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Own child's face is one of the most socially salient stimuli for parents, and a faster search for it than for other children's faces may help provide warmer and more sensitive care. However, it has not been experimentally examined whether parents find their child's face faster. In addition, although own child's face is specially processed, the search time for own child's face may be similar to that for other socially salient stimuli, such as own or spouse's faces. This study tested these possibilities using a visual search paradigm. Participants (parents) searched for their child's, own, spouse's, other child's, same-sex adult's, or opposite-sex adult's faces as search targets. Our findings indicate that both mothers and fathers identified their child's face more quickly than other children's faces. Similarly, parents found their own and spouse's faces more quickly than other adults' faces. Moreover, the search time for family members' faces increased with the number of faces on the search display, suggesting an attentional serial search. These results suggest that robust face representations learned within families and close relationships can support reduced search times for family members' faces., (© 2024. The Author(s).)

Background: Initial chemotherapy (Initial-C) followed by surgery is a promising treatment strategy for peritoneal lavage cytology-positive gastric cancer (CY1 GC) with no other noncurative factors. The aim of this study was to investigate the survival advantage of Initial-C compared to initial surgery (Initial-S) for this disease according to the macroscopic type, which was associated with prognosis and the efficacy of chemotherapy in GC., Methods: One hundred eighty-nine patients who were diagnosed with CY1 GC with no other noncurative factors at four institutions from January 2007 to December 2018 were enrolled. The patients were divided into a macroscopic type 4 group (N = 48) and a non-type 4 group (N = 141). The influence of initial treatment on overall survival (OS) in each group was evaluated., Results: In the type 4 group, the 5-year OS rates of Initial-C (N = 35) and Initial-S (N = 13) were 11.6% and 0%, respectively (P = 0.801). The multivariate analysis could not show the survival advantage of Initial-C. In the non-type 4 group, the 5-year OS rates of Initial-C (N = 41) and Initial-S (N = 100) were 48.4% and 29.0%, respectively (P = 0.020). The multivariate analysis revealed that Initial-C was independently associated with prolonged OS (hazard ratio, 0.591; 95% confidence interval, 0.375-0.933: P = 0.023)., Conclusions: Initial-C improves the prognosis of non-type 4 CY1 GC with no other noncurative factors. On the other hand, further development of effective chemotherapeutic regimens and innovative treatment strategies are required for type 4 CY1 GC., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Purpose: Post-operative infectious complication (IC) is a well-known negative prognostic factor, while showing neoadjuvant chemotherapy (NAC) may cancel out the negative influence of IC. This analysis compared the clinical impacts of IC according to the presence or absence of NAC in gastric cancer patients enrolled in the phase III clinical trial (JCOG0501) which compared upfront surgery (arm A) and NAC followed by surgery (arm B) in type 4 and large type 3 gastric cancer., Methods: The subjects were 224 patients who underwent R0 resection out of 316 patients enrolled in JCOG0501. The prognoses of the patients with or without ICs in each arm were investigated by univariable and multivariable Cox regression analyses., Results: There were 21 (20.0%) IC occurrences in arm A and 15 (12.6%) in arm B. In arm A, the overall survival (OS) of patients with ICs was slightly worse than those without IC (3-year OS, 57.1% in patients with ICs, 79.8% in those without ICs; adjusted hazard ratio (95% confidence interval), 1.292 (0.655-2.546)). In arm B, patients with ICs showed a trend of better survival than those without ICs (3-year OS, 80.0% in patients with IC, 74.0% in those without IC; adjusted hazard ratio, 0.573 (0.226-1.456))., Conclusion: This study could not indicate the negative prognostic influence of ICs in gastric cancer patients receiving NAC, which might be canceled by NAC. To build exact evidence, further investigation with prospective and large numbers of data might be expected., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: De novo malignancy (DNM) is a major cause of death in long-term recipients of liver transplantation (LT). We herein report our experience with DNM after living-donor LT (LDLT)., Patients and Methods: A total of 111 LDLT procedures were performed in our institute from 1999 to 2022. Among them, 70 adult (>13 years old) LDLT recipients who survived for more than 1 year were included in this study., Results: During a median follow-up of 146 (range, 12-285) months, 7 out of 70 recipients developed 8 DNMs, including lung cancer in 4, post-transplant lymphoproliferative disease in 3, and skin cancer in 1. One patient developed metachronal skin cancer and post-transplant lymphoproliferative disease. The pre-LT smoking history rate in patients with DNM was higher than in patients without DNM (P = .004). The survival time after DNM was 6 (1-166) months. Only 2 patients underwent R0 resection. DNM did not recur during follow-up. Other patients who underwent R1 resection and/or chemotherapy and/or radiotherapy all died due to DNMs during the follow-up. The cumulative DNM incidence was 3.5% at 10 years and 18.4% at 20 years after LDLT. The cumulative survival rate in patients with DNM was significantly worse than that in patients without DNM after LDLT (P = .049)., Conclusion: The survival rate of patients with DNM was lower than that of those without DNM. A pre-LT smoking history is a risk factor for DNM. R0 resection is effective for improving the prognosis of patients with DNM. Regular cancer screening is important for detecting DNM early after LDLT., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The patient was a 61-year-old man with a diagnosis of carcinoma of the pancreatic head. Abdominal computed tomography( CT)showed no distant metastasis, and he underwent subtotal stomach-preserving pancreatoduodenectomy. Immediately after surgery, he received liver perfusion chemotherapy with 5-fluorouracil followed by systemic gemcitabine. Eighteen months after surgery, CT revealed liver metastasis in the S6 segment, and partial hepatectomy was performed. The pathological diagnosis was liver metastasis of pancreatic cancer. Postoperatively, the patient was treated with gemcitabine and S-1 therapy for 1 year and then switched to S-1 monotherapy for about 6 months. Four years after the initial surgery, CT showed 2 metastases in the right lung. After 2 months of S-1 monotherapy, wedge resection of the upper and lower lobes of the right lung was performed. Gemcitabine and nab-paclitaxel therapy were administered, after the metastasectomy, but pleural dissemination appeared on CT 5 years after the initial surgery. Modified FOLFIRINOX therapy was started and continued for 8 months, but CT revealed further disseminated lesions in the diaphragm. Palliative irradiation was provided, but the disease gradually progressed. After multidisciplinary treatment, the patient survived for 6 years and 3 months after the initial surgery.

Background: Postoperative adjuvant chemotherapy with S-1 for 1 year (corresponding to eight courses) is the standard treatment for pathological stage II gastric cancer. The phase III trial (JCOG1104) investigating the non-inferiority of four courses of S-1 to eight courses was terminated due to futility at the first interim analysis. To confirm the primary results, we reported the results after a 5-years follow-up in JCOG1104., Methods: Patients histologically diagnosed with stage II gastric cancer after radical gastrectomy were randomly assigned to receive S-1 for eight or four courses. In detail, 80 mg/m 2 /day S-1 was administered for 4 weeks followed by a 2-week rest as a single course., Results: Between February 16, 2012, and March 19, 2017, 590 patients were enrolled and randomly assigned to 8-course (295 patients) and 4-course (295 patients) regimens. After a 5-years follow-up, the relapse-free survival at 3 years was 92.2% for the 8-course arm and 90.1% for the 4-course arm, and that at 5 years was 87.7% for the 8-course arm and 85.6% for the 4-course arm (hazard ratio 1.265, 95% CI 0.846-1.892). The overall survival at 3 years was 94.9% for the 8-course arm, 93.2% for the 4-course arm, and that at 5 years was 89.7% for the 8-course arm, and 88.6% for the 4-course arm (HR 1.121, 95% CI 0.719-1.749)., Conclusions: The survival of the four-course arm was slightly but consistently inferior to that of the eight-course arm. Eight-course S-1 should thus remain the standard adjuvant chemotherapy for pathological stage II gastric cancer., (© 2023. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

We report a case of biliary cystadenocarcinoma in which long-term survival was achieved after 2 operations for intrahepatic recurrence. A 72-year-old man with biliary cystadenocarcinoma located mainly in segment 3 of the liver underwent left hepatectomy, extrahepatic bile duct resection, and lymph node dissection. Seven years and 9 months after the initial resection, he underwent partial liver resection(segment 5)for intrahepatic recurrence detected by computed tomography. Fifteen years and 7 months after the initial resection, he underwent repeat partial resection of the liver(segment 5)for intrahepatic recurrence. Histologically, these tumors were confirmed to be recurrence of biliary cystadenocarcinoma. He remains alive and well with no further recurrence 21 years and 6 months after the initial resection. This case and a literature review suggest that hepatic resection is a useful treatment option for intrahepatic recurrence of biliary cystadenocarcinoma.

A 66-year-old man was referred to our hospital with fever and abdominal pain. CT showed a mass in the intrapancreatic bile duct but no wall thickness in the perihilar bile ducts. Neither regional lymphadenopathy nor distant metastasis was observed. Biliary cytology showed adenocarcinoma. The diagnosis was distal cholangiocarcinoma, and pancreatoduodenectomy was performed. Intraoperative frozen section examination of the ductal resection margins at the right and left hepatic ducts was positive for carcinoma in situ, and the operation ultimately completed with R1 resection. Histological examination confirmed a diagnosis of cholangiocarcinoma with superficial spread and a single positive lymph node. Adjuvant chemotherapy with S-1 was administered for 1 year. Anastomotic recurrence at the hepaticojejunostomy was found 5 years after resection; biopsy specimens revealed adenocarcinoma. Thereafter, S-1 chemotherapy was resumed, and the patient remains alive and well 9 years and 1 month after resection.

A 58-year-old woman presented with a complaint of weight loss. Abdominal computed tomography showed dilatation of the biliary and pancreatic ducts and a mural nodule in the pancreatic duct. The diagnosis was intraductal papillary mucinous neoplasm(IPMN). Endoscopic retrograde cholangiopancreatography(ERCP)and cholangioscopy revealed a fistula between the common bile duct and the IPMN. A sudden increase in hepatobiliary enzymes was noted preoperatively. ERCP showed that the common bile duct was obstructed by mucus. A nasobiliary drainage tube was inserted into the bile duct endoscopically and kept open by daily tube washing, and the liver dysfunction improved. Total pancreatectomy, splenectomy, and regional lymph node dissection were performed. Histological examination confirmed that the primary tumor was mixed invasive intraductal papillary mucinous adenocarcinoma. The patient remains alive and well with no evidence of recurrence 18 months after resection.

A fast-sampling fast-ion D-alpha (F-FIDA) measurement has been developed in the large helical device in order to investigate fast ion dynamics associated with helically trapped fast-ion-driven Magnetohydrodynamic (MHD) bursts. F-FIDA consists of a multi-anode photomultiplier tube (PMT) and achieves a sampling rate of 10 kHz. During the deuterium experiment campaign in 2022, F-FIDA measured the spectrum of perpendicular fast ions, using perpendicular lines of sight. We compared F-FIDA with conventional FIDA, using an electron multiplying charge coupled device, and confirmed that the time-averaged images were generally consistent between the two. The statistical properties of the temporal evolution associated with MHD bursts were analyzed using a conditional sampling technique. The results showed that the PMT signal varied in different spatial and wavelength channels. Although the signal-to-noise ratio was poor and there was room for improvement, it could provide useful information for studies on the phase-space dynamics of fast ions., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

The fat-derived factor, adiponectin, is considered a salutary circulating factor. We recently demonstrated that native adiponectin binds T-cadherin and promotes intracellular biogenesis and secretion of the exosome. Exosomes play important roles in various aspects of homeostasis, including glucose and energy metabolism. However, it remains unclear whether and how the promotion of exosome production by adiponectin in vivo is beneficial for glucose and lipid metabolism. In the present study, overexpression of human adiponectin in mice resulted in an increased number of circulating exosomes, but it did not significantly improve glucose metabolism, change body weights, or change triglyceride clearance under a high-fat diet. Multiple small doses of streptozotocin increased blood glucose and decreased triglyceride clearance similarly in both wild-type and transgenic mice. Thus, these results indicated that human adiponectin overexpression in mice increases plasma exosomes but does not significantly influence glucose and lipid metabolism.

Background: Surgical resection of oligo-metastasis in gastric cancer (GC) is weakly recommended for patients without other incurable factors in the Japanese GC Treatment Guidelines. While post-operative chemotherapy is the standard treatment in patients with stage II or III GC, its efficacy for resected stage IV GC is unclear. This study aimed to evaluate the efficacy of post-operative chemotherapy after curative resection of GC with oligo-metastasis., Methods: We retrospectively reviewed the medical records of patients with GC who were diagnosed with synchronous oligo-metastasis at 20 institutions in Japan between 2007 and 2012. The selection criteria were: adenocarcinoma, stage IV with oligo-metastasis at liver or lymph node without other distant metastasis, curative resection including synchronous oligo-metastasis, and no prior treatment of GC before surgery., Results: A total of 110 patients were collected. Of the 94 eligible patients, 84 underwent gastrectomy with surgical resection of oligo-metastasis (39 [41%] liver metastasis and 55, [59%] distant lymph node metastasis), followed by post-operative chemotherapy with S-1 (S1: n = 55), S1 plus cisplatin (CS: n = 22), or Others (n = 7). Moreover, 10 patients did not receive post-operative chemotherapy (Non-Cx). The median overall survival (OS) was 35.2 and 11.1 months in the post-operative chemotherapy and Non-Cx groups (hazard ratio, 3.56; 95% confidence interval, 1.74-7.30; p < 0.001), respectively. In multivariable analysis, Non-Cx and age over 70 years were identified as poor prognostic factors for OS (p < 0.05)., Conclusions: Curative resection followed by post-operative chemotherapy in patients with GC with synchronous oligo-metastasis showed favorable survival., (© 2023. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Background: The effects of uric acid (UA)-lowering therapy with xanthine oxidoreductase (XOR) inhibitors on the development of cardiovascular diseases remain controversial. Based on recent findings that plasma XOR activity increased in liver disease conditions, we conducted a sub-analysis of the BEYOND-UA study to examine the differential effects of topiroxostat on arterial stiffness based on liver function in hyperuricemic individuals with hypertension., Methods: Sixty-three subjects treated with topiroxostat were grouped according to baseline alanine aminotransferase (ALT) levels (above or below cut-off values of 22, 30, or 40 U/L). The primary endpoint was changes in the cardio-ankle vascular index (CAVI) from baseline to 24 weeks., Results: Significant reductions in CAVI during topiroxostat therapy occurred in subjects with baseline ALT ≥30 U/L or ≥40 U/L, and significant between-group differences were detected. Brachial-ankle pulse wave velocity significantly decreased in the ALT-high groups at all cut-off values. Reductions in morning home blood pressure and serum UA were similar regardless of the baseline ALT level. For eleven subjects with available data, ALT-high groups showed high plasma XOR activity, which was significantly suppressed by topiroxostat., Conclusions: Topiroxostat improved arterial stiffness parameters in hyperuricemic patients with liver dysfunction, which might be related to its inhibitory effect on plasma XOR.

Background: Recent improvements in systemic chemotherapy have provided an opportunity for patients with stage IV gastric cancer (GC) to undergo conversion surgery (CS). The aim of this study was to evaluate the long-term outcomes of patients who underwent CS and to elucidate the prognostic factors for CS in stage IV GC., Methods: A total of 79 patients who underwent CS with the aim of R0 resection for stage IV GC at six institutions from January 2008 to July 2019 were enrolled. We retrospectively reviewed the clinicopathological data and prognosis., Results: Of the 79 patients, 23 (31.1%) had initially resectable disease (IR) before chemotherapy, defined as positive for cancer on peritoneal cytology (CY1), resectable hepatic metastasis, or para-aortic lymph node No. 16a2/b1 metastasis. Of the 56 remaining patients with primary unresectable disease, 39 had peritoneal dissemination. R0 resection was accomplished in 63 patients (79.7%). The 3-year OS rates for patients with IR and unresectable disease were 78.3% and 44.5%, respectively. Multivariate analysis showed that IR (P = 0.014) and R0 (P = 0.014) were statistically significant independent prognostic factors for favorable OS. Among patients with peritoneal dissemination alone, OS was significantly better for patients with R0 resection than for patients with R1/2 resection, with the 3-year OS rates of 65.5% and 23.1%, respectively (P = 0.011)., Conclusions: CS is a treatment option for selected patients with stage IV GC. Patients with IR and patients who achieve R0 resection may obtain a survival benefit from CS., (© 2022. The Author(s).)

High-spatial resolution observation of high-wavenumber broadband turbulence is achieved by controlling the magnetic field to be relatively low and measuring with a azimuthally arranged multi-channel Langmuir array in a basic laboratory plasma. The observed turbulence consists of narrowband low-frequency fluctuations and broadband high-frequency turbulent fluctuations. The low-frequency fluctuations have a frequency of about 0.7 times the ion cyclotron frequency and a spatial scale of 1/10 of the ion inertial scale. In comparison, high-frequency fluctuations have a higher frequency than the ion cyclotron frequency and spatial scales of 1/10-1/40 of the ion inertial scale. Two-dimensional correlation analysis evaluates the spatial and temporal correlation lengths and reveals that the high-wavenumber broadband fluctuations have turbulent characteristics. The measurements give us further understanding of small scale turbulence in space and fusion plasmas., (© 2022. The Author(s).)

Background: Natural orifice specimen extraction (NOSE) has been developed as a means of decreasing the incidence of surgical wound complications. We refined the procedure for totally laparoscopic colectomy with transvaginal specimen extraction using the reduced port surgery technique with the ultimate goal of attenuating damage to the abdominal wall. We herein report this innovative technique and its short- and long-term outcomes., Methods: We prospectively collected data on seven patients who underwent totally laparoscopic colectomy using transvaginal specimen extraction with a 10-mm-long abdominal incision for right-sided colon cancer from January 2014 to December 2021. Two 5-mm ports were used in the procedure without laparotomy. Transverse transabdominal posterior colpotomy was then performed. We introduced a GelPOINT Mini advanced access platform (Applied Medical, Rancho Santa Margarita, CA, USA) into the transvaginal route for the insertion of a laparoscope, forceps, and stapling device. Lymph node dissection and transection of the ileum and distal colon were performed with transvaginal assistance. A specimen was then extracted transvaginally. Intracorporeal functional end-to-end anastomosis was conducted using a linear stapler through the vagina. After the removal of GelPOINT Mini, the vaginal incision was closed transvaginally., Results: Seven patients successfully underwent this procedure. Median operative time was 219 min (range 174-255 min), median blood loss was 23 ml (range 10-37 ml), median number of harvested lymph nodes was 21 (range 17-35 lymph nodes) and median margins were 17.0 cm (range 9.0-25.0 cm) for the proximal margin and 9.5 cm (range 5.0-13.0 cm) for the distal margin. There were no complications more severe than Clavien-Dindo Grade II and there was no mortality. The median frequency of use intravenous analgesics from postoperative day 1 to discharge was once. Two patients did not require analgesics. A node-positive patient developed recurrence at the lung and paraaortic lymph nodes., Conclusions: This procedure appears to be feasible, safe, and oncologically acceptable for selected cases., (© 2022. Springer Nature Switzerland AG.)

Background: Indications for adjuvant chemotherapy for advanced gastric cancer are determined based on the pathological diagnosis. However, macroscopic diagnoses have been reported as predictors of peritoneal recurrence and survival. This study investigated the predictability of peritoneal recurrence and survival based on macroscopically (sT) and pathologically (pT) diagnosed serosal invasion to identify more sensitive predictors of peritoneal recurrence., Methods: This study included 396 patients who underwent R0 resection without adjuvant chemotherapy with S-1 in the JCOG0110 study. Tumor depth limited to the subserosa (SS) was defined as serosal invasion negative (T-), while tumors with serosal invasion (SE, SI) were defined as serosal invasion positive (T+). The predictability of peritoneal recurrence based on sT and pT was evaluated using the Fine and Gray model. Cox regression analyses were performed for overall survival (OS) and relapse-free survival (RFS) with sT or pT as covariates., Findings: A total of 150 patients (37.9%) were sT+ and 82 (26.3%) were pT+. Sixty-two patients (15.7%) were sT+/pT+, 88 (22.2%) were sT+/pT-, 20 (5.1%) were sT-/pT+, and 226 (57.1%) were sT-/pT-. Both sT and pT were found to be independent predictors of peritoneal recurrence, OS, and RFS. The 5-year RFS rates of sT+/pT+, sT+/pT-, sT-/pT+, and sT-/pT-patients were 45.2%, 63.6%, 55.0%, and 81.8%, respectively., Conclusion: Intraoperatively diagnosed macroscopic serosal invasion showed a similar predictive value for peritoneal recurrence as pathologically diagnosed serosal invasion. The establishment of a novel staging system incorporating macroscopic serosal invasion is recommended., Competing Interests: Declaration of competing interest MT reports lecture fees from Taiho Pharmaceutical, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol-Myers Squibb, Yakult Honsha, Takeda Pharmaceutical, Eli Lilly Japan KK, Pfizer Pharmaceutical, Daiichi Sankyo, Johnson and Johnson, Medtronic Japan, Intuitive Japan, Olympus outside the submitted work. JM reports the funding from National Cancer Center, Japan and the Ministry of Labour and Welfare, Japan for the present study, and personal fees from Chugai Pharmaceutical, outside the submitted work. TS reports personal fees from Taiho Pharma, Chugai Pharma, Ono Pharma, Eli Lilly, outside the submitted work. TY reports grants from Eli Lilly japan, personal fees from MSD, BMS, Ono, Taiho, Lilly, Chugai, Pfizer, Nihon Kayaku, Terumo, Otsuka, Myarisan, EA pharma, Astra-Zeneca, Covidien, Johnson and Johnson outside the submitted work. NB received a research grant from Ono and Takeda and honorarium from Taiho, Ono, Bristol-Myers Squibb outside the submitted work. MS reports lecture fees from Taiho Pharmaceutical and Eli Lilly, travel support from Eli Lilly outside the submitted work, and has served as Chairman of the board of directors of the Japan Gastric Cancer Association and member of the Guideline committee of the Japan Gastric cancer Association during the study period. All the other authors declare no competing interests. Red lines represent serosal invasion positive and blue lines represent serosal invasion negative. The C-index was calculated using the Fine and Gray model., (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Aims/hypothesis: Immunomodulators blocking cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) have improved the treatment of a broad spectrum of cancers. These immune checkpoint inhibitors (ICIs) reactivate the immune system against tumour cells but can also trigger autoimmune side effects, including type 1 diabetes. Mesenchymal stem cell (MSC) therapy is the most prevalent cell therapy, with tissue-regenerating, anti-fibrosis and immunomodulatory functions provided by the secretome of the cells. Here, we examined whether systemic MSC treatment could prevent the development of type 1 diabetes in a NOD mouse model., Methods: The purified PD-L1 monoclonal antibody was administered to induce diabetes in male NOD mice which normally do not develop diabetes. Human adipose-derived MSCs were administered by tail vein injections. T cells, macrophages and monocyte-derived macrophages expressing C-X-C motif chemokine ligand 9 (CXCL9) in pancreatic sections of NOD mice and a cancer patient who developed diabetes following the ICI treatments were analysed by immunofluorescence. Tissue localisation of the injected MSCs, plasma exosome levels and plasma cytokine profiles were also investigated., Results: PD-1/PD-L1 blockade induced diabetes in 16 of 25 (64%) NOD mice which received anti-PD-L1 mAb without hMSCs [MSC(-)], whereas MSC administration decreased the incidence to four of 21 (19%) NOD mice which received anti-PD-L1 mAb and hMSCs [MSC(+)]. The PD-1/PD-L1 blockade significantly increased the area of CD3-positive T cells (6.2-fold) and macrophage-2 (Mac-2) antigen (2.5-fold)- and CXCL9 (40.3-fold)-positive macrophages in the islets. MSCs significantly reduced T cell (45%) and CXCL9-positive macrophage (67%) accumulation in the islets and the occurrence of diabetes. The insulin content (1.9-fold) and islet beta cell area (2.7-fold) were also improved by MSCs. T cells and CXCL9-positive macrophages infiltrated into the intricate gaps between the beta cells in the islets by PD-1/PD-L1 blockade. Such immune cell infiltration was largely prevented by MSCs. The most striking difference was observed in the CXCL9-positive macrophages, which normally did not reside in the beta cell region in the islets but abundantly accumulated in this area after PD-1/PD-L1 blockade and were prevented by MSCs. The CXCL9-positive macrophages were also observed in the islets of a cancer patient who developed diabetes following the administration of ICIs but few CXCL9-positive macrophages were observed in a control patient. Mechanistically, the injected MSCs accumulated in the lung but not in the pancreas and strongly increased plasma exosome levels and changed plasma cytokine profiles., Conclusions/interpretation: Our results suggest that MSCs can prevent the incidence of diabetes associated with immune checkpoint cancer therapy and may be worth further consideration for new adjuvant cell therapy., (© 2022. The Author(s).)

Background: To improve the diagnostic accuracy of preoperative T staging in gastric cancer, the authors evaluated tumor-related factors that might affect the diagnosis. Materials & methods: The authors analyzed the data of cT2-4b gastric cancer patients enrolled in the prospective, multicenter JCOG1302A study. They used contrast-enhanced computed tomography to analyze the association between tumor-related factors and the diagnostic accuracy of T3-4b staging for gastric cancer. Results: Among 876 cT3-4b tumors, the diagnostic accuracy was relatively low in the lower third of the stomach compared with those in the upper or middle. A multivariable analysis revealed that accuracy was higher in the lesser curvature or entire circumference region than in other areas (p < 0.001), in macroscopic types 3/5 than in types 0/1/2 (p = 0.003) and in the undifferentiated histological type than in the differentiated type (p = 0.011). Conclusion: The authors found tumor-related factors affecting preoperative T staging by enhanced computed tomography.

Purposes: The spread of coronavirus disease 2019 (COVID-19) has affected socioeconomic and healthcare systems in many countries. Accordingly, many individuals may have canceled their annual health-check programs, including esophagogastroduodenoscopy, which would have resulted in lower numbers of newly diagnosed patients with gastric cancer in comparison to other times., Methods: Questionnaires were distributed to 62 hospitals every week from May 2020 to August 2020 (total 744) through mailing lists of the Stomach Cancer Study Group of the Japan Clinical Oncology Group. The number of patients with gastric cancer and hospital systems during the COVID-19 pandemic were surveyed., Results: In total, 74% (551 out of 744) of the questionnaires were answered and analyzed. In early May, approximately 50% of hospitals had to restrict surgical slots due to the COVID-19 pandemic. However, they gradually loosened the restrictions thereafter. The number of gastrectomies was < 80% that of the same period in the previous year, and hospitals in Tokyo were seriously affected by a 50% decrease in the number of gastrectomies., Conclusions: The number of gastrectomies was lower than that in the previous year. Further multi-center follow-up studies are required to evaluate the long-term effects of COVID-19 on the clinical outcomes of patients with gastric cancer., (© 2021. Springer Nature Singapore Pte Ltd.)

Paradoxical reaction (PR) occurs when a drug elicits a reaction contrary to what was expected. To clarify the clinical features and genetic background of individuals susceptible to PR, we analyzed the clinical course of patients in whom psoriatic eruptions worsened or newly developed during tumor necrosis factor (TNF) antagonist administration and the role of focal infections and genetic variations. Of 125 patients who received TNF antagonist therapy for psoriasis, acrodermatitis continua of Hallopeau (ACH), generalized pustular psoriasis (GPP), or palmoplantar pustular psoriasis (PPP), eight patients with PR were surveyed at our hospital Dermatology Department between 2010 and 2021. A survey was also done on six patients who received TNF antagonist therapy for Crohn's disease, rheumatoid arthritis, ankylosing spondylitis, and hidradenitis suppurativa and were referred to our department due to PR. Additionally, Sanger sequencing analysis was performed for all exons and flanking introns of IL36RN (interleukin 36 receptor antagonist), CARD14 (caspase recruitment domain-containing protein 14), and AP1S3 (adaptor-related protein complex 1 subunit sigma 3). The clinical assessment of the 14 patients demonstrated an average age at PR onset of 48.4 years, a male : female ratio of 5:9, and a mean administration period until onset of 9.2 months. The clinical types of PR were plaque psoriasis, PPP, GPP, pustulosis, acne, ACH, hair loss, and exacerbation of arthralgia. Histopathology revealed psoriasiform dermatitis in three patients. One patient continued TNF antagonist therapy. All of the patients with psoriasis and GPP had dental infections, suggesting that focal infection may be a risk factor of the development of PR following TNF antagonist therapy. Gene analysis demonstrated CARD14 gene variants associated with RA, CD, AS, or PPP in four patients. In addition, all of the patients with ACH and PPP experienced PR, suggesting that these diseases may predispose patients to PR to TNF antagonist therapy., (© 2021 Japanese Dermatological Association.)

The velocity distribution function is a statistical description that connects particle kinetics and macroscopic parameters in many-body systems. Laser-induced fluorescence (LIF) spectroscopy is utilized to measure the local velocity distribution function in spatially inhomogeneous plasmas. However, the analytic form of such a function for the system of interest is not always clear under the intricate factors in non-equilibrium states. Here, we propose a novel approach to select the valid form of the velocity distribution function based on Bayesian statistics. We formulate the Bayesian inference of ion velocity distribution function and apply it to LIF spectra locally observed at several positions in a linear magnetized plasma. We demonstrate evaluating the spatial inhomogeneity by verifying each analytic form of the local velocity distribution function. Our approach is widely applicable to experimentally establish the velocity distribution function in plasmas and fluids, including gases and liquids., (© 2021. The Author(s).)

Xanthine oxidoreductase (XOR) is an enzyme that catalyzes hypoxanthine to xanthine and xanthine to uric acid, respectively. However, the underlying mechanisms of increased plasma XOR and its pathological roles in systemic diseases, such as atherosclerosis, are not fully understood. In this study, we found that changes in plasma XOR activity after bariatric surgery closely associated with those in liver enzymes, but not with those in BMI. In a mouse model of nonalcoholic fatty liver disease/steatohepatitis (NAFLD/NASH), plasma XOR activity markedly increased. Besides, purine catabolism was accelerated in the plasma per se of NASH mice and human patients with high XOR activity. In our NASH mice, we observed an increased vascular neointima formation consisting of dedifferentiated vascular smooth muscle cells (SMCs), which was significantly attenuated by topiroxostat, a selective XOR inhibitor. In vitro, human liver S9-derived XOR promoted proliferation of SMCs with phenotypic modulation and induced ROS production by catabolizing hypoxanthine released from human endothelial cells. Collectively, the results from human and mouse models suggest that increased plasma XOR activity, mainly explained by excess hepatic leakage, was involved in the pathogenesis of vascular injury, especially in NAFLD/NASH conditions.

Aim: Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignancy. However, the characteristics and prognosis of ICC is not well known. This study aims to reveal the relationship between liver function and prognosis of ICC., Methods: A total of 83 ICC patients were recruited retrospectively from March 2009 to August 2020. Child-Pugh (CP) and albumin-bilirubin (ALBI) scores were used to assess liver function. The extent of portal vein tumor thrombosis (PVTT) was classified from Vp0 to Vp4. The end-point for this analysis was overall survival (OS)., Results: The median age was 72 (44-88) years, 48 patients were male (57.8%), and 70 patients were classified as CP grade A (84.3%). At baseline, chronic liver disease (hepatitis B, 9.6%; hepatitis C, 15.7%; alcoholic liver disease, 9.6%; and nonalcoholic fatty liver disease, 4.8%) were diagnosed. The median OS of all ICC patients was 21.2 months. A total of 27 patients underwent surgical resection; these patients showed a longer median OS compared to those who did not undergo surgery (50.8 months vs. 5.5 months, p < 0.001). The prognosis of patients with ICC can be stratified by ALBI grade (grade 1, 54.3 months; grade 2a, 8.4 months; grade 2b, 3.9 months; and grade 3, 1.4 months; p < 0.001) and the extent of PVTT (Vp0, 54.3 months; Vp1/2, 8.4 months; and Vp3/4, 3.9 months; p = 0.0039)., Conclusion: In this study, viral hepatitis (25.3%) was identified as the most prevalent background liver disease of ICC. Assessing liver function using ALBI grade is useful for stratifying the prognosis of patients with ICC., (© 2021 The Japan Society of Hepatology.)

Aims/introduction: Xanthine oxidoreductase (XOR) is an enzyme that catalyzes hypoxanthine and xanthine to xanthine and uric acid, respectively. Plasma XOR activity has recently been measured in humans. However, limited information is known about plasma XOR activity in patients with type 2 diabetes mellitus, and its changes after short-term glycemic control treatment., Materials and Methods: We enrolled 28 Japanese patients (10 men/18 women) with type 2 diabetes mellitus who were hospitalized to undergo medical treatment for diabetes. Plasma XOR activity, quantified using triple quadrupole mass spectrometry and liquid chromatography, and other clinical parameters were examined at admission and 2 weeks after treatment during hospitalization. Changes in plasma XOR activity after treatment during hospitalization and associated clinical parameters were assessed., Results: At the time of admission, the median plasma XOR activity was 83.1 pmol/h/mL, with a wide range of 14.4-1150 pmol/h/mL. Multiple regression analysis identified serum aspartate transaminase and alanine transaminase levels as significant and independent factors correlating with the baseline plasma XOR. Two weeks of treatment during hospitalization was associated with a significant decrease in plasma XOR activity. Changes in serum aspartate transaminase were also the only significant and independent factor correlating with changes in plasma XOR activity., Conclusions: A close relationship was observed between plasma XOR activity and liver transaminases in patients with type 2 diabetes mellitus, cross-sectionally, and also across treatment during hospitalization., (© 2020 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

A tomography system is installed as one of the diagnostics of new age to examine the three-dimensional characteristics of structure and dynamics including fluctuations of a linear magnetized helicon plasma. The system is composed of three sets of tomography components located at different axial positions. Each tomography component can measure the two-dimensional emission profile over the entire cross-section of plasma at different axial positions in a sufficient temporal scale to detect the fluctuations. The four-dimensional measurement including time and space successfully obtains the following three results that have never been found without three-dimensional measurement: (1) in the production phase, the plasma front propagates from the antenna toward the end plate with an ion acoustic velocity. (2) In the steady state, the plasma emission profile is inhomogeneous, and decreases along the axial direction in the presence of the azimuthal asymmetry. Furthermore, (3) in the steady state, the fluctuations should originate from a particular axial position located downward from the helicon antenna.

Adiponectin (APN) is a circulating protein specifically produced by adipocytes. Native APN specifically binds to T-cadherin, a glycosylphosphatidylinositol-anchored protein, mediating the exosome-stimulating effects of APN in endothelial, muscle, and mesenchymal stem cells. It was previously reported that APN has beneficial effects on kidney diseases, but the role of T-cadherin has not been clarified yet. Here, our immunofluorescence study indicated the existence of both T-cadherin and APN protein in pericytes, subsets of tissue-resident mesenchymal stem/progenitor cells positive for platelet-derived growth factor receptor β (PDGFRβ), surrounding peritubular capillaries. In an acute renal ischemia-reperfusion (I/R) model, T-cadherin-knockout (Tcad-KO) mice, similar to APN-KO mice, exhibited the more progressive phenotype of renal tubular damage and increased vascular permeability than wild-type mice. In addition, in response to I/R-injury, the renal PDGFRβ-positive cell area increased in wild-type mice, but opposingly decreased in both Tcad-KO and APN-KO mice, suggesting severe pericyte loss. Mouse primary pericytes also expressed T-cadherin. APN promoted exosome secretion in a T-cadherin-dependent manner. Such exosome production from pericytes may play an important role in maintaining the capillary network and APN-mediated inhibition of renal tubular injury. In summary, our study suggested that APN protected the kidney in an acute renal injury model by binding to T-cadherin. NEW & NOTEWORTHY In the kidney, T-cadherin-associated adiponectin protein existed on peritubular capillary pericytes. In an acute renal ischemia-reperfusion model, deficiency of adiponectin or T-cadherin exhibited the more progressive phenotype of renal tubular damage and increased vascular permeability, accompanied by severe pericyte loss. In vitro, adiponectin promoted exosome secretion from mouse primary pericytes in a T-cadherin-dependent manner. Adiponectin plays an important role in maintaining the capillary network and amelioration of renal tubular injury by binding to T-cadherin.

Torovirus (ToV) has recently been classified into the new family Tobaniviridae , although historically, it belonged to the Coronavirus (CoV) family. The nucleocapsid (N) proteins of CoVs are predominantly localized in the cytoplasm, where the viruses replicate, but in some cases the proteins are partially located in the nucleolus. Many studies have investigated the subcellular localization and nucleocytoplasmic trafficking signals of the CoV N proteins, but little is known about ToV N proteins. Here, we studied the subcellular localization of the bovine ToV (BToV) N protein (BToN) and characterized its nucleocytoplasmic trafficking signals. Unlike other CoVs, BToN in infected cells was transported mainly to the nucleolus during early infection but was distributed predominantly in the nucleoplasm rather than in the nucleolus during late infection. Interestingly, a small quantity of BToN was detected in the cytoplasm during infection. Examination of a comprehensive set of substitution or deletion mutants of BToN fused with enhanced green fluorescent protein (EGFP) revealed that clusters of arginine (R) residues comprise nuclear/nucleolar localization signals (NLS/NoLS), and the C-terminal region served as a chromosomal maintenance 1 (CRM1)-independent nuclear export signal (NES). Moreover, recombinant viruses with mutations in the NLS/NoLS, but retaining nuclear accumulation, were successfully rescued and showed slightly reduced growth ability, while the virus that lost the NLS/NoLS-mediated nuclear accumulation of BToN was not rescued. These results indicate that BToN uniquely accumulates mainly in nuclear compartments during infection, regulated by an R-rich NLS/NoLS and a CRM1-independent NES, and that the BToN accumulation in the nuclear compartment driven by NLS/NoLS is important for virus growth. IMPORTANCE ToVs are diarrhea-causing pathogens detected in many species, including humans. BToV has spread worldwide, leading to economic loss, and there is currently no treatment or vaccine available. Positive-stranded RNA viruses, including ToVs, replicate in the cytoplasm, and their structural proteins generally accumulate in the cytoplasm. Interestingly, BToN accumulated predominantly in the nucleus/nucleolus during all infectious processes, with only a small fraction accumulating in the cytoplasm despite being a major structural protein. Furthermore, we identified unique nucleocytoplasmic trafficking signals and demonstrated the importance of NLS/NoLS for virus growth. This study is the first to undertake an in-depth investigation of the subcellular localization and intracellular trafficking signals of BToN. Our findings additionally suggest that the NLS/NoLS-mediated nuclear accumulation of BToN is important for virus replication. An understanding of the unique features of BToV may provide novel insights into the assembly mechanisms of not only ToVs but also other positive-stranded RNA viruses., (Copyright © 2021 American Society for Microbiology.)

Mesenchymal stem/stromal cells (MSCs) are cultured adult stem cells that originally reside in virtually all tissues, and the gain of MSCs by transplantation has become the leading form of cell therapy in various diseases. However, there is limited knowledge on the alteration of its efficacy by factors in recipients. Here, we report that the cardioprotective properties of intravenously injected MSCs in a mouse model of pressure-overload heart failure largely depend on circulating adiponectin, an adipocyte-secreted factor. The injected MSCs exert their function through exosomes, extracellular vesicles of endosome origin. Adiponectin stimulated exosome biogenesis and secretion through binding to T-cadherin, a unique glycosylphosphatidylinositol-anchored cadherin, on MSCs. A pharmacological or adenovirus-mediated genetic increase in plasma adiponectin enhanced the therapeutic efficacy of MSCs. Our findings provide novel insights into the importance of adiponectin in mesenchymal-progenitor-mediated organ protections., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

A disintegrin and metalloproteinase (ADAM)12 is considered to promote cardiac dysfunction based on the finding that a small-molecule ADAM12 inhibitor, KB-R7785, ameliorated cardiac function in a transverse aortic constriction (TAC) model by inhibiting the proteolytic activation of heparin-binding-EGF signaling. However, this compound has poor selectivity for ADAM12, and the role of ADAM12 in cardiac dysfunction has not yet been investigated using genetic loss-of-function mice. We revealed that ADAM12 knockout mice showed significantly more advanced cardiac hypertrophy and higher mortality rates than wild-type mice 4 wk after TAC surgery. An ADAM12 deficiency resulted in significantly more expanded cardiac fibrosis accompanied by increased collagen-related gene expression in failing hearts. The results of a genome-wide transcriptional analysis suggested a strongly enhanced focal adhesion- and fibrosis-related signaling pathway in ADAM12 knockout hearts. The loss of ADAM12 increased the abundance of the integrinβ1 subunit and transforming growth factor (TGF)-β receptor types I and III, and this was followed by the phosphorylation of focal adhesion kinase, Akt, mammalian target of rapamycin, ERK, and Smad2/3 in the heart, which resulted in cardiac dysfunction. The present results revealed that the loss of ADAM12 enhanced focal adhesion and canonical TGF-β signaling by regulating the abundance of the integrinβ1 and TGF-β receptors. NEW & NOTEWORTHY In contrast to a long-believed cardio-damaging role of a disintegrin and metalloproteinase (ADAM)12, cardiac hypertrophy was more severe, cardiac function was lower, and mortality was higher in ADAM12 knockout mice than in wild-type mice after transverse aortic constriction surgery. The loss of ADAM12 enhanced focal adhesion- and fibrosis-related signaling pathways in the heart, which may compromise cardiac function. These results provide insights for the development of novel therapeutics that target ADAM12 to treat heart failure.

Background: Gastric cancer (GC) patients with positive peritoneal lavage cytology (CY1) and/or localized peritoneum metastasis (P1a) are defined as stage IV in the 15th edition of the Japanese Classification of Gastric Cancer. In Japan, the most common treatment for patients with CY1 and/or P1a is gastrectomy followed by postoperative chemotherapy., Patients and Methods: Subjects in this multi-institutional retrospective study were GC patients with CY1 and/or P1a who received surgical resection that leaves no macroscopically visible disease. Patients were selected from 34 institutions in Japan between 2007 and 2012. Selection criteria included adenocarcinoma, no distant metastasis except CY1 and P1a, and no prior treatment for GC before surgery., Results: Among 824 patients registered, 506 were identified as eligible, with a background of P0CY1, P1aCY0, or P1aCY1 (72.5%, 16.0%, and 11.5% of subjects, respectively). Sixty-two patients had not received postoperative chemotherapy (no-Cx), whereas 444 patients had received postoperative chemotherapy: S-1 monotherapy (S-1; n = 267, 52.7%), cisplatin plus S-1 (CS; n = 114, 22.5%), and others (n = 63, 12.6%). Overall survival (OS) was 29.5, 24.7, 25.4 and 9.9 months in the S-1, CS, 'others', and no-Cx groups, respectively [CS vs. S-1: hazard ratio (HR) 1.15, 95% confidence interval (CI) 0.89-1.50; p = 0.275]. In multivariate analysis, OS was similar between the S-1 and CS groups (CS vs. S-1: HR 1.19, 95% CI 0.92-1.55; p = 0.18)., Conclusions: Postoperative chemotherapy after gastrectomy that leaves no macroscopically visible disease may have some survival benefits for GC patients with CY1 and/or P1a. In contrast, S-1 plus cisplatin seems to have no additional benefit over S-1 treatment alone.

We examined the influence of expansion and contraction on visual short-term memory (VSTM) using a change-detection task. In each trial, several expanding/contracting line segments with various orientations were presented in two successive displays. The orientation of objects in the second display was either identical to, or different from, that of the first display. Observers were asked to judge the presence or absence of an orientation change in successive displays. Results showed that memory performance for expanding objects was higher than for contracting objects (expansion benefit: Experiments 1A and 1B). Further experiments focused on VSTM processing (encoding, storage, and retrieval). Regarding the retrieval stage, an expansion benefit was replicated only when the direction of motion was consistent between two successive displays (Experiment 2A). A cueing stimulus enhanced the memory performance for both expanding and contracting motions and eliminated the expansion benefit (Experiment 2B). Regarding the storage stage, we found the expansion benefit occurred only for shorter blank intervals between the two displays (Experiment 3). Regarding the encoding stage, the expansion benefit was observed regardless of presentation times (Experiment 4). These results indicate the possibility that expanding and contracting motions modulate VSTM., (Copyright: © 2019 University of Economics and Human Sciences in Warsaw.)

When individuals are forced to choose between similarly preferable alternatives, a negatively arousing cognitive conflict occurs, and the preference attitudes toward the chosen and rejected alternatives diverge. This phenomenon, often referred to as "cognitive dissonance", is of interest in psychological and decision neuroscience research. The dorsal anterior cingulate cortex (dACC) is involved in representing the cognitive conflict induced by difficult-choice tasks. Previous studies have shown age-related decline of the dACC function. However, whether the heightened activity of the dACC regarding cognitive conflict, and choice-induced preference change that behaviorally occur in young subjects also occur in the elderly is unclear. Furthermore, recent studies have noted substantial methodological flaw with the free-choice paradigm that often used in studies focusing on cognitive dissonance. Here, we used functional magnetic resonance imaging (fMRI) and a modified free-choice paradigm to formally test the effect of aging on choice-induced cognitive conflict. In the young participants, behavioral data confirmed the existence of cognitive conflict and preference change for the alternatives that they rejected in the difficult-choice trials. The imaging data revealed that the right dACC displayed an interaction effect associated with cognitive conflict. In contrast, we did not observe such effects in the elderly participants. These suggest a possibility that elderly people likely feel less cognitive dissonance., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Postoperative adjuvant chemotherapy with S-1 for 1 year (corresponding to eight courses) is standard care for stage II gastric cancer. Whether the duration of S-1 could be shortened to 6 months (corresponding to four courses) without worsening survival is unclear. The aim of this study was to investigate the non-inferiority of four courses of S-1 compared with eight courses of S-1 for patients with stage II gastric cancer., Methods: We did a phase 3, open-label, randomised controlled, non-inferiority trial at 59 hospitals in Japan. Patients aged 20-80 years with stage II adenocarcinoma of the stomach were randomly assigned (1:1) to eight courses or four courses of S-1. Randomisation was done by the Japan Clinical Oncology Group Data Center website, using a minimisation method with a random component using institution, stage (IIA vs IIB), age (<70 years vs ≥70 years), and mode of operation (open gastrectomy with bursectomy vs open gastrectomy without bursectomy vs laparoscopic gastrectomy) as adjustment factors. One course was 80 mg/day per m 2 of S-1 administered for 4 weeks followed by a rest for 2 weeks. The primary endpoint was relapse-free survival, analysed by intention to treat, with a non-inferiority margin for the hazard ratio (HR) set at 1·37. This study is registered at UMIN-Clinical Trial Registry, number UMIN000007306., Findings: Between Feb 16, 2012, and March 19, 2017, 590 patients were enrolled (295 per group). 528 (89%) patients were analysed at the first planned interim analysis in March, 2017, at which time the point estimate of HR for the four-course group compared with the eight-course group was 2·52 (95% CI 1·11-5·77), which exceeded 1·37 and met the prespecified criteria for early termination. Predictive probability for showing non-inferiority at the final analysis was calculated to be 2·9%. The study was stopped for futility. Updated 3-year relapse-free survival analysed in May, 2017, was 93·1% (95% CI 87·8-96·1) for the eight-course group and 89·8% (84·2-93·5) for the four-course group (HR 1·84, 95% CI 0·93-3·63). The most common grade 3-4 adverse event was neutropenia, observed in 46 (16%) patients in the eight-course group and 51 (17%) patients in the four-course group., Interpretation: S-1 for 1 year should remain as standard adjuvant chemotherapy for stage II gastric cancer., Funding: Japan Agency for Medical Research and Development; the Ministry of Health, Labour and Welfare of Japan; the National Cancer Center Research and Development Fund, Japan., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Daiokanzoto (DKT) and lubiprostone (LPS) are drugs used for constipation, but few studies have compared them. This study examined the effectiveness, adverse events, and medical economic efficiency of DKT and LPS for constipation. Patients who received DKT (DKT group) and those who received LPS (LPS group) during admission to Ogaki Municipal Hospital between November 2012 and May 2016 were enrolled. Drug efficacy was evaluated based on the median value of bowel movement frequency over 1 week before and after drug administration, and their safety was evaluated by the presence or absence of diarrhea, abdominal pain, nausea, and vomiting. To assess medical economic efficiency, drug costs for constipation per week were calculated. The median values (quartile ranges) of bowel movement frequency at 1 week after drug administration were 8.5 (6.0-12.0) in the DKT group and 5 (3.0-7.0) in the LPS group, which was significantly different (p < 0.01). Diarrhea occurred significantly less often in the DKT group (4 cases) than in the LPS group (17 cases) (p < 0.01). The median cost of drugs administered for constipation for 1 week was significantly lower in the DKT group (631 [quartile range, 513-653] yen) than in the LPS group (1431 [1135-2344] yen) (p < 0.01). DKT had a higher immediate effect on constipation and was associated with more frequent bowel movement and fewer adverse events of diarrhea than LPS, suggesting that it may be effective and safe for treating constipation, and DKT is inexpensive.

The success of human life in modern society is highly dependent on occupation. Therefore, it is very important for people to identify and develop a career plan that best suits their aptitude. Traditional test batteries for vocational aptitudes are not oriented to measure developmental changes in job suitability because repeated measurements can introduce bias as the content of the test batteries is learned. In this study, we attempted to objectively assess vocational aptitudes by measuring functional brain networks and identified functional brain networks that intrinsically represented vocational aptitudes for 19 job divisions in a General Aptitude Test Battery. In addition, we derived classifiers based on these networks to predict the aptitudes of our test participants for each job division. Our results suggest that the measurement of brain function can indeed yield an objective evaluation of vocational aptitudes; this technique will enable a person to follow changes in one's job suitability with additional training or learning, paving a new way to advise people on career development., (© 2018 Wiley Periodicals, Inc.)

The patient-a Jehovah's Witness-was a woman in her 60s, with locally advanced sigmoid colon cancer. She had severe anemia, and a computed tomography scan of her abdomen showed a tumor with abscess formation and perforation that had invaded into the left urinary duct and the left ovary, without distant metastasis. It was difficult to perform curative resections without transfusion; therefore, CapeOX therapy was plannedas the neoadjuvant treatment. After 3 courses of CapeOX therapy, the patient's anemia improved, and the tumor and abscess had shrunk. Subsequently, a sigmoidectomy with D3 lymph node dissection, partial resection of the small intestine, and the left adnexectomy, as a radical surgery, were performed without blood transfusion. In cases of concomitant colon cancer with anemia that are treated with highly invasive surgery, it might be necessary to conduct systematic treatment in order to complete non-transfusion therapy.

Many human characteristics must be evaluated to comprehensively understand an individual, and measurements of the corresponding cognition/behavior are required. Brain imaging by functional MRI (fMRI) has been widely used to examine brain function related to human cognition/behavior. However, few aspects of cognition/behavior of individuals or experimental groups can be examined through task-based fMRI. Recently, resting state fMRI (rs-fMRI) signals have been shown to represent functional infrastructure in the brain that is highly involved in processing information related to cognition/behavior. Using rs-fMRI may allow diverse information about the brain through a single MRI scan to be obtained, as rs-fMRI does not require stimulus tasks. In this study, we attempted to identify a set of functional networks representing cognition/behavior that are related to a wide variety of human characteristics and to evaluate these characteristics using rs-fMRI data. If possible, these findings would support the potential of rs-fMRI to provide diverse information about the brain. We used resting-state fMRI and a set of 130 psychometric parameters that cover most human characteristics, including those related to intelligence and emotional quotients and social ability/skill. We identified 163 brain regions by VBM analysis using regression analysis with 130 psychometric parameters. Next, using a 163 × 163 correlation matrix, we identified functional networks related to 111 of the 130 psychometric parameters. Finally, we made an 8-class support vector machine classifiers corresponding to these 111 functional networks. Our results demonstrate that rs-fMRI signals contain intrinsic information about brain function related to cognition/behaviors and that this set of 111 networks/classifiers can be used to comprehensively evaluate human characteristics.

Background: Daikenchuto (DKT) is a Kampo medicine used for the treatment of constipation. In this study, we evaluated the effectiveness of DKT against constipation., Patients and Methods: Thirty-three patients administered DKT for constipation were selected and divided into low-dose (7.5 g DKT; n = 22) and high-dose (15 g DKT; n = 11) groups. We retrospectively evaluated weekly defaecation frequency, side effects, and clinical laboratory data., Results: Median defaecation frequencies after DKT administration (5, 5.5, 5, and 8 for the first, second, third, and fourth weeks, resp.) were significantly higher than that before DKT administration (2) in all 33 cases ( P < 0.01). One case (3%) of watery stool, one case of loose stools (3%), and no cases of abdominal pain (0%) were observed. Median defaecation frequencies in the high-dose group (7 and 9) were significantly higher than those in the low-dose group (4 and 3) in the first ( P = 0.0133) and second ( P = 0.0101) weeks, respectively. There was no significant change in clinical laboratory values., Conclusion: We suggest that DKT increases defaecation frequency and is safe for treating constipation.

Background: Neoadjuvant chemotherapy (NAC) followed by radical surgery is a promising strategy to improve survival of patients with stage III gastric cancer, but is associated with the risk of preoperative overdiagnosis by which patients with early disease may receive unnecessary intensive chemotherapy., Methods: We assessed the validity of a preoperative diagnostic criterion in a prospective multicenter study. Patients with gastric cancer with a clinical diagnosis of T2/T3/T4, M0, except for diffuse large tumors and extensive bulky nodal disease, were eligible. Prospectively recorded clinical diagnoses (cT category, cN category) were compared with postoperative pathological diagnoses (pT category, pN category, and pathological stage). The primary endpoint was the proportion of pathological stage I tumors among those diagnosed as cT3/T4, which we expected to be 5% or less., Results: Data from 1260 patients enrolled from 53 institutions were analyzed. The proportion of pathological stage I tumors in those with a diagnosis of cT3/T4 (primary endpoint) was 12.3%, which was much higher than the prespecified value. The positive predictive value and the sensitivity for pathological stage III tumors were 43.6% and 87.8% respectively. The sensitivity and specificity of contrast-enhanced CT for lymph node metastasis were 62.5% and 65.7% respectively. After exploring several diagnostic criteria, we propose, for future NAC trials in Japan, a diagnosis of "cT3/T4 with cN1/N2/N3," by which inclusion of pathological stage I tumors was reduced to 6.5%, although its sensitivity for pathological stage III tumors decreased to 64.5%., Conclusion: Clinical diagnosis of T3/T4 tumors was not an optimal criterion to select patients for intensive NAC trials because more than 10% of patients with pathological stage I disease were included. We propose the criterion "cT3/T4 and cN1/N2/N3" instead.

Blackcurrants (Ribes nigrum L.) have various benefits for human health. In particular, a polysaccharide derived from blackcurrant was found to be an immunostimulating food ingredient in a mouse model. We named a polysaccharide derived from blackcurrant cassis polysaccharide (CAPS). In a previous clinical study, we reported that CAPS affects skin dehydration, demonstrating its effectiveness against skin inflammation was related to atopic dermatitis; skin inflammation caused skin dehydration. However, there are no studies regarding CAPS effectiveness against skin dehydration. The current study aimed to investigate CAPS effectiveness against skin dehydration. We further demonstrate the effect of oral administration of CAPS on skin dehydration caused by ultraviolet (UV) irradiation-induced inflammation in mice. We found that CAPS administration suppresses skin dehydration caused by UV irradiation. We also found that CAPS decreases interleukin-6 and matrix metalloproteinase transcription levels in the mouse skin. These results show that CAPS improves skin hydration in UV-irradiated mice.

Atopic dermatitis (AD) is a chronic inflammatory skin disease that causes dry skin and functional disruption of the skin barrier. AD is often accompanied by allergic inflammation. AD patient suffer from heavy itching, and their quality of life is severely affected. Some pharmaceuticals for AD have some side effects such as skin atrophy. So it is necessary to develop mild solutions such as food ingredients without side effects. There are various causes of AD. It is especially induced by immunological imbalances such as IFN-γ reduction. IFN-γ has an important role in regulating IgE, which can cause an allergy reaction. NC/Nga mice develop AD and IgE hyperproduction. In a previous study, we revealed that administration of polysaccharide from black currant ( R. nigrum ) has an effect on immunomodulation. It induces IFN-γ production from myeloid dendritic cells. We named this polysaccharide cassis polysaccharide (CAPS). In this report, we studied the effect of administering CAPS on atopic dermatitis in NC/Nga mice. Thirty NC/Nga mice that developed symptoms of atopic dermatitis were used. We divided them into three groups (control, CAPS administration 12 mg/kg/day, CAPS administration 60 mg/kg/day). For 4 weeks, we evaluated clinical score, serum IgE levels, gene expression of spleen, and skin pathology. We revealed that CAPS administration improves atopic dermatitis symptoms. We also found that CAPS administration suppresses IgE hyperproduction and induces IFN-γ gene transcription in the spleen. Finally, we confirmed that CAPS administration suppresses mast cell migration to epidermal skin. These results indicated that CAPS has an effect on AD.

Background: Bochdalek hernias are one of the most common types of diaphragmatic hernia, with most cases diagnosed during the neonatal period. In contrast, diagnosis of a Bochdalek hernia in an adult is rare and is typically observed on the left side of the diaphragm. Even more rare is the diagnosis of a right-sided Bochdalek hernia in an adult, where there is concurrent visceral malformation in most cases., Case Presentation: We describe a case of an 89-year-old female who presented with abdominal pain. An abdominal computed tomography (CT) scan showed decreased intravenous contrast uptake and thickening of the wall of herniated small intestine through the right side of the diaphragm, which led to the diagnosis of a strangulated diaphragmatic hernia. The patient underwent emergent laparotomy and required a partial resection of the necrotic ileum and a hernia repair with direct closure. Interestingly, in this case, organ malformation was not observed. The patient was discharged approximately 2 weeks after surgery without complication., Conclusions: Adult right-sided Bochdalek hernia with strangulation in the absence of hepatic atrophy is a rare entity. Considering the severity of this condition, accurate diagnosis and proper treatment are needed. A tailored operative approach is required on an individual case basis.

The aim of this study was to determine the effective waist circumference (WC) reduction rate in avoiding the development of type 2 diabetes mellitus (T2DM) in <55 years and ≥55 years Japanese men with abdominal obesity. The study subjects were 795 men with WC ≥85 cm, fasting plasma glucose <126 mg/dL, 2-hr plasma glucose on 75 g of oral glucose tolerance test <200 mg/dL, and HbA1c 5.6-6.4 % (38-40 mmol/mol) at baseline who underwent general health checkups more than twice between April 2007 and May 2015. They were divided into 5 groups based on the change in WC during the observation period (WC gain group, and four groups stratified according the rate of WC loss). The subjects were also divided into the <55 years and ≥55 years (at baseline) subgroups. The cumulative incidence rate of T2DM was analyzed and compared among the groups. The cumulative incidence rates of the largest WC loss quartile (≥5.45 %) in all age, of the largest WC loss quartile (≥5.60 %) and second largest WC loss quartile (3.44-5.59 %) in the <55 years subgroup, and of the largest WC loss quartile (≥5.37 %) in the ≥55 years subgroup were significantly lower than that of the gain group (p<0.001, p=0.009, 0.012, and 0.012, respectively). WC reduction rate of at least about 3 % in the younger (<55 years) and at least about 5 % in the older (≥55 years) non-diabetic Japanese men with abdominal obesity can effectively reduce the chance of development of T2DM.

In municipal hospitals, there are few cases of thyroid cancer for which the multi-kinase inhibitor lenvatinib is used. Moreover, there are very few reports of lenvatinib use. We examined interventions related to the use of lenvatinib made at the pharmaceutical outpatient clinic in our facility. Seven patients received lenvatinib. The prescription proposals from the pharmacist( 45 cases)provided advice on dosage(15.6%), discontinuation of medication(11.1%), supportive care(64.4%), and other advice(9.0%). The prescription acceptance rate was 84.4%. Among the prescription proposals of supportive care, there were suggestions regarding blood pressure(26.7%), diarrhea(8.9%), nausea(8.9%), and oral hemorrhage(6.7%). Some patients also experienced side effects, such as abnormalities in equilibrioception and visual field defects; however, the relationship between such abnormalities and lenvatinib is unclear. In addition, we asked physicians to confirm if the outpatient pharmacists contributed to the examination process. We believe that lenvatinib administration can be continued safely with pharmaceutical outpatient clinic support for patients, even in municipal hospitals.