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Purpose Capecitabine-based adjuvant chemotherapy for colorectal cancer patients often causes adverse events (AEs), such as diarrhea, stomatitis, anorexia, and hand-foot syndrome (HFS). Cystine and theanine were reported to attenuate some chemotherapy-associated AEs, and hence are also expected to attenuate capecitabine-induced AEs. Therefore, we aimed to investigate the safety and efficacy of cystine/theanine treatment in colorectal cancer patients undergoing capecitabine-based adjuvant chemotherapy after surgery. Methods A total of 100 colorectal cancer patients treated with capecitabine as an adjuvant chemotherapy after surgery were randomly allocated into the cystine/theanine group (n = 52) or the placebo group (n = 48). The primary endpoint was incidence rate of diarrhea of grade 1 or higher in accordance with the Common Terminology Criteria for AEs (CTCAE) v.4.0, Japanese Clinical Oncology Group (JCOG) version. The secondary endpoints included incidence rates of other AEs (CTCAE v.4.0-JCOG), as well as the incidence rate of HFS according to the HFS grading scale. Results There were no significant differences in capecitabine-induced AEs between the two groups. However, the incidence rate of diarrhea of grade 1 or higher tended to be lower in the cystine/theanine group than the placebo group (18.4% vs. 28.9%, p = 0.169) as well as the incidence rate of HFS of grade 1 or higher (CTCAE v.4.0-JCOG or HFS grading scale) (67.4% vs. 77.8%, p = 0.185, 67.3% vs. 80.0%, p = 0.124, respectively). Conclusion This trial demonstrated that cystine/theanine treatment of colorectal cancer patients undergoing capecitabine-based adjuvant chemotherapy after surgery is safe and has the tendency to reduce the incidence rate of diarrhea or HFS. Trial registration UMIN000024784

We apply novel inner-iteration preconditioned Krylov subspace methods to the interior-point algorithm for linear programming (LP). Inner-iteration preconditioners recently proposed by Morikuni and Hayami enable us to overcome the severe ill-conditioning of linear equations solved in the final phase of interior-point iterations. The Krylov subspace methods do not suffer from rank-deficiency and therefore no preprocessing is necessary even if rows of the constraint matrix are not linearly independent. By means of these methods, a new interior-point recurrence is proposed in order to omit one matrix-vector product at each step. Extensive numerical experiments are conducted over diverse instances of 138 LP problems including the Netlib, QAPLIB, Mittelmann and Atomizer Basis Pursuit collections. The largest problem has 434,580 unknowns. It turns out that our implementation is more robust than the standard public domain solvers SeDuMi (Self-Dual Minimization), SDPT3 (Semidefinite Programming Toh-Todd-T\"ut\"unc\"u) and the LSMR iterative solver in PDCO (Primal-Dual Barrier Method for Convex Objectives) without increasing CPU time. The proposed interior-point method based on iterative solvers succeeds in solving a fairly large number of LP instances from benchmark libraries under the standard stopping criteria. The work also presents a fairly extensive benchmark test for several renowned solvers including direct and iterative solvers., Comment: 30 pages, 14 figures

A space charge layer (SCL) at the (0001) oriented ZnO thin-film/lithium-ion conducting glass ceramics interface was investigated using in situ hard X-ray photoelectron spectroscopy (HAXPES) and Mot...

Aim Endoscopic decompression using the self‐expandable metallic colonic stent (SEMS) or transanal decompression tube (TDT) can convert emergency surgery into elective one‐stage surgery for obstructive colorectal cancer (OCRC). The aim of the present study was to clarify the effect of SEMS and TDT on long‐term oncological outcomes. Methods We retrospectively analyzed 76 consecutive pathological stage II and III OCRC patients who were inserted with SEMS or TDT as a bridge to curative surgery between 2009 and 2018. Results There were 53 SEMS cases and 23 TDT cases. The tumor was located in the left colon in 58 cases and in the right colon in 18 cases. The interval between the decompression and the surgery was 16.5 days in the SEMS group and 13.0 days in the TDT group (P = 0.09). Technical and clinical success rates were 100% and 100% for SEMS, and 95% and 91% for TDT, respectively. Stoma was created in four patients in the SEMS group, and in five in the TDT group (P = 0.08). Three‐year overall survival rates of the SEMS and TDT groups were 82% and 86% (P = 0.94), and disease‐free survival rates were 68% and 62% (P = 0.79), respectively. The recurrence pattern was not significantly different. Conclusion This study found no statistically significant differences between the effects of SEMS and TDT for OCRC as a bridge to surgery on long‐term outcomes.

An emerging concept of “nanoarchitectonics” has been proposed as a way to apply the progress of nanotechnology to materials science. In the introductory parts, we briefly explain the progress in understanding materials through nanotechnology, the overview of nanoarchitectonics, the effects of nanoarchitectonics on the development of functional materials and devices, and outline of nanoarchitectonics intelligence as a main subject of this review paper. In the following sections, we explain the process of constructing intelligent devices based on atomic switches, in which the behavior of atoms determines the device functions, by integrating them with nanoarchitectonics. The contents are categorized into (i) basic operation of atomic switch, (ii) artificial synapse, (iii) neuromorphic network system, (iv) hetero-signal conversion, (v) decision making device, and (vi) atomic switch in practical uses. The atomic switches were originally relatively simple ON/OFF binary-type electrical devices, but their potential as multi-level resistive memory devices for artificial synapses and neuromorphic applications. Furthermore, network-structured atomic switches, which are complex and have regression pathways in their structure and resemble cranial neural circuits. For example, A decision-making device that reproduces human thinking based on a principle different from brain neural circuits was developed using atomic switches and proton-conductive electrochemical cells. Furthermore, atomic switches have been progressively developed into practical usages including application in harsh environments (e.g. high temperature, low temperature, space). Efforts toward information processing and artificial intelligence applications based on nanoarchitectonics tell remarkable success stories of nanoarchitectonics, linking the control of atomic motion to brain-like information control through nanoarchitecture regulations.

We apply a modified version of the multistate contracted variational quantum eigensolver method to calculate vibrational eigenstates of ${\mathrm{CO}}_{2}$ on a quantum computer. A two-mode model of ${\mathrm{CO}}_{2}$ is employed, and the vibrational wave function is expanded using three harmonic-oscillator basis functions for each mode. The wave functions are mapped to four qubits by a compact mapping method. The Hamiltonian matrix elements are evaluated on a simulator including noise and on a quantum computer available at IBM Quantum, while the Hamiltonian matrix is diagonalized on a classical computer. We propose an error mitigation method by which the shift of the numerical values of the matrix elements originating from the noise can be corrected, and examine the dependence of the statistical uncertainties on the number of executions of each quantum circuit. We find that, at about $8\ifmmode\times\else\texttimes\fi{}{10}^{6}$ executions, the energy eigenvalues of the Fermi resonance states in ${\mathrm{CO}}_{2}$ can be obtained with an uncertainty within 1 ${\mathrm{cm}}^{\ensuremath{-}1}$.

A 59-year-old man with chief complaints of right-sided rib pain and fever was admitted to our hospital. A type 2 tumor in the ascending colon was revealed by total colonoscopy. Computed tomography examination revealed multiple tumors in the liver. The white blood cell count was high as 13,740/μL. Chemotherapy was planned after treatment with antibiotics, but it was not successful. Right colectomy was performed for infection control. mFOLFOX6 therapy was performed, but liver metastases progressed rapidly, and he died on the 39th postoperative day. The immunohistochemistry revealed G-CSF producing colon cancer. G-CSF producing colon cancer progresses rapidly with poor prognosis. It is necessary to think carefully about indication of surgery and chemotherapy.

The number of elderly patients and colorectal cancer patients is increasing, so laparoscopic surgery for colorectal cancer in elderly patients is suspected to increase. In 456 patients who underwent laparoscopic surgery for colorectal cancer, we investigated whether laparoscopic surgery for elderly patients with colon cancer patients could be performed equally compared to non-elderly patients. Preoperative ASA-PS was slightly poorer in elderly patients. There was no significant difference in pStage. The 5-year overall survival rate was lower in the elderly, but there were no significant differences in blood loss, operation time, postoperative hospital stays and incidence of complications of Clavien-Dindo classification grade 3 or higher. It was suggested that laparoscopic surgery for elderly patients with colorectal cancer may be safely performed compared with non-elderly patients.

Cystine and theanine are amino acids that contribute to the production of glutathione, which is the most potent antioxidant in the body, and it has been reported that these amino acids prevent immunosuppression, has anti- inflammatory effect, and reduce invasiveness.To evaluate the effect of oral administration of amino acids cystine and theanine on stomatitis during chemotherapy.For 17 patients with Grade 1(CTCAE v4.0)or worse stomatitis during chemotherapy for gastrointestinal cancer or breast cancer, cystine 700 mg and theanine 280 mg/ day were orally administered for 28 days, and the degree of stomatitis was evaluated objectively and subjectively.As an objective evaluation, changes in Grade showed improvement in 11 cases(64.7%), 5 cases unchanged(29.4%), and 1 case was worse(5.9%). Subjective assessment, pain was in remission(30.8%)or disappeared(61.5%)in 4 of 13 cases. Food intake increased in 5 patients(29.4%). 15 of 17 patients(88.2%)felt it was effective.Oral administration of amino acids cystine and theanine during chemotherapy can reduce the symptoms of stomatitis.

A 67-year-old man with complaints of upper abdominal pain visited a clinic and was diagnosed with type 3 gastric cancer. Contrasted-enhanced CT revealed gastric wall thickening and extensive metastatic lymph nodes particularly around the celiac artery and also invasion to pancreas. He was diagnosed with cT4b, cN2, cM0, cStage ⅢB and we treated with neoadjuvant chemotherapy(NAC)consisting of 4 courses of S-1 and cisplatin regimen. After the NAC, primary cancer and metastatic lymph nodes were reduced remarkably. A curative operation could be performed and the histopathological examination showed"Grade 3, pathological complete response".

Solid state ionics is a field that elucidates and applies the phenomena of ion transport in solids, in contrast to electronics which elucidates and applies the phenomena to electron transport. In recent years, unique functional solid state ionics devices have been developed for information and communication equipment, using not only solid electrolyte but also mixed conductors that transport ions and electrons in solids, and the fused field of solid state ionics devices and electronics devices is gaining importance. Herein we provide an overview of solid state ionics and various solid state ionics devices that have been developed to date, with emphasis on recently introduced solid state ionics devices made of solid electrolytes and mixed conductors. Such devices are expected to be indispensable for the future development of information and communication equipment, especially in relation to artificial intelligence, where electronic devices have been predominant.

Effective therapies for alcohol-associated liver disease (ALD) are limited; therefore, the discovery of new therapeutic agents is greatly warranted. Toll-like receptor 7 (TLR7) is a pattern recognition receptor for single-stranded RNA, and its activation prevents liver fibrosis. We examined liver and intestinal damage in Tlr7(−/−) mice to determine the role of TLR7 in ALD pathogenesis. In an alcoholic hepatitis (AH) mouse model, hepatic steatosis, injury, and inflammation were induced by chronic binge ethanol feeding in mice, and Tlr7 deficiency exacerbated these effects. Because these results demonstrated that endogenous TLR7 signaling activation is protective in the AH mouse model, we hypothesized that TLR7 activation may be an effective therapeutic strategy for ALD. Therefore, we investigated the therapeutic effect of TLR7 agonistic agent, 1Z1, in the AH mouse model. Oral administration of 1Z1 was well tolerated and prevented intestinal barrier disruption and bacterial translocation, which thus suppressed ethanol-induced hepatic injury, steatosis, and inflammation. Furthermore, 1Z1 treatment up-regulated the expression of antimicrobial peptides, Reg3b and Reg3g, in the intestinal epithelium, which modulated the microbiome by decreasing and increasing the amount of Bacteroides and Lactobacillus, respectively. Additionally, 1Z1 up-regulated intestinal interleukin (IL)-22 expression. IL-22 deficiency abolished the protective effects of 1Z1 in ethanol-induced liver and intestinal damage, suggesting intestinal IL-22 as a crucial mediator for 1Z1-mediated protection in the AH mouse model. Collectively, our results indicate that TLR7 signaling exerts protective effects in the AH mouse model and that a TLR7 ligand, 1Z1, holds therapeutic potential for the treatment of AH.

An all-solid-state redox device, composed of magnetite (Fe3O4) thin film and Li+ conducting electrolyte thin film, was fabricated for the manipulation of a magnetization angle at room temperature (...

A pancreatic β-cell line MIN6 was previously established in our lab from an insulinoma developed in an IT6 transgenic mouse expressing the SV40 T antigen in β-cells. This cell line has been widely used for in vitro analysis of β-cell function, but tends to lose the mature β-cell features, including glucose-stimulated insulin secretion (GSIS), in long-term culture. The aim of this study was to develop a stable β-cell line that retains the characteristics of mature β-cells. Considering that mice derived from a cross between C3H and C57BL/6 strains are known to exhibit higher insulin secretory capacity than C57BL/6 mice, an IT6 male mouse of this hybrid background was used to isolate insulinomas, which were independently cultured. After 7 months of continuous culturing, we obtained the MIN6-CB4 β-cell line, which stably maintains its GSIS. It has been noted that β-cell lines express the glucagon (Gcg) gene at certain levels. MIN6-CB4 cells were utilized to assess the effects of differential Gcg expression on β-cell function. Our data show the functional importance of Gcg expression and resulting basal activation of the GLP-1 receptor in β-cells. MIN6-CB4 cells can serve as an invaluable tool for studying the regulatory mechanisms of insulin secretion, such as the GLP-1/cAMP signaling, in β-cells.

Oxaliplatin frequently causes severe peripheral neuropathy as a dose-limiting toxicity. However, this toxicity lacks a strategy for prevention. Cystine/Theanine is a supplement, which includes precursors for the biosynthesis of glutathione. In this study, we investigated the effects of Cystine/Theanine on oxaliplatin-induced peripheral neuropathy using an in vivo model. Repeated injection of oxaliplatin (4 mg/kg intraperitoneally twice a week for 2 weeks) caused mechanical allodynia, cold hyperalgesia and axonal degeneration of the sciatic nerve in rats. Mechanical allodynia and axonal degeneration, but not cold hyperalgesia, were ameliorated by daily co-administration of Cystine [200 mg/kg orally (p.o.)] and Theanine (80 mg/kg p.o.). Moreover, co-administration of Cystine and Theanine to rats significantly increased the glutathione level in the sciatic nerve compared with the oxaliplatin group. Furthermore, Cystine and Theanine did not attenuate the tumour cytotoxicity of oxaliplatin in C-26 tumour cell-bearing mice. These findings suggest that Cystine and Theanine may be beneficial for preventing oxaliplatin-induced peripheral neuropathy.

Nanoionic devices for physical property tuning and enhancement have been developed to generate novel functions overcoming limitations of conventional materials synthesis and semiconductor technology. Local ionic transport near the solid/solid interface enabled in-situ tuning and enhancement of various physical properties. Two electronic carrier doping methods can be used to achieve extremely high-density electronic carriers: one is electrochemical carrier doping using a redox reaction; the other is electrostatic carrier doping using an electric double layer (EDL). Optical bandgap and photoluminescence are tuned for various applications including smart windows and biosensors. Magnetization and magnetoresistance are tuned for low-power-consumption magnetic storage devices. Superconducting transition temperature is enhanced for exploring high temperature superconductivity. Nanoionic devices for physical property tuning and enhancement are promising derivative of atomic switch technology.

In recent years, illegal money transfer using man-in-the-browser (MITB) attacks with malware in internet banking has become a social problem. This study focuses on transaction-tampering MITB attacks and considers countermeasures to combat them. The existing countermeasures require that another device, such as a token device, other than the device used to carry out the actual money-transfer operation is utilized to ensure a secure route different from that carrying out the actual money-transfer operation. However, because MITB attackers have become more sophisticated, malware will be able to infect all the devices in the end and the multiple routes approach will have become ineffective against this type of attack. Therefore, we constructed a human-to-machine communication protocol that requires only one device for each user and is secure against transaction-tampering MITB attacks, even if the device is taken over by malware.

This multicenter, randomized controlled study evaluates the safety of early oral feeding following gastrectomy, and its effect on the length of postoperative hospital stay. The subjects of this study were patients who underwent distal gastrectomy (DG) or total gastrectomy (TG) for gastric cancer between January 2014 and December 2015. Patients were randomly assigned to the early oral feeding group (intervention group) or the conventional postoperative management group (control group) for each procedure. We evaluated the length of postoperative hospital stay and the incidence of postoperative complications in each group. No significant differences in length of postoperative stay were found between the intervention and control groups of the patients who underwent DG. The incidence of postoperative complications was significantly greater in the DG intervention group. In contrast, the length of postoperative stay was significantly shorter in the TG intervention group, although the TG group did not attain the established target sample size. Early oral feeding did not shorten the postoperative hospital stay after DG. The higher incidence of postoperative complications precluded the unselected adoption of early oral feeding for DG patients. Further confirmative studies are required to definitively establish the potential benefits of early oral feeding for TG patients.

Perioperative nutritional therapy requires the consideration of metabolic changes, and it is desirable to reduce stress aiming at early metabolic normalization. Glutathione (GSH) is a tripeptide composed of glutamic acid, cysteine, and glycine. It is one of the strongest antioxidants in the body and important for adjusting immune function. Cystine and theanine (γ-glutamylethylamide) provide substrates of GSH, cysteine and glutamic acid, promoting the synthesis of GSH. It has been reported that the ingestion of cystine (700 mg) and theanine (280 mg) exhibits inhibitory effects against excess inflammation after strong exercise loads in athletes, based on which its application for invasive surgery has been tried. In patients undergoing gastrectomy, ingestion of cystine (700 mg) and theanine (280 mg) for 10 days from 5 days before surgery inhibited a postoperative increase in resting energy expenditure, promoted recovery from changes in interleukin-6, C-reactive protein, lymphocyte ratio, and granulocyte ratio and inhibited an increase in body temperature. In a mouse small intestine manipulation model, preoperative 5-day administration of cystine/theanine inhibited a postoperative decrease in GSH in the small intestine and promoted recovery from a decrease in behavior quantity. Based on the above, cystine/theanine reduces surgical stress, being useful for perioperative management as stress-reducing amino acids.

Three kinds of components are known in the insertion of Li+ into electrochromic WO3 (LixWO3): (i) reversible Li+, (ii) irreversible Li2WO4 formation and (iii) irreversible Li+ trapping. To develop LixWO3-based electrochromic devices, in situ hard X-ray photoelectron spectroscopy (HAXPES), in situ Raman spectroscopy and electrochemical measurements were performed. In situ HAXPES can quantitatively distinguish (i) reversible Li+ and (iii) irreversible Li+ trapping as the variation in the oxidation state of the W ion whereas the electrochemical measurements can evaluate (i) reversible Li+ and the sum of (ii) irreversible Li2WO4 formation and (iii) irreversible Li+ trapping. Furthermore, in situ Raman spectroscopy detected the enhancement of crystallinity due to Li+ insertion with high sensitivity. The combination of the in situ HAXPES and the electrochemical measurements enables the separation and quantitative evaluation of (i), (ii) and (iii). The inserted Li+ conversion ratios of (i) reversible Li+, (ii) irreversible Li2WO4 formation and (iii) irreversible Li+ trapping to the entire inserted Li+ were clarified. (i.e., 41.4 %, 50.9 %, and 7.7 %, respectively).

We herein report the case of a 74-year-old man who underwent surgery 9 years after his initial visit and who was pathologically diagnosed with signet-ring cell carcinoma (SRCC) derived from a main-duct-type intraductal papillary mucinous neoplasm (MD-IPMN). At the first imaging examination, only a small pancreatic cyst with mild dilation of the main pancreatic duct (MPD) was detected in the pancreatic head. Eventually, MD-IPMN with mural nodules and MPD dilation (30 mm) developed in the pancreatic body, while the pancreatic head cyst remained unchanged. Total pancreatectomy was performed and the MD-IPMN was pathologically diagnosed as SRCC derived from an intestinal-type MD-IPMN.

In this work we present an extension of Chubanov’s algorithm to the case of homogeneous feasibility problems over a symmetric cone $$ {\mathcal {K}}$$ . As in Chubanov’s method for linear feasibility problems, the algorithm consists of a basic procedure and a step where the solutions are confined to the intersection of a half-space and $$ {\mathcal {K}}$$ . Following an earlier work by Kitahara and Tsuchiya on second order cone feasibility problems, progress is measured through the volumes of those intersections: when they become sufficiently small, we know it is time to stop. We never have to explicitly compute the volumes, it is only necessary to keep track of the reductions between iterations. We show this is enough to obtain concrete upper bounds to the minimum eigenvalues of a scaled version of the original feasibility problem. Another distinguishing feature of our approach is the usage of a spectral norm that takes into account the way that $$ {\mathcal {K}}$$ is decomposed as simple cones. In several key cases, including semidefinite programming and second order cone programming, these norms make it possible to obtain better complexity bounds for the basic procedure when compared to a recent approach by Pena and Soheili. Finally, in the appendix, we present a translation of the algorithm to the homogeneous feasibility problem in semidefinite programming.