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Human symbiotic mobile robots are required to smoothly reach destinations while avoiding humans. Human-intent information, e.g., a moving direction, must be carefully estimated since its lack leads to the hesitation and repetitious avoidance. Conventional studies address human intent estimation and conveyance but do not consider cases of failing communication as a systematic framework, even though the intent is essentially difficult for humans to estimate due to its interiority. In response to this problem, we propose a framework of error-tolerant navigation (ETN) with a process to actively estimate the human intent by iterative interaction from the robot. As a preliminary study, we focus on ‘the intent conveyance from robot to human’ and ‘its achievement’ as core information. The ETN estimates interference possibility to determine the need for inducement, human awareness (HA) to select an inducement method, and inducement achievement (IA) to judge the need for action again. If the ETN estimates the interference, the robot provides inducements according to HA, e.g., route indication when HA is high or voice/physical interaction when HA is low. Each inducement corresponds to an expected behavior change in the human. IA is calculated from the difference between the expected and actual changes. If the robot observes no change within a specified time after the inducement, it executes inducements with a stronger intent conveyance. When IA is none after the strongest action, it selects another route. This error-collection loop in the ETN could prevent a fatal mistake by recognizing a small mistake and recovering it. The static and dynamic experimental results indicated that the ETN could achieve smoother human movement and reduce psychological burden by correcting the robot behaviors, compared with a conventional navigation system, which can contribute to constructing a practical ETN framework.

ObjectiveTo date, there are no predictive biomarkers to guide selection of patients with gastric cancer (GC) who benefit from paclitaxel. Stomach cancer Adjuvant Multi-Institutional group Trial (SAMIT) was a 2×2 factorial randomised phase III study in which patients with GC were randomised to Pac-S-1 (paclitaxel +S-1), Pac-UFT (paclitaxel +UFT), S-1 alone or UFT alone after curative surgery.DesignThe primary objective of this study was to identify a gene signature that predicts survival benefit from paclitaxel chemotherapy in GC patients. SAMIT GC samples were profiled using a customised 476 gene NanoString panel. A random forest machine-learning model was applied on the NanoString profiles to develop a gene signature. An independent cohort of metastatic patients with GC treated with paclitaxel and ramucirumab (Pac-Ram) served as an external validation cohort.ResultsFrom the SAMIT trial 499 samples were analysed in this study. From the Pac-S-1 training cohort, the random forest model generated a 19-gene signature assigning patients to two groups: Pac-Sensitive and Pac-Resistant. In the Pac-UFT validation cohort, Pac-Sensitive patients exhibited a significant improvement in disease free survival (DFS): 3-year DFS 66% vs 40% (HR 0.44, p=0.0029). There was no survival difference between Pac-Sensitive and Pac-Resistant in the UFT or S-1 alone arms, test of interaction pConclusionUsing machine-learning techniques on one of the largest GC trials (SAMIT), we identify a gene signature representing the first predictive biomarker for paclitaxel benefit.Trial registration numberUMIN Clinical Trials Registry: C000000082 (SAMIT); ClinicalTrials.gov identifier, 02628951 (South Korean trial)

Additional file 1: Supplementary Figure S1. Localization of TP53 mutations at CpG and non-CpG sites in GC samples from Eastern Europe, China, and Japan (exon 4-8). Mutation-distribution maps were created using the cBioPortal mutation mapper ( http://www.cbioportal.org/mutation_mapper ). Black dots indicate truncating mutations (nonsense and frameshift mutations). The light purple dot indicates a silent mutation. P53_TAD, TP53 transcriptional activation domain; P53, TP53 DNA-binding domain; P53 tetramer, TP53 tetramer domain.

Additional file 5: Supplementary Figure S5. Mutation spectrum of the TP53 gene in GC in each population. Six substitution types are depicted in the bar graph as follows: C > A (light blue), C > G (black), C > T (red), T > A (gray), T > C (yellow-green), and T > G (pale orange).

Additional file 4: Supplementary Figure S4. Designations of populations based on TCGA classification. The majority of the data were from the “White” population. The “Asian” population was not defined, especially whether they were only residing in Asia or not. NA, not available.

Additional file 3: Supplementary Figure S3. Mutation spectra in intestinal and diffuse-type GCs in East Europe, China, and Japan. The TP53 mutations were classified into six types of single nucleotide substitutions, as well as deletions (del), insertions (ins), deletion-insertion (delins), and splice mutations. The G:C > A:T transition was subdivided into G:C > A:T at CpG and non-CpG sites. Each spectrum is shown in the pie graph as follows: G:C > A:T at CpG sites (blue), G:C > A:T at non-CpG sites (orange), A:T > G:C (gray), G:C > C:G (yellow), G:C > T:A (light blue), A:T > C:G (light green), A:T > T:A (dark blue), del (brown), delins (dark gray), ins (light brown), and splice mutations (light navy). The prevalence of G:C > A:T at non-CpG sites (orange) in diffuse-type GCs in Asia was significantly different from that in Eastern Europe (p < 0.05). * Statistically significant difference (p < 0.05).

Additional file 2: Supplementary Figure S2.TP53 mutation types in the intestinal and diffuse types of GC samples from Eastern Europe, China, and Japan (exon 4-8). The pie graphs show the percentages of the mutations, including missense (blue), nonsense (orange), and silent mutations (gray), deletions (del) (yellow), deletion-insertion (delins) (light blue), insertions (ins) (light green), and splice site mutations (dark blue) in TP53 in GC samples from Eastern Europe, China, and Japan. The prevalence of silent mutations (gray) in diffuse-type GCs was significantly different between Europe and Asia (P < 0.01). * Statistically significant difference (p < 0.05).

Background Gastric cancer (GC) is mostly related to Helicobacter pylori (Hp) infection, and risk-stratified screening (RS) for GC has been adopted in some cities. We aimed to investigate the efficacy of RS as compared with barium X-ray screening (XR) recommended by Japan for GC. Methods Repeated cross-sectional study from the data of Yokosuka Public Health Center. The GC screening participants were ≥ 40 years old from 2002 to 2018. RS was classified by pepsinogen test screening (PG) and Helicobacter pylori (Hp) tests into low and high-risk groups. The primary endpoints were detection rates of all GC and early GC (TNM T1). Secondary endpoints were participation rate and GC detection cost. For GC detection, the odds ratios were calculated by logistic regression models adjusted for age, sex, and first visit or revisit. Results A total of 448,244 participants’ data were included. In multivariable analyses, the odds ratios of PG and RS vs XR were 2.26 and 3.73 for GC detection, and 4.64 and 10.63 for early GC detection, respectively (p

Mutation spectrum of TP53 in gastric cancer (GC) has been investigated world-widely, but a comparison of mutation spectrum among GCs from various regions in the world are still sparsely documented. In order to identify the difference of TP53 mutation spectrum in GCs in Eastern Europe and in East Asia, we sequenced TP53 in GCs from Eastern Europe, Lujiang (China), and Yokohama, Kanagawa (Japan) and identified the feature of TP53 mutations of GC in these regions.In total, 689 tissue samples of GC were analyzed: 288 samples from East European populations (25 from Hungary, 71 from Poland and 192 from Romania), 268 from Yokohama, Kanagawa, Japan and 133 from Lujiang, Anhui province, China. DNA was extracted from FFPE tissue of Chinese, East European cases; and from frozen tissue of Japanese GCs. PCR products were direct-sequenced by Sanger method, and in ambiguous cases, PCR product was cloned and up to 8 clones were sequenced. We used No. NC_000017.11(hg38) as the reference sequence of TP53. Mutation patterns were categorized into nine groups: six base substitutions, insertion, deletion and deletion-insertion. Within G:C A:T mutations the mutations in CpG and non-CpG sites were divided. The Cancer Genome Atlas data (TCGA, ver.R20, July, 2019) having somatic mutation list of GCs from Whites, Asians, and other ethnicities were used as a reference for our data.The most frequent base substitutions were G:C A:T transition in all the areas investigated. The G:C A:T transition in non-CpG sites were prominent in East European GCs, compared with Asian ones. Mutation pattern from TCGA data revealed the same trend between GCs from White (TCGA category) vs Asian countries. Chinese and Japanese GCs showed higher ratio of G:C A:T transition in CpG sites and A:T G:C mutation was more prevalent in Asian countries.The divergence in mutation spectrum of GC in different areas in the world may reflect various pathogeneses and etiologies of GC, region to region. Diversified mutation spectrum in GC in Eastern Europe may suggest GC in Europe has different carcinogenic pathway of those from Asia.

Whole-exome sequencing (WES) can detect not only single-nucleotide variants in causal genes, but also pathogenic copy-number variations using several methods. However, there may be overlooked pathogenic variations in the out of target genome regions of WES analysis (e.g., promoters), leaving many patients undiagnosed. Whole-genome sequencing (WGS) can potentially analyze such regions. We applied long-read nanopore WGS and our recently developed analysis pipeline "dnarrange" to a patient who was undiagnosed by trio-based WES analysis, and identified a heterozygous 97-kb deletion partially involving 5'-untranslated exons of MBD5, which was outside the WES target regions. The phenotype of the patient, a 32-year-old male, was consistent with haploinsufficiency of MBD5. The transcript level of MBD5 in the patient's lymphoblastoid cells was reduced. We therefore concluded that the partial MBD5 deletion is the culprit for this patient. Furthermore, we found other rare structural variations (SVs) in this patient, i.e., a large inversion and a retrotransposon insertion, which were not seen in 33 controls. Although we considered that they are benign SVs, this finding suggests that our pipeline using long-read WGS is useful for investigating various types of potentially pathogenic SVs. In conclusion, we identified a 97-kb deletion, which causes haploinsufficiency of MBD5 in a patient with neurodevelopmental disorder, demonstrating that long-read WGS is a powerful technique to discover pathogenic SVs.

Perioperative treatment for locally advanced gastric cancer has been inconsistent between Japan and the Western countries. In Japan, D2 gastrectomy followed by adjuvant chemotherapy is regarded as standard treatment, while neoadjuvant or perioperative chemotherapy is considered to be a standard in the Western countries. Stomach Cancer Study Group of Japan Clinical Oncology Group (JCOG) has conducted many perioperative chemotherapy trials. After the publishing of positive results of ACTS-GC trial, stage-specific adjuvant chemotherapy protocols are planned. JCOG1104 was conducted as to demonstrate the non-inferiority of four courses of S-1 to standard eight courses of S-1, because the efficacy of S-1 appears to be sufficient in stage II. The trial failed to demonstrate the non-inferiority of four courses of S-1. S-1 for 1 year is still recognized to be a standard for stage II gastric cancer. For stage III, studies with more intensive treatments were planned as the efficacy of S-1 monotherapy seems to be insufficient. As in the Western countries, JCOG planned the perioperative chemotherapy. However, the clinical staging is a serious issue to select optimal patients for perioperative chemotherapy. JCOG conducted a prospective cohort study to evaluate the validity of clinical staging in JCOG1302A. From the results of this study, cT3-4 and cN1–3 are selected as optimal candidate for perioperative chemotherapy. JCOG1509 was conducted to demonstrate the superiority of perioperative chemotherapy to adjuvant chemotherapy in these cohorts. Perioperative chemotherapy for marginally resectable tumours such as linitis plastica or extensive nodal disease and special type of cancer like HER2 positive are also conducted.

It has been suggested that the therapeutic efficacy of S-1 + cisplatin (SP) and capecitabine + cisplatin (XP) may differ depending on the histology of the tumor, but no clear evidence exists. Individual participant data were obtained from three randomized phase II trials in which such patients received either SP (S-1 [40–60 mg twice daily for 21 days] plus cisplatin [60 mg/m2 on day 8], every 5 weeks) or XP (capecitabine [1000 mg/m2 twice daily for 14 days] plus cisplatin [80 mg/m2 on day 1], every 3 weeks). A total of 162 patients were included, with 79 patients in the SP arm and 83 patients in the XP arm. Although there was also no difference between arms in ORR according to histological classification, differentiated tumors showed a significantly better OS (but not PFS) for SP versus XP that was associated with a deeper tumor shrinkage. Undifferentiated tumors showed a consistently better OS, and PFS for SP versus XP, likely because cases without tumor shrinkage tended to be fewer for SP. Our data thus showed that SP was superior to XP in this setting, but there were qualitative differences in therapeutic efficacy dependent on tumor histology.

Aim Gastric cancer is the second leading cause of cancer death worldwide. Surgery is the mainstay treatment for gastric cancer. There are no prediction models that examine the severity of postoperative morbidity. Herein, we constructed prediction models that analyze the risk for postoperative morbidity based on severity. Methods Perioperative data were retrieved from the National Clinical Database in patients who underwent elective gastric cancer resection between 2011 and 2012 in Japan. Severity of postoperative complications was determined by Clavien‐Dindo classification. Patients were randomly divided into two groups, the development set and the validation set. Logistic regression analysis was used to build prediction models. Calibration powers of the models were assessed by a calibration plot in which linearity between the observed and predicted event rates in 10 risk bands was assessed by the Pearson R 2 statistic. Results We obtained 154 278 patients for the analysis. Prediction models were constructed for grade ≥2, grade ≥3, grade ≥4, and grade 5 in the development set (n = 77 423). Calibration plots of these models showed significant linearity in the validation set (n = 76 855): R 2 = 0.995 for grade ≥2, R 2 = 0.997 for grade ≥3, R 2 = 0.998 for grade ≥4, and R 2 = 0.997 for grade 5 (all: P

Gastric cancer with extensive lymph node metastasis is commonly regarded as unresectable, while preoperative chemotherapy followed by gastrectomy has been tested since 2000 in JCOG (JCOG0001 and JCOG0405). The survivals were quite different between the trials despite the similar eligibility criteria. The aim of this study was to investigate if survival is still better in JCOG0405 after adjusting baseline factors and if there is any subset of patients who benefit more from either treatment. Eligibility criteria for both trials included histologically proven gastric adenocarcinoma; bulky nodal involvement around the celiac artery and its major branches (bulky N) and/or para-aortic lymph node (PAN); cM0 (except PAN); negative lavage cytology; not linitis plastica type; PS of 0 or 1. Patients received two or three cycles of preoperative chemotherapy of irinotecan plus cisplatin in JCOG0001, or S-1 plus cisplatin in JCOG0405, followed by D3 gastrectomy. Multivariable analysis for overall survival adjusting baseline and treatment factors was performed with the Cox regression model. After adjusting baseline factors, S-1 plus cisplatin was superior to irinotecan plus cisplatin for overall survival (HR = 0.39: 95% CI 0.22–0.67). The 5-year overall survival was poor for patients with bulky N+/PAN+ (19.2%) compared with bulky N+/PAN− (50.7%) or bulky N−/PAN+ (43.5%). S-1 plus cisplatin was shown to be a favorable preoperative treatment for gastric cancer with extensive lymph node metastasis by multivariable analysis, while poor prognosis in patients having both bulky N+ and PAN+ may necessitate further treatment improvement.

As a candidate microRNA antifibrotic effector in skin wounds, miR-146b-5p was upregulated by basic FGF, and PDGFRα was identified as a direct target of miR-146b-5p in fibroblasts. The treatment of fibroblasts with a miR-146b-5p mimic markedly downregulated the expression of PDGFRα and collagen type I. miR-146b-5p mimic transfection in wounds markedly attenuated cutaneous fibrosis, whereas a miR-146b-5p inhibitor strongly promoted fibrosis, with increases in PDGFRα and collagen I levels. These results indicate the positive effects of miR-146b-5p for the suppression of fibrosis, possibly through the inhibition of PDGFRα. The miR-146b-5p inhibitor markedly increased CD34

Biomarkers for selecting gastric cancer (GC) patients likely to benefit from sequential paclitaxel treatment followed by fluorinated-pyrimidine-based adjuvant chemotherapy were searched for using samples of patients recruited into SAMIT, a phase III randomized controlled trial. Total RNA was extracted from 556 GC patients and the expression of 105 genes were quantified using real-time PCR. Genes predicting positive effects of sequential paclitaxel on overall survival (OS), disease-free survival (DFS), or cumulative incidence of relapse were identified based on p-values associated with the interaction between the biomarker and sequential paclitaxel or monotherapy group. Low VSNL1 and CD44v expression predicted the positive effects of sequential paclitaxel in all above three endpoints. In the patient subgroup with combined low expression of both genes, sequential paclitaxel therapy was associated with a significantly improved OS (hazard ratio [HR] = 0.48 [95% confidence interval (CI), 0.30–0.78]; p