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Abstract Background Immune checkpoint inhibitors (ICIs) are crucial in cancer treatment; however, they carry the risk of immune-related adverse events (irAEs), such as enteritis. Case presentation: This study investigated the role of the gut microbiota during the onset and remission of irAE enteritis in a patient with stage IV melanoma undergoing anti-PD-1 and anti-CTLA-4 therapy. Following commencement of ICI treatment, the patient developed severe diarrhea and was diagnosed with grade 3 irAE enteritis. Steroid and probiotic treatments provided swift symptom relief and remission, as confirmed by reduced fecal calprotectin levels and gastrointestinal imaging. Microbiota diversity analysis conducted via 16S rRNA gene sequencing identified a decrease in Streptococcus prevalence with improvement in enteritis symptoms. Conversely, genera Fusobacterium, Faecalibacterium, Bacteroides, Prevotella, and Bifidobacterium showed increased representation after remission. These genera are associated with anti-inflammatory properties and fibrous substrate degradation, aiding gut health. Immunological assessment demonstrated fluctuations in cytokine expression and the modulation of costimulatory molecules, aligning with therapeutic interventions and microbiota alterations. Conclusions Our findings indicate a significant correlation between gut microbiota and immune responses in irAE enteritis. This underscores the potential utility of microbiome profiling in predicting irAE occurrence and in providing treatment strategies, thereby promoting a more comprehensive approach to managing the adverse effects of ICIs.

Abstract Background Although proton pump inhibitors (PPIs) or potassium-competitive acid blocker (PCAB) are useful in peptic ulcer prevention, their efficacy in preventing other gastrointestinal bleeding remains unclear. This study aimed to identify the status of gastrointestinal bleeding in the modern era when PPIs are widely used. Methods This study included patients who underwent percutaneous coronary intervention (PCI) between 2018 and 2019 at two high-volume centers. Patients were categorized based on whether they experienced gastrointestinal bleeding within 2 years of PCI into groups A (patients who experienced gastrointestinal bleeding within 2 years after PCI) and B (patients who did not experience gastrointestinal bleeding). Results Groups A and B included 21 (4.1%) and 494 (95.9%) patients, respectively (a total of 515 patients). Age at the initial PCI (77.8±2.4 and 72.0±0.5 years in groups A and B, respectively; p = 0.02), weight (53.8±3.2 and 61.8±0.7 kg in groups A and B, respectively; p = 0.01), and concomitant warfarin use (14.3% and 2.0% in groups A and B, respectively; p = 0.0005) were significantly different between the groups. The high bleeding risk rate (90.5% and 47.6% in groups A and B, respectively; p = 0.0001) was significantly different between the groups. A total of 95.9% of patients were taking PPIs or PCAB without significant differences between the groups. However, only one patient, who was taking steroids, had a gastric ulcer during PCAB treatment. Conclusions Acid-related upper gastrointestinal bleeding is largely controlled by PPIs in post-PCI patients. Furthermore, the risk factors for non-acid-related bleeding include older age, lower weight, and concomitant warfarin use.

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Objective:. To determine the magnitude of the perioperative costs associated with robotic gastrectomy (RG). Background:. A robotic surgery platform has a high implementation cost and requires maintenance costs; however, whether the overall cost of RG, including all perioperative costs, is higher than conventional open gastrectomy (OG) remains unknown. Methods:. Patients who underwent a major gastrectomy during February 2018 through December 2021 were retrospectively identified. We calculated the perioperative costs of RG and OG and compared them overall as well as in different phases, including intraoperative costs and 30-day postsurgery inpatient and outpatient costs. We investigated factors potentially associated with high cost and estimated the likelihood of RG to reduce overall cost under a Bayesian framework. All cost data were converted to ratios to the average cost of all operations performed at our center in year FY2021. Results:. We identified 119 patients who underwent gastrectomy. The incidence of postoperative complications (Clavien-Dindo >IIIa; RG, 10% vs OG, 13%) did not significantly differ between approaches. The median length of stay was 3 days shorter for RG versus OG (4 vs 7 days, P < 0.001). Intraoperative cost ratios were significantly higher for RG (RG, 2.6 vs OG, 1.7; P < 0.001). However, postoperative hospitalization cost ratios were significantly lower for RG (RG, 2.8 vs OG, 3.9; P < 0.001). Total perioperative cost ratios were similar between groups (RG, 6.1 vs OG, 6.4; P = 0.534). The multiple Bayesian generalized linear analysis showed RG had 76.5% posterior probability of overall perioperative cost reduction (adjusted risk ratio of 0.95; 95% credible interval, 0.85–1.07). Conclusions:. Despite increased intraoperative costs, total perioperative costs in the RG group were similar to those in the OG group because of reduced postoperative hospitalization costs.

Background and aimUstekinumab, a new anti-interleukin-12/23 antibody, is an effective treatment for ulcerative colitis; however, data regarding predictive factors of its efficacy are limited. Predicting treatment efficacy in advance would be useful for selecting a therapeutic agent. This study aimed to identify biomarkers that can predict the long-term outcome of ustekinumab treatment.Materials and methodsWe retrospectively reviewed the records of patients with active ulcerative colitis treated with ustekinumab at Osaka Medical and Pharmaceutical University Hospital from June 2020 to January 2023. We divided patients into non-remission and remission groups, and examined whether baseline biomarkers, including C-reactive protein-to-lymphocyte ratio, and early treatment response could predict clinical remission at week 48 of ustekinumab treatment.ResultsOf the 33 patients included in the study, 21 (63.6%) were in clinical remission at week 48 of ustekinumab treatment. Baseline C-reactive protein-to-lymphocyte ratio values were significantly higher in the non-remission than in the remission group. The baseline C-reactive protein-to-lymphocyte ratio value was identified as an independent prognostic factor for clinical remission at week 48 (odds ratio: 10, 95% confidence interval: 1.6-62.4, p = 0.014), with the cutoff value of 3.353 showing excellent prognostic performance (sensitivity: 71.4%, specificity: 83.3%). Furthermore, the clinical response at week 4 (odds ratio: 10, confidence interval: 1.78-56.1, p = 0.009) and that at week 8 (odds ratio: 12, confidence interval: 2.16-66.5, p = 0.005) were significantly associated with clinical remission at week 48.ConclusionsThe baseline C-reactive protein-to-lymphocyte ratio value and early treatment response are useful biomarkers to predict the long-term efficacy of ustekinumab treatment.

Abstract Background The current standard operation for proximal gastric and gastroesophageal junction (P/GEJ) cancers with limited esophageal extension is total gastrectomy (TG). TG is associated with impaired appetite and weight loss due to the loss of gastric functions such as production of ghrelin and with anemia due to intrinsic factor loss and vitamin B12 malabsorption. Theoretically, proximal gastrectomy (PG) can mitigate these problems by preserving gastric function. However, PG with direct esophagogastric reconstruction is associated with severe postoperative reflux, delayed gastric emptying, and poor quality of life (QoL). Minimally invasive PG (MIPG) with antireflux techniques has been increasingly performed by experts but is technically demanding owing to its complexity. Moreover, the actual advantages of MIPG over minimally invasive TG (MITG) with regards to postoperative QoL are unknown. Our overall objective of this study is to determine the short-term QoL benefits of MIPG. Our central hypotheses are that MIPG is safe and that patients have improved appetite after MIPG with effective antireflux techniques, which leads to an overall QoL improvement when compared with MITG. Methods Enrollment of a total of 60 patients in this prospective survey-collection study is expected. Procedures (MITG versus MIPG, antireflux techniques for MIPG [double-tract reconstruction versus the double-flap technique]) will be chosen based on surgeon and/or patient preference. Randomization is not considered feasible because patients often have strong preferences regarding MITG and MIPG. The primary outcome is appetite level (reported on a 0-10 scale) at 3 months after surgery. With an expected 30 patients per cohort (MITG versus MIPG), this study will have 80% power to detect a one-point difference in appetite level. Patient-reported outcomes will be longitudinally collected (including questions about appetite and reflux), and specific QoL items, body weight, body mass index and ghrelin, albumin, and hemoglobin levels will be compared. Discussion Surgeons from the US, Japan, and South Korea formed this collaboration with the agreement that the surgical approach to P/GEJ cancers is an internationally important but controversial topic that requires immediate action. At the completion of the proposed research, our expected outcome is the establishment of the benefit and safety of MIPG. Trial registration This trial was registered with Clinical Trials Reporting Program Registration under the registration number NCI-2022–00267 on January 11, 2022, as well as with ClinicalTrials.gov under the registration number NCT05205343 on January 11, 2022.

We investigated the factors associated with the success of switching to faricimab for type 1 macular neovascularization (MNV) refractory to intravitreal aflibercept (IVA). This retrospective cohort study included patients with type 1 MNV who were switched to faricimab because they were refractory to IVA at two centers. The primary endpoint was a more than two-week extension of the treatment interval after 6 months. In addition, factors related to the success or failure of extension and visual and anatomical outcomes were assessed. The analysis included 43 eyes from 43 patients. Extended dosing intervals of >2 weeks were identified in 14 eyes (32.6%). A short dosing interval before switching, absence of polypoidal lesions, and thin central choroidal thickness before switching were identified as factors involved in successful extension. For patients with refractory type 1 MNV, switching to faricimab is a safe and potential option to extend existing dosing intervals.

Application of segment-structured tetrahedral amorphous carbon (ta-C) film on soft metal substrate is proposed to improve wear resistance of mechanical parts. It was generally considered that continuous structure ta-C film was effective when applied to hard materials because it could not follow deformation of substrate material and the film tended to delaminate. In contrast, by applying segment structure on ta-C film, tribological properties of ta-C film coated on soft substrate were further improved, and sliding surface exhibited excellent wear resistance even under high sliding loads. Effectiveness of the use of brass substrate in improving wear resistance was demonstrated through large-scale wear resistant test of valve-plate used in oil pump of construction machine. Segment-structured ta-C coated brass valve-plate reduced maximum wear by approximately 80 % as compared with uncoated brass plate.

Abstract The appropriate timing of treatment cessation after treat and extend (TAE) regimen for age-related macular degeneration has not been established. This study aimed to investigate the incidence and risk factors of recurrence after cessation of the TAE regimen. We included patients who received and discontinued the TAE regimen, after extension of the treatment interval to ≥ 12 weeks. Forty-nine patients were included in the study. The estimated recurrence rates were 33% at 1 year and 48% at 2 years after treatment cessation, respectively. Good visual acuity at cessation and a large number of injections in the 6 months before cessation were significant risk factors. Higher chances of recurrence were associated with

Diamond-like carbon (DLC) films had been formed as a surface treatment for intracorporal device for decreasing the coefficient of friction. DLC film showed significant stability without being damaged during acid immersion and high-pressure steam sterilization. However, bacteria that adhere to medical devices lead to the induction of infectious diseases associated with therapeutic actions. Therefore, maintenance of a hygienic surface condition has been strictly required. This study demonstrated the fabrication of DLC films (gas source: CH4), which incorporated Cu (Cu-DLC). The Cu-DLC films were synthesized on a Si (100) substrate via plasma-enhanced chemical vapor deposition and magnetron sputtering. The surface morphology, microstructure, element contents, wear resistance, hardness, and antibacterial properties of the films were experimentally analyzed. Cu particles were considered not uniformly distributed in the DLC film, they embedded in DLC films formed a three-dimensional structure led to higher roughness. The Cu-DLC exhibited wear resistance and higher hardness compared to Cu. After inoculation, Cu-DLC films showed higher antibacterial activity against E. coli than pure DLC. It is expected that the hygienic films with excellent mechanical properties demonstrated in the present study will be utilized in various medical and industrial sectors.

Background: In recent years, various biomarkers of ulcerative colitis (UC) have emerged; however, few studies have simultaneously examined the utility of multiple biomarkers for monitoring disease activity. Additionally, serum leucine-rich alpha-2 glycoprotein (LRG), a new biomarker, may show a blunt response to anti-TNF antibody therapy. This prospective study explored effective biomarkers that could monitor disease activity changes in patients with UC. In addition, we examined the effect of anti-TNF antibody therapy on changes in LRG. Methods: Blood and stool samples were collected twice from patients with UC: at baseline and at least 8 weeks later. Changes in serum LRG, interleukin (IL)-6, prealbumin (pre-Alb), high-sensitivity C-reactive protein (hs-CRP), CRP, and fecal calprotectin (FC) were measured and correlated with changes in disease activity. The relationship between anti-TNF antibody therapy and LRG levels was also examined in patients with the same disease activity. Results: Forty-eight patients with UC (96 samples) were analyzed. ΔLRG and ΔIL-6 correlated strongly with the change in the partial Mayo (pMayo) score between the two time points (ΔpMayo) (r = 0.686, 0.635, respectively). In contrast, FC and IL-6 were particularly accurate predictors of clinical remission, and their area under the curves (AUCs) were significantly higher than that of CRP (AUC: 0.81, 0.76 vs. 0.50; p = 0.001, 0.005). No association was found between the administration of anti-TNF antibody preparations and the LRG values. Conclusions: Correlations were found between changes in UC disease activity and LRG, IL-6, pre-Alb, hs-CRP, CRP, and FC. LRG reflects disease activity during anti-TNF antibody therapy.

In gastroesophageal junction (GEJ) adenocarcinoma cases, a prognosis based on ypTNM staging could be affected by preoperative therapy. Patients with esophageal adenocarcinoma and gastric adenocarcinoma who underwent preoperative therapy followed by surgical resection from 2006 through 2017 were identified in the National Cancer Database. To enable stage-by-stage OS comparisons, tumors were classified into four gross ypTNM groups: ypT1/2, N-negative; ypT1/2, N-positive; ypT3/4, N-negative; and ypT3/4, N-positive. Prognostic factors were examined, and an OS prediction nomogram was developed for patients with abdominal/lower esophageal and gastric cardia adenocarcinoma, representing GEJ cancers. We examined 25,463 patient records. When compared by gross ypTNM group, the abdominal/lower esophageal and gastric cardia adenocarcinoma groups had similar OS rates, differing from those of other esophageal or gastric cancers. Cox regression analysis of patients with GEJ cancers showed that preoperative chemoradiotherapy was associated with shorter OS than preoperative chemotherapy after adjustment for the ypTNM group (hazard ratio 1.31, 95% CI 1.24–1.39, p < 0.001), likely owing to downstaging effects. The nomogram had a concordance index of 0.833 and a time-dependent area under the curve of 0.669. OS prediction in GEJ adenocarcinoma cases should include preoperative therapy regimens. Our OS prediction nomogram provided reasonable OS prediction for patients with GEJ adenocarcinoma, and future validation is needed.

Background: Tacrolimus (TAC) effectively induces remission in refractory ulcerative colitis (UC). However, TAC therapy usually lasts for 3 months. Although azathioprine (AZA) is often used in maintenance therapy, the relapse rate remains high. Herein, we evaluated the efficacy of adalimumab (ADA) for remission maintenance in patients with UC after induction therapy with TAC. Methods: We prospectively enrolled patients with moderate-to-severe UC who achieved clinical remission after 3 months of TAC therapy with endoscopic non-mucosal healing (Cohort A). After TAC discontinuation, the remission maintenance rate up to 1 year after starting ADA therapy was examined. We retrospectively enrolled patients with UC treated with TAC (Cohort B). Among patients in clinical remission after TAC treatment for 3 months, those who received AZA as remission maintenance therapy after TAC discontinuation constituted the AZA group. Patients in Cohort A who received ADA and AZA as remission maintenance therapy after TAC discontinuation constituted the ADA + AZA group. We compared the remission maintenance rates in the AZA and ADA + AZA groups for up to 5 years after TAC discontinuation. Results: In Cohort A, of the 46 patients with UC treated with TAC, 17 were eligible for analysis after receiving ADA as remission maintenance therapy. A notable 88.2% (15/17) were still in remission 1 year after starting ADA. The ADA + AZA group (n = 16) exhibited a significantly higher relapse-free rate than the AZA group (n = 26) (p < 0.05; log-rank test). Conclusion: switching to ADA for remission maintenance in patients with refractory UC who achieved clinical remission with TAC is clinically useful.

Epithelial-mesenchymal plasticity (EMP) refers to the reversible cellular transition between epithelial and mesenchymal status. Spontaneous EMP is also reported in breast and prostate cancer, leading to the acquisition of stem-cell properties and chemoresistance. However, the presence of spontaneous EMP is still not reported in esophageal cancer. We screened 11 esophageal squamous cancer cell (ESCC) cell lines by CD44 isoform expression. KYSE520 was found to comprise heterogenous populations consisting of CD44v+ and CD44v– subpopulations. CD44v+ and CD44v– cells showed the expression of epithelial and mesenchymal markers, respectively. Single-cell sorting of CD44v+ and CD44v– cells revealed both cells gave rise to cell populations consisting of CD44v+ and CD44v– cells, indicating CD44v+ epithelial-like and CD44v− mesenchymal-like cells can generate counterparts, respectively. The ablation of Epithelial splicing regulatory protein 1 (ESRP1), a major regulator of CD44 mRNA splicing, resulted in the shift from CD44v+ to CD44v– cells in KYSE520. However, the expression of epithelial-mesenchymal transition (EMT)-related markers or transcriptional factors were almost not affected, suggesting ESRP1 functions downstream of EMP. Our results revealed the presence of spontaneous EMP in esophageal cancer and KYSE520 is useful model to understand spontaneous EMP.

Abstract Whipple's disease is a systemic chronic bacterial infection caused by Tropheryma whipplei, a gram‐positive bacillus. T. whipplei infection in the small intestine often causes malabsorption and is often accompanied by gastrointestinal symptoms such as diarrhea and abdominal pain. In this report, we describe our experience with a case of Whipple's disease in which the affected patient did not have the typical gastrointestinal symptoms. The patient was an 80‐year‐old male who presented with complaints of weight loss and lower leg edema due to malabsorption and shortness of breath during exertion. A blood test revealed a decreased albumin level and an elevated C‐reactive protein level. Endoscopic images revealed diffuse white villi, the presence of which extended from the duodenum to the upper jejunum. We made a diagnosis of Whipple's disease based on pathological findings associated with the duodenum, electron microscopic findings, and findings of polymerase chain reaction (PCR) tests (performed using mucosal tissue). Clinical symptoms and endoscopic findings improved with antibiotics. Real‐time PCR tests were performed for a quantitative evaluation of the effect of treatment. Endoscopy is useful for diagnosing Whipple's disease when there is an absence of gastrointestinal symptoms, and hypoalbuminemia of unknown etiology is observed.

Abstract Background Frailty results in a high risk for disability, hospitalization, and mortality. This study aimed to investigate perioperative details of frail patients who underwent pancreatectomy and whether frailty can be a predictive factor of postoperative complications, especially of clinically relevant postoperative pancreatic fistula (CR-POPF). Methods This retrospective study included patients who underwent pancreatectomy in our hospital between August 2016 and March 2019. The patients were divided into frail and pre-/non-frail groups. The diagnostic criteria were based on the Japanese version of the Cardiovascular Health Study. Results Of 93 patients, 11 (11.8%) and 82 (88.2%) were frail and pre-/non-frail patients, with median ages of 82 and 72 years, respectively (p = 0.041). Postoperative complications (Clavien-Dindo ≧ IIIa) were found in 8 and 32 patients (p = 0.034), CR-POPF in 3 and 13 patients (p = 0.346), and postoperative hospital stays were 21 and 17 days (p = 0.041), respectively. On multivariate analysis, frailty was an independent predictive factor (odds ratio [OR] 5.604, 95.0% confidence interval [CI] 1.002-30.734; p = 0.047) of postoperative complications (Clavien-Dindo ≧ IIIa) after pancreaticoduodenectomy. On multivariate analysis, a soft pancreas (OR 5.696, 95.0% CI 1.142-28.149; p = 0.034) was an independent and significant predictive factor of CR-POPF after pancreaticoduodenectomy. Conclusions Frailty may be a useful predictive factor of postoperative complications in patients undergoing pancreaticoduodenectomy.

A certain number of patients with ulcerative colitis (UC) are refractory to anti-TNF-α antibodies; biomarkers are thus needed to predict treatment efficacy. This study aimed to evaluate whether serum biomarkers that were reported to be associated with UC or anti-TNF-α antibody could predict the response to golimumab, a human anti-TNF-α monoclonal antibody, in bio-naïve patients with UC. We prospectively enrolled 23 consecutive patients with UC who were treated with golimumab. Serum samples were collected before the first golimumab dose. Eleven molecules were measured by electrochemiluminescence (ECL) or enzyme-linked immunosorbent assay (ELISA) and their association with efficacy after 10 weeks of golimumab treatment. Among the serum biomarkers, IL-13 levels were significantly higher in the non-remission group than in the remission group (p = 0.014). IL-15 levels were significantly lower in the non-response group than in the response group (p = 0.04). For clinical remission at week 10, the IL-13 0.20 concentration of pg/mL was associated with a sensitivity and specificity of 82.4% and 83.3%, respectively. Serum IL-13 may be a biomarker to predict golimumab efficacy in biologic-naïve patients with UC, and thus may help to tailor personalized treatment strategies.

Eosinophilic gastroenteritis is an eosinophilic inflammatory disease that responds well to steroids but often relapses upon their discontinuation, necessitating maintenance treatment. The anti–interleukin-5 antibody mepolizumab is useful for treating bronchial asthma and eosinophilic polyangiitis granulomatosa, and its efficacy in eosinophilic esophagitis has also been investigated. However, there are few reports of cases of eosinophilic gastroenteritis treated with mepolizumab. Here we report a case of steroid-dependent eosinophilic enteritis associated with asthma treated with mepolizumab that was maintained in steroid-free remission.

Concentrated polymer brush (CPB) is the polymer film with a structure that possesses greatly extended polymer chains densely grafted to substrate. CPB is known to swell in good solvents, which have high affinity for the polymer. Swollen CPB by a good solvent shows excellent micro-tribological properties such as super lubrication with the extremely low friction coefficient (μ~10-4). However, macro-tribological properties of CPB surface on steel have not been explored sufficiently. In this study, macroscopic tribological properties of a CPB on rough steel were evaluated using a block-on-ring type tribo-tester under lubrication with an ionic liquid. The CPB showed a significant friction reduction effect with the low friction coefficient of 0.005 on macroscale.

Abstract Background We aimed to investigate how high-dose ecabet sodium affects low-dose aspirin-induced small intestinal mucosal injury in healthy volunteers. Methods Healthy volunteers were enrolled randomly into one of two groups with the following drug regimens for 2 weeks: group A, low-dose aspirin once per day and group B, low-dose aspirin and 4.0 g of ecabet sodium. Small bowel capsule endoscopy was performed before and 2 weeks after low-dose aspirin administration. Results A significant difference was found in the median number [range] of small intestinal lesions between baseline and two weeks after low-dose aspirin administration in group A (baseline: 1 [0–5], after: 5 [1–11]; p = 0.0059) but not in group B (baseline: 0.5 [0–9], after: 3 [0–23]; p = 0.0586). In group B, although the median number [range] of lesions in the first tertile of the small intestine did not increase two weeks after low-dose aspirin administration (baseline: 0 [0–4], after: 1.5 [0–8]; p = 0.2969), the number of lesions in the second and third tertiles of the small intestine increased significantly (baseline: 0 [0–5], after: 2 [0–15]; p = 0.0469). Conclusions Ecabet sodium had a preventive effect on low-dose aspirin-induced small intestinal mucosal injury in the upper part of the small intestine. Trial registration ISRCTN 99322160, 01/10/2018.

The graphitization process of a tetrahedral amorphous carbon (ta-C) film under lubrication was investigated using a laboratory-built in situ Raman tribometer. The coating was lubricated with poly-alpha-olefin (PAO), PAO with an added friction modifier (FM), glycerol mono-oleate (GMO). Friction tests were carried out using a ball-on-disk setup, in which a 19-mm diameter ta-C-coated ball was loaded and rubbed against a steel disk that was immersed in a lubricant solution. In situ optical microscopy and Raman spectroscopy were used to monitor the graphitization process and wear tracks of the ta-C-coated ball. Raman analysis was conducted on the rubbed surface of the rotating ta-C-coated ball when it was located under an objective lens every three minutes during sliding. In this study, the degree of graphitization of the ta-C surface was estimated by calculating the intensity ratio of the D-peak and G-peak (ID/IG) in the Raman spectra of the ta-C film during friction tests with different lubricants. All our results suggest that the friction modifier inhibits the progression of graphitization of DLC films by reducing friction, in other words, reducing the contact temperature, and the wear progression of DLC films under boundary lubrication can be induced by graphitization of DLC surfaces at the sliding contact.

The effects of the molecular structure of zinc dialkyldithiophosphates (ZDDPs) on the tribological properties of a hydrogenated amorphous carbon (a-C:H) film under boundary lubrication were investigated. Friction tests were performed at a-C:H/a-C:H and steel/steel contacts under lubrication with poly-alpha olefin (PAO) and PAO containing five types of ZDDPs with different alkyl groups (primary-C4 ZDDP, secondary-C4 ZDDP, primary-C6 ZDDP, primary-C8 ZDDP and primary-C12 ZDDP). All our results suggest that the structure of the alkyl chain of ZDDPs strongly influence the tribological properties of the a-C:H/a-C:H and steel/steel tribopairs lubricated with ZDDP solutions.

Abstract Background Intertumoral heterogeneity represents a significant hurdle to identifying optimized targeted therapies in gastric cancer (GC). To realize precision medicine for GC patients, an actionable gene alteration-based molecular classification that directly associates GCs with targeted therapies is needed. Methods A total of 207 Japanese patients with GC were included in this study. Formalin-fixed, paraffin-embedded (FFPE) tumor tissues were obtained from surgical or biopsy specimens and were subjected to DNA extraction. We generated comprehensive genomic profiling data using a 435-gene panel including 69 actionable genes paired with US Food and Drug Administration-approved targeted therapies, and the evaluation of Epstein-Barr virus (EBV) infection and microsatellite instability (MSI) status. Results Comprehensive genomic sequencing detected at least one alteration of 435 cancer-related genes in 194 GCs (93.7%) and of 69 actionable genes in 141 GCs (68.1%). We classified the 207 GCs into four The Cancer Genome Atlas (TCGA) subtypes using the genomic profiling data; EBV (N = 9), MSI (N = 17), chromosomal instability (N = 119), and genomically stable subtype (N = 62). Actionable gene alterations were not specific and were widely observed throughout all TCGA subtypes. To discover a novel classification which more precisely selects candidates for targeted therapies, 207 GCs were classified using hypermutated phenotype and the mutation profile of 69 actionable genes. We identified a hypermutated group (N = 32), while the others (N = 175) were sub-divided into six clusters including five with actionable gene alterations: ERBB2 (N = 25), CDKN2A, and CDKN2B (N = 10), KRAS (N = 10), BRCA2 (N = 9), and ATM cluster (N = 12). The clinical utility of this classification was demonstrated by a case of unresectable GC with a remarkable response to anti-HER2 therapy in the ERBB2 cluster. Conclusions This actionable gene-based classification creates a framework for further studies for realizing precision medicine in GC.

Hydrogenated amorphous carbon (a-C:H) films have optical and electrical properties that vary widely depending on deposition conditions; however, the electrical conduction mechanism, which is dependent on the film structure, has not yet been fully revealed. To understand the relationship between the film structure and electrical conduction mechanism, three types of a-C:H films were prepared and their film structures and electrical properties were evaluated. The sp2/(sp2 + sp3) ratios were measured by a near-edge X-ray absorption fine structure technique. From the conductivity–temperature relationship, variable-range hopping (VRH) conduction was shown to be the dominant conduction mechanism at low temperatures, and the electrical conduction mechanism changed at a transition temperature from VRH conduction to thermally activated band conduction. On the basis of structural analyses, a model of the microstructure of a-C:H that consists of sp2 and sp3-bonded carbon clusters, hydrogen atoms and dangling bonds was built. Furthermore, it is explained how several electrical conduction parameters are affected by the carrier transportation path among the clusters.

Diamond-like carbon (DLC) films have attracted considerable interest for application as protective films in diverse industrial parts. This is attributed to their desirable characteristics, such as high hardness, low coefficient of friction, gas-barrier properties, and corrosion resistance. Antiseizure properties, in addition to wear resistance, are required during the die molding of polymer and polymer-matrix composite parts. Graphite films can be easily peeled because the vertically stacked graphene sheets are bonded via weak van der Waals forces. The present study demonstrates the fabrication of multilayered DLC/Cu films, where the Cu film functions as a catalyst for the formation of a graphite-like layer between the DLC and Cu films. The DLC/Cu film was synthesized on a Si (100) substrate via plasma-enhanced chemical vapor deposition and magnetron sputtering. The peelability, wear resistance, microstructure, texture, and cross-section of the film were experimentally analyzed. The results indicated a variation in the peelability with the deposition conditions of the Cu film that comprised particles with diameters of several nanometers. The DLC film at the interface in contact with the Cu film was transformed into a graphite-like state i.e., graphitized. The surface of the multilayered film exhibited antiseizure properties with the peeling of the upper DLC film. The multilayered film also exhibited wear resistance owing to the repeated appearances of a new DLC film. It is expected that the wear-resistant films with antiseizure properties demonstrated in the present study will be utilized in various industrial sectors.

BACKGROUND AND AIM:Autophagy is an essential process involved in the pathogenesis of inflammatory bowel disease (IBD). Although there are many data showing the roles of autophagy in intestinal epithelial cells (IECs), the mechanisms involved remain to be fully elucidated. We investigated the influence of autophagy in IECs on gastrointestinal tract inflammation. METHODS:Mice with conditional knockout of Atg5 in IECs (Atg5flox/flox/villin-Cre mice) were subjected to dextran sulfate sodium (DSS)-induced colitis and analyzed for colitis susceptibility. Additionally, we used Atg5-silenced rat IECs (IEC6shAtg5 cells) for in vitro assays. RESULTS:Sensitivity to DSS markedly increased in Atg5flox/flox/villin-Cre mice compared to that in wild-type mice. In IEC6shAtg5 cells, apoptosis was enhanced, and cell viability significantly decreased compared to IEC-6 cells. The expression of proinflammatory cytokines increased upon suppression of autophagy. Furthermore, silencing of Atg5 was associated with inflammation of IECs, activation of the mitogen-activated protein kinase (MAPK) signaling pathway by the intracellular reactive oxygen species accumulation, and NF-κB p65 phosphorylation. CONCLUSIONS:Autophagy in IECs plays an essential role in the maintenance of intestinal homeostasis, and autophagy deficiency triggers inflammation. Development of methods targeting autophagy might be beneficial in the treatment of IBD.

Amorphous boron carbon nitride (a-BCN) films exhibit excellent properties such as high hardness and high wear resistance. However, the correlation between the film structure and its mechanical properties is not fully understood. In this study, a-BCN films were prepared by an arc-sputtering hybrid process under various coating conditions, and the correlations between the film’s structure and mechanical properties were clarified. Glow discharge optical emission spectroscopy, X-ray photoelectron spectroscopy, Fourier-transform infrared spectroscopy, and Raman spectroscopy were used to analyze the structural properties and chemical composition. Nanoindentation and ball-on-disc tests were performed to evaluate the hardness and to estimate the friction coefficient and wear volume, respectively. The results indicated that the mechanical properties strongly depend on the carbon content in the film; it decreases significantly when the carbon content is

Lightweight Al-Si alloy is expected as a substitute material for the cast iron of engine parts to improve fuel consumption of automobiles. In this study, the tribological properties of Al-Si alloys against diamond-like carbon (DLC) films were examined to comprehend the influences of Si particles on Al-Si alloy surfaces under lubricated with a fully formulated oil. Sliding tests were performed with a hydrogenated amorphous carbon (a-C:H) film coated steel cylinder against the five kind of Al-Si alloy disks with different Si contents. Sliding tests and surface analysis results showed that the friction coefficient of a-C:H/Al-Si tribo-pairs depended on the exposure height of Si particles on the Al-Si alloy surfaces rather than the area ratio of Si particles. The exposure height of Si particles plays important roles in determining the frictional properties of a-C:H/Al-Si tribo-pairs under lubrication with the fully formulated oil.