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Abstract Introduction Mutated human epidermal growth factor receptor 2 (HER2) is an oncogene with critical pathogenic roles in breast cancer. HER2-low-positive breast cancer is a recently described subtype. We aimed to explore the clinical and molecular characteristics of gastric cancer with low HER2 expression, drawing on recent developments in breast cancer subtypes. Materials and methods This retrospective study involved 129 patients with HER2-non-amplified gastric cancer treated in Iwate prefectural Iwai Hospital from 2013 to 2019. Tumors were classified as HER2-null or low-positive based on immunohistochemistry score 0 or 1 + or 2 + with HER2 negativity in situ hybridization, respectively. Statistical analyses, including Kaplan–Meier analyses and Cox proportional hazards model were conducted. Results Low HER2 expression was present in 26% (33/129) of the patients. Clinicopathological characteristics were not significantly different between the HER2-low and null groups. Kaplan–Meier analysis of overall survival was significantly longer in the HER2-low group than in the HER2-null group (P = 0.01). In multivariate Cox regression analysis, HER2-null status was associated with worse survival (hazard ratio 3.01; 95% confidence interval 1.18–7.65; and P = 0.02). Conclusion This study highlights the prognostic importance of low HER2 expression in gastric cancer, similar to that observed in HER2-low-positive breast cancer, and suggests reclassification of gastric cancer to improve personalized treatment. Future studies should elucidate the molecular underpinnings of low HER2 expression in gastric cancer to guide novel therapeutic strategies and improve outcomes.

Abstract The current study aimed to identify the indications for manual reduction in incarcerated obturator hernias (OH). Further, whether time to symptom onset and manual reduction outcomes can be predictors of bowel viability and the need for bowel resection in incarcerated OH were examined. This retrospective study included 26 patients with incarcerated OH who underwent surgery. All patients underwent manual reduction, and computed tomography scan after manual reduction confirmed hernia release. Multivariate analyses were performed to determine the predictors of bowel resection. The bowel resection group had a significantly longer average time to symptom onset than the nonbowel resection group (88 vs 36 h). Further, the bowel resection group was more likely to have failed manual reduction than the nonbowel resection group. A time to symptom onset of ≥ 72 h and failed manual reduction were significant predictors of bowel viability. Age, sex, hernia localization, American Society of Anesthesiologists physical status score, and laboratory findings did not differ significantly between the bowel resection and nonbowel resection groups. Time to symptom onset and manual reduction outcomes are significant predictors of bowel viability in incarcerated OH. Patients with a time to symptom onset of ≥ 72 h and failed manual reduction require surgical evaluation due to a high risk of bowel nonviability. Therefore, a cautious approach is required in the management of OH, and further research on optimized treatment protocols should be conducted.

Abstract Emergent surgery is a common approach for incarcerated obturator hernias, with high morbidity and mortality rates. Moreover, there have been reports of elective surgery cases after noninvasive manual reduction. For a decade, the initial approach in our institution is also manual reduction unless bowel viability is poor. This study aimed to clarify the efficacy and safety of manual reduction followed by elective surgery. We retrospectively reviewed 50 cases of incarcerated obturator hernia from 2010 to 2022 at Iwate Prefectural Iwai Hospital. Manual reduction was attempted in 31 (62%) patients. The reduction was successful in 21 (42%) patients, and most of them received mesh repair using the extraperitoneal approach as elective surgery. However, two patients underwent emergent surgery in the waiting period because of late-onset constriction and a small bowel perforation. Patients with irreducible hernia underwent emergent surgery, except for two patients who received the best supportive care. Postoperative complications were observed in 5% and 22% of reducible and irreducible cases, respectively. Postoperative mortality was zero in both groups. Manual reduction is useful in some cases, but careful observation is needed because late-onset constriction and perforation could occur.

Abstract Oxidative stress increases the production of the predominant mucin MUC5AC in airway epithelial cells and is implicated in the pathogenesis of bronchial asthma and chronic obstructive pulmonary disease. Oxidative stress impairs mitochondria, releasing mitochondrial DNA into the cytoplasm and inducing inflammation through the intracytoplasmic DNA sensor STING (stimulator of interferon genes). However, the role of innate immunity in mucin production remains unknown. We aimed to elucidate the role of innate immunity in mucin production in airway epithelial cells under oxidative stress. Human airway epithelial cell line (NCI‐H292) and normal human bronchial epithelial cells were used to confirm MUC5AC expression levels by real‐time PCR when stimulated with hydrogen peroxide (H2O2). MUC5AC transcriptional activity was increased and mitochondrial DNA was released into the cytosol by H2O2. Mitochondrial antioxidants were used to confirm the effects of mitochondrial oxidative stress where antioxidants inhibited the increase in MUC5AC transcriptional activity. Cyclic GMP‐AMP synthase (cGAS) or STING knockout (KO) cells were generated to investigate their involvement. H2O2‐induced MUC5AC expression was suppressed in STING KO cells, but not in cGAS KO cells. The epidermal growth factor receptor was comparably expressed in STING KO and wild‐type cells. Thus, mitochondria and STING play important roles in mucin production in response to oxidative stress in airway epithelial cells.

Background: Penetration of the thyroid gland by a fish bone is rare, and there is no literature describing a patient with hyperthyroidism at initial examination in whom the thyroid gland was penetrated by a fish bone. Case presentation: A 51-year-old woman visited our hospital with left-sided neck pain. She had sensed a foreign body in her throat when eating a fish the previous day, but no abnormality was found by endoscopy. Blood examination revealed hyperthyroidism, and ultrasonography (US) revealed enlargement of the bilateral lobe with multiple adenomatous nodules and heterogeneous hypoechoic areas. The presumptive diagnosis was subacute thyroiditis, and treatment with prednisolone was initiated. Pain was reduced and tenderness moved to the right lobe. The phenomenon was diagnosed as creeping thyroiditis. However, computed tomography (CT) on day 4 demonstrated a linear hyperdense body in the left lobe. Esophagogastroduodenoscopy was repeated and revealed a fissure at the cervical esophagus. Her condition was then diagnosed as penetration of a fish bone into the thyroid gland. She was treated conservatively with monitoring to observe the course. Inflammatory signs significantly improved, so she was discharged on day 15. Subsequent CT and US did not show the presence of the fish bone. Conclusions: Penetration of the thyroid gland by a fish bone could result in a clinical course resembling subacute thyroiditis. CT and careful endoscopic inspection should be performed for patients with hyperthyroidism if foreign body insertion is not ruled out from the medical history.

Background: Non-IgE-mediated gastrointestinal food allergies (non-IgE-GI-FAs) are one type of food allergy found in neonates and infants. Few reports have defined the severity of non-IgE-GI-FAs in these populations. Methods: Grading scales of the severity of non-IgE-GI-FAs according to extra-GI symptoms, such as poor weight gain, as well as systemic symptoms, including fever and shock, were developed and retrospectively applied to patients with non-IgE-GI-FAs. The relationship between the severity of non-IgE-GI-FAs and both clinical and laboratory findings were examined. Results: Elevation of C-reactive protein levels and a decrease in total protein and albumin were observed in accordance with allergy severity. In an endoscopic examination, inflammatory findings were confirmed in large areas of the colonic mucosa in case of higher severity levels, and infiltration of inflammatory cells other than eosinophils was found in the severest grade. Extensively hydrolyzed milk or amino acid-based milk was required for all patients with the severest grade. In addition, the timing of acquiring tolerance tended to be late for this grade. Conclusions: Classification and determination of the severity of non-IgE-GI-FAs in neonates and infants may not only contribute to elucidation of the pathogenesis but may also be useful in the clinical setting. Keywords: Food hypersensitivity, Gastroenteritis, Infant, Milk, Prognosis

Background and study aims: Delayed gastric emptying (DGE) is an important factor in determining the clinical outcome in patients with stent placement for malignant gastric outlet obstruction but the factors associated with DGE remain unclear. The aim of this study was to investigate whether clinicopathologic data could be used to identify the factors for DGE in such patients. Patients and methods: A prospective, single-arm, observational clinical study was performed in a referral hospital in Japan. A total of 54 patients with stent placement for malignant gastric outlet obstruction were enrolled. A gastric emptying scintigraphy test was performed 1 week after stent placement. The relationship between DGE and clinicopathologic factors was investigated, and also the relationship between DGE and stent patency time, eating period (when the patient was able to maintain oral intake), and survival time. Results: A total of 38.9 % (21 /54) of patients had DGE. The following were identified as independent predictive factors of DGE: opioid use (odds ratio, 5.32; 95 % confidence interval [95 %CI], 1.07 – 26.41; p = 0.04), chemotherapy before stent placement (odds ratio, 8.03; 95 %CI, 1.85 – 34.95; p = 0.006), and smaller stent diameter (odds ratio, 13.59; 95 %CI, 1.72 – 107.41; p = 0.01). No relationship was found between DGE and the level of oral intake, stent patency time, eating period, and survival time. Conclusions: The factors associated with DGE after stent placement include those associated with the patient’s tumor as well as factors relating to their treatment, including stenting. The clinical and functional results after stent placement appear to be unrelated to the gastric emptying findings.

In a curved surface design, the overall shape features that emerge from combinations of shape elements are important. However, controlling the features of the overall shape in curved profiles is difficult using conventional microscopic shape information such as dimension. Herein two types of macroscopic shape information, curvature entropy and quadrature curvature entropy, quantitatively represent the features of the overall shape. The curvature entropy is calculated by the curvature distribution, and represents the complexity of a shape (one of the overall shape features). The quadrature curvature entropy is an improvement of the curvature entropy by introducing a Markov process to evaluate the continuity of a curvature and to approximate human cognition of the shape. Additionally, a shape generation method using a genetic algorithm as a calculator and the entropy as a shape generation index is presented. Finally, the applicability of the proposed method is demonstrated using the side view of an automobile as a design example.

As a mechanical system has larger number of degree-of freedom (DOF) of motion in order to generate diverse behavior, it becomes more difficult to design the control scheme for its motion to achieve a specific function required for the system. This paper proposes a novel design methodology for the control scheme in order to deal with the above-mentioned difficulty. The design methodology proposed is inspired from the concept of emergence observed in living organisms, that is, diverse behavior is emerged to an ultra multi-DOF dynamic system only with a single set of local rules using local information between neighboring subsystems. This study simplifies the ultra multi-DOF system as an 11×11 lattice mass system, neighboring masses are connected with a linear actuator, and aims to prevent a target mass point (control subsystem) from moving even if any external forces are input to the system, which we call this function “displacement controllability.” Hence the P/D gains of the actuators are turned ON/OFF by the proposed local rule for displacement controllability. As a result of computation, the displacement controllability was successfully emerged to the mass system under the various environments, i.e., diverse external force inputs. That means, the diverse behavior dealing with various environments was generated to the system only using the single local rule. Consequently, the effectiveness of the proposed behavior design methodology for an ultra-multi-DOF system was confirmed.

This paper describes a basic study on an emergent design system in which serendipity is exerted from interactions between computer and human. The system is proposed to support idea generation in the early design process. In the early design process, which is composed of conceptual and basic design, new and novel ideas of design should be obtained from global solution search because the design objective and conditions are unclear. Therefore, we propose an emergent design system, which enhances designer's serendipity, intended to support idea generation. Serendipity is a natural ability to unexpectedly make interesting or valuable discoveries. This ability is influenced by designer's experiences and knowledge. The possibility of generating new and novel design ideas will increase if we can utilize serendipity. This emergent design system consists of incidental form generation and representation methods. Based on form organizing phenomenon seen in nature, the system can generate diverse forms. These self-organized forms enable designer's serendipity. Moreover, the designer can add or delete elements of the forms like clay modeling. In this process of modification, the designer will have more chance to get inspiration. We perform elementary experiments of this emergent design system with designers. As a result, we confirm both self-organization and representation methods help designers to generate design ideas with characteristic form by inspiring designer's serendipity. Furthermore, the possibility, that the iterations of these functions propose more opportunities to exert designer's serendipity during the computer-human interactions, is indicated.

The precise role of AMP-activated protein kinase (AMPK), a target of metformin, in pancreatic β cells remains controversial, even though metformin was recently shown to enhance the expression of incretin receptors (GLP-1 and GIP receptors) in pancreatic β cells. In this study, we investigated the effect of AMPK in the regulation of incretin receptors expression in pancreatic islets. The phosphorylation of AMPK in the mouse islets was decreased by increasing glucose concentrations. We showed the expression of incretin receptors in bell-shaped response to glucose. Expression of the incretin receptors in the isolated islets showed higher levels under a medium glucose concentration (11.1 mM) than that under a low glucose concentration (2.8 mM), but was suppressed under a high glucose concentration (22.2 mM). Both treatment with an AMPK inhibitor and DN-AMPK expression produced a significant increase of the incretin receptors expression under a low glucose concentration. By contrast, in hyperglycemic db/db islets, the enhancing effect of the AMPK inhibitor on the expression of incretin receptors was diminished under a low glucose concentration. Taken together, AMPK is involved in the regulation of incretin receptors expression in pancreatic islets under a low glucose concentration.

Background: Perianeurysmal cyst formation after endovascular treatment of cerebral aneurysms is a rare complication; however, the number of reports has gradually increased in recent years due to the development of several endovascular treatments. Case Description: We present a case of delayed perianeurysmal cyst enlargement 8 years after endovascular treatment for multiple recurrences of a large cerebral aneurysm in the anterior communicating artery. The patient presented with obstructive hydrocephalus caused by an enlarged perianeurysmal cyst. The patient underwent cyst fenestration using neuroendoscopy and ventriculoperitoneal shunting, recovered from the clinical symptoms, and had a good prognosis. Histopathological findings showed that the cyst wall contained a fibrotic layer under the monoependymal layer with hemosiderosis without evidence of neovascularization or inflammatory cell infiltration. These findings suggest that the origin of the perianeurysmal cyst wall is not the aneurysm itself but the adjacent brain tissue. Conclusion: Perianeurysmal cysts can develop during long-term follow-up, and clinicians should consider surgical treatment, including cyst fenestration, using neuro-endoscopy if the cyst presents with clinical symptoms. [ABSTRACT FROM AUTHOR]