (CDL) on Cu(In,Ga)Se2 (CIGS) promotes Cd diffusion from CdS buffer layer and forms a valence band offset (ΔEV) between CDL and CIGS. We quantitively demonstrate the effects of CDL formation on the performance of CIGS solar cells through experiments and theoretical simulation. To investigate the effects of Cd diffusion and ΔEV by CDL, theoretical analysis was carried out for a CIGS solar cell with a surface layer which simulated the CDL at CdS/CIGS interface. It was revealed that when electron concentration in n‐type surface layer is higher than the absolute carrier concentration in CIGS absorber (ND > |NA, CIGS|), open‐circuit voltage and fill factor are improved. Additionally, ΔEV ≥ 0.15 eV leads to the highest open‐circuit voltage by suppression of interfacial recombination. Transmission electron microscope energy dispersive X‐ray spectrometry and scanning spreading resistance microscopy were employed for the same cross section of a CIGS solar cell fabricated by three‐stage process. Despite CDL with Cu/(Ga + In) of 0.31 formed on the surface had high Cd contents of 3.4 at%, its carrier concentration of 4.8 × 1010 cm−3 was lower than that of 1014 –1016 cm−3 in grain interior owing to insufficient activation of Cd atoms. These results indicate the effectiveness of ΔEV formation by introducing CDL with low Cu/(Ga + In) of 0.31 to boost CIGS solar cell performance and difficulty in realizing ND > |NA, CIGS| by surface Cd doping. [ABSTRACT FROM AUTHOR]

Aim To enhance the usefulness of splenic perfusion evaluated by means of dynamic computed tomography (CT) and spleen size in assessing the degree of liver fibrosis. Methods We retrospectively studied 133 patients who had undergone dynamic CT before hepatectomy. Fibrosis was histologically established in all. First we calculated splenic perfusion parameters K1 (inflow rate constant), 1/k2 (mean transit time; MTT), and K1/k2 (distribution volume; Vd), using compartment model analysis. Then we compared the stage of fibrosis with splenic perfusion and spleen size (long axis, R), using the Kruskal-Wallis test and multiple comparisons. After that, we assessed the diagnostic accuracy of the combination of splenic perfusion, spleen size, age, gender, and the presence or absence of hepatitis B and hepatitis C viral infection in detecting liver fibrosis, using stepwise regression and receiver operating characteristic analysis. Results Significant differences ( P < 0.05) in MTT were observed in comparisons between fibrosis stages F0 and F4, between F1 and F4, and between F2 and F4. Significant differences ( P < 0.05) in R were observed in comparisons between F0 and F4, and between F1 and F4. Considering the presence or absence of hepatitis B and C viral infection along with MTT and R, the areas under the receiver operating characteristic curves were 0.89 for ≥F1, 0.83 for ≥F2, 0.82 for ≥F3, and 0.82 for F4. Conclusion Splenic MTT and spleen size are helpful in assessing liver fibrosis. [ABSTRACT FROM AUTHOR]

This randomized phase II study investigated the immunological efficacy of herbal medicines ( HM) using Hochu-ekki-to and Keishi-bukuryo-gan in combination with personalized peptide vaccination ( PPV) for castration-resistant prostate cancer ( CRPC). Seventy patients with CRPC were assigned to two arms; PPV plus HM or PPV alone. Two to four peptides were chosen from 31 peptides derived from cancer antigens for a s.c. injection of PPV given eight times according to the patient's human leukocyte antigen type and levels of antigen-specific IgG titer before PPV treatment. Peptide-specific CTL, IgG, regulatory T cells (Treg), monocytic myeloid-derived suppressor cells (Mo- MDSC), and interleukin-6 ( IL-6) responses were measured before and at the eighth vaccination. Clinical outcomes were also analyzed. Combination therapy of PPV with HM was well tolerated without severe adverse events. There was no significant change in antigen-specific IgG, CTL, Treg or clinical outcomes. Combination therapy of PPV with HM stabilized the frequency of Mo- MDSC (1.91%-1.92%, P = 0.96) and serum levels of IL-6 (19.2 pg/ mL to 16.1 pg/ mL, P = 0.63) during the treatment. In contrast, the frequency of Mo- MDSC and levels of IL-6 in the PPV-alone group were significantly increased (0.91%-1.49% for Mo- MDSC and 9.2 pg/ mL to 19.4 pg/ mL for IL-6, respectively). These results suggest that the combined use of HM has the potential to prevent the immunosuppression induced by Mo- MDSC or IL-6 during immunotherapy. More research is needed to validate the findings of the present study. [ABSTRACT FROM AUTHOR]

Molecular beam epitaxy was used to fabricate Ag(In,Ga)Se2 (AIGS) thin films. To improve the diffusion of Ag, high-temperature deposition and high-temperature annealing methods were applied to fabricate AIGS films. The as-grown AIGS thin films were then used to make AIGS solar cells. We found that grain size and crystallinity of AIGS films were considerably improved by increasing the deposition and annealing temperature. For high-temperature deposition, temperatures over 600 °C led to decomposition of the AIGS film, desorption of In, and deterioration of its crystallinity. The most appropriate deposition temperature was 590 °C and a solar cell with a power conversion efficiency of 4.1% was obtained. High-temperature annealing of the AIGS thin films showed improved crystallinity as annealing temperature was increased and film decomposition and In desorption were prevented. A solar cell based on this film showed the highest conversion efficiency of 6.4% when annealed at 600 °C. When the annealing temperature was further increased to 610 °C, the performance of the cell deteriorated due to loss of the out-of-plane Ga gradient. [ABSTRACT FROM AUTHOR]

Overall survival of patients with hepatocellular carcinoma ( HCC) refractory to locoregional therapy is dismal, even following treatment with sorafenib, a multikinase inhibitor. To develop a more efficacious treatment, we undertook a feasibility study of personalized peptide vaccination ( PPV) for HCC, in which the peptides were selected from 31 peptide candidates based on the pre-existing immunity. Twenty-six HCC patients refractory to locoregional therapies (cohort 1) and 30 patients refractory to both locoregional and systemic therapies (cohort 2) were entered into the study. There were no severe adverse events related to PPV except for one injection site reaction. At the end of the first cycle of six vaccinations, successful CTL or IgG boosting was observed in 57% or 46% of patients in cohort 1 and in 54% or 52% of patients in cohort 2, respectively. Successful IgG boosting at the end of the second cycle was observed in the majority of patients tested. Median overall survival was 18.7 months (95% confidence interval, 12.2-22.5 months) in cohort 1, and 8.5 months (95% confidence interval, 5.9-12.2 months) in cohort 2. Based on the higher rates of immune boosting and the safety profile of PPV, further clinical studies of PPV would be warranted for patients with HCC refractory to not only locoregional therapy but also both locoregional and systemic therapies. The protocol of this study was registered with the UMIN Clinical Trials Registry ( UMIN000001882 and UMIN000003590). [ABSTRACT FROM AUTHOR]

Aim Simeprevir (SMV)-based triple therapy is an effective retreatment option following failure of telaprevir (TVR)-based triple therapy. However, it is unclear whether the persistence of resistance-associated variants (RAVs) induced by TVR-based therapy may reduce the treatment effect of SMV-based therapy. Methods The factors associated with the treatment effect, including RAVs in the NS3 region, were examined in 21 patients with genotype 1b HCV infection who were treated with SMV-based therapy after failure of TVR-based therapy. Ultra-deep sequencing was carried out to detect RAVs. Results With the exception of one patient who discontinued treatment owing to adverse events, the sustained virologic response (SVR) rate was 50% (10/20). Ultra-deep sequencing at the start of SMV-based therapy revealed that TVR-resistant variants were detected in six patients (29%), and no variants were observed at position 168. Cross-resistance between TVR and SMV with low frequency was detected in only one patient, and this patient achieved SVR. Higher SVRs for SMV-based therapy were attained in patients who discontinued treatment owing to the adverse effects of prior TVR-based therapy (discontinuation 100% vs. non-discontinuation 29%, P = 0.005), and patients who relapsed following prior pegylated interferon plus ribavirin therapy (relapse 100% vs. non-response 20%, P = 0.007). Conclusions In this study, ultra-deep sequencing analysis revealed that TVR and/or SMV-resistant variants may have no influence on the effect of SMV-based therapy after failure of TVR-based therapy. Patients who discontinued treatment owing to adverse effects of TVR-based therapy and relapsers to previous pegylated interferon/ribavirin therapy would be good candidates for retreatment with SMV-based therapy. [ABSTRACT FROM AUTHOR]

Since the prognosis of advanced biliary tract cancer ( aBTC) still remains very poor, new therapeutic approaches, including immunotherapies, need to be developed. In the current study, we conducted an open-label randomized phase II study to test whether low dose cyclophosphamide ( CPA) could improve antigen-specific immune responses and clinical efficacy of personalized peptide vaccination ( PPV) in 49 previously treated aBTC patients. Patients with aBTC refractory to at least one regimen of chemotherapies were randomly assigned to receive PPV with low dose CPA (100 mg/day for 7 days before vaccination) ( PPV/ CPA, n = 24) or PPV alone ( n = 25). A maximum of four HLA-matched peptides were selected based on the pre-existing peptide-specific IgG responses, followed by subcutaneous administration. T cell responses to the vaccinated peptides in the PPV/ CPA arm tended to be greater than those in the PPV alone arm. The PPV/ CPA arm showed significantly better progression-free survival (median time: 6.1 vs 2.9 months; hazard ratio ( HR): 0.427; P = 0.008) and overall survival (median time: 12.1 vs 5.9 months; HR: 0.376; P = 0.004), compared to the PPV alone arm. The PPV alone arm, but not the PPV/ CPA arm, showed significant increase in plasma IL-6 after vaccinations, which might be associated with inhibition of antigen-specific T cell responses. These results suggested that combined treatment with low dose CPA could provide clinical benefits in aBTC patients under PPV, possibly through prevention of IL-6-mediated immune suppression. Further clinical studies would be recommended to clarify the clinical efficacy of PPV/ CPA in aBTC patients. [ABSTRACT FROM AUTHOR]

High-mobility group box 1 (HMGB1) is a nuclear protein that is known to be secreted into extracellular fluids from injured cells, activated macrophages, and tumor cells. The clinical correlation of circulating HMGB1 levels with various diseases including cancer has been reported. However, there is no information on HMGB1 levels in cancer patients treated with peptide vaccination. In the present study, we investigated the plasma levels of HMGB1 during personalized peptide vaccination in patients with recurrent ovarian cancer. Frozen plasma samples of 39 patients from previously conducted clinical trials were used in this study. HMGB1 levels were decreased after the 1st cycle of vaccination from their prevaccination levels. However, no correlation was observed between HMGB1 and overall survival (OS). The correlation between plasma HMGB1 levels and other biomarker levels was further analyzed by scatter plot, revealing that HMGB1 levels after the 1st cycle of vaccination were significantly correlated with myeloid-derived suppressor cell (MDSC) frequency after the 1st cycle of vaccination (r = 0.357, p = 0.032). Chi-square test showed that epitope spreading was significantly related with changes of HMGB1 (p = 0.030). These results suggest that plasma HMGB1 is a possible biomarker for cancer vaccine therapy, although direct correlation with OS has not been obtained. This trial is registered with Clinical Trial Registry under trial numbers UMIN000003083 and UMIN000001482. [ABSTRACT FROM AUTHOR]

The HLA-A11 or -A33 allele is found in approximately 18% or 10% of the Asian population, respectively, but each of which is a minor allele worldwide, and therefore no clinical trials were previously conducted. To develop a therapeutic peptide vaccine for each of them, we investigated immunological responses of advanced cancer patients with the HLA-A11+/A11+ ( n = 18) or -A33+/A33+ ( n = 13) allele to personalized peptide vaccine ( PPV) regimens. The primary sites of HLA-A11+/A11+ or -A33+/A33+ patients were the colon ( n = 4 or 2), stomach (2 or 3), breast (3 or 2), lung and pancreas (2 or 2), and so on. For PPV, a maximum of four peptides were selected from nine different peptides capable of binding to HLA-A11 and -A33 molecules based on the pre-existing peptide-specific IgG responses. There were no severe adverse events related to PPV. At the end of the first cycle, peptide-specific CTL responses were augmented in 4/12 or 2/9 of HLA-A11+/A11+ or -A33+/A33+ patients, while peptide-specific IgG responses were augmented in 6/14 or 4/10 patients, respectively. Clinical responses consisted of four stable diseases and 14 progressive diseases in HLA-A11+/A11+patients, versus seven and six in -A33+/A33+patients, respectively. Further clinical study of PPV could be recommended because of the safety and positive immunological responses. [ABSTRACT FROM AUTHOR]

A 46-year-old woman presented with headache and right hemiparesis. MRI demonstrated a mass in the left middle fossa. Total resection was performed. A histological examination of the tumor specimen showed several characteristic morphological features. A chordoid meningioma showing an epithelial-like palisade arrangement was observed. An anaplastic short spindle cell tumor exhibiting a fascicular pattern was considered to be a rhabdomyosarcoma. After conventional radiotherapy, the tumor was well controlled without any neurological deficit for 20 months. When subsequent recurrences were observed, the patient was treated by surgery, stereotactic radiosurgery and chemotherapy. Thirty-two months after the initial treatment, the patient died due to intracranial dissemination and an autopsy was performed. The histological examination of the recurrent and autopsy specimens showed a prominent sarcoma component. This case appears to be the first reported intracranial tumor diagnosed as a dedifferentiated chordoid meningioma with rhabdomyosarcomatous differentiation. [ABSTRACT FROM AUTHOR]

High mobility group box 1 ( HMGB1) is a member of the family of damage-associated molecular patterns, which cause inflammation and trigger innate immunity through Toll-like receptors 2/4 and the receptor for advanced glycation end products. We examined the effect of glycyrrhizin, a selective inhibitor of HMGB1, on the induction of CTLs in mice. B6 mice, either OT-1 spleen cell-transferred or untransferred, were immunized with an s.c. injection of OVA257-264 peptide with topical imiquimod, and glycyrrhizin was mixed with the antigen peptide. Proliferation of OT-1 cells after immunization was enhanced by glycyrrhizin. The effect of glycyrrhizin was confirmed in other adjuvant systems, such as CpG oligonucleotide and monophosphoryl lipid A, but glycyrrhizin was not effective in Freund's incomplete adjuvant system. The augmenting effects of glycyrrhizin were also observed in other synthetic HMGB1 inhibitors, gabexate mesilate, nafamostat, and sivelestat. Thus, the effects are common to the HMGB1 inhibitors. Induction of CTLs detected by γ-interferon enzyme-linked immunospot assay was similarly augmented by glycyrrhizin. In a therapeutic vaccine model, glycyrrhizin inhibited the growth of s.c. transplanted EG.7 tumors. Expression of inflammatory cytokines in the skin inoculation site was downregulated by glycyrrhizin. These results suggest that HMGB1 inhibitors might be useful as a co-adjuvant for peptide vaccination with an innate immunity receptor-related adjuvant. [ABSTRACT FROM AUTHOR]

Aim The therapeutic efficacy of branched-chain amino acid (BCAA) when added to sorafenib has not been fully assessed in patients with advanced hepatocellular carcinoma (HCC). This multicenter study investigated whether BCAA supplementation improves prognosis in patients with advanced HCC who underwent sorafenib treatment. Methods This retrospective analysis included 256 patients with advanced HCC treated with sorafenib, including 55 who did and 201 who did not receive BCAA supplementation. Clinical characteristics and outcomes in relation to Child-Pugh classification were compared in the two groups. Statistical analyses of univariate, multivariate and propensity score-based procedures were used for this study. Results Assessment of 216 Child-Pugh A patients showed that median overall survival was significantly longer in patients with BCAA supplementation than in those without it (440 vs 299 days, P = 0.023). Multivariate analysis showed that BCAA supplementation ( P = 0.023), low α-fetoprotein (<100 ng/mL) ( P < 0.001), less progressive Barcelona Clinic Liver Cancer stage (A and B) ( P = 0.007) and male sex ( P = 0.018) were significant independent contributors to better overall survival. The significantly longer overall survival by BCAA supplementation was verified in the analysis using the propensity score in combination with the inverse probability of treatment weighted adjustment ( P = 0.026). Assessment of the 40 Child-Pugh B patients showed no significant differences in overall survival between patients with and without BCAA supplementation. Conclusion BCAA supplementation may be a valuable adjunctive therapy for improving prognosis in sorafenib-treated Child-Pugh A patients with advanced HCC. [ABSTRACT FROM AUTHOR]

Key points Strenuous endurance exercise induces transient functional and biochemical cardiac perturbations that persist for 24-48 h., The magnitude and time-course of exercise-induced reductions in ventricular function and increases in cardiac injury markers are influenced by the intensity and duration of exercise., In a human experimental model, exercise-induced reductions in ventricular strain and increases in cardiac troponin are greater, and persist for longer, when exercise is performed within the heavy- compared to moderate-intensity exercise domain, despite matching for total mechanical work., The results of the present study help us better understand the dose-response relationship between endurance exercise and acute cardiac stress/injury, a finding that has implications for the prescription of day-to-day endurance exercise regimes., Abstract Strenuous endurance exercise induces transient cardiac perturbations with ambiguous health outcomes. The present study investigated the magnitude and time-course of exercise-induced functional and biochemical cardiac perturbations by manipulating the exercise intensity-duration matrix. Echocardiograph-derived left (LV) and right (RV) ventricular global longitudinal strain (GLS), and serum high-sensitivity cardiac troponin (hs-cTnI) concentration, were examined in 10 males (age: 27 ± 4 years; [ABSTRACT FROM AUTHOR]

Objectives. To evaluate the efficacy and safety of personalized peptide vaccination (PPV) combined with chemotherapy for patients with previously treated advanced non-small-cell lung cancer (NSCLC). Patients and Methods. Previously treated PS0-1 patients with IIIB/IV EGFR (epidermal growth factor receptor) wild genotype NSCLC were randomly assigned to docetaxel (60 mg/m(2) on Day 1) plus PPV based on preexisting host immunity or docetaxel plus placebo. Docetaxel administration was repeated every 3 weeks until disease progression. Personalized peptides or placebo was injected subcutaneously weekly in the first 8 weeks and biweekly in subsequent 16 weeks. The primary efficacy endpoint was progression-free survival (PFS). Results. PPV related toxicity was grade 2 or less skin reaction. The median PFS for placebo arm and PPV arm was 52 days and 59 days, respectively. There was no significant difference between two arms by log-rank test (p = 0.42). Interestingly, PFS and overall survival (OS) in humoral immunological responder were significantly longer than those in nonresponder. Conclusion. PPV did not improve the survival in combination with docetaxel for previously treated advanced NSCLC. However, PPV may be efficacious for the humoral immunological responders and a further clinical investigation is needed. [ABSTRACT FROM AUTHOR]

A phase I study of a new cancer vaccine (KRM-10), consisting of a mixture of 10 different short peptides, was conducted for patients with advanced gastrointestinal cancers. Primary or secondary endpoints included the dose-limiting toxicity (DLT), or safety and immune responses, respectively. Peptide-specific cytotoxic T lymphocytes (CTL) and immunoglobulin G (IgG), together with soluble inflammatory factors, were measured before and after vaccination. Twenty-one patients were vaccinated with KRM-10 at dose levels of 10 ( n = 6), 20 ( n = 8) or 30 mg ( n = 7) of peptides every week for 6 weeks. No DLT were observed in the dose range evaluated. Common treatment-related adverse events were a grade 1 injection site reaction in 15 patients, and fever in three patients (grade 1 in two patients and grade 2 in one patient). CTL activity to at least one peptide at the time of the third and sixth vaccination increased in 2 and 3 of 6 (10 mg), 2 of 8 and 4 of 6 (20 mg), or 2 and 1 of 6 (30 mg) patients, respectively. IgG levels, at the third and sixth vaccination, were also increased in 1 and 1 of 6 (10 mg), 2 of 8 and 4 of 6 (20 mg), or 1 and 3 of 6 (30 mg) patients, respectively. The KRM-10 vaccine consisting of 20 mg of peptides was determined as the optimal dose for a coming phase II trial because of its safety, and also for demonstrating the most potent activity for augmenting the immune response of the three doses tested. This trial was registered at the UMIN Clinical Trials Registry as UMIN000008820. [ABSTRACT FROM AUTHOR]

Left ventricular ( LV) twist mechanics are routinely assessed via echocardiography in clinical and research trials investigating the function of obliquely oriented myocardial fibers. However, echocardiograph-derived measures of LV twist may be compromised by nonstandardized acquisition of the apical image. This study examined the reproducibility of echocardiograph-derived parameters of apical twist mechanics at multiple levels of the apical myocardium. Two sets of 2D LV parasternal short-axis images were obtained in 30 healthy subjects (24 men; 19-57 year) via echocardiography. Images were acquired immediately distal to the papillary muscles (apical image 1), immediately above the point of LV cavity obliteration at end systole (apical image 3), and midway between apical image 1 and apical image 3 (apical image 2). Repeat scans were performed within 1 hour, and twist mechanics (rotation and rotation rate) were calculated via frame-by-frame tracking of natural acoustic echocardiographic markers (speckle tracking). The magnitude of apical rotation increased progressively toward the apex (apical image 1: 4.2 ± 2.1°, apical image 2: 7.2 ± 3.9°, apical image 3: 11.8 ± 4.6°). apical images 1, 2, and 3 each had moderate to good correlations between repeat scans ( ICC: 0.531-0.856). When apical images 1, 2, and 3 were averaged, rotation was 7.7 ± 2.7° and between-scan correlation was excellent ( ICC: 0.910). Similar results were observed for systolic and diastolic rotation rates. Averaging multiple standardized apical images, tending progressively toward the apex, generated the most reproducible rotation indices and may be optimal for the assessment of LV twist mechanics across therapeutic, interventional, and research studies; however, care should be taken given the influence of acquisition level on the magnitude of apical rotation. [ABSTRACT FROM AUTHOR]

The present study attempted to identify T helper epitope long peptides capable of inducing cytotoxic T lymphocytes (CTL) from Lck antigen (p56Lck), the src family tyrosine kinase, which is known to be aberrantly expressed in metastatic cancers cells, in order to develop a long peptide-based cancer vaccine for HLA-A2+ cancer patients. Based on the biding motif to the HLA-DR and HLA-A2 alleles, 94 peptides were prepared from the Lck antigen. These peptides were screened for their reactivity to immunoglobulin G (IgG) from plasma of cancer patients, followed by testing of their ability to induce both CD4+ and CD8+ T lymphocytes showing not only peptide-specific IFN-γ production but cytotoxicity against HLA-A2+ cancer cells from peripheral blood mononuclear cells (PBMC) of HLA-A2+ cancer patients. Among 94 peptides tested, the three T helper epitope long peptides and their inner CTL epitope short peptides with HLA-A2 binding motifs were frequently recognized by IgG of cancer patients, and efficiently induced both CD4+ IFN-γ+ and CD8+ IFN-γ+ T lymphocytes. Patients' PBMC stimulated with these long peptides showed cytotoxicity against HLA-A2+ Lck+ cancer cells in HLA-class I and HLA-class II dependent manners. These three peptides might be useful for long peptide-based vaccines for HLA-A2+cancer patients with Lck+ tumor cells. [ABSTRACT FROM AUTHOR]

Objective. To evaluate safety and immune responses of personalized peptide vaccination (PPV) for hepatitis C virus- (HCV-) positive advanced hepatocellular carcinoma (HCC). Patients and Methods. Patients diagnosed with HCV-positive advanced HCC were eligible for this study. A maximum of four HLA-matched peptides were selected based on the preexisting IgG responses specific to 32 different peptides, which consisted of a single HCV-derived peptide at core protein positions 35-44 (C-35) and 31 peptides derived from 15 different tumor-associated antigens (TAAs), followed by subcutaneous administration once per week for 8 weeks. Peptide-specific cytotoxic T lymphocyte (CTL) and IgG responses were measured before and after vaccination. Results. Forty-two patients were enrolled. Grade 3 injection site skin reaction was observed in 2 patients, but no other PPV-related severe adverse events were noted. Peptide-specific CTL responses before vaccination were observed in only 3 of 42 patients, but they became detectable in 23 of 36 patients tested after vaccination. Peptide-specific IgG responses were also boosted in 19 of 36 patients. Peptide-specific IgG1 responses to both C-35 and TAA-derived peptides could be potentially prognostic for overall survival. Conclusion. Further clinical study of PPV would be warranted for HCV-positive advanced HCC, based on the safety and strong immune induction. [ABSTRACT FROM AUTHOR]

To develop a peptide vaccine for cancer patients with the HLA-A26 allele, which is a minor population worldwide, we investigated the immunological responses of HLA-A26+/A26+ cancer patients to four different CTL epitope peptides under personalized peptide vaccine regimens. In personalized peptide vaccine regimens, two to four peptides showing positive peptide-specific IgG responses in pre-vaccination plasma were selected from the four peptide candidates applicable for HLA-A26+/A26+ cancer patients and administered s.c. Peptide-specific CTL and IgG responses along with cytokine levels were measured before and after vaccination. Cell surface markers in PBMCs and plasma cytokine levels were also measured. In this study, 21 advanced cancer patients, including seven lung, three breast, two pancreas, and two colon cancer patients, were enrolled. Their HLA-A26 genotypes were HLA-A26:01 ( n = 24), HLA-A26:03 ( n = 10), and HLA-A26:02 ( n = 8). One, 14, and 6 patients received two, three, and four peptides, respectively. Grade 1 or 2 skin reactions at the injection sites were observed in the majority of patients, but no severe adverse events related to the vaccination were observed. Peptide-specific CTL responses were augmented in 39% or 22% of patients after one or two cycles of vaccination, respectively. Notably, peptide-specific IgG were augmented in 63% or 100% of patients after one or two cycles of vaccination, respectively. Personalized peptide vaccines with these four CTL epitope peptides could be feasible for HLA-A26+ advanced cancer patients because of their safety and higher rates of immunological responses. [ABSTRACT FROM AUTHOR]

A feasibility study was performed to evaluate the immunological efficacy and safety of a personalized peptide vaccine ( PPV) for cervical cancer patients who have received platinum-based chemotherapy. A total of 24 patients with standard chemotherapy-resistant cervical cancer, including 18 recurrent cases, were enrolled in this study and received a maximum of 4 peptides based on HLA-A types and IgG levels to the vaccine candidate peptides in pre-vaccination plasma. The parental protein expression of most of the vaccine peptides was confirmed in the cervical cancer tissues. No vaccine-related systemic grade 3 or 4 adverse events were observed in any patients. Due to disease progression, 2 patients failed to complete the first cycle of vaccinations (sixth vaccination). Cytotoxic T-lymphocyte ( CTL) or IgG responses specific for the peptides used for vaccination were augmented in half of cases after the first cycle. The median overall survival was 8.3 months. The clinical responses of the evaluable 18 cases consisted of 1 case with a partial response and 17 cases with disease progression; the remaining 6 cases were not evaluable. Performance status, injection site skin reaction and circulating PD-1+ CD4+ T-cells were significantly prognostic of overall survival, and multivariate analysis also indicated that the performance status and circulating PD-1+ CD4+ T-cells were prognostic. Because of the safety and immunological efficacy of PPV and the possible prolongation of overall survival, further clinical trials of PPV at a larger scale in advanced or recurrent cervical cancer patients who have received prior platinum-based chemotherapy are recommended. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the features of hepatic congestion on gadoxetate disodium (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) and the mechanisms responsible for the radiological findings in a rat model of partial liver congestion. Materials and Methods A conventional T1-weighted spin-echo sequence of the liver was performed using a 1.5T magnetic resonance imager with an 80-mm magnetic aperture for animal studies. We induced regional congestion using partial left lateral hepatic vein ligation ( n = 5) and evaluated the following in both congestive liver (CL) and noncongestive liver (non-CL): 1) chronological changes in the relative enhancement (RE) up to 60 minutes after Gd-EOB-DTPA administration, and 2) mRNA and protein expression of rat organic anion transporting protein 1a1 (Oatp1a1). Results The RE in the CL reached a small peak (18%) at 5 minutes, corresponding to approximately half of the value observed in the non-CL, then slowly decreased in a linear manner thereafter. The degree of RE in the CL was significantly lower than that in the non-CL for up to 30 minutes (P < 0.05). An immunohistological examination showed that Oatp1a1 protein expression was downregulated in the CL. The mRNA level of Oatp1a1 in the CL was significantly upregulated, compared with that in control rat liver ( P = 0.046), whereas no significant difference was observed between the CL and the non-CL ( P = 0.698). Conclusion The reduced signal intensity in the CL on Gd-EOB-DTPA-enhanced MRI could be explained by the decreased uptake of Gd-EOB-DTPA via Oatp1a1 protein in the congestive area. J. Magn. Reson. Imaging 2015;42:828-836. [ABSTRACT FROM AUTHOR]

It was found that Cu(In,Ga)Se2 (CIGS) solar cells with single graded (SG) band profile and average bandgap Eg(avg) of 1.15 eV has higher efficiency than double graded (DG) band profile with the same Eg(avg), despite no intentional bandgap-widening at a CdS/CIGS interface in SG-CIGS. To explain this contradiction, we focused on the band structure at the CdS/CIGS interface and proposed that the contradiction can be explained by the formation of an ordered vacancy chalcopyrite compound (OVC) layer on the surface of CIGS. Device simulation using wxAMPS revealed that if an OVC layer exists at the interface, conversion efficiency of SG-CIGS solar cells overcomes that of DG-CIGS solar cells due to suppression of surface recombination at the interface, leading to open-circuit voltage ( VOC) improvement. We applied the SG structure to CIGS solar cells with high Ga contents. As a result, the conversion efficiency of 15.1% for the SG-CIGS solar cell with Eg(avg) of 1.4 eV was achieved, although in contrast, that of the DG-CIGS solar cells was 12.9%. This efficiency is comparable to the highest efficiency in CIGS solar cells with high Ga contents. Therefore, SG band profile is promising structure and it is expected to achieve high efficiency predicted essentially in CIGS solar cells with high Ga contents. [ABSTRACT FROM AUTHOR]

The 19th International Conference on Ternary and Multinary Compounds (ICTMC-19) was held on 1-5 September 2014 at Toki Messe, Niigata, Japan. This conference, part of the series of conferences that began in 1973 in Bath, was held traditionally as an interdisciplinary forum for the exchange of information and experience in the exciting field of materials science of ternary and multinary compounds. It was then held in Strasbourg (1975), Edinburgh (1977), Tokyo (1980), Cagliari (1982), Caracas (1984), Snowmass (1986), Kishinev (1990), Yokohama (1993), Stuttgart (1995), Salford (1997), Hsin-chu (2000), Paris (2002), Denver (2004), Kyoto (2006), Berlin (2008), Baku (2010), and Salzburg (2012). The conference brought together researchers for the discussion of the latest developments and achievements in the field of these complex materials. The scientific program included two plenary talks, 20 invited talks, 13 symposium talks, 50 oral presentations, and 112 poster presentations from the following 15 countries: Japan, Taiwan, Azerbaijan, Germany, Korea, Thailand, USA, Philippines, France, Belgium, China, Mexico, Moldova, Turkey, and UK. Of the papers, 95 are included in the present proceedings volumes of physica status solidi. The Conference covered physics, chemistry, materials science, device engineering, and the growth and theory of various ternary and multinary compounds: chalcopyrite-type (I-III-VI2, II-IV-V2), kesterite-type (I2-II-IV-VI4), sphalerite-type and wurtzite-type (III-V, II-VI, etc.), perovskite-type, skutterudite-type, complex-oxides, complex-nitrides, and so on. Three symposiums in the conference were focused on new photovoltaic materials superior to CIGS, advanced characterization of solar cells, and mulitinary materials in the next generation. The Program Committee picked up three young members as the winners of the 'Best Young Scientists Award' for their excellent presentations. The winners are Galina Gurieva, Ayaka Kanai, and Tsuyoshi Maeda. The Guest Editors wish to express their gratitude to the members of the International Advisor Committee, the Program Committee, the sponsors, the Japanese Professional Group of Multinary Compounds and Solar Cells in the Japanese Society of Applied Physics, and thank all those who have contributed to this conference for their support and advice. We are very grateful to the referees for their contributions during the editorial process. The next anniversary conference of ICTMC-20 will be held in Germany, chaired by Prof. Roland Scheer. We convey our best wishes to the organizers for a successful meeting. (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

Surface treatments for the purpose of contamination elimination and surface passivation were performed to as-deposited CZTSSe thin films before CdS buffer layer deposition. It was found that HCl etching treatment removes contaminations such as sulfide and oxide on CZTSSe surface and helps enhancement of thiourea treatment carried out after HCl etching. Thiourea treatment drastically improves solar cell characteristics, especially FF and JSC, and it would have the effect of surface passivation, although surface sulfuration does not occur. The improvement of characteristics seems to be due to improvement of the film quality and increase in the width of a depletion layer. As a result, conversion efficiency of CZTSSe solar cells was improved from 6.3% to 10.3% with sequential treatment of HCl etching and thiourea treatment. 10.5% was achieved by air anneal after fabrication with both treatments. [ABSTRACT FROM AUTHOR]

PD-1 expression in peripheral blood T-cells has been reported in several kinds of cancers, including lung cancer. However, the relationship between PD-1 expression in peripheral blood T-cells and prognosis after treatment with a cancer vaccine has not been reported. To elucidate this relationship, we analyzed PD-1 expression in the peripheral blood T-cells of patients with non-small cell lung cancer. The blood samples used in this study were obtained from patients enrolled in phase II clinical trials of a personalized peptide vaccine. Seventy-eight samples obtained before and after a single vaccination cycle (consisting of six or eight doses) were subjected to the analysis. PD-1 was expressed on lymphocytes in the majority of samples. The relative contents of PD1+ CD4+ T-cells against total lymphocytes before and after the vaccination cycle correlated with overall survival ( OS) with a high degree of statistical significance ( P < 0.0001 and P = 0.0014). A decrease in PD-1+ CD8+ T-cells after one cycle of vaccination also correlated with longer OS ( P = 0.032). The IgG response to the non-vaccinated peptides suggested that the epitope spreading seemed to occur more frequently in high- PD-1+ CD4+ T-cell groups. Enrichment of CD45 RA− CCR7− effector-memory phenotype cells in PD-1+ T-cells in PBMCs was also shown. These results suggest that PD-1 expression on the peripheral blood T-cell subsets can become a new prognostic marker in non-small cell lung cancer patients treated with personalized peptide vaccination. [ABSTRACT FROM AUTHOR]

Aim: Central obesity, insulin resistance and alcohol consumption are thought to be major risk factors for fatty liver formation. Adiponectin (APN) prevents fatty liver formation, and its serum levels are lower in subjects with central obesity and/or insulin resistance. The aim of this study was to explore the association among serum APN levels, central obesity, insulin resistance and liver dysfunction with or without fatty liver classified by alcohol consumption in healthy subjects. Methods: A total of 5588 Japanese male subjects who underwent a health check-up were classified into three groups according to alcohol consumption: non- or light drinkers (15 g/day ≥ ethanol); mild drinkers (15 g/day < ethanol ≤ 30 g/day); and moderate- or heavy drinkers (30 g/day < ethanol). Central obesity and insulin resistance were assessed by waist circumference (WC) and Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR), respectively. Results: WC was significantly increased, while HOMA-IR was significantly decreased according to the extent of alcohol consumption. Serum alanine aminotransferase levels were significantly lower and serum APN levels were significantly higher in mild drinkers than in the other two groups. Multiple linear regression analysis showed that serum APN level served as the significant and independent determinant for liver dysfunction in the subjects with fatty liver, irrespective of alcohol consumption. However, WC became a non-significant determinant of liver dysfunction as alcohol consumption increased. Conclusion: Hypoadiponectinemia is a significant determinant for steatotic dysfunction for all levels of alcohol consumption, but central obesity was not a significant determinant for alcoholic fatty liver-induced liver dysfunction. [ABSTRACT FROM AUTHOR]

Many clinical trials of peptide vaccines have been carried out since the first clinical trial of a melanoma antigen gene-1-derived peptide-based vaccine was reported in 1995. The earlier generations of peptide vaccines were composed of one to several human leukocyte antigen class I-restricted CTL-epitope peptides of a single human leukocyte antigen type. Currently, various types of next-generation peptide vaccines are under development. In this review, we focus on the clinical trials of the following categories of peptide vaccines mainly published from 2008 to 2012: (i) multivalent long peptide vaccines; (ii) multi-peptide vaccines consisting of CTL- and helper-epitopes; (iii) peptide cocktail vaccines; (iv) hybrid peptide vaccines; (v) personalized peptide vaccines; and (vi) peptide-pulsed dendritic cell vaccines. ( Cancer Sci 2013; 104: 15-21) [ABSTRACT FROM AUTHOR]

BACKGROUND: Because only a subset of patients show clinical responses to peptide-based cancer vaccination, it is critical to identify biomarkers for selecting patients who would most likely benefit from this treatment. METHODS: The authors characterized the gene expression profiles in peripheral blood of vaccinated patients to identify biomarkers to predict patient prognosis. Peripheral blood was obtained from advanced castration-resistant prostate cancer patients, who survived for >900 days (long-term survivors, n = 20) or died within 300 days (short-term survivors, n = 20) after treatment with personalized peptide vaccination. Gene expression profiles in prevaccination and postvaccination peripheral blood mononuclear cells (PBMCs) were assessed by DNA microarray. RESULTS: There were no statistically significant differences in the clinical or pathological features between the 2 groups. Microarray analysis of prevaccination PBMCs identified 19 genes that were differentially expressed between the short-term and long-term survivors. Among the 15 up-regulated genes in the short-term survivors, 13 genes, which were also differentially expressed in postvaccination PBMCs, were associated with gene signatures of granulocytes. When a set of 4 differentially expressed genes were selected as the best combination to determine patient survival, prognosis was correctly predicted in 12 of 13 patients in a validation set (accuracy, 92%). CONCLUSIONS: These results suggested that abnormal granulocytes present in the PBMC faction may contribute to poor prognosis in advanced prostate cancer patients receiving personalized peptide vaccination. Gene expression profiling in peripheral blood might thus be informative for devising better therapeutic strategies by predicting patient prognosis after cancer vaccines. Cancer 2012;118: 3208-21. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]