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ABSTRACT Aims/Introduction This study evaluated the risk factors for insulin therapy before 24 gestational weeks (early insulin therapy) in pregnant women with gestational diabetes diagnosed before 24 gestational weeks (E‐GDM). Materials and Methods This study included 530 singleton mothers with E‐GDM who underwent a 75 g oral glucose tolerance test (OGTT) in the first trimester at Keio University Hospital between January 2013 and December 2021. E‐GDM can be classified according to its management into only diet therapy until delivery (Diet E‐GDM), insulin therapy started before 24 gestational weeks (EarlyIns E‐GDM), and insulin therapy started after 24 gestational weeks (LateIns E‐GDM). We analyzed the risk factors for EarlyIns E‐GDM. Results Patients with EarlyIns E‐GDM had a significantly higher maternal age at delivery, pre‐pregnancy BMI, first trimester hemoglobin A1c, 1 h plasma glucose levels (1 h‐PG), and 2 h‐PG, as well as a more pronounced initial increase and subsequent decrease, compared with those in the Diet E‐GDM group. However, the Apgar scores at both 1 and 5 min were significantly lower in patients with EarlyIns E‐GDM than in those with Diet E‐GDM. The number of abnormal values in the OGTT showed the largest area under the receiver operating characteristic curve (AUC) for predicting EarlyIns E‐GDM (0.83, 95% confidence interval [CI]: 0.79–0.86), followed by the 1 h‐PG value (AUC: 0.81, 95% CI: 0.77–0.85). The initial increase showed the third largest AUC (0.78, 95% CI: 0.74–0.82). Conclusions Although further research is needed, our data suggest the importance of early insulin therapy in cases of E‐GDM with multiple abnormal OGTT values, especially with high 1 h‐PG levels and initial increase.

ABSTRACT A 6‐month‐old Afshari male lamb was examined on a semi‐intensive farm due to anorexia and neurologic signs, including head tilt, circling, bilateral positive menace response and stupor. The sheep was slaughtered and necropsied. After routine parasitology and histopathology procedures, the occurrence of cerebral hydatidosis was confirmed. This study represents the first report of cerebral hydatidosis in sheep and suggests that cerebral hydatid cysts should be considered possible etiological agents for neurological syndromes in sheep. The studied hydatid cyst was sequenced for the COX1 partial gene and submitted as a new strain to the NCBI GenBank with the accession number OR984434.1 and name Jabbasi1. The sequence of this isolate was also compared with other sequences in GenBank using a phylogenetic tree. On the basis of phylogenetic analysis, our strain was classified as a G1 strain and showed high homology to other G1 strains reported from Iran, Iraq and so forth.

Abstract While autonomic dysregulation and repolarization abnormalities are observed in subarachnoid hemorrhage (SAH), their relationship remains unclear. We aimed to measure skin sympathetic nerve activity (SKNA), a novel method to estimate stellate ganglion nerve activity, and investigate its association with electrocardiogram (ECG) alterations after SAH. We recorded a total of 179 SKNA data from SAH patients at three distinct phases and compared them with 20 data from controls. Compared with control data, in the acute phase data (days 1–3 of SAH), T peak‐to‐end (Tp‐e) interval was significantly prolonged (81 [interquartile range {IQR}: 71–93] vs. 58 [IQR: 54–64] ms, p

Abstract The study explores the relationship between phase angle (PhA), an indicator of cellular health, and metabolic health parameters among junior sumo wrestlers in Japan. Given the demanding lifestyle and high‐energy diets of sumo wrestlers that predispose them to metabolic syndrome post‐retirement, this study focuses on a younger cohort. The primary aim is to evaluate if PhA could serve as an early indicator of metabolic health issues within this unique demographic. A total of 14 sumo wrestlers aged 9–17 years were assessed to determine the relationship between PhA and various metabolic markers, including glycated hemoglobin (HbA1c), using a TANITA MC‐780A‐N body composition analyzer and standard blood tests. Bivariate regression analysis and Pearson's correlation revealed a negative relationship between PhA and HbA1c even after adjusting for age and weight (ß = −0.496, r2 = 0.776, r = −0.756, p = 0.004). The results indicate a significant negative relationship between PhA and HbA1c levels, suggesting that lower PhA values, which indicate poorer cellular integrity, are associated with higher HbA1c levels, signifying impaired glycemic control. These findings underscore the potential of PhA as a valuable biomarker for monitoring metabolic health in young sumo wrestlers, with implications for early intervention and management strategies.

Abstract A 3‐year‐old Holstein cow was examined in an intensive system due to unilateral swelling in the mandible. A right mandibular mass was associated with painful mastication and Ptyalism. In palpation, the mass was raised, ulcerated, attached to the mandible bone and firm, approximately 17 × 12 × 10 cm3 in size. The lesion was sampled, and after routine bacteriology and histopathology procedures, the occurrence of lumpy jaw caused by Nocardia farcinica was confirmed. The bacterium was analysed using genome sequencing and new strain called Najm 114. Due to the risk of zoonosis of the isolated agent, the cow was euthanized. This is the first report of lumpy jaw caused by N. farcinica in a cow. This study showed that N. farcinica should be considered a possible etiological agent for lumpy jaw in cattle.

Abstract Objective Videoendoscopic evaluation of swallowing is an objective swallowing function evaluation method used in dysphagia rehabilitation. However, it is anatomically difficult to detect the entry of foreign substances through the posterior tracheal wall using a conventional endoscope (CE). In this study, we developed an endoscope that can observe the posterior tracheal wall and investigated its reliability and validity in healthy adults. Methods Twenty healthy adults were included. The trachea was observed from inside the larynx using a CE and a portable, flexible two‐step angulation endoscope (two‐AE) with a two‐step curved shaft tip. The visibility of the anterior and posterior walls was recorded. The time from the endoscope tip entering the larynx to the posterior tracheal wall was measured. Additionally, discomfort events were assessed after the examination. McNemar's test and a paired t‐test were used for statistical analysis. Kappa coefficients and concordance rates were calculated. Results The anterior tracheal wall was observed using both endoscopes. The posterior tracheal wall was significantly observed in 18 participants with the two‐AE (p

Abstract A man in his 70s on maintenance dialysis for autosomal dominant polycystic kidney disease was admitted with epigastralgia and a fever lasting for 1 week. Computed tomography showed a thickened liver cyst measuring 121 mm in the caudate lobe, suggesting infection. Percutaneous drainage was impossible because multiple liver cysts and ascites entered the puncture route. Endoscopic ultrasound (EUS) revealed a huge liver cyst with debris‐like echoes. Transgastric EUS‐guided drainage was performed, and internal and external drainage was performed without adverse events. After the procedure, the symptoms quickly improved, and the external drain was removed after 12 days. The internal drainage stent remained in place, and the patient was discharged from the hospital 53 days after the EUS‐guided drainage. EUS‐guided drainage is an effective alternative treatment for infected liver cysts where a percutaneous approach is impossible.

Abstract Background Adhesion of cancer cells to extracellular matrix laminin through the integrin superfamily reportedly induces drug resistance. Heterodimers of integrin α6 (CD49f) with integrin β1 (CD29) or β4 (CD104) are major functional receptors for laminin. Higher CD49f expression is reportedly associated with a poorer response to induction therapy in childhood B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL). Moreover, a xenograft mouse model transplanted with primary BCP‐ALL cells revealed that neutralized antibody against CD49f improved survival after chemotherapy. Aims Considering the poor outcomes in Philadelphia chromosome (Ph)‐positive ALL treated with conventional chemotherapy without tyrosine kinase inhibitors, we sought to investigate an involvement of the laminin adhesion. Methods and results Ph‐positive ALL cell lines expressed the highest levels of CD49f among the BCP‐ALL cell lines with representative translocations, while CD29 and CD104 were ubiquitously expressed in BCP‐ALL cell lines. The association of Ph‐positive ALL with high levels of CD49f gene expression was also confirmed in two databases of childhood ALL cohorts. Ph‐positive ALL cell lines attached to laminin and their laminin‐binding properties were disrupted by blocking antibodies against CD49f and CD29 but not CD104. The cell surface expression of CD49f, but not CD29 and CD104, was downregulated by imatinib treatment in Ph‐positive ALL cell lines, but not in their T315I‐acquired sublines. Consistently, the laminin‐binding properties were disrupted by the imatinib pre‐treatment in the Ph‐positive ALL cell line, but not in its T315I‐acquired subline. Conclusion BCR::ABL1 plays an essential role in the laminin adhesion of Ph‐positive ALL cells through upregulation of CD49f.

Abstract A 3‐year‐old castrated male Jack Russell Terrier with a history of cholestatic hepatitis was presented with a non‐painful and non‐pruritic, subcutaneous nodule following vaccine injection. The dog was otherwise healthy. The nodule was surgically removed. Upon gross inspection, a firm, glistening and loculated tissue was seen within the panniculus. Histopathologically, extensive pyogranulomatous panniculitis was diagnosed, composed of variably sized lipocyst surrounded by neutrophils and an outer zone of foamy epithelioid macrophages, neutrophils and occasional Langhans form giant cells. Although histopathologic findings were most compatible with mycobacteriosis, other infectious and sterile conditions were considered differential diagnoses. Gram, acid‐fast and periodic acid Schiff staining were negative. However, PCR analyses for mycobacterial rpoB gene and sequencing revealed infection with Mycobacterium avium subsp. avium. Empirical treatment was avoided through the 3‐week course of histopathological and molecular investigations. Considering that there were no newly formed cutaneous masses, marbofloxacin (2 mg/kg, PO q24h) was administered for 2 weeks, and clarithromycin was avoided due to its potential cholestatic hepatitis adverse effects. Eight months following surgery, there are no new or relapsing cutaneous lesions or disease‐specific complications. This suggests that marbofloxacin monotherapy may be sufficient in immunocompetent dogs with early detection of localized cutaneous mycobacteriosis lacking lymph node or organ involvement.

Abstract Pericarditis means inflammation in the pericardial sac. Pericarditis is divided into three categories based on morphology, including fibrinous, purulent, and constrictive. In the present study, a 7‐month‐old male Ghezel breed sheep was examined for low weighting rate for three months. Tachypnea, tachycardia, heart friction sound, absence of fever and normal appetite were recorded in the clinical examination. In the patient's history, there was a history of perforated chest trauma behind the left scapula about three months ago. After the echocardiography examination and bacteriology procedures, purulent pericarditis caused by Proteus mirabilis was diagnosed. The bacterium was analysed using genome sequencing and new strain called Abhar114 was diagnosed. This is the first report of pericarditis caused by Proteus mirabilis in sheep.

Abstract Twelve 30‐ to 75‐day‐old mixed breed lambs were examined in an intensive system because of sudden recumbency and death. Clinical examination revealed sudden recumbency, visceral pain, and auscultation of respiratory crackles. Lambs died shortly (between 30 minutes and 3 hours) after the onset of clinical signs. The lambs were necropsied, and after routine parasitology, bacteriology and histopathology procedures, the occurrence of acute cysticercosis caused by Cysticercus tenuicollis was confirmed. The use of the suspect infested feed (newly purchased starter concentrate) was discontinued and other lambs of the flock were treated with praziquantel (15 mg/kg, single dose, orally). After these actions, no new cases were observed. The present study showed the importance of preventive measures against cysticercosis in intensive sheep farming systems which include proper storage of feed, preventing feed and environmental access by potential definitive hosts, and implementing consistent parasite control programs in dogs that are in contact with sheep.

Combination chemotherapy with gemcitabine and cisplatin (GC) is recommended as the primary treatment for advanced bladder cancer (BC). However, the benefits of this approach are limited owing to the acquisition of drug resistance. Here, we found that gemcitabine‐resistant and cisplatin‐resistant BCs do not exhibit cross‐resistance, and that these BCs exhibit different mRNA patterns, as revealed using RNA sequence analysis. To overcome drug resistance, we used the newly developed pan‐RAS inhibitor Compound 3144. Compound 3144 inhibited cell viability through suppression of RAS‐dependent signaling in gemcitabine‐ and cisplatin‐resistant BCs. RNA sequencing revealed that several genes and pathways, particularly those related to the cell cycle, were significantly downregulated in Compound 3144‐treated BCs. These findings provide insights into potential therapeutic strategies for treating BC.

Abstract Cysticercosis develops in lambs following a Cysticercus tenuicollis infestation, which is the larval stage of Taenia hydatigena. A 7‐day‐old lamb was examined for depression, anorexia, fever (40.5°C), congested mucus membranes, reluctance to move, and a hunched back. Upon necropsy, congestion was noted in the intestines and brain, and the heart had a loose consistency. Soft and pulpy kidneys were evident coupled with watery intestinal contents. Epsilon toxin (Clostridium perfringens type D toxin) was detected using enzyme‐linked immunosorbent assay. A transparent cystic structure was incidentally found attached to the pancreas, within which a scolex was well demonstrated upon histopathology. Chronic active peritonitis was diagnosed at the cyst attachment site. C. tenuicollis was confirmed by polymerase chain reaction and genome sequencing. This report describes prenatal transmission of C. tenuicollis in the present lamb, although this condition is quite rare.

Abstract Background Exposure to environmental carcinogens, such as through smoking, is a major factor in the carcinogenesis of non‐small cell lung cancer (NSCLC). However, genetic factors may also contribute. Methods To identify candidate tumor suppressor genes for NSCLC, we included 23 patients (10 related pairs and 3 individuals) with NSCLC who had other NSCLC‐affected first‐degree relatives in a local hospital. Exome analyses for both germline and somatic (NSCLC specimens) DNA were performed for 17 cases. Germline exome data of these 17 cases revealed that most of the short variants were identical to the variants in 14KJPN (a Japanese reference genome panel of more than 14 000 individuals) and only a nonsynonymous variant in the DHODH gene, p.A347T, was shared between a pair of NSCLC patients in the same family. This variant is a known pathogenic variant of the gene for Miller syndrome. Results Somatic genetic alterations in the exome data of our samples showed frequent mutations in the EGFR and TP53 genes. Principal component analysis of the patterns of 96 types of single nucleotide variants (SNVs) suggested the existence of unique mechanisms inducing somatic SNVs in each family. Delineation of mutational signatures of the somatic SNVs with deconstructSigs for the pair of germline pathogenic DHODH variant‐positive cases showed that the mutational signatures of these cases included SBS3 (homologous recombination repair defect), SBS6, 15 (DNA mismatch repair), and SBS7 (ultraviolet exposure), suggesting that disordered pyrimidine production causes increased errors in DNA repair systems in these cases. Conclusion Our results suggest the importance of the detailed collection of data on environmental exposure along with genetic information on NSCLC patients to identify the unique combinations that cause lung tumorigenesis in a particular family.

Abstract To disseminate, educate, and validate psychiatric clinical practice guidelines, the Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE) project was launched in 2016. In this study, we investigated whether the web‐based courses offered by this project would be as effective as the face‐to‐face courses. We analyzed and compared survey answers about overall participant satisfaction with the course and answers regarding clinical knowledge of schizophrenia and major depressive disorder between 170 participants who took the web‐based courses in 2020 and 689 participants who took the face‐to‐face courses from 2016 to 2019. The web‐based course participants completed the survey questions about satisfaction with the web‐based courses. The web‐based courses were conducted using a combination of web services to make it as similar as possible to the face‐to‐face courses. The degree of satisfaction assessed by the general evaluation of the web‐based courses was higher than what was expected from the face‐to‐face courses. The degree of satisfaction was similar for the courses on schizophrenia and major depressive disorder. In addition, there were no significant differences in overall satisfaction and clinical knowledge between web‐based and face‐to‐face courses. In conclusion, the web‐based courses on clinical practice guidelines provided by the EGUIDE project were rated as more satisfying than the face‐to‐face course that the participants expected to take and no differences in the effectiveness of either course. The results suggest that, after the COVID‐19 pandemic, it would be possible to disseminate this educational material more widely by adopting web‐based courses additionally face‐to‐face courses.

Introduction Small‐cell carcinoma of the urinary bladder has a poor prognosis, and no standard treatment has been established. We encountered a case of a patient with metastasis in which complete response and long‐term survival were obtained by treating the primary lesion with a combination of irinotecan, carboplatin chemotherapy, and radiation therapy. Case presentation An 83‐year‐old man was diagnosed with a bladder tumor with liver metastasis. Small‐cell carcinoma was diagnosed via transurethral resection. Second‐line chemotherapy with irinotecan and carboplatin and irradiation of the primary lesion were significantly effective. The imaging evaluation showed a complete response. The therapeutic effect was maintained for 1 year, even after the discontinuation of chemotherapy. Conclusion Irinotecan and carboplatin should be considered for the treatment of small‐cell carcinoma of the bladder. Irradiation of the primary lesion may also be useful if the extent of metastasis is low.

Abstract Pyoderma is a purulent skin infection usually caused by bacteria and can be divided into primary and secondary categories based on histology. In the present study, an 18‐month‐old female mixed breed sheep was examined for pyoderma at the injection site of the enterotoxemia vaccine. After routine bacteriology and histopathology procedures, secondary pyoderma caused by Proteus mirabilis was diagnosed. The bacterium analysed using genome sequencing and new strain called AJJ 2021 was diagnosed. This is the first report of pyoderma caused by Proteus mirabilis in sheep.

Abstract Aims/Introduction Diabetes mellitus is reported as a risk factor for increased coronavirus disease 2019 (COVID‐19) severity and mortality, but there have been few reports from Japan. Associations between diabetes mellitus and COVID‐19 severity and mortality were investigated in a single Japanese hospital. Materials and Methods Patients aged ≥20 years admitted to Osaka City General Hospital for COVID‐19 treatment between April 2020 and March 2021 were included in this retrospective, observational study. Multivariable logistic regression analysis was carried out to examine whether diabetes mellitus contributes to COVID‐19‐related death and severity. Results Of the 262 patients included, 108 (41.2%) required invasive ventilation, and 34 (13.0%) died in hospital. The diabetes group (n = 92) was significantly older, more obese, had longer hospital stays, more severe illness and higher mortality than the non‐diabetes group (n = 170). On multivariable logistic regression analysis, age (odds ratio [OR] 1.054, 95% confidence interval [CI] 1.023–1.086), body mass index (OR 1.111, 95% CI 1.028–1.201), history of diabetes mellitus (OR 2.429, 95% CI 1.152–5.123), neutrophil count (OR 1.222, 95% CI 1.077–1.385), C‐reactive protein (OR 1.096, 95% CI 1.030–1.166) and Krebs von den Lungen‐6 (OR 1.002, 95% CI 1.000–1.003) were predictors for COVID‐19 severity (R2 = 0.468). Meanwhile, age (OR 1.104, 95% CI 1.037–1.175) and Krebs von den Lungen‐6 (OR 1.003, 95% CI 1.001–1.005) were predictors for COVID‐19‐related death (R2 = 0.475). Conclusions Diabetes mellitus was a definite risk factor for COVID‐19 severity in a single Japanese hospital treating moderately‐to‐severely ill patients.

Abstract Objective To investigate the presence of exacerbating factors of persistent perceptual‐postural dizziness (PPPD) in patients with vestibular symptoms during the early period after vestibular symptoms onset, and to examine possible predictive factors for developing PPPD later. Methods One hundred and fifty‐five consecutive patients with vestibular symptoms who presented less than 90 days from the onset were included in this study. They filled out the Niigata PPPD Questionnaire (NPQ) that consists of 12 questions on the exacerbating factors of PPPD. The NPQ scores of patients who developed PPPD were compared with those of patients who did not develop PPPD during the follow‐up. Results Seventy‐eight of the155 patients (50.3%) showed positive NPQ scores (≥27 points). High NPQ scores were found in patients diagnosed with psychogenic dizziness and vestibular neuritis. During the follow up for an average of 543.3 days after the initial presentation, eight patients (10.3%) developed PPPD. Seven of these eight patients (87.6%) showed positive NPQ scores and all of them had all three exacerbating factors of PPPD at their initial presentation. The NPQ scores of the patients who developed PPPD (40.6 ± 11.6) were significantly higher than those of the patients who did not develop PPPD (26.4 ± 18.3; p

Patients with advanced bladder cancer are generally treated with a combination of chemotherapeutics, including gemcitabine, but the effect is limited due to acquisition of drug resistance. Thus, in this study, we investigated the mechanism of gemcitabine resistance. First, gemcitabine‐resistant cells were established and resistance confirmed in vitro and in vivo. Small RNA sequencing analyses were performed to search for miRNAs involved in gemcitabine resistance. miR‐99a‐5p, selected as a candidate miRNA, was downregulated compared to its parental cells. In gain‐of‐function studies, miR‐99a‐5p inhibited cell viabilities and restored sensitivity to gemcitabine. RNA sequencing analysis was performed to find the target gene of miR‐99a‐5p. SMARCD1 was selected as a candidate gene. Dual‐luciferase reporter assays showed that miR‐99a‐5p directly regulated SMARCD1. Loss‐of‐function studies conducted with si‐RNAs revealed suppression of cell functions and restoration of gemcitabine sensitivity. miR‐99a‐5p overexpression and SMARCD1 knockdown also suppressed gemcitabine‐resistant cells in vivo. Furthermore, β‐galactosidase staining showed that miR‐99a‐5p induction and SMARCD1 suppression contributed to cellular senescence. In summary, tumor‐suppressive miR‐99a‐5p induced cellular senescence in gemcitabine‐resistant bladder cancer cells by targeting SMARCD1.

Abstract Liver cirrhosis is the final stage of chronic liver disease (CLD) and is associated with high morbidity and mortality. Various complications such as portal hypertension, ascites retention, hepatic encephalopathy, and hepatorenal syndrome deeply affect patient outcome. The most common tools to predict the outcome of a CLD patient include the following: assessing severity of portal hypertension; scoring systems such as the model of end‐stage liver disease and Child–Pugh score and blood biomarkers related to complications and/or survival rate. In this article, we summarize recent studies of noninvasive markers for predicting impending complications related to CLD and discuss the clinical value of currently available blood biomarkers based on evidence from the literature. In addition, noninvasive blood biomarker assays for different prognostic functions were validated on 113 liver cirrhosis patients at our institution using Kaplan–Meier curve analysis to confirm that these markers can satisfactorily predict CLD‐related patient death.

Abstract The power conversion efficiencies of organic solar cells (OSCs) have routinely lagged far behind those of their inorganic counterparts. However, owing to the enormous contributions of many researchers, the power conversion efficiencies of OSCs have rapidly improved and now exceed 19%. The charge generation mechanisms in OSCs have been heavily debated during this period while acquiring valuable knowledge. This review highlights fundamental and cutting‐edge research that rationalizes why OSCs can generate photocurrent so efficiently. In particular, a photophysicist's views on exciton diffusion to donor:acceptor interfaces, charge transfer at the donor:acceptor interface, and long‐range spatial dissociation of charge transfer states are discussed. Although a general consensus in this area has not been reached yet, recent time‐resolved spectroscopic measurements provide important photophysical insights that can help achieving a better understanding of the charge generation mechanism in OSCs. Based on these observations, future research directions for realizing further improvements in OSC performance are discussed.

Abstract Background Physical frailty is related to adverse outcomes, and poor oral health has been linked to malnourishment. Subjective measures of oral health‐related quality of life (OHRQoL) have been used as indicators of the oral health problems of older adults, and they have been associated with malnourishment. This study aimed to assess OHRQoL's association with physical frailty. Methods Cross‐sectional study was conducted using data from the Nagasaki Islands Study that enrolled participants aged ≥60 years at Japanese national medical check‐ups from 2014 to 2019. Physical frailty phenotype criteria were determined using the modified Fried frailty phenotype model. OHRQoL was assessed using the Geriatric Oral Health Assessment Index (GOHAI). Dentists conducted clinical dental examinations. Simple correlation and linear regression analyses were performed to investigate the associations of number of physical frailty phenotype criteria with GOHAI and other oral health indicators. Results Among 1341 participants with a mean age of 72 years, GOHAI score was significantly associated with number of physical frailty phenotype criteria (B = −0.01, 95% confidence interval: −0.02 to −0.01, p

Abstract Interleukin‐6 is a pleiotropic cytokine that plays a pathogenic role in type 1 diabetes. Therefore, anti‐interleukin‐6 receptor antibody, tocilizumab, used for the treatment of rheumatoid arthritis, is considered a candidate for immune intervention in type 1 diabetes. Here, we report the case of a 73‐year‐old woman (HLA‐DR9‐DQ3 homozygote) with well‐controlled rheumatoid arthritis who developed type 1 diabetes while receiving tocilizumab treatment. At 57 years‐of‐age, the patient was diagnosed with rheumatoid arthritis, for which she underwent tocilizumab therapy that enabled complete suppression of her joint inflammation. A total of 17 months after starting tocilizumab therapy, she noticed polydipsia, polyuria, general fatigue and weight reduction (−2 kg/month), and was diagnosed with type 1 diabetes with diabetic ketoacidosis based on an arterial pH of 7.26, serum ketone body of 7,437 μmol/L, blood glucose level of 925 mg/dL, glycated hemoglobin of 13.2% and the presence of anti‐islet autoantibodies. This case report shows valuable insight regarding the effect of anti‐interleukin‐6 receptor antibody therapy on type 1 diabetes prevention.

Abstract Background Effective treatments for cancer harboring mutant RAS are lacking. In Drosophila, it was reported that PP6 suppresses tumorigenicity of mutant RAS. However, the information how PP6 regulates oncogenic RAS in mammals is limited. Methods We examined the effects of PP6 gene (Ppp6c) deficiency on tongue tumor development in K (K‐rasG12D)‐ and KP (K‐rasG12D + Trp53‐deficient)‐inducible mice. Results Mice of K and KP genotypes developed squamous cell carcinoma in situ in the tongue approximately 2 weeks after the induction of Ppp6c deficiency and was euthanized due to 20% loss of body weight. Transcriptome analysis revealed significantly different gene expressions between tissues of Ppp6c‐deficient tongues and those of Ppp6c wild type, while Trp53 deficiency had a relatively smaller effect. We then analyzed genes commonly altered by Ppp6c deficiency, with or without Trp53 deficiency, and identified a group concentrated in KEGG database pathways defined as ‘Pathways in Cancer’ and ‘Cytokine‐cytokine receptor interaction’. We then evaluated signals downstream of oncogenic RAS and those regulated by PP6 substrates and found that in the presence of K‐rasG12D, Ppp6c deletion enhanced the activation of the ERK‐ELK1‐FOS, AKT‐4EBP1, and AKT‐FOXO‐CyclinD1 axes. Ppp6c deletion combined with K‐rasG12D also enhanced DNA double‐strand break (DSB) accumulation and activated NFκB signaling, upregulating IL‐1β, COX2, and TNF.

Abstract We present a rare case of acute duodenal variceal rupture after B‐RTO that was successfully treated with endoscopic CA injection therapy. A 74‐year‐old Japanese woman was transferred to our hospital due to progressive general malaise and hematemesis. Gastroduodenoscopy (GDS) showed duodenal varices without active bleeding in the second portion of duodenum. Balloon‐occluded retrograde transvenous obliteration (B‐RTO) was carried out to prevent duodenal variceal rebleeding. Good pooling of ethanolamine oleate with iopamidol (EOI) was observed in duodenal varices using balloon catheters. However, massive melena was observed immediately after B‐RTO. Emergent GDS revealed a white plug on the treated varix, thus endoscopic cyanoacrylate (CA) injection therapy was performed. We speculated that the injection of EOI increased the pressure in the duodenal varices which resulted in rupture of duodenal varices. B‐RTO was effective therapy to prevent duodenal variceal rebleeding, but postprocedural monitoring is required as illustrated by this case. We suggest that careful monitoring and backup system for endoscopy are required during or after B‐RTO.

Abstract Background and Aim Percutaneous radiofrequency ablation (RFA) is a minimally invasive and curative local treatment for hepatocellular carcinoma (HCC). However, serious concerns remain regarding critical recurrences such as metastasis, dissemination, and/or seeding due to RFA. In August 2006, we introduced selective feeding artery ablation before tumor ablation to reduce the risk of critical recurrence by blocking tumor blood flow. The aim of the present study was to clarify whether feeding artery ablation before tumor ablation can reduce the risk of critical recurrence after RFA. Methods This study retrospectively analyzed 279 patients with primary, solitary, and hypervascular HCC ≤5 cm in diameter who were treated with RFA alone between April 2001 and August 2013. Critical recurrence was defined as intra‐ or extrahepatic metastasis, dissemination, or seeding that was difficult to treat radically. Results Of the 279 HCC patients, 157 patients were treated with conventional RFA alone, and 122 patients underwent RFA with prior feeding artery ablation. Although no significant differences were seen in the rates of local tumor progression‐free survival, overall recurrence‐free survival, or overall survival between a conventional RFA group and a prior feeding artery ablation group, significant differences were seen in rates of critical recurrence‐free survival and cancer‐specific survival (5‐year, 69 vs 81%, P = 0.01 and 76 vs 88%, P = 0.03, respectively). On multivariate analysis, prior feeding artery ablation, tumor diameter, and alpha‐fetoprotein were independent factors related to critical recurrence. Conclusions Feeding artery ablation before tumor ablation may reduce the risk of critical recurrence.

Abstract Statins are widely used medications for the treatment of hypercholesterolemia, as well as prevention of cardiovascular disease. We report two patients with type 1 diabetes who developed autoimmune hepatitis after the administration of statin. The first patient developed the marked elevation of liver enzymes 6 months into atorvastatin therapy. The second patient developed liver dysfunction 8 months after the initiation of rosuvastatin therapy. Liver biopsies in both patients showed either portal, interface and lobular hepatitis or a piece‐meal necrosis with lymphocytes and plasma cell infiltration that were compatible with autoimmune hepatitis. Then, both patients were started on prednisolone, to which they responded well. Liver biopsy is to be considered for type 1 diabetes patients if there is no improvement of liver dysfunction after discontinuation of statins.

Abstract This study aimed to characterize diabetic patients incidentally found to be positive for glutamic acid decarboxylase autoantibodies (GADA) in general practice. Using bridging‐type enzyme‐linked immunosorbent assay, we screened 1,040 patients with phenotypic type 2 diabetes for GADA, finding 25 (2.4%) to be positive. However, on retesting, with a median interval of 19 days, 44% of GADA‐positive patients turned negative (Disappearing Group). The mean age at diabetes onset was significantly higher (P

Abstract Background and Aim Portosystemic shunt occlusion using endovascular treatment can transiently improve liver function in patients with decompensated cirrhosis. In recent years, viral hepatitis can be easily controlled. The present study aimed to clarify the safety and efficacy of endovascular treatment in decompensated cirrhotic patients, and to elucidate whether viral treatment improves the prognosis after shunt occlusion. Methods Among 98 cirrhotic patients who received portosystemic shunt occlusion from January 2007 to June 2016, we retrospectively analyzed 61 decompensated cirrhotic patients. Results Forty‐five patients had viral hepatitis. Recovery rates of liver function to Child A within 6 months in viral hepatitis, non‐viral hepatitis, and overall were 78% (35/45), 81% (13/16), and 79% (48/61), respectively. Recovery rates according to baseline Child‐Pugh score were as follows: score 7, 88% (15/17); score 8, 89% (24/27); score 9, 69% (9/13); and score ≥ 10, 0% (0/4). Three‐year reprogression rates to decompensated cirrhosis for non‐virus, non‐sustained viral negativity (SVN), and SVN groups were 23 100, and 0%, respectively (P

Abstract Objective To evaluate the visibility of colorectal lesions using a novel image processing algorithm, texture and color enhancement imaging (TXI), that allows the acquisition of brighter images with enhanced color and surface structure. Methods During August–September 2019, patients referred for endoscopic treatment were prospectively recruited. Electronic data acquired while observing colorectal lesions using white light imaging (WLI) were obtained and recorded: WLI, TXI mode1 (with color enhancement), and TXI mode2 (without color enhancement) videos were constructed. The lesions were also recorded using narrow‐band imaging (NBI) from the same perspective as WLI. Four video clips (WLI, TXI mode1, TXI mode2, and NBI) were made per lesion. Thereafter, video files for evaluations were prepared by randomly arranging all video clips. Finally, visualization scores were evaluated by four endoscopists, and the WLI, TXI mode1, TXI mode2, and NBI results were compared. Results Overall, 22 patients with 68 lesions were recruited; the video file for evaluation subsequently comprised 272 randomly arranged video clips. Mean visualization scores using WLI, TXI mode1, TXI mode2, and NBI were 70.0 (±20.1), 80.5 (±18.6), 75.6 (±18.1), and 69.0 (±20.6), respectively. Mean visualization scores for flat lesions using WLI, TXI mode1, TXI mode2, and NBI were 64.1 (±21.2), 76.5 (±20.18), 71.8 (±19.4), and 64.2 (±22.0), respectively. Visualization scores using TXI mode1 were significantly better than those using WLI, TXI mode2, or NBI. Conclusions TXI enables improved visualization of colorectal lesions, even flat lesions, than WLI and NBI. TXI may allow better detection of colorectal lesions, although further prospective studies are required.

Abstract Obesity causes multiple conditions such as type 2 diabetes, cardiovascular disease, and so on, and an intervention is needed for controlling weight and improving metabolic syndrome. However, the effectiveness of lifestyle interventions and pharmacotherapy are restrictive for losing weight. Endoscopic sleeve gastroplasty (ESG) was developed as a new therapy, picking the best of both medication and surgery, less invasive and more effective. Recently, ESG is gradually spreading in Western countries, but there is Case report doesn't need conclusion/result for Japanese patients. We herein reported the first clinical case of ESG in Japan. Given the situation of the pandemic of COVID‐19, we could not invite a proctor from Western countries and receive the instruction of the device setting and maneuver face to face. Thus, we conducted the training for device setting, maneuver, and operation under a web‐based international remote collaboration. Eventually, we completed ESG without an adverse event. We could prove this web‐based proctor system was useful through the introduction of ESG in Japan. The international remote collaboration could become a new normal even in the endoscopy field post‐COVID‐19 era.

Abstract Carney complex (CNC) is a rare hereditary syndrome that involves endocrine dysfunction and the development of various types of tumors. Chromosome 2p16 and PRKAR1A on chromosome 17 are known susceptibility loci for CNC. Here we report a mother and son with CNC caused by an 8.57‐kb deletion involving the transcription start site and non‐coding exon 1 of PRKAR1A. The proband is a 28‐year‐old male with bilateral large‐cell calcified Sertoli cell testicular tumors and pituitary adenoma. Comprehensive genomic profiling for cancer mutations using Foundation One CDx failed to detect any mutations in PRKAR1A in DNA from the testicular tumor. Single‐nucleotide polymorphism array analysis of the proband’s genomic DNA revealed a large deletion in the 5′ region of PRKAR1A. Genomic walking further delineated the region an 8.57‐kb deletion. A 1.68‐kb DNA fragment encompassed by the deleted region showed strong promoter activity in a NanoLuc luciferase reporter assay. The patient’s mother, who is suffering from recurrent cardiac myxoma, a critical sign for CNC, carried an identical deletion. The 8.57‐kb deleted region is a novel lesion for CNC and will facilitate molecular diagnosis of the disease.

Abstract Aim/Introduction Autoantibodies to the 65 kDa isoform of glutamic acid decarboxylase (GADA) are a valuable diagnostic and predictive marker for type 1 diabetes. Recently, it has been reported that a significant proportion of sera in the commercial RSR radioimmunoassay (RIA) that have tested positive for GADA have then turned negative in RSR enzyme‐linked immunosorbent assay (ELISA) tests in patients with type 1 diabetes. The present study aimed to investigate whether the GADA result discrepancies between RSR‐RIA and RSR‐ELISA are related to autoantibody affinity. Methods GADA affinity was measured by a competitive binding experiment using unlabeled recombinant human GAD65 in 12 discordant samples (5 RIA[+]/ELISA[−] and 7 RIA[−]/ELISA[+] sera). Furthermore, the effect of the initial incubation time on the GADA positivity was also examined using the ELISA test. Results GADA affinities were >1010 L/mol in two of five RIA(+)/ELISA(−) and all of seven RIA(−)/ELISA(+) sera. After an initial incubation time longer than the recommended 1 h, the GADA titer in three of five RIA(+)/ELISA(−) sera and all RIA(−)/ELISA(+) sera increased 1.6‐ to 100‐fold. However, the titer in 12 GADA‐negative sera from healthy controls remained unchanged after the longer incubation. The increment ratio of GADA titer was positively correlated with GADA affinity (r = 0.991, P