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Abstract Objectives Three‐tesla MRI with gadolinium‐based contrast agents is important in diagnosing Ménière's disease. However, contrast agents cannot be used in some patients. By using the compositional difference between the inner ear endolymph and perilymph, we performed basic and clinical research focused on potassium ions and protein to find the optimal parameters for visualizing endolymphatic hydrops on MRI without contrast. We then examined the relationship between severity stage and visualization rate of endolymphatic hydrops. Methods In phantom experiments simulating the endolymph and perilymph, we explored MRI parameters that could be used to separate endolymph from perilymph by gradually changing the inversion time. We then used these parameters to perform both new non‐contrast MRI and contrast MRI on the same day in Ménière's disease patients, and we compared the visualization rates of endolymphatic hydrops under the two modalities. Fifty patients were selected from 478 patients with Ménière's disease of different severity stages; 12 patients had asthma and allergy to contrast agents. Results The higher the disease stage, the higher the endolymphatic hydrops visualization rate. The new non‐contrast MRI gave significantly higher (p

Abstract Background Zinc (Zn), an essential trace element, has an adverse influence on the prognosis of several cancers. However, the association between the preoperative serum Zn level and outcomes in patients with advanced esophageal cancer in the current neoadjuvant treatment era remains unclear. Methods This study involved 185 patients with esophageal cancer who underwent R0 surgery after neoadjuvant chemotherapy from August 2017 to February 2021. We retrospectively investigated the relationship between the preoperative serum Zn level and the patients' outcomes. Results The patients were divided into a low Zn group (

Abstract Aim The anti‐tumor effects of natural killer (NK) cells vary among individuals. Tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) expressed on liver NK cells is a marker of anti‐tumor cytotoxicity against hepatocellular carcinoma (HCC) in immune cell therapy. This study aimed to develop a liver immune status index (LISI) that predicts low TRAIL expression and validates its ability to predict recurrence after initial hepatectomy for primary HCC. Methods A functional analysis of liver NK cells co‐cultured with interleukin‐2 for 3 days was performed of 40 liver transplant donors. The LISI, which predicted low TRAIL expression (25% quartile:

Abstract We studied the pathophysiology of aplastic anaemia (AA) in six different pairs of relatives without a family history of hematologic disorders or congenital AA. Five and four of the six pairs shared the HLA‐DRB1*15:01 and B*40:02 alleles, respectively. Glycosylphosphatidylinositol‐anchored protein‐deficient blood cells were detected in eight of the 10 patients evaluated. In a mother‐daughter pair from one family, flow cytometry detected leukocytes lacking HLA‐A2 due to loss of heterogeneity in chromosome 6p. Whole‐exome sequencing of the family pair revealed a missense mutation in MYSM1. These results suggest that genetic inheritance of immune traits might underlie familial AA in some patients.

Abstract Aim Osteopenia and sarcopenia, features of the aging process, are recognized as major health problems in an aging society. This study investigated the prognostic impact of osteosarcopenia, the coexistence of osteopenia and sarcopenia, in older adults undergoing curative resection for colorectal cancer. Methods We retrospectively reviewed data of older adults aged 65–98 y who had undergone curative resection for colorectal cancer. Osteopenia was evaluated by bone mineral density measurement in the midvertebral core of the 11th thoracic vertebra on preoperative computed tomography images. Sarcopenia was evaluated by measuring the skeletal muscle cross‐sectional area at the third lumbar vertebra level. Osteosarcopenia was defined as the coexistence of osteopenia and sarcopenia. We explored the relationship of preoperative osteosarcopenia with the disease‐free and overall survival after curative resection. Results Among the 325 patients included, those with osteosarcopenia had significantly lower overall survival rates than those with osteopenia or sarcopenia alone (P

Abstract Aim The purpose of this study is to evaluate the safety and pharmacokinetics of the novel morpholino oligomer NS‐089/NCNP‐02 which can induce exon 44 skipping, in patients with DMD. Additionally, we aimed to identify markers predictive of therapeutic efficacy and determine the optimal dosing for future studies. Methods This is an open‐label, dose‐escalation, two‐center phase I/II trial in ambulant patients with DMD, presence of an out‐of‐frame deletion, and a mutation amenable to exon 44 skipping. Part 1 is a stepwise dose‐finding stage (4 weeks) during which NS‐089/NCNP‐02 will be administered intravenously at four dose levels once weekly (1.62, 10, 40, and 80 mg/kg); Part 2 is a 24‐week evaluation period based on the dosages determined during Part 1. The primary (safety) endpoints are the results of physical examinations, vital signs, 12‐lead electrocardiogram and echocardiography tests, and adverse event reporting. Secondary endpoints include expression of dystrophin protein, motor function assessment, exon 44 skipping efficiency, plasma and urinary NS‐089/NCNP‐02 concentrations, and changes in blood creatine kinase levels. Discussion Exon‐skipping therapy using ASOs shows promise in selected patients, and this first‐in‐human study is expected to provide critical information for subsequent clinical development of NS‐089/NCNP‐02.

Abstract The prognosis of acute myeloid leukemia (AML) patients with der(1;7)(q10;p10) who underwent allogeneic hematopoietic stem cell transplantation (allo‐SCT) is unclear due to its rarity. We retrospectively analyzed 151 AML patients with der(1;7)(q10;p10) and compared the findings with those of 853 AML patients with monosomy 7 or chromosome 7q deletion (‐7/del(7q)) using Japanese nationwide registry data. The der(1;7)(q10;p10) group showed significantly better transplant outcomes than the ‐7/del(7q) group. In the multivariate analysis of the der(1;7)(q10;p10) group, additional chromosomal abnormalities and a poor performance status significantly influenced the survival. In conclusion, allo‐SCT is a feasible treatment option for AML patients with der(1;7)(q10;p10).

Abstract Background and Aim Helicobacter pylori (H. pylori) eradication has become popular as it prevents the development of gastric cancer. There have been no comprehensive studies on advanced gastric cancer (AGC) after eradication; thus, the clinical characteristics remain unclear. This study aimed to compare the characteristics of AGC after eradication and with current H. pylori infection and evaluate the esophagogastroduodenoscopy (EGD) follow‐up after eradication. Methods This single‐center, retrospective study included 261 consecutive patients diagnosed with AGC through EGD. The patients were grouped based on their H. pylori status: eradication (n = 48) and infection (n = 213) groups. Univariate analysis was conducted to compare clinicopathological characteristics between groups. The clinical course of the eradication group was analyzed by dividing the patients into three groups according to the interval from the last EGD until AGC detection: short‐interval ( 20 years after eradication. The R0 rates in the short‐, intermediate‐, and long‐interval groups were 83.3%, 71.4%, and 60%, respectively. Conclusions AGC after eradication was more often detected at the phase in which R0 resection was possible. EGD follow‐up with tight intervals of at least 5 years after eradication is advisable.

Abstract To determine the significance of increased Wilms tumor 1 (WT1) gene expression in the peripheral blood of patients with acquired aplastic anemia (AA), we analyzed serial changes in WT1 mRNA copy number (WT1cn) in 63 patients with AA as well as in five patients with myelodysplastic syndromes (MDS) and seven patients with paroxysmal nocturnal hemoglobinuria (PNH). WT1cn was higher than the cut‐off (≥50 copies/μg RNA) at the time of the first measurement in 41% of untreated (60–190 copies/μg RNA [median 130]) and 59% of treated (59–520 copies/μg RNA [median 150]) AA patients. Although WT1cns gradually increased in most AA patients during the 2–105 months follow‐up period, they did not lead to clonal evolution except in three patients in whom the maximum change ratio of WT1cn (WT1cn‐change max), defined as the ratio of WT1cn at the first examination to that of the maximum value, exceeded 20.0 and who developed MDS at 2, 46, and 105 months. Increased WT1 gene expression was enriched in granulocytes rather than in mononuclear cells in most WT1‐positive AA patients and did not correlate with mutations of genes associated with myeloid malignancy. WT1cns were high at 690–5700 (median 2000) in MDS patients and remained high thereafter, while WT1cns in PNH patients (77–200; median 96) were similar to those in AA. Thus, moderate increases in WT1cns up to 600 are common in AA patients in stable remission. An increase in the WT1cn‐change max over 20.0 may portend transformation from AA to MDS.

Abstract The relationships among esophagectomy for esophageal cancer, dysphagia, and sarcopenia are still unclear. We considered appropriate interventions for patients with resectable esophageal cancer for the purpose of reducing postoperative dysphagia and aspiration pneumonia. Dysphagia in patients with esophageal cancer is caused by patient characteristics, such as pathophysiology and age, or complications after esophagectomy. Recently, sarcopenic dysphagia, defined as dysphagia associated with whole‐body sarcopenia, has attracted attention in various fields, and a large proportion of patients with esophageal cancer are expected to have sarcopenic dysphagia. Our systematic review and meta‐analysis suggested that preoperative sarcopenia in patients with esophageal cancer is related to pulmonary complications after esophagectomy, and some reports also suggested that sarcopenia in swallowing‐related muscles, such as the geniohyoid muscle and tongue, might be associated with postoperative pneumonia or dysphagia after esophagectomy. However, clinical studies on sarcopenic dysphagia in patients with esophageal cancer have been limited. To prevent sarcopenic dysphagia after esophagectomy, perioperative interventions involving not only swallowing rehabilitation, but also physical exercise and nutritional support are important. Moreover, several reports have suggested that the chin‐down maneuver might be effective for preventing aspiration after an esophagectomy. To inhibit the progression of sarcopenic dysphagia after esophagectomy, evaluations and interventions by multidisciplinary staff are likely to be necessary.

Abstract The phenotypic changes in hematopoietic stem progenitor cells (HSPCs) with somatic mutations of malignancy‐related genes in patients with acquired aplastic anemia (AA) are poorly understood. As our initial study showed increased CXCR4 expression on HLA allele‐lacking (HLA[−]) HSPCs that solely support hematopoiesis in comparison to redundant HLA(+) HSPCs in AA patients, we screened the HSPCs of patients with various types of bone marrow (BM) failure to investigate their CXCR4 expression. In comparison to healthy individuals (n = 15, 12.3%–49.9%, median 43.2%), the median CXCR4+ cell percentages in the HSPCs of patients without somatic mutations were low: 29.3% (14.3%–37.3%) in the eight patients without HLA(−) granulocytes, 8.8% (4.1%–9.8%) in the five patients with HLA(−) cells accounting for >90% of granulocytes, and 7.8 (2.1%–8.7%) in the six patients with paroxysmal nocturnal hemoglobinuria. In contrast, the median percentage was much higher (78% [61.4%–88.7%]) in the five AA patients without HLA(−) granulocytes possessing somatic mutations (c‐kit, t[8;21], monosomy 7 [one for each], ASXL1 [n = 2]), findings that were comparable to those (66.5%, 63.1%–88.9%) in the four patients with advanced myelodysplastic syndromes. The increased expression of CXCR4 may therefore reflect intrinsic abnormalities of HSPCs caused by somatic mutations that allow them to evade restriction by BM stromal cells.

Background We aimed to clarify which time‐to‐maximum of the tissue residue function (Tmax) mismatch ratio is useful in predicting anterior intracranial atherosclerotic stenosis (ICAS)–related large‐vessel occlusion (LVO) before endovascular therapy. Methods and Results Patients with ischemic stroke who underwent perfusion‐weighted imaging before endovascular therapy for anterior intracranial LVO were divided into those with ICAS‐related LVO and those with embolic LVO. Tmax ratios of >10 s/>8 s, >10 s/>6 s, >10 s/>4 s, >8 s/>6 s, >8 s/>4 s, and >6 s/>4 s were considered Tmax mismatch ratios. Binominal logistic regression was used to identify ICAS‐related LVO, and the adjusted odds ratio (aOR) and 95% CI for each Tmax mismatch ratio increase of 0.1 were calculated. A similar analysis was performed for ICAS‐related LVO with and without embolic sources, using embolic LVO as the reference. Of 213 patients (90 women [42.0%]; median age, 79 years), 39 (18.3%) had ICAS‐related LVO. The aOR (95% CI) per 0.1 increase in Tmax mismatch ratio in ICAS‐related LVO with embolic LVO as reference was lowest with Tmax mismatch ratio >10 s/>6 s (0.56 [0.43–0.73]). Multinomial logistic regression analysis also showed the lowest aOR (95% CI) per 0.1 increase in Tmax mismatch ratio with Tmax >10 s/>6 s (ICAS‐related LVO without embolic source: 0.60 [0.42–0.85]; ICAS‐related LVO with embolic source: 0.55 [0.38–0.79]). Conclusions A Tmax mismatch ratio of >10 s/>6 s was the optimal predictor of ICAS‐related LVO compared with other Tmax profiles, with or without an embolic source before endovascular therapy. Registration clinicaltrials.gov. Identifier NCT02251665.

Introduction Transvaginal mesh surgery can cause mesh complications including rare rectovaginal fistula. We report a case of a rectovaginal fistula treated transvaginally without colostomy. Case presentation A 57‐year‐old female was referred to us due to post‐hysterectomy prolapse and had transvaginal mesh surgery. She underwent transvaginal hysterectomy because of uterine prolapse at age 33 and had taken steroids to treat pemphigus. Two years later, she developed vaginal bleeding and discharge. Transvaginal mesh removal was planned to treat vaginal mesh exposure, but immediately before the operation digital rectal examination revealed rectovaginal fistula. Mesh removal and fistula closure were performed transvaginally without colostomy. Three years of follow‐up showed no recurrence of mesh exposure, fistula, or prolapse. Conclusion Rectovaginal fistula following mesh surgery may be treated transvaginally without colostomy if infection is minimal. To evaluate mesh exposure on the posterior vaginal wall, rectal examination should be done along with vaginal examination.

Introduction We encountered six post‐bath incontinence cases caused by bathwater entrapment in the vagina. Case presentation The age of onset was distributed from 16 to 78 (average 38) and five out of six patients were parous. Three patients developed post‐bath incontinence immediately after vaginal delivery. One patient developed post‐bath incontinence after beginning to bathe in a reclined position and another after undergoing transvaginal mesh surgery to treat prolapse. All patients showed dribbling incontinence without urgency limited to within 30 min after bathing. Patients were instructed to put a towel between their legs and apply abdominal pressure to evacuate the entrapped water. Additionally, they were advised to squat in the bathtub to prevent water entrapment. This simple behavioral therapy relieved symptoms. Conclusion The differential diagnosis of incontinence in women should include entrapped fluid incontinence such as bathwater incontinence, pool water incontinence, and vaginal reflux during micturition.

Abstract We report a case in which analysis of copy number variation revealed local recurrence of submucosal invasive colorectal cancer after curative endoscopic submucosal dissection (ESD). An 86‐year‐old man with a history of abdominoperineal resection of the rectum for rectal cancer underwent resection with ESD for early‐stage sigmoid cancer 5 cm away from the stoma opening. At the same time, ileocecal resection was performed for advanced cecal cancer. Twelve months after ESD, advanced cancer occurred in the area of the ESD lesion. It was unclear if the cancer was a local recurrence after ESD, implantation of cecal cancer, or a new lesion. Copy number variation analysis performed for the three lesions revealed that the new lesion originated from residual tumor cells from ESD and was unlikely to be cecal cancer.

Abstract Background The aim of the present study was to use surgical and histological results to develop a simple noninvasive technique to improve nodal staging using preoperative PET/CT in patients with resectable lung cancer. Methods Preoperative PET/CT findings (pStage IB–III 182 patients) and pathological diagnoses after surgical resection were evaluated. Using PET/CT images to determine the standardized uptake value (SUV) ratio, the SUVmax of a contralateral hilar lymph node (on the side of the chest opposite to the primary tumor) was measured simultaneously. The I/C‐SUV ratio was calculated as ipsilateral hilar node SUV/contralateral hilar node SUV. Receiver operating characteristic (ROC) curves were then used to analyze those data. Results Based on ROC analyses, the cutoff I/C‐SUV ratio for diagnosis of lymph node metastasis was 1.34. With a tumor ipsilateral lymph node SUVmax ≥2.5, an IC‐SUV ratio ≥1.34 had the highest accuracy for predicting N1/N2 metastasis; the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of nodal staging were 60.66, 85.11, 84.09, 62.5 and 71.29%, respectively. Conclusions When diagnosing nodal stage, a lymph node I/C‐SUV ratio ≥1.34 can be an effective criterion for determining surgical indications in advanced lung cancer.

Abstract Background and Aim The risk factors for lymph node metastasis (LNM) of duodenal neuroendocrine tumors (DNETs) are not well identified, and a definitive standard of treatment for DNETs has not been established. In this study, we aimed to identify the risk factors for LNM and establish the indication of local resection for DNETs. Methods We retrospectively reviewed 55 patients with 60 non‐ampullary and nonfunctional DNETs. We evaluated the risk factors for LNM and compared the outcomes between endoscopic resection (ER) for DNETs

Abstract Purpose To identify the efficacy of endometrial curettage on antibiotic‐resistant chronic endometritis (CE) in infertile women. Methods Of 1580 women with CE, 87 with antibiotic‐resistant CE after two to five cycles of antibiotic treatment were recruited between 2019 and 2021. The women who underwent endometrial curettage without applying any force and, in the subsequent menstrual cycle, endometrial sampling for CD138 immunostaining without antibiotic use. Pregnancy outcomes after in vitro fertilization treatment were analyzed in women who did not desire endometrial curettage and in those with cured and persistent CE after endometrial curettage. Results In 64 women who underwent endometrial curettage, the number of CD138‐positive cells decreased from 28.0 ± 35.3 to 7.7 ± 14.0 (p

Abstract Aims Isometric handgrip (IHG) training reduces the blood pressure in patients with hypertension. It is unclear how IHG exercise affects the haemodynamics and cardiovascular function through the muscle reflex in patients with heart failure (HF) with reduced (HFrEF) and preserved ejection fraction (HFpEF). Methods and results Twenty patients (HFrEF: n = 10, HFpEF: n = 10) underwent left ventricular (LV) pressure–volume assessments using a conductance catheter and microtip manometer to evaluate haemodynamics, LV and arterial function, and LV‐arterial coupling during 3 min of IHG at 30% of maximal voluntary contraction (MVC), followed by 3 min of post‐exercise circulatory arrest (PECA). Three minutes of IHG exercise produced significant and modest increases in the heart rate (HR) and LV end‐systolic pressure (LVESP), respectively, in both HFpEF and HFrEF groups. In HFrEF, the increase in LVESP was caused by the variable increase in effective arterial elastance (Ea), which was counterbalanced by the increase in LV end‐systolic elastance (Ees), resulting in a maintained Ees/Ea. In HFpEF, the increase in LVESP was not accompanied by changes in Ea, Ees, Ees/Ea, or LV end‐diastolic pressure. LVESP during PECA was not maintained in HFpEF, suggesting smaller metabo‐reflex activity in HFpEF. Conclusions The IHG exercise used in this study may increase the LVESP and LVEDP without detrimental effects on cardiac function or ventricular‐arterial coupling, especially in HFpEF patients. The effects of IHG exercise on haemodynamics and ventricular‐arterial coupling may be affected by the patient background and the type and intensity of the exercise.

Abstract This study sought to investigate whether the relation between increased blood pressure (BP) variability and increased arterial stiffness confers a risk for cardiovascular disease (CVD) events. We analyzed 2648 patients from a practitioner‐based population (mean ± SD age 64.9 ± 11.4 years: 75.8% taking antihypertensive medication) with at least one cardiovascular risk factor who underwent home BP monitoring in the Japan Morning Surge‐Home Blood Pressure Study. The standard deviation (SDSBP), coefficient of variation (CVSBP), and average real variability (ARVSBP) were assessed as indexes of day‐by‐day home systolic BP (SBP) variability. The authors assessed arterial stiffness by brachial‐ankle pulse wave velocity (baPWV) and divided patients into lower (

Abstract Amyloid transthyretin (ATTR) depositions cause left ventricular (LV) hypertrophy, diastolic dysfunction, and heart failure. The time course of changes in LV geometry and diastolic dysfunction has not been fully reported in patients with ATTR cardiomyopathy. A 79‐year‐old woman with previous myocardial infraction presented with shortness of breath on exertion, and progressive bilateral lower extremity weakness and polyneuropathy. She was diagnosed with Val30Met hereditary ATTR cardiomyopathy by cardiac biopsy and genetic testing. During the past 5 year period, significant LV concentric remodelling with small LV cavity occurred, resulting in an increased LV stiffness and prolonged LV relaxation. This case report highlights the time course of changes in LV geometry and diastolic function and the importance of early diagnosis of ATTR cardiomyopathy.

Abstract Background and Aim Helicobacter pylori antibody levels in the blood are currently measured using an ELISA. In April 2016, FUJIFILM Wako Pure Chemical Corporation launched the “l‐type Wako Helicobacter pylori antibody J" test, which is based on the latex agglutination turbidimetric immunoassay. In this study, we investigated the usefulness of the Wako test. Methods We measured H. pylori antibody levels using both the ELISA and Wako test in 180 patients who underwent upper gastrointestinal endoscopy at our hospital between September 2017 and February 2019. Ninety patients were infected with H. pylori. We calculated the diagnostic accuracy, sensitivity, and specificity of each test and the concordance rate between the ELISA and Wako test. If lower limits of 90% confidence intervals (CIs) for each diagnostic validity exceeded the 85% threshold, the usefulness of the diagnostic test was confirmed. Results The diagnostic accuracy, sensitivity, and specificity were 94.4% (90% CI, 90.8–97.0%), 94.4% (90% CI, 88.7–97.8%), and 94.4% (90% CI, 88.7–97.8%), respectively, when the Wako test was used, and 94.4% (90% CI, 90.8–97.0%), 88.9% (90% CI, 81.9–93.8%), and 100% (90% CI, 96.0–100%), respectively, when the ELISA was used. The concordance rate between the two tests was high (κ = 0.8444). Conclusions We confirmed the usefulness of the Wako test, especially when screening for H. pylori infection, due to its high sensitivity.

Abstract Background and Aim l‐Menthol has smooth muscle‐relaxing and antiperistaltic effects. We examined its effectiveness against peristalsis resumption during endoscopic submucosal dissection (ESD) of gastric tumors. Methods We retrospectively examined clinical data of 485 patients (501 lesions) who underwent ESD for upper gastrointestinal tumors in 2017. We included 119 patients (127 lesions) in whom peristaltic movement resumed during ESD and l‐menthol was applied; 366 patients (374 lesions) without l‐menthol application were used as controls. Video recordings were reviewed to determine whether l‐menthol suppressed peristalsis resumption. Results In cases with l‐menthol application, 2 (2.9%), 36 (14.3%), and 89 (71.2%) lesions were found in the upper (U), middle (M), and lower (L) regions, respectively. In the control group, the corresponding values were 66 (17.6%), 215 (57.5%), and 93 (24.9%), respectively. l‐Menthol efficacy was observed in 116 of the 127 treated lesions (91.3%), over 90% of which were in the posterior wall of the U region, anterior wall and greater curvature of the M region, and anterior wall and lesser curvature of the L region. The most and least effective areas for l‐menthol application were the anterior wall of gastric antrum and posterior wall of the M region, respectively. The mean time from application to peristalsis inhibition was 8.7 s. No adverse effects were observed; perforation and secondary hemorrhage were not significantly different between the groups. Conclusion Direct l‐menthol application to the submucosal layer during mucosal resection affects smooth muscles and rapidly inhibits peristalsis resumption. Clinically, l‐Menthol can be used to suppress peristalsis recurrence during ESD, without adverse effects.

Abstract Background We evaluated patient‐reported outcomes (PRO) during neoadjuvant androgen deprivation therapy (ADT) plus external beam radiation therapy (EBRT) followed by either adjuvant continuous ADT (CADT) or intermittent ADT (IADT) for patients with locally advanced prostate cancer (Pca). Methods A multicenter, randomized phase III trial enrolled 303 patients with locally advanced Pca. The patients were treated with 6 months (M) of ADT followed by 72 Gy of EBRT, and were randomly assigned to CADT or IADT after 14 M. The PROs were evaluated at sic points: baseline, 6 M, 8 M, 14 M, 20 M, and 38 M using FACT‐P questionnaires and EPIC urinary, bowel, and sexual bother subscales. Results The FACT‐P total scores were significantly better (p

Abstract The Green Revolution allowed a large amount of nitrogen (N) fertilization to increase crop yield but has led to severe environmental pollution. Therefore, increasing the crop grain yield must be achieved without such considerable input of N fertilization. A large‐grain japonica rice cultivar, Akita 63, significantly increased grain yield and improved N‐use efficiency (NUE) for yield per amount of N absorbed by plants. This study found that the nonsense mutated GS3 gene, the gs3 allele of Akita 63, has a superior yield production with enlarged grain size. The gs3 allele increased the yield with improvements in harvest index and NUE for yields per plant N content by analyzing the near‐isogenic line of rice plants with a large grain (LG‐Notohikari), which was developed by introducing the gs3 allele of Akita 63 into normal‐grain japonica cultivar, Notohikari. Thus, the gs3 allele would be promising for further yield increase without additional large input of N fertilization in non‐gs3‐allele rice varieties.

Abstract There are no studies assessing short‐term blood pressure (BP) changes induced by daily exercise load in young trained individuals. The authors enrolled 25 healthy, trained (mean age 19.7 ± 0.1 years, 36% female) and 26 healthy, untrained (mean age 20.4 ± 0.3 years, 50% female) individuals and measured BP after the Master two‐step test. Among them, 42 individuals underwent echocardiography after BP measurements to assess left ventricular mass index (LVMI). The baseline systolic BP (SBP) levels of trained and untrained individuals were 122.7 ± 2.9 versus 117.4 ± 1.5 mmHg, respectively (p = .016). Trained individuals showed a significant suppression of the SBP increase soon after exercise loads and lower SBP levels at 1, 2, and 3 min after exercise loads compared with untrained individuals. The peak SBP level over the study period was also significantly lower in trained individuals than in untrained individuals: 156.4 ± 3.3 versus 183.7 ± 5.2 mmHg (p

Abstract The effects of inflammatory responses and polymorphisms of the genes encoding cytochrome P450 (CYP) (CYP2C19 and CYP3A5), flavin‐containing monooxygenase 3 (FMO3), pregnane X receptor (NR1I2), constitutive androstane receptor (NR1I3), and CYP oxidoreductase (POR) on the ratio of voriconazole (VRCZ) N‐oxide to VRCZ (VNO/VRCZ) and steady‐state trough concentrations (C0h) of VRCZ were investigated. A total of 56 blood samples were collected from 36 Japanese patients. Results of multiple linear regression analyses demonstrated that the presence of the extensive metabolizer CYP2C19 genotype, the dose per administration, and the presence of the NR1I2 rs3814057 C/C genotype were independent factors influencing the VNO/VRCZ ratio in patients with CRP levels of less than 40 mg/L (standardized regression coefficients (SRC) = 0.448, −0.301, and 0.390, respectively; all p

Abstract Background The three dominant recurrence patterns of gastric cancer are peritoneal, hematogenous, and nodal recurrence. Correlation between initial recurrence site and prognosis is poorly understood, particularly after standardization of postoperative S‐1 adjuvant chemotherapy. Methods We analyzed a multi‐institutional database of 3484 patients who underwent gastrectomy for gastric cancer between 2010 and 2014. Patients who experienced recurrences after curative gastrectomy classified into peritoneal, hematogenous, or nodal recurrence groups, according to their initial recurrence sites, and their prognoses were compared. Results We included 313 patients in the analysis, of whom 190 patients (63%) were treated with postoperative adjuvant chemotherapy. Pathological disease states were stage I: n = 20 (6%), stage II: n = 62 (20%), and stage III: n = 231 (74%). Patients were categorized into groups by peritoneal (n = 127), hematogenous (n = 123), and nodal (n = 63) recurrence. The peritoneal recurrence group tended to have longer recurrence‐free survival, but shorter post‐recurrence survival, than the other two groups. Median disease‐specific survival after curative resection by group were peritoneal: 25.8 months, hematogenous: 29.0 months, and nodal: 27.8 months (peritoneal vs hematogenous, P = .152; hematogenous vs nodal, P = .955; peritoneal vs nodal, P = .213). Conclusions Prognoses after curative resection for gastric cancer were similar among patients with peritoneal, hematogenous, or nodal recurrences.

Abstract To identify factors affecting responsiveness to eltrombopag (EPAG), we retrospectively analyzed 38 aplastic anemia patients treated with EPAG who were refractory (n = 29) or showed an inadequate response (n = 9) to conventional therapies. The efficacy was evaluated at 16 weeks after starting EPAG and at any given time when the best response was achieved. Hematologic responses were observed in 15 patients (39%) at week 16 and in 25 (66%) at any given time. Ten of 19 (53%) achieved transfusion independence. A univariate analysis revealed the presence of PNH‐phenotype cells and the relatively higher platelet counts as associated with a good response to EPAG.

Background The standard treatment for patients with unresectable locally advanced (LA) non‐small cell lung cancer (NSCLC) is chemoradiotherapy (CRT). Consolidation therapy with durvalumab after CRT demonstrated survival benefits and was approved in Japan in July 2018. The use of immune checkpoint inhibitors (ICIs) is entering routine oncological practice, and here we investigate the feasibility of concurrent CRT for LA‐NSCLC patients based on the PACIFIC criteria. Methods We performed a retrospective study to evaluate the feasibility and efficacy of concurrent CRT prior to the approval of durvalumab. We assessed consecutive patients with LA‐NSCLC treated with CRT between January 2012 and June 2018. Results We analyzed a total of 108 consecutive patients who received radical thoracic radiotherapy and concurrent platinum‐based chemotherapy. Of those patients, 105 (97%) completed the planned radiotherapy. Radiation pneumonitis was observed in 93 patients (85%), with a median of 130 days (range: 41–317 days) from the initiation of radiation to the onset of the complication. Among the patients, 74 (69%) were considered eligible for consolidation therapy with durvalumab. The overall response rate was 64%, and the two‐year survival rate was 63%. Patients who received an ICI after relapse were associated with significantly better survival than those who did not receive an ICI (two‐year survival rate: 87% vs. 41%, respectively; P = 0.001). Conclusions Prior to the approval of durvalumab, the clinical application of ICIs improved the outcome of patients with relapsed NSCLC after CRT for LA‐NSCLC. The management of radiation pneumonitis remains a challenge following the approval of durvalumab.

Abstract Background At its earliest stages, mammalian embryonic development is apparently simple but vulnerable. The environment during the preimplantation period, which only lasts a couple of days, has been implicated in adult health, extending to such early stages the concept of the developmental origin of health and disease (DOHaD). Methods In this review, we first provide a brief history of assisted reproductive technology (ART) focusing on in vitro culture and its outcomes during subsequent development mainly in mice and humans. Further, we introduce the “MEM mouse,” a novel type 2 diabetes mouse model generated by in vitro culture of preimplantation embryos in alpha minimum essential medium (αMEM). Main findings The association between ART and its long‐term effects has been carefully examined for its application in human infertility treatment. The “MEM mouse” develops steatohepatitis and kidney disease with diabetes into adulthood. Conclusion The close association between the environment of preimplantation and health in postnatal life is being clarified. The approach by which severe mouse phenotypes are successfully induced by manipulating the environment of preimplantation embryos could provide new chronic disease animal models, which we call “modified ART‐DOHaD” animal models. This will also offer insights into the mechanisms underlying their long‐term effects.

Abstract Large carnivores encounter various threats from human activities. Population trend detection among carnivore species and implementation of management policies based on monitoring are urgently needed for human–carnivore coexistence. We demonstrate how young citizens have helped reveal long‐term trends in brown bear field sign detection rates following a government policy change (i.e., abolishment of the spring cull). We used a 40‐year dataset of field signs collected by volunteer college students in northern Japan and analyzed the resulting data using state‐space models. The spring cull had a significant negative impact on the number of grids with field signs; the detection rate under spring cull pressure declined from 19 to 0% between 1976 and 1990. However, abolishment of the spring cull in 1990 had a significant positive effect on the number of grids with field signs; the detection rate increased from 0 to 13% between 1991 and 2015, suggesting that the government policy change strongly affected the threatened brown bear population. Structured monitoring schemes, simplicity and/or attractiveness in monitoring targets may ensure the data quality and duration of citizen‐based monitoring. These findings suggest a high potential for engaging college students in developing sustainable monitoring of large carnivore populations and in supporting wildlife management.

Abstract Background and purpose The management of post‐stroke epilepsy (PSE) should ideally include prevention of both seizure and adverse effects; however, an optimal antiseizure medications (ASM) regimen has yet been established. The purpose of this study is to assess seizure recurrence, retention, and tolerability of older‐generation and newer‐generation ASM for PSE. Methods This prospective multicenter cohort study (PROgnosis of Post‐Stroke Epilepsy [PROPOSE] study) was conducted from November 2014 to September 2019 at eight hospitals. A total of 372 patients admitted and treated with ASM at discharge were recruited. Due to the non‐interventional nature of the study, ASM regimen was not adjusted and followed standard hospital practices. The primary outcome was seizure recurrence in patients receiving older‐generation and newer‐generation ASM. The secondary outcomes were the retention and tolerability of ASM regimens. Results Of the 372 PSE patients with ASM at discharge (median [IQR] age, 73 [64–81] years; 139 women [37.4%]), 36 were treated with older‐generation, 286 with newer‐generation, and 50 with mixed‐generation ASM. In older‐ and newer‐generation ASM groups (n = 322), 98 patients (30.4%) had recurrent seizures and 91 patients (28.3%) switched ASM regimen during the follow‐up (371 [347–420] days). Seizure recurrence was lower in newer‐generation, compared with the older‐generation, ASM (hazard ratio [HR], 0.42, 95%CI 0.27–0.70; p = .0013). ASM regimen withdrawal and change of dosages were lower in newer‐generation ASM (HR, 0.34, 95% CI 0.21–0.56, p

Abstract Subclavian central venous catheterization can cause severe complications, including tension pneumothorax, subcutaneous emphysema, and pneumomediastinum. Re‐expansion pulmonary edema after thoracentesis is a life‐threatening complication.

Introduction Regression of non‐irradiated metastatic lesions after radiation therapy is known as the abscopal effect. We report a case of urothelial carcinoma in which the abscopal effect was possibly observed after immune checkpoint inhibitor administration. Case presentation A 68‐year‐old woman diagnosed with left renal pelvic cancer underwent total nephroureterectomy and regional lymph node dissection. Eight months later, imaging studies detected local recurrence and paraaortic lymph node metastasis. The tumor progressed despite cisplatin + gemcitabine, pembrolizumab, and gemcitabine + docetaxel therapy. Radiation therapy was administered to a painful back lesion, which resulted in dramatic symptom relief. Computed tomography 2 months after radiation therapy indicated reduced size of the irradiated lesion and some non‐irradiated lymph nodes. Conclusion Combined radiation therapy and immune checkpoint inhibitors can provide additional benefits for certain cancers, possibly due to negative immunomodulatory response blockade. Thus, this combined therapy may be a new metastatic urothelial carcinoma treatment strategy.