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Abstract Background Chemotherapy‐induced anorexia is a common occurrence in patients undergoing treatment for advanced lung cancer. However, the relationship between chemotherapy‐induced anorexia and weight loss during platinum‐based chemotherapy combined with immune checkpoint inhibitors is unclear. This study explored the relationship between chemotherapy‐induced anorexia and therapeutic outcomes in patients with stage IV non‐small‐cell lung cancer undergoing platinum‐based chemotherapy combined with immune checkpoint inhibitors. Methods The study retrospectively reviewed the medical records of 106 patients with stage IV non‐small‐cell lung cancer treated with platinum‐based chemotherapy and immune checkpoint inhibitors between January 2019 and October 2022. The incidence of weight loss and its association with treatment efficacy was assessed in the chemotherapy‐induced anorexia group. Chemotherapy‐induced anorexia, nausea, and vomiting were evaluated using Common Terminology Criteria for Adverse Events v 5.0. Progression‐free and overall survival were used to measure treatment efficacy. Results Chemotherapy‐induced anorexia was observed in 13.2% of patients. These patients exhibited significant weight loss at 6 and 9 weeks after treatment initiation compared to those in the non‐chemotherapy‐induced anorexia group. Progression‐free and overall survival were shorter in the chemotherapy‐induced anorexia group than in the non‐chemotherapy‐induced anorexia group, but the difference was not statistically significant. Conclusions Chemotherapy‐induced anorexia was associated with significant weight loss and reduced treatment efficacy in patients with stage IV non‐small‐cell lung cancer. These results highlight the importance of implementing robust supportive care for chemotherapy‐induced anorexia to mitigate weight loss and uphold treatment effectiveness during platinum‐based chemotherapy combined with immune checkpoint inhibitors.

Abstract Background The Mt FUJI study was a multicenter, prospective, randomized, single‐blind, controlled trial comparing delivery catheter‐based and stylet‐based right ventricular (RV) lead placement at the RV septum. This study extended the follow‐up duration to 1 year after implantation. Methods Seventy patients with pacemaker indications for atrioventricular block were randomly assigned to the delivery catheter and stylet groups. We compared the mid‐term efficacy and safety between the two groups at 1 year after implantation. The primary outcome was the change in the left ventricular ejection fraction (LVEF), and the secondary outcomes were changes in brain natriuretic peptide (BNP) levels, lead parameters, paced QRS duration, and the incidence of adverse events. Results At the 1‐year follow‐up, no significant differences were observed in the changes in the LVEF (+1.0% ± 8.6% vs. +3.1% ± 8.1%, p = .332), BNP levels (+8.0 [−11.1, 26.5] pg/mL vs. −8.7 [−15.3, 13.2] pg/mL, p = .193), or lead performance between the delivery catheter and stylet groups. The QRS duration was significantly shorter in the delivery catheter group than in the stylet group (128 ± 23 ms vs. 146 ± 17 ms, p

Abstract A 34‐year‐old woman received umbilical cord blood transplantation for refractory T‐cell prolymphocytic leukemia after salvage therapy with alemtuzumab. She developed right angular cheilitis on the 46th day after transplantation, which worsened after receiving systemic steroid therapy for extensive chronic graft versus host disease. The treatment dosage of acyclovir (ACV), ganciclovir, and vidarabine ointment was not effective due to ACV‐resistant mutations of the herpes simplex virus type 1 (HSV‐1) in the thymidine kinase domain. Foscarnet is expected to be effective against ACV‐resistant HSV‐1 infection. However, it could not be used because the patient developed renal dysfunction. Several viral thymidine kinase mutations related to ACV resistance were found in the patient's sample. Nevertheless, amenamevir, a helicase‐primase complex inhibitor, was effective in our patient who was significantly immunocompromised after allogeneic hematopoietic stem cell transplantation (allo‐HSCT). ACV‐resistant HSV infection after allo‐HSCT is an rare but important complication in the era of low‐dose long‐term ACV prophylaxis. To date, there is no established treatment against ACV‐resistant HSV infection. This case report showed that amenamevir could be a promising treatment option for ACV‐resistant HSV infection in patients with renal failure after allo‐HSCT.

Abstract The singlet fission characteristics of aqueous nanoparticles, self‐assembled from ion pairs of tetracene dicarboxylic acid and various amines with or without chirality, are thoroughly investigated. The structure of the ammonium molecule, the counterion, is found to play a decisive role in determining the molecular orientation of the ion pairs and its regularity, spectroscopic properties, the strength of the intermolecular coupling between the tetracene chromophores, and the consequent singlet fission process. Using chiral amines has led to the formation of crystalline nanosheets and efficient singlet fission with a triplet quantum yield as high as 133% ±20% and a rate constant of 6.99 × 109 s−1. The chiral ion pairs also provide a separation channel to free triplets with yields as high as 33% ±10%. In contrast, nanoparticles with achiral counterions do not show singlet fission, which gave low or high fluorescence quantum yields depending on the size of the counterions. The racemic ion pair produces a correlated triplet pair intermediate by singlet fission, but no decorrelation into two free triplets is observed, as triplet‐triplet annihilation dominates. The introduction of chirality enables higher control over orientation and singlet fission in self‐assembled chromophores. It provides new design guidelines for singlet fission materials.

ABSTRACT Background Mutations in the epidermal growth factor receptor (EGFR) gene are the most common targetable gene alterations in non‐small cell lung cancer (NSCLC). In Japan, approximately 40% of patients who undergo surgical resection for non‐squamous NSCLC have EGFR mutations. However, no long‐term studies have been conducted including a large number of EGFR‐positive NSCLC patients with postoperative recurrence (PR). Methods We conducted a retrospective observational study of the data of EGFR‐positive NSCLC patients with PR who had undergone surgery at the Shizuoka Cancer Center between October 2002 and November 2017. We evaluated post‐recurrence overall survival (PRS) and postoperative overall survival (POS) using the Kaplan–Meier method and identify any associations between the clinical variables at recurrence and PRS using univariate and multivariate analysis. Results We enrolled 162 patients. The median observation time for PRS was 4.95 years (range, 0.82–13.25) and POS was 5.81 years (range, 2.84–16.71). The median PRS was 5.17 years (95% confidence interval [CI], 3.90–5.61) and POS was 7.07 years (95% CI, 5.88–8.01). Univariate analysis identified male sex (median PRS: 3.32 vs. 5.39 years; p

Introduction Patients with hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome have high risks of uterine and cutaneous leiomyomas and renal cell carcinoma (RCC), which are caused by germline mutation of the fumarate hydratase (FH) gene. RCC lesions are mostly high‐grade tumors with a poor prognosis. Case presentation A 37‐year‐old man who had previously undergone treatment for a left RCC was referred to our hospital with a diagnosis of right RCC. Robot‐assisted partial nephrectomy was performed, and the pathological diagnosis revealed fumarate hydratase (FH)‐deficient RCC. The left RCC, which was originally diagnosed as mucinous tubular and spindle cell carcinoma, was reviewed and diagnosed as FH‐deficient RCC. The patient's father and uncle both died of RCC, and the father's tumor was also immunohistochemically proven to be FH‐deficient RCC. Conclusion HLRCC‐related RCC should be considered in a differential diagnosis of young patients with a family history of RCC.

Introduction As an aggressive adenocarcinoma phenotype, primary signet ring cell carcinoma of the urinary bladder is an extremely rare variant. The prognosis of metastatic signet ring cell carcinoma of the urinary bladder is extremely poor and the clinical course for its specific pathogenesis remains unelucidated. Case presentation A 64‐year‐old Japanese male patient was diagnosed with invasive urothelial carcinoma with glandular differentiation of a signet ring cell–type with pT4aN0M0, and he was eventually diagnosed with metastatic signet ring cell carcinoma of the urinary bladder. He was initially responsive to systemic combination induction chemotherapy of S‐1 and cisplatin followed by avelumab switch maintenance therapy; however, signet ring cell carcinoma of the urinary bladder relapse occurred in the pathological findings of a biopsy from the right thigh. Immunohistochemical analysis of this specimen identified strong positive staining for nectin‐4 and, following enfortumab–vedotin treatment, the patient showed a good response. Conclusion We thus describe a rare case of metastatic signet ring cell carcinoma of the urinary bladder with nectin‐4 expression diagnosed by a biopsy of a metastatic site.

Introduction The bladder exstrophy‐epispadias complex is a rare congenital disease. Urothelial carcinomas rarely occur in patients with this disease, and there have been few reports on its treatment. Case presentation We report the case of a 44‐year‐old man with a hemorrhage from the external urethral meatus. He was diagnosed with bladder exstrophy‐epispadias complex and underwent urinary diversion with substitution cystoplasty and Mitrofanoff appendicovesicostomy. Because computed tomography and magnetic resonance imaging suggested invasive bladder carcinoma in the defunctionalized bladder, we performed a cystectomy. The patient was diagnosed with urothelial carcinoma with glandular differentiation. One month after the surgery, nivolumab adjuvant chemotherapy was administered. The patient showed no signs of recurrence or metastasis after the treatment. Conclusion This is the first case of adjuvant nivolumab therapy for urothelial carcinoma with the bladder exstrophy‐epispadias complex.

Abstract Background and Aim Increased liver fibrosis scores (LFS), such as fibrosis‐4 index (FIB‐4) or non‐alcoholic fatty liver disease fibrosis score (NFS), and fatty liver are known risk factors for severe coronavirus disease 2019 (COVID‐19). The purpose of this study was to identify the best scores, which predict the prognosis of COVID‐19. Methods Participants comprised consecutive Japanese COVID‐19 patients admitted to our hospital between February 14, 2020, and April 14, 2021. Multivariate logistic regression analysis was performed to evaluate the relationships between LFS (FIB‐4, NFS, aspartate aminotransferase‐to‐platelet ratio index [APRI], BARD score, and hepatic steatosis index [HSI]) or fatty liver on computed tomography (CT), and severity of COVID‐19. Results Of the 415 patients (mean age, 59 years), 177 patients (42.7%) needed oxygen therapy, 90 patients (21.7%) worsened to severe COVID‐19, and 45 patients (10.8%) died during admission. Multivariate logistic regression analysis showed that increased FIB‐4 and NFS were risk factors for death, severe COVID‐19, and oxygen demand; that increased BARD was a risk factor for severe COVID‐19 and oxygen demand; and that increased APRI and HSI were not risk factors for any status of COVID‐19. Furthermore, increased NFS or BARD and fatty liver were independent risk factors for severe COVID‐19 and oxygen demand. Conclusions This study showed that FIB‐4 and NFS were the best liver fibrosis scores that predicted worse prognosis for COVID‐19, and that increased NFS or BARD and fatty liver evident on CT represented independent risk factors for severe COVID‐19 and oxygen demand.

Abstract Sildenafil, a phosphodiesterase‐5 (PDE5) inhibitor, has been shown to improve insulin sensitivity in animal models and prediabetic patients. However, its other metabolic effects remain poorly investigated. This study examines the impact of sildenafil on insulin secretion in MIN6‐K8 mouse clonal β cells. Sildenafil amplified insulin secretion by enhancing Ca2+ influx. These effects required other depolarizing stimuli in MIN6‐K8 cells but not in KATP channel‐deficient β cells, which were already depolarized, indicating that sildenafil‐amplified insulin secretion is depolarization‐dependent and KATP channel‐independent. Interestingly, sildenafil‐amplified insulin secretion was inhibited by pharmacological inhibition of R‐type channels, but not of other types of voltage‐dependent Ca2+ channels (VDCCs). Furthermore, sildenafil‐amplified insulin secretion was barely affected when its effect on cyclic GMP was inhibited by PDE5 knockdown. Thus, sildenafil stimulates insulin secretion and Ca2+ influx through R‐type VDCCs independently of the PDE5/cGMP pathway, a mechanism that differs from the known pharmacology of sildenafil and conventional insulin secretory pathways. Our results reposition sildenafil as an insulinotropic agent that can be used as a potential antidiabetic medicine and a tool to elucidate the novel mechanism of insulin secretion.

Abstract Anaplastic lymphoma kinase (ALK) fusion gene‐positive lung cancer often shows brain metastasis at initial diagnosis or during the course of treatment. However, molecular‐targeted drugs are known to pass through the blood–brain barrier and present positive effects for central nervous system lesions. There are few reports suggesting how effective molecular‐targeted drug therapy alone is for brain metastasis lesions of ALK fusion‐positive lung cancer, especially after the first use of ALK‐tyrosine kinase inhibitor (TKI) or for bulky brain metastases. A patient in his mid‐fifties with stage IV pleural dissemination developed brain metastases after 10 years of crizotinib use, but showed a complete response after switching to brigatinib. Moreover, a patient in her early sixties with stage III recurrent large brain metastases 5 years after chemoradiation therapy experienced dramatic tumor shrinkage with brigatinib. In each case of ALK fusion gene‐positive lung cancer with brain metastases, brigatinib showed a high efficacy and was well‐tolerated after previous ALK‐TKI and for bulky lesions.

Abstract Background Which patients benefit from the addition of immune checkpoint inhibitors (ICIs) to chemotherapy for small cell lung cancer (SCLC) remains unclear. There have been few reports on the efficacy of ICIs based on conventional immunohistochemical neuroendocrine (NE) markers (synaptophysin, chromogranin A, and neural cell adhesion molecule [NCAM]). In the present study, we aimed to analyze the relationship between the expression of immunohistochemical NE markers and the efficacy of ICIs in patients with extensive disease (ED)‐SCLC, to assess whether conventional NE markers are predictive of ICIs. Methods Patients with untreated ED‐SCLC who received first‐line therapy at the Shizuoka Cancer Center between November 2002 and July 2021 were retrospectively reviewed. We evaluated the efficacy of first‐line chemotherapy according to the expression status of each immunohistochemical NE marker in patients treated with ICI plus chemotherapy (ICI‐chemo group) and with chemotherapy alone (chemo group). Results A total of 227 patients were included in the ICI‐chemo and chemo groups, respectively. The progression‐free survival (PFS) tended to be better in patients in the ICI‐chemo group than those treated with chemotherapy alone in patients with NE marker‐positive SCLC. In particular, it was statistically significant in patients with chromogranin A‐positive SCLC (p = 0.036). In patients with NE marker‐negative SCLC, no significant differences were observed in PFS between the two groups. There were no significant differences in overall survival (OS), regardless of the expression of any conventional NE marker. Conclusion Our study suggests that the efficacy of ICIs in addition to chemotherapy may be poor in patients with NE marker‐negative SCLC.

Introduction Condyloma acuminatum usually occurs in the external genitalia and rarely in the bladder mucosa. Here, we report a case of condyloma acuminatum of the bladder that was detected concurrently with urothelial carcinoma. Case presentation A 42‐year‐old man was referred to our urology department with positive urine cytology for urothelial carcinoma. Cystoscopy revealed a broad‐base nonpapillary bladder tumor. The patient underwent a transurethral resection of the bladder tumor. Pathological examination revealed urothelial carcinoma, high‐grade pT1, and concurrent resection of condyloma acuminatum. DNA was extracted from the paraffin‐embedded transurethral resection of the bladder tumor tissue specimens. HPV11 was detected in condylomas by PCR and in situ hybridization, whereas HPV was not detected in urothelial carcinomas. Conclusion We report a rare case of condyloma acuminatum of the bladder that was concurrently diagnosed with urothelial carcinoma from the same site.

Abstract Background Amrubicin (AMR) regimens have shown efficacy as second‐line treatment in patients with small cell lung cancer (SCLC); however, adverse events such as febrile neutropenia (FN) sometimes preclude their use. Further, the safety and efficacy of AMR with primary prophylactic pegfilgrastim (P‐PEG) have not been sufficiently evaluated. In this study, we evaluated the safety and efficacy of AMR with or without P‐PEG as second‐line chemotherapy for SCLC. Methods We retrospectively reviewed patients with SCLC who received AMR as second‐line chemotherapy at Shizuoka Cancer Center, between December 2014 and November 2021. Based on presence/absence of P‐PEG in their regimen, patients (n = 60) were divided into P‐PEG (n = 21) and non‐P‐PEG groups, and their clinical outcomes were evaluated. Results Median of AMR treatment cycles was five (range: 1–39 cycles) in P‐PEG group and four (range: 1–15 cycles) in non‐P‐PEG group. The incidence of FN (4.8% vs. 30.8%; p = 0.02) and AMR dose reduction because of adverse events (4.8% vs. 25.6%; p = 0.08) were lower in the P‐PEG group than in the non‐P‐PEG group. The objective response rates were 52.4% and 30.8%, and median progression‐free and overall survival were 4.7 and 3.0 months, and 9.6 and 6.8 months, in the P‐PEG and non‐P‐PEG groups, respectively. Conclusions AMR with P‐PEG as second‐line chemotherapy for SCLC reduced the incidence of FN at a maintained AMR dose intensity and was associated with favorable tumor responses and survival outcomes. P‐PEG should be considered for patients treated with AMR for SCLC including refractory relapsed SCLC.

Abstract A 57‐year‐old woman with no significant medical history was referred after a colonoscopy for abdominal distension, which revealed a tumor in the lower rectum. Pre‐operative colonoscopy showed the tumor was 12 mm in size, located from the anorectal junction to beyond the dentate line, and was diagnosed as high‐grade intramucosal neoplasia or shallow submucosal invasive cancer. Endoscopic submucosal dissection was performed, and the lesion was resected en bloc. Pathological examination revealed moderately differentiated tubular adenocarcinoma with tubulovillous adenoma. The stratified squamous epithelium adjacent to the anal side of the lesion showed pagetoid spread of atypical cells with positive horizontal margins. We referred her to a surgeon for radical treatment. The mucosa surrounding the endoscopic submucosal dissection scar was normal on narrow‐band imaging magnification. We marked its oral side endoscopically as the resected boundary. Transanal local excision was performed. The horizontal margins were positive because atypical cells had spread into the stratified squamous epithelium of the anorectal side of the lesion. The patient was followed on an outpatient basis. Sixty days postoperatively, residual tumor growth was observed. The second local resection was performed after mapping biopsy. All resection margins were negative, there was no lymphovascular invasion. One year after surgery, no recurrence was observed. Regarding endoscopic findings, there are no reports of endoscopic findings of the rectal mucosa, or the squamous epithelium of the anus of pagetoid spread. Here, we report a review of perianal Paget's Disease that resulted in difficulties in borderline diagnosis of pagetoid spread, resulting in multiple therapeutic interventions.

Abstract A 51‐year‐old woman visited our hospital with the chief complaint of tarry stools. Contrast‐enhanced abdominal computed tomography revealed leakage of contrast medium into the lumen of the small intestine. Subsequently, a double‐balloon endoscopy was performed, which revealed a submucosal mass‐like lesion in the jejunum. Although hemostasis was attempted with clips, complete hemostasis was difficult to achieve, and angiographic embolization was performed. Nevertheless, the anemia progressed, and a small bowel resection was performed. Histopathological examination led to a diagnosis of a ruptured submucosal aneurysm of the small intestine. Endoscopic hemostasis is often difficult to achieve for submucosal aneurysms in the intestine. The submucosal tumor‐like finding observed on endoscopy in submucosal aneurysms is termed an “SMT‐like sign” and is considered an important finding to diagnose aneurysms.

Abstract A 25‐year‐old man was referred to our center for investigation of a gastric submucosal tumor and an ulcer that had developed on its oral side. Endoscopic ultrasonography findings suggested the presence of an ectopic pancreas, and treatment with an oral proton pump inhibitor was planned for the ulcer. Over the subsequent 3 years, the patient endured recurring epigastric pain and episodes of passing black stools. Emergency endoscopy revealed that the morphology of the gastric submucosal tumor had transformed into a pedunculated polyp‐like morphology with a bleeding ulcer at the apex of the lesion. Endoscopic hemostasis using hemostatic forceps was performed. However, the patient continued to pass black stools. In light of the persistent symptoms and unique morphology of the lesion, endoscopic resection was attempted as a curative approach. The lesion was excised by hot snare polypectomy. Post‐treatment, the patient exhibited no signs of recurrence, marking a successful resolution. Three months later, a gastroduodenal endoscopy showed that the excised site had undergone scar formation without recurrence of the lesion. This case holds significant clinical value as it demonstrates the efficacy of a minimally invasive treatment strategy in managing repeated bleeding ulcerations of an ectopic pancreas, ultimately achieving a complete cure.

Background Nonobstructive general angioscopy (NOGA) can identify vulnerable plaques in the aortic lumen that serve as potential risk factors for cardiovascular events such as embolism. However, the association between computed tomography (CT) images and vulnerable plaques detected on NOGA remains unknown. Methods and Results We investigated 101 patients (67±11 years; women, 13.8%) who underwent NOGA and contrast‐enhanced CT before or after 90 days in our hospital. On CT images, the aortic wall thickness, aortic wall area (AWA), and AWA in the vascular area were measured at the thickest point from the 6th to the 12th thoracic vertebral levels. Furthermore, the association between these measurements and the presence or absence of NOGA‐derived aortic plaque ruptures (PRs) at the same vertebral level was assessed. NOGA detected aortic PRs in the aortic lumens at 145 (22.1%) of the 656 vertebral levels. The presence of PRs was significantly associated with greater aortic wall thickness (3.3±1.7 mm versus 2.1±1.2 mm), AWA (1.33±0.68 cm2 versus 0.89±0.49 cm2), and AWA in the vascular area (23.2%±9.3% versus 17.2%±7.6%) (P

Introduction Intravesical Bacillus Calmette–Guérin immunotherapy is an effective treatment for non‐muscle‐invasive bladder cancer, which is occasionally associated with side effects and complications. The incidence of significant renal complications after intravesical Bacillus Calmette–Guérin immunotherapy is less than 2%. We report a case of renal granuloma after intravesical Bacillus Calmette–Guérin immunotherapy for bladder cancer, which radiologically resembled a papillary renal cell carcinoma. Case presentation A 65‐year‐old man, who had a medical history of urothelial carcinoma and received intravesical Bacillus Calmette–Guérin therapy, was referred to our Urology Department with a right renal tumor. Imaging findings suggested papillary renal cell carcinoma. Robot‐assisted partial nephrectomy was performed, and the histopathological examination revealed epithelioid cell granuloma, which were considered to be Bacillus Calmette–Guérin‐related renal granuloma. Conclusion Bacillus Calmette–Guérin‐related renal granuloma mimicking papillary renal cell carcinoma have been reported. We should consider the possibility of renal granulomas when encountering image abnormalities for patients treated with intravesical Bacillus Calmette–Guérin therapy.

Abstract Background This study aimed to assess the relationship between immune response adverse events (irAEs) and treatment efficacy in patients with extensive disease small cell lung cancer (ED‐SCLC). Methods We retrospectively evaluated the clinical effects in 40 ED‐SCLC patients who had received immune‐checkpoint inhibitors (ICIs), platinum agents, and etoposide between September 2019 and September 2021. We identified and compared patients belonging to two groups: irAE and non‐irAE. Results Fifteen patients experienced irAEs, and 25 did not. The median progression‐free survival in patients with irAE was longer than that in patients without irAE (12.6 months [95% CI: 6.3–19.3 months] vs. 7.2 months [95% CI: 5.8–7.9 months], p = 0.0108). However, the median overall survival (OS) was similar between irAE and non‐irAE groups (27.6 months [95% CI: 15.4–NA] vs. 24.9 months [95% CI: 13.7–NA], p = 0.268). Seven (46.7%) in the irAE group and 20 (80%) in the non‐irAE group received sequential therapy. The median OS was prolonged in patients who received first‐ and second‐line therapy than in those who received first‐line therapy alone (27.6 months [95% CI: 19.2–NA] vs. 6.6 months [95% CI: 0.3–NA], p = 0.053). Grade ≧ 3 irAEs occurred in five (12.5%) patients. Among them, grade 5 irAEs were observed in two patients, including exacerbation of polymyositis and pulmonary arterial embolism. Conclusion In this study, the development of irAEs did not affect OS in patients with ED‐SCLC who received platinum‐based agents, etoposide, or ICI therapy. We determined that managing irAEs and administering first‐ and second‐line therapies could contribute to prolonged OS.

Abstract Aims Tafamidis improves prognosis in patients with transthyretin amyloid cardiomyopathy (ATTR‐CM). However, real‐world data on the therapeutic effect of tafamidis are lacking. This study aimed to evaluate the clinical course, outcomes, and effectivity monitoring of the therapeutic effect of tafamidis in patients with ATTR‐CM. Methods and results This is a single‐centre, retrospective observational study. We evaluated the clinical characteristics and outcomes in 125 consecutive patients with wild‐type ATTR‐CM (ATTRwt‐CM) treated with tafamidis (treatment group) and 55 untreated patients (treatment‐naïve group). We monitored the therapeutic effect of tafamidis for 12 months by evaluating serial cardiac biomarker and imaging findings. The treatment group had significantly more favourable outcome in all‐cause mortality and hospitalization due to heart failure than the treatment‐naïve group in both the entire cohort (P 0.05 ng/mL, B‐type natriuretic peptide (BNP) > 250 pg/mL, and estimated glomerular filtration rate (eGFR)

Abstract This paper proposes and experimentally evaluates, a reconfigurable intelligent surface (RIS) control system for multiple users using stereo camera images. The aim is to enable fast and fair received signal strength (RSS) beamforming for multiple users. In the proposed system, a stereo camera is mounted on top of the RIS. Human bodies are recognized from the obtained images. Subsequently, the beam directions and the phase of the RIS are calculated for the estimated positions. The stereo camera‐based scheme enables fast beamforming because channel state information estimation is omitted. Moreover, identical RSS beamforming is enabled by calculating the weighted sums of the RIS phases for multiple users utilizing distance and angle information of users from the RIS obtained using the stereo camera. Experiments are conducted in an anechoic chamber using RIS operating at 28 GHz. The efficacy of the RIS control system using stereo camera images and its ability to increase the RSS fairly for multiple users is validated via simulations and experiments.

Abstract Infection with certain viruses is an important cause of cancer. The Pan‐Cancer Analysis of Whole Genomes (PCAWG) Consortium recently analyzed the whole‐genome sequencing (WGS) data from 2656 cases across 21 cancer types, and indicated that Epstein–Barr virus (EBV) is detected in many different cancer cases at a higher frequency than previously reported. However, whether EBV‐positive cancer cases detected by WGS‐based screening correspond to those detected by conventional histopathological techniques is still unclear. In this study, to elucidate the involvement of EBV in various cancers, we reanalyzed the WGS data of the PCAWG cohort combined with the analysis of clinical samples of gastric and pancreatic cancer in our cohort. Based on EBV copy number in each case, we classified tumors into three subgroups: EBV‐High, EBV‐Low, and EBV‐Negative. The EBV‐High subgroup was found to be EBV‐positive in the cancer cells themselves, whereas the EBV‐Low subgroup was EBV‐positive in the surrounding lymphocytes. Further, the EBV‐Low subgroup showed a significantly worse prognosis for both gastric cancer and across cancer types. In summary, we classified tumors based on EBV copy number and found a unique cancer subgroup, EBV‐positive in the surrounding lymphocytes, which was associated with a poor prognosis.

Abstract Aim This study aimed to clarify the usefulness of tumor markers from peritoneal lavage in selecting patients with a high risk of recurrence and predicting site‐specific recurrence in patients with pancreatic cancer. Methods The levels of serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19–9 (sCEA/sCA 19–9) and paired peritoneal lavage CEA and CA 19–9 (pCEA/pCA 19–9) were measured in 90 patients with pancreatic cancer who underwent surgery. Using the cutoff values determined by maximally selected rank statistics for disease‐free survival (DFS), the risk of recurrence and its patterns were evaluated in combination with different markers and different test specimens. Results In univariate and multivariate analysis, an elevated pCA 19–9 level (>1.3 U/mL) was an independent prognostic marker for both DFS (hazard ratio [HR], 2.391; P = .018) and overall survival (HR, 3.194; P = .033). Combination analyses contributed to further stratification of a very high risk of recurrence. Of the 58 patients with resectable pancreatic cancer who underwent curative resection, elevated pCA19–9 was also associated with inferior DFS and overall survival (OS). Patients with elevated pCA 19–9 levels were more likely to have an earlier onset of peritoneal recurrence than those with normal pCA 19–9 levels (P = .048, Gehan–Breslow–Wilcoxon test). Conclusion pCA 19–9 is a reliable marker for predicting postoperative recurrence in patients with pancreatic cancer after surgery. Further risk stratification can be achieved by using combination assays. The combination of pCA 19–9 and sCA19–9 also serves as a predictor of recurrence site‐specific recurrence.

Introduction The prognosis of adrenal metastasis from non‐small cell lung cancer is very poor. A recent report described the efficacy of the surgical removal of adrenal metastasis when solitary. However, metachronous bilateral adrenal metastasis is extremely rare, and a treatment strategy has not been established. Case presentation Herein, we describe a 52‐year‐old Asian male who presented with a right adrenal metastasis of non‐small cell lung cancer 8 months after immunochemotherapy and surgical resection of the lung. He underwent combined systemic treatment and a laparoscopic right adrenalectomy; however, after 9 months, a metachronous left adrenal metastasis emerged. A subsequent laparoscopic left adrenalectomy and systemic treatment led to long‐term progression‐free survival. Conclusion The appropriate surgical indication and combined systemic treatment of a metachronous bilateral adrenal metastasis in non‐small cell lung cancer may extend the prognosis.

Abstract Here, we report a case of a pulmonary invasive mucinous adenocarcinoma harboring KRAS G12D, diagnosed from tumor samples containing a very small amount of tumor cells using next‐generation sequencing (NGS) and the recently developed Lung Cancer Compact Panel. A 79‐year‐old woman without any respiratory symptoms underwent chest computed tomography, which revealed a tumor in the left lower lobe. During endobronchial ultrasound (EBUS)‐guided transbronchial biopsy (TBB) using a guide sheath (GS), a sufficient specimen for pathological diagnosis could not be obtained because the patient had a severe cough and pulmonary bullae located adjacent to the tumor. In the absence of EBUS transbronchial biopsy findings using a guide sheath, brush cytology was used to categorize the tumor as class II (Papanicolaou classification). However, the wash fluid from the cytological examination contained enough cells to obtain sufficient nucleic acid for use in sequencing analysis. The latter revealed KRAS G12D expression. Although the patient underwent surgery without pathological evidence, the evaluation of the surgical specimen confirmed a diagnosis of pulmonary invasive mucinous adenocarcinoma. Use of the Lung Cancer Compact Panel enabled the detection of KRAS G12D in the wash fluid of a brush cytology sample and thus a diagnosis of pulmonary invasive mucinous adenocarcinoma.

Abstract In the southwest Japan forearc, slab‐fluids produced from subducted materials migrate to crustal levels and appear as deep‐seated brine. We have analyzed for the first‐time stable strontium isotopes in non‐volcanic spring water with high salinity, referred to as Arima‐type saline water that likely originate from slab‐fluid that upwelled along major faults. The stable strontium isotope compositions of the saline water are isotopically light (δ88/86Sr = 0.122–0.157‰) and different from those of local bedrock and near‐surface water. The light strontium‐enriched and radiogenic signature of the saline water reflects the primary characteristic of slab‐fluids without an isotopic overprint in the crust. The Arima‐type brines show signatures of slab‐fluids at forearc depth, which is different from the slab‐fluids at subarc depth estimated from arc lavas. The characteristic features of the Arima‐type brines are explained by a larger contribution of subducted sediments and strontium isotope fractionation during fluids generation at shallower depth.

Abstract While duodenal neoplasms of the gastric phenotype are uncommon and their natural history is unknown, gastric neoplasms of gastric phenotype reportedly grow rapidly and can invade the submucosa. Several studies suggest that duodenal neoplasms of gastric phenotype might have a high risk of deep invasion and lymph node metastasis. Duodenal neoplasms of gastric phenotype might also have a high biological malignancy and likely require early treatment if detected. Here, we report two cases of intramucosal duodenal carcinoma with a gastric phenotype that grew rapidly but was successfully resected endoscopically.

Abstract Aims/Introduction We investigated the association between gestational diabetes mellitus (GDM) and perinatal outcomes stratified by pre‐pregnancy body mass index (BMI) and/or gestational weight gain (GWG). Materials and Methods Data from the national birth cohort in the Japan Environment and Children's Study from 2011 to 2014 (n = 85,228) were used. Japan uses the GDM guidelines of the International Association of Diabetes and Pregnancy Study Groups. The odds ratios (ORs) of perinatal outcomes were compared between women with and those without GDM. Results The OR (95% confidence interval) of having a small for gestational age infant in the GDM group with a pre‐pregnancy BMI of ≥25.0 kg/m2 and insufficient GWG (7.25 kg) was 2.04 (1.56–2.67). The OR of hypertensive disorders of pregnancy was higher in women with a BMI ≥18.5 kg/m2 in the GDM group than in the non‐GDM group. Conclusions Large for gestational age and hypertensive disorders of pregnancy were associated with pre‐pregnancy BMI and GWG in either normal weight or overweight/obese women, and the relationship was strengthened when GDM was present. Women with GDM and a BMI of ≥25.0 kg/m2 are at risk of having small for gestational age and large for gestational age infants depending on GWG.

Abstract Background Individuals with hoarding disorder (HD) presented a persistent difficulty in detaching from objects and/or animals. Unhealthy conditions, frequently found in cases of animal HD (AHD), may favour environmental contamination and the spread of zoonotic pathogens. Despite that, only one study of zoonotic diseases in individuals with AHD and their companion animals has been conducted to date. Objectives This study aimed to assess the seroprevalence of anti‐Leptospira spp. antibodies in individuals with AHD and their dogs in a major city of Southern Brazil. Methods Blood samples were obtained from 264 dogs (21 households) and 19 individuals with AHD (11 households) and tested by microscopic agglutination test. Results All human samples were seronegative. Seropositivity was found in 16/264 (6.1%; CI 95% 3.3–9.6%) dogs from 11/21 (52.38%) households, with titres ranging from 100 up to 400, and Copenhageni (10/16; 62.5%) was the most frequent serovar. Surprisingly, seropositivity of hoarded dogs found herein was among the lowest reportedly observed in other dog populations of Brazil. Two epidemiological variables were significantly associated with seropositivity in dogs: the presence of cat hoarding (p = 0.004) and the report of flood occurrence in the household (p = 0.031). Conclusions No individuals with AHD were seropositive, and besides the lower seroprevalence of dogs, they probably had contact with Leptospira spp. at some point in their life. Since dogs can be considered potential sentinels in leptospirosis, public health programs must become aware of the risk of leptospirosis cases in households of individuals with AHD and nearby communities.

Glioma‐initiating cells (GICs), a major source of glioblastoma recurrence, are characterized by the expression of neural stem cell markers and the ability to grow by forming nonadherent spheres under serum‐free conditions. Bone morphogenetic proteins (BMPs), members of the transforming growth factor‐β family, induce differentiation of GICs and suppress their tumorigenicity. However, the mechanisms underlying the BMP‐induced loss of GIC stemness have not been fully elucidated. Here, we show that paired related homeobox 1 (PRRX1) induced by BMPs decreases the CD133‐positive GIC population and inhibits tumorigenic activity of GICs in vivo. Of the two splice isoforms of PRRX1, the longer isoform, pmx‐1b, but not the shorter isoform, pmx‐1a, induces GIC differentiation. Upon BMP stimulation, pmx‐1b interacts with the DNA methyltransferase DNMT3A and induces promoter methylation of the PROM1 gene encoding CD133. Silencing DNMT3A maintains PROM1 expression and increases the CD133‐positive GIC population. Thus, pmx‐1b promotes loss of stem cell‐like properties of GICs through region‐specific epigenetic regulation of CD133 expression by recruiting DNMT3A, which is associated with decreased tumorigenicity of GICs.

Abstract Background In this study we aimed to clarify the PD‐L1 positive expression in lung adenocarcinoma, including various adenocarcinoma subtypes paying particular attention to its component. Methods A total of 307 lung adenocarcinoma patients who underwent lobectomy or segmentectomy, as well as systematic lymph node dissection (ND2a), from February 2008 to March 2020 at our hospital, were enrolled into the study. A final diagnosis of adenocarcinoma was obtained from the resected lung specimens of all 307 patients to determine the histological type, adenocarcinoma subtype, and component of adenocarcinoma by ethics of 5%. PD‐L1 was immunohistochemically stained using the murine monoclonal antibody clone 22C3. Results When PD‐L1 expression‐positive was defined by tumor proportion score (TPS) ≥1%, the positive cases were 6/33 in adenocarcinoma (Ad) in situ (AIS), 2/26 in minimally invasive Ad (MIA), 12/60 in lepidic predominant Ad (LPA), 44/91 in papillary predominant Ad (PPA), 24/49 in acinar predominant Ad (APA), 23/28 in solid predominant Ad (SPA), 4/7 in micropapillary predominant Ad (MPA), and 0/13 in invasive mucinous Ad (IMA). In the high proportion group (APA, PPA, SPA, and MPA) of PD‐L1 expression, SPA was the only subtype which was statistically significant when both PD‐L1 expression‐positive was defined by TPS ≥ 1% (p

Abstract Objective Burnout negatively affects the wellness and performance of emergency physicians (EPs). This study aimed to clarify the actual prevalence of burnout and its associated factors among Japanese EPs. Methods We conducted a cross‐sectional questionnaire study of selected 27 Japanese emergency departments (EDs). We examined the Maslach Burnout Inventory‐Human Services Survey score and its associations with ED‐level‐ and EP‐level factors in a multivariable analysis. Results A total of 267 EPs (81.9%) completed survey. Of these, 43 EPs (16.1%) scored severe emotional exhaustion (EE), 53 (19.8%) scored severe depersonalization (DP), and 179 (67.0%) scored severe personal accomplishment (PA), and 24 (8.9%) scored severely in all three domains. In our multivariable analysis, emergency medical service centers were associated with severe PA scores (odds ratio [OR], 10.56; 95% confidence interval [CI], 1.78–62.66; p = 0.009). A 3 to 6 hour‐sleep period was associated with severe EE scores (OR, 2.04; 95% CI, 1.04–3.98; p = 0.036), and EPs in their 20s were associated with severe DP scores (OR, 7.37; 95% CI, 1.41–38.38; p = 0.018). Conclusion Our results suggest that 8.9% of Japanese EPs are in higher degrees of burnout. In particular, Japanese EPs scored more severely on PA. To avoid burnout in Japanese EPs, it is important to improve the working environment by ensuring more than 6 h of sleep, providing more support for young EPs, and taking effective action to combat low EP self‐esteem.

Abstract Background and Aims An autonomic nervous disorder is an important characteristic of cardiac amyloidosis; however, the prevalence of autonomic dysfunction in wild‐type transthyretin amyloidosis (ATTRwt) has not been established. Analysis of the R‐R interval coefficient of variation (CVR‐R) is a noninvasive method to measure parasympathetic activity. We aimed to assess autonomic dysfunction of ATTRwt and determine the utility of CVR‐R for the detection of ATTRwt in other cardiac diseases. Methods This is a single‐center, retrospective, case‐control study. Fifty patients with heart failure (HF) were studied. The etiologies of HF were as follows: ATTRwt, n = 10; previous myocardial infarction (MI), n = 20; and left ventricular hypertrophy (LVH) due to other disease processes (e.g., aortic stenosis), n = 20. We measured the CVR‐R at rest (CVR‐Rrest), CVR‐R with deep breaths (CVR‐Rbreath), and the change rate (CVR‐Rdiff rate). The relative change formula is as follows: CVR‐Rdiff rate = (CVR‐Rbreath − CVR‐Rrest)/CVR‐Rrest× 100 (%). Results There was no difference in the CVR‐Rrest levels among the three groups. The CVR‐Rdiff rate levels in the ATTRwt group were significantly lower (ATTRwt: −8.77 [−43.8 to 10.9]; LVH: 67.4 [38.7 to 89.4]; MI: 83.7 [60.4 to 142.9]). Based on the receiver operative characteristic curve analysis to identify ATTRwt in HF, the best cut‐off value for the CVR‐Rdiff rate was 19.7 (area under the curve: 0.848). Conclusion Our data suggested autonomic dysfunction in patients with ATTRwt. Measurement of the CVR‐R in HF patients may be a convenient support tool for the detection of ATTRwt.

Abstract Introduction The chromosomal region 17q21 harbors the human orosomucoid‐like 3 (ORMDL3) gene and has been linked to asthma and other inflammatory diseases. ORMDL3 is involved in the unfolded protein response (UPR), lipid metabolism, and inflammatory reactions. We investigated the effects of ORMDL3 overexpression in RBL‐2H3 cells to determine the contribution of ORMDL3 to inflammatory disease development. Methods We generated ORMDL3 stably overexpressing RBL‐2H3 cells to assess degranulation, transcriptional upregulation of interleukin‐4 (IL‐4), tumor necrosis factor‐α (TNF‐α), monocyte chemoattractant protein‐1 (MCP‐1), and mitogen‐activated protein kinase (MAPK) phosphorylation via FcεRI. In addition, we examined the effects of ORMDL3 overexpression on thapsigargin (TG)‐mediated proinflammatory cytokine transcription and UPR by monitoring MAPK, protein kinase‐like endoplasmic reticulum kinase (PERK), and inositol‐requiring enzyme 1 (IRE1) phosphorylation. Results Overexpression of ORMDL3 enhanced IL‐4, TNF‐α, and MCP‐1 expression after FcεRI cross‐linking, whereas the sphingosine‐1‐phosphate (S1P) agonist FTY720 suppressed this enhancement. There was no significant difference in degranulation and MAPK phosphorylation via FcεRI‐mediated activation between vector‐transfected and ORMDL3‐overexpressing cells. ORMDL3 overexpression accelerated TG‐mediated PERK phosphorylation, while MAPK phosphorylation and proinflammatory cytokine expression showed no significant changes in ORMDL3‐overexpressing cells. Conclusions Our findings suggest that ORMDL3 plays an important role in regulating proinflammatory cytokine expression via the S1P pathway and selectively affects the UPR pathway in mast cells.

Abstract Aim Cancer patients with personal/family histories of pancreatic/breast/ovarian/prostate cancer are associated with a higher likelihood of harboring DNA damage repair (DDR)‐related germline mutations. Here, we aimed to obtain a better understanding of DDR‐related germline mutations in Japanese pancreatic ductal adenocarcinoma (PDAC) patients with personal and/or family histories of BRCA‐related cancers of the pancreas, breast, ovary, and prostate. Methods We performed next‐generation sequencing (NGS) and evaluated germline mutations in nine DDR‐related genes (BRCA1, BRCA2, ATM, PALB2, CHEK2, MLH1, MSH2, MSH6, and PMS2) in PDAC patients with personal and/or family histories. Results Of 196 patients with PDAC, 39 (19.9%) fulfilled the criteria for at least one family history of pancreatic/breast/ovarian/prostate cancer in first‐degree relatives (sibling–sibling or parent‐child) or the personal history of these malignancies. Targeted NGS revealed that four (10.2%) of 39 patients with personal/family histories harbored deleterious germline mutations—two in BRCA2, one in ATM, and one in MLH1. Both the BRCA2 variants showed frameshift mutations due to short insertion/deletions. In the 39 patients undergoing NGS, a similar distribution of the clinicopathological characteristics was observed between those with deleterious mutations/variants of unknown significance (VUSs) and with benign/wild types. Patients with deleterious germline mutations/VUSs in DDR‐related genes showed a significantly more favorable prognosis than those with benign mutations/wild‐type genes (hazard ratio: 0.160, P = .040). Conclusions A significant fraction of PDAC patients with personal/family histories of BRCA‐related cancers harbored deleterious germline mutations in DDR‐related genes. DDR‐related germline gene mutations might be a favorable prognostic factor in patients with pancreatic cancer.

Abstract Background Consolidation therapy with durvalumab after concurrent chemoradiotherapy has been reported to significantly prolong progression‐free survival and overall survival in patients with stage III unresectable non‐small cell lung cancer (NSCLC). However, which chemotherapy regimen should be selected for consolidation therapy with durvalumab is currently unknown. Methods We retrospectively reviewed consecutive patients with unresectable stage III NSCLC who received concurrent definitive chemoradiotherapy with platinum‐based chemotherapy. We reviewed the timing and severity of radiation pneumonitis by assessing chemotherapy regimens and histology. Results A total of 103 patients were identified. Fourteen patients (13.6%) developed grade 2 or greater radiation pneumonitis within 42 days after chemoradiotherapy. No adenocarcinoma patients treated with a regimen of cisplatin plus pemetrexed developed grade 2 or greater radiation pneumonitis within 42 days; however, 20% of patients who were treated with carboplatin plus paclitaxel developed grade 2 or greater radiation pneumonitis. Furthermore, the objective response rates and disease control rates of cisplatin plus pemetrexed were equal to or greater than those of carboplatin plus paclitaxel in adenocarcinoma patients. Conclusion Cisplatin plus pemetrexed regimen may be a preferable option to consider for subsequent consolidation therapy with durvalumab in patients with unresectable stage III adenocarcinoma.

Abstract Background A cisplatin plus irinotecan (CPT‐11) regimen is used for patients with extensive disease small cell lung cancer (ED‐SCLC). Amrubicin (AMR) is primarily used for relapsed SCLC. The HOT1401/NJLCG1401 trial, an open‐label randomized phase II trial, was designed to assess the benefit of maintenance therapy in patients with ED‐SCLC who responded to induction therapy. Methods Patients with histologically‐ or cytologically‐confirmed ED‐SCLC were included and were treated with an induction therapy of four cycles of cisplatin (60 mg/m2 on day 1) plus CPT‐11 (60 mg/m2 on days 1, 8, and 15) every four weeks. After induction therapy, patients who had nonprogressive disease were randomized to receive either maintenance CPT‐11 (60 mg/m2 on days 1 and 8) every three weeks, or AMR (35 mg/m2 on days 1–3) every three weeks. Results A total of 34 patients were enrolled; 20 patients had progressive disease or received incomplete induction chemotherapy. Finally, 14 patients were randomly assigned to receive CPT‐11 (n = 7) or AMR (n = 7). This study was terminated prematurely because of low patient accrual. The overall objective response rate was 73%, the median PFS was 5.7 months (95% confidence interval [CI]: 3.6–11.8), and the median overall survival was 20.1 months (95% CI: 13.7–not reached). No statistically significant difference in progression‐free survival (PFS) were noted between patients treated with CPT‐11 and those treated with AMR. There were no treatment‐related deaths in this study. Conclusions Maintenance therapy with CPT‐11 or AMR after induction therapy might be effective in some patients.

Abstract Aims/Introduction This cohort study assessed the risk for bodyweight gain and development of glucose intolerance based on the frequency of consumption of balanced meals including grain, fish or meat and vegetables. Materials and Methods The participants (8,573 men, 3,327 women) were employees of a company in Japan. A self‐administered questionnaire was used to evaluate the frequency of balanced meal consumption. Bodyweight changes and the incidence of glucose intolerance (glycated hemoglobin >6.0%) during the 3‐year follow‐up period were determined through annual health examinations. Results The mean bodyweight change over a period of 3 years was 0.78 kg for men and 0.84 kg for women. A lower frequency of balanced meals was associated with a higher bodyweight gain for men (P for trend = 0.004), but not for women. During the study, 464 men and 115 women developed glucose intolerance. Overall, the frequency of balanced meals was not associated with the risk of glucose intolerance in either sex. However, the interaction between the frequency of balanced meals and degree of obesity had a significant effect on the incidence of glucose intolerance in men (P = 0.005), with less frequent consumption of balanced meals being associated with a higher risk for glucose intolerance among men with a BMI ≥25.0 kg/m2 (P for trend = 0.007). Conclusions A higher frequency of balanced meals, including grain, fish or meat and vegetable dishes – important components of healthy Japanese food – was associated with a lower risk of glucose intolerance in obese men, but not in non‐obese men and women.

Development of innovative therapeutic modalities would address an unmet clinical need in the treatment of triple negative breast cancer (TNBC). Activation of retinoic acid‐inducible gene‐I (RIG‐I)‐like receptors (RLRs) such as melanoma differentiation‐associated gene 5 (MDA5) and RIG‐I in cancer cells is suggested to suppress tumor progression by inducing cell death. Transfection of polyI:C, a conventionally used synthetic double‐stranded RNA (dsRNA) analogue that activates RLRs, has been evaluated in clinical trials. However, detailed mechanisms of tumor suppression by RLRs, especially interactions with other signaling pathways, remain elusive. Here, we showed that transfection of polyI:C suppressed transforming growth factor‐β (TGF‐β) signaling in a MDA5‐ and RIG‐I‐dependent manner. We found that suppression of TGF‐β signaling by polyI:C promoted cancer cell death, which was attenuated by forced expression of constitutively active Smad3. More detailed analysis suggested that cell death by polyI:C transfection exhibited characteristics of pyroptosis, which is distinct from apoptosis. Therapeutic efficacy of polyI:C transfection was also demonstrated using a mouse model. These results indicated that intratumor administration of polyI:C and related dsRNA analogues may be promising treatments for TNBC through inhibition of the anti‐pyroptotic function of TGF‐β.

Abstract Objectives Epigenetic phenomena are changes in gene expression not involving the DNA sequence. DNA methylation is a major occurrence underlying epigenetic changes in human cells. Although aberrant DNA methylation is well documented in malignant lesions, limited information has been shown on the involvement of DNA methylation in oral lichen planus and oral lichenoid lesions (OLP). The present study aimed to investigate DNA methylation of E‐cadherin and p16 in OLP, and compare the findings with those in non‐inflamed gingiva (Non), radicular cyst (RC), and oral squamous cell carcinoma (SCC). Materials and methods Paraffin‐embedded surgical biopsy specimens were sliced, DNA was extracted, bisulfite treatment was applied, and methylation‐specific polymerase chain reaction was performed. Immunohistochemistry was performed to observe the relative expression patterns of these genes. Results E‐cadherin was hypermethylated in OLP (p

Abstract Severe fever with thrombocytopenia syndrome (SFTS) has a high fatality rate and is caused by SFTS virus (SFTSV). Currently, SFTS is endemic to some areas in western Japan, and wild animals are considered to play important roles in the circulation of SFTSV in the environment. Previous retrospective surveys using samples mainly obtained between 2006 and 2015 revealed serological evidence of SFTSV infection in wild animals; however, seroprevalence before 2006 remains unclear. In this study, we investigated the presence of anti‐SFTSV antibodies in a total of 521 serum samples from nine wild animal species collected from 11 prefectures in central and eastern Japan between 1980 and 2000. All samples yielded negative results for antibodies to SFTSV, suggesting that there had been few or no SFTSV infections before 2000 in the sampled areas.

Abstract The full‐mouth disinfection protocol implemented in this case can be integrated into established protocols for treating severe periodontitis in the context of a hematological malignancy, without any interference with the cancer treatment.

Abstract The prevalence of chronic diarrhea in the general population is reported to be 4%–5%. Since various pathological conditions cause diarrheal symptoms, etiological diagnosis of chronic diarrhea is difficult in many cases. Medical history taking, physical examinations, and laboratory testing are not adequately sensitive or specific, thus a colonoscopic investigation is frequently employed for etiological evaluation. However, for cases with non‐bloody chronic diarrhea, the diagnostic yield of a colonoscopy procedure is reported to be not high enough. Furthermore, endoscopically identifiable findings are not adequately specific for the diagnosis of diarrheal disease, except for inflammatory bowel disease, while microscopic colitis, amyloidosis, eosinophilic gastroenteritis, celiac disease, and bile acid diarrhea are difficult to definitively diagnose using endoscopic findings. Thus, a histopathological examination of biopsy samples obtained with endoscopy is critically important. Endoscopists should consider obtaining biopsy samples from even normal‐appearing gastrointestinal mucosa for chronic diarrhea diagnosis.