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Abstract Fluorescence imaging of tumours facilitates rapid intraoperative diagnosis. Thus far, a promising activatable fluorescence probe for hepatocellular carcinoma (HCC) has not been developed. Herein, the utility of the fluorescence imaging of HCC using a β-galactosidase (β-Gal)-activatable fluorescence probe SPiDER-βGal was examined. β-Gal activity was measured in cryopreserved tissues from 68 patients. Live cell imaging of HCC cell lines and imaging of tumour-bearing model mice were performed using SPiDER-βGal. Furthermore, fluorescence imaging was performed in 27 freshly resected human HCC specimens. In cryopreserved samples, β-Gal activity was significantly higher in tumour tissues than in non-tumour tissues. Fluorescence was observed in HCC cell lines. In mouse models, tumours displayed stronger fluorescence than normal liver tissue. In freshly resected specimens, fluorescence intensity in the tumour was significantly higher than that in non-tumour liver specimens as early as 2 min after spraying. Receiver operating characteristic curves were generated to determine the diagnostic value of SPiDER-βGal 10 min after its spraying; an area under the curve of 0.864, sensitivity of 85.2%, and specificity of 74.1% were observed for SPiDER-βGal. SPiDER-βGal is useful for the rapid fluorescence imaging of HCC. Fluorescence imaging guided by SPiDER-βGal would help surgeons detect tumours rapidly and achieve complete liver resection.

A 40-year-old female (gravida 3 para 1) presented with menstrual, urinary, and anal pain. Computed tomography revealed type II acquired uterine arteriovenous malformation, a common dilated venous sac with bilateral uterine arteries, and multiple branches of iliac arteries draining to the bilateral ovarian veins. Venous sac transvenous embolization via the left ovarian vein of dominant outflow was planned, since complete arteriovenous malformation occlusion was difficult with super-selective transarterial embolization of multiple feeders. Therefore, transarterial embolization of the minor feeder was performed before completing transvenous embolization using coils and 50% glue under left iliac artery flow control. Immediately thereafter, angiography confirmed the complete disappearance of the uterine arteriovenous malformation, and all pain symptoms remitted. In conclusion, transvenous embolization combined with adjunctive transarterial embolization can be an effective and radical treatment for type II uterine arteriovenous malformations.

Abstract Aim Young carers (YCs) refer to children under the age of 18 who assume responsibilities that would normally be assumed by adults, such as caring for family members in need of care. In recent years, the concept of YCs has been expanding in Japan, and the government has been rapidly implementing strategies to support them. There is a need for a survey scale for YCs that uses standardized methods that can be compared internationally. Method The BBC/University of Nottingham Survey for estimating the prevalence of YCs and caring activities of United Kingdom adolescents was translated into Japanese, and its reliability and validity were tested with 313 adolescents. Moreover, the prevalence of YCs was estimated in a school‐based survey among 5000 adolescents. Results The Young Carers Scale Japanese version (YCS‐J) was acceptably reliable and valid. The original six‐factor model for caring activity in the Multidimensional Assessment of Caring Activities Checklist for Young Carers (MACA‐YC18) was supported by confirmatory factor analysis. The prevalence of YCs among 5000 adolescents in the Tokyo metropolitan area was estimated to be 7.4%, comparable to that reported in Western countries and in recent surveys in Japan using nonstandardized methods. YCs exhibited significantly higher scores for prosocial behavior and emotional symptoms than non‐YCs. Conclusions The YCS‐J, as an internationally comparable instrument, will be useful for understanding the actual situation of YCs in Japan, and to disseminate and implement support through cooperation among education, welfare, and healthcare sectors.

If a piping system under high pressure is damaged and steam is ejected into the atmosphere, human safety and safety equipment may be damaged by the impingement of the steam jet. Therefore, it is necessary to evaluate the region affected by the steam jet impinging on the surrounding equipment and people. This study is conducted to identify the problems with the evaluation model of the region affected by the jet specified in the ANSI standard and to reconstruct the evaluation model of the affected region based on the experimental results. From the visualization experiment and CFD analysis results, we found that the ANSI standard can be used to appropriately evaluate the experimental and CFD results for the steam spread angle and asymptotic plane area. On the other hand, the results of asymptotic length were different from the experimental and CFD results owing to the assumption in the ANSI standard that the expanding angle of the steam jet is constant at 45° regardless of any pressure change. A correlation equation for the expansion angle of the steam jet caused by a pressure change was developed referring to the experimental and CFD results, and the improved model was used to evaluate the asymptotic length. By using this improved model, it is possible to evaluate the region affected by the steam jet in the event of pipe failure, under a wide range of pressure and nozzle conditions.

Objectives: This study compared cardiac function, morphology, and tissue characteristics between two common subtypes of primary aldosteronism (PA) using a 3T MR scanner. Design: A retrospective, single-center, observational study. Methods: We retrospectively reviewed 143 consecutive patients with PA, who underwent both adrenal venous sampling and cardiac magnetic resonance. We acquired cine, late gadolinium enhancement, and pre- and postcontrast myocardial T1-mapping images. Results: PA was diagnosed as unilateral aldosterone-producing adenoma (APA) in 70 patients and bilateral hyperaldosteronism (BHA) in 73. The APA group showed significantly higher plasma aldosterone concentration (PAC) and aldosterone to renin rate (ARR) than the BHA group. After controlling for age, sex, antihypertensive drugs, systolic and diastolic blood pressure, and disease duration, the parameters independently associated with APA were: left ventricular end-diastolic volume index (EDVI: adjusted odds ratio (aOR) = 1.06 (95% CI: 1.030–1.096), P < 0.01), end-systolic volume index (ESVI: 1.06 (1.017–1.113), P < 0.01), stroke index (SI: 1.07 (1.020–1.121), P < 0.01), cardiac index (CI: 1.001 (1.000–1.001), P < 0.01), and native T1 (1.01 (1.000–1.019), P = 0.038). Weak positive correlations were found between PAC and EDVI (R = 0.28, P < 0.01), ESVI (0.26, P < 0.01), and SI (0.18, P = 0.03); and between ARR and EDVI (0.25, P < 0.01), ESVI (0.24, P < 0.01), and native T1 (0.17, P = 0.047). Conclusions: APA is associated with greater LV volumetric parameters and higher native T1 values, suggesting a higher risk of volume overload and myocardial damage.

Primary aldosteronism (PA) is the most common cause of secondary hypertension, and is associated with an increased incidence of cardiovascular events. PA itself is clinically classified into the following two types: unilateral PA, mostly composed of aldosterone-producing adenoma (APA); and bilateral hyperaldosteronism, consisting of multiple aldosterone-producing micronodules (APMs) and aldosterone-producing diffuse hyperplasia. Histopathologically, those disorders above are all composed of compact and clear cells. The cellular morphology in the above-mentioned aldosterone-producing disorders has been recently reported to be closely correlated with patterns of somatic mutations of ion channels including KCNJ5, CACNA1D, ATP1A1, ATP2B3, and others. In addition, in non-pathological adrenal glands, APMs are frequently detected regardless of the status of the renin-angiotensin-aldosterone system (RAAS). Aldosterone-producing nodules have been also proposed as non-neoplastic nodules that can be identified by hematoxylin and eosin staining. These non-neoplastic CYP11B2-positive nodules could represent possible precursors of APAs possibly due to the presence of somatic mutations. On the other hand, aging itself also plays a pivotal role in the development of aldosterone-producing lesions. For instance, the number of APMs was also reported to increase with aging. Therefore, recent studies indicated the novel classification of PA into normotensive PA (RAAS-independent APM) and clinically overt PA.

Background & Aims: The reason why small intestinal cancer is rarer than colorectal cancer is not clear. We hypothesized that intraepithelial lymphocytes (IELs), which are enriched in the small intestine, are the closest immune cells to epithelial cells, exclude tumor cells via cell-to-cell contact. Methods: We developed DPE-green fluorescent protein (DPE-GFP) × adenomatous polyposis coli; multiple intestinal neoplasia (APCmin ) mice, which is a T-cell–reporter mouse with spontaneous intestinal tumors. We visualized the dynamics of IELs in the intestinal tumor microenvironment and the interaction between IELs and epithelial cells, and the roles of cell-to-cell contact in anti-intestinal tumor immunity using a novel in vivo live-imaging system and a novel in vitro co-culture system. Results: In the small intestinal tumor microenvironment, T-cell movement was restricted around blood vessels and the frequency of interaction between IELs and epithelial cells was reduced. Genetic deletion of CD103 decreased the frequency of interaction between IELs and epithelial cells, and increased the number of small intestinal tumors. In the co-culture system, wild-type IELs expanded and infiltrated to intestinal tumor organoids from APCmin mice and reduced the viability of them, which was cell-to-cell contact and CD103 dependent. Conclusions: The abundance of IELs in the small intestine may contribute to a low number of tumors, although this system may not work in the colon because of the sparseness of IELs. Strategies to increase the number of IELs in the colon or enhance cell-to-cell contact between IELs and epithelial cells may be effective for the prevention of intestinal tumors in patients with a high cancer risk.

Abstract The characteristics of aortic valvular outflow jet affect aortopathy in the bicuspid aortic valve (BAV). This study aimed to elucidate the effects of BAV morphology on the aortic valvular outflow jets. Morphotype-specific valve-devising apparatuses were developed to create aortic valve models. A magnetic resonance imaging-compatible pulsatile flow circulation system was developed to quantify the outflow jet. The eccentricity and circulation values of the peak systolic jet were compared among tricuspid aortic valve (TAV), three asymmetric BAVs, and two symmetric BAVs. The results showed mean aortic flow and leakage did not differ among the five BAVs (six samples, each). Asymmetric BAVs demonstrated the eccentric outflow jets directed to the aortic wall facing the smaller leaflets. In the asymmetric BAV with the smaller leaflet facing the right-anterior, left-posterior, and left-anterior quadrants of the aorta, the outflow jets exclusively impinged on the outer curvature of the ascending aorta, proximal arch, and the supra-valvular aortic wall, respectively. Symmetric BAVs demonstrated mildly eccentric outflow jets that did not impinge on the aortic wall. The circulation values at peak systole increased in asymmetric BAVs. The bicuspid symmetry and the position of smaller leaflet were determinant factors of the characteristics of aortic valvular outflow jet.

Abstract Aim Online classes were implemented in numerous schools during the school closure due to COVID‐19. The present study examined the relationship between online classes during national school closure and mental health symptoms after the reopening of schools. Methods We conducted a cross‐sectional survey from October 1 to November 7, 2020 using an anonymous self‐reported questionnaire to evaluate 21 junior and senior high schools in the Saitama prefecture of Japan. Out of the 5538 students who were recruited, 5000 agreed to participate. The relationship between the implementation of online classes and mental health symptoms (emotional symptoms, psychotic experience [PE], and smartphone addiction) was evaluated using mixed‐effect logistic regression models, while controlling for individual and class‐level covariates (e.g., gender, grades). Results Implementation of online classes was reported by 78.2% of classroom teachers, and it was associated with lower rates of emotional symptoms (OR = 0.79, 95% CI = 0.63–0.99, p = 0.040) and smartphone addiction (OR = 0.79, 95% CI = 0.65–0.96, p = 0.020), but not related to PE (OR = 0.91, 95% CI = 0.61–1.36, p = 0.637). Conclusions Implementing online classes during the national school closure might have had a potential protective effect for adolescents' mental health symptoms (especially emotional symptoms and smartphone addiction) after the reopening of schools during the ongoing COVID‐19 pandemic.

Abstract Background Recent improvements in stone extraction implements and apparatus have lessened the complexity of the endoscopic bile duct stone treatment. However, despite confirmation of complete removal, cases of residual stones have been reported, which can result in recurrent biliary symptoms, cholangitis, and pancreatitis and considerably increase cost given the need for repeat imaging and/or procedures. To date, risk factors for residual bile duct stones following endoscopic retrograde cholangiopancreatography (ERCP) extraction have not been thoroughly evaluated. This study retrospectively investigated the incidence and risk factors of residual bile duct stones following extraction via ERCP. Methods We retrospectively reviewed all ERCP cases that underwent endoscopic bile duct stone extraction between April 2014 and March 2019. A total of 505 patients were enrolled and evaluated for the incidence and risk factors of residual bile duct stones after ERCP. Results The rate of residual stones was 4.8% (24/505). Residual stones were detected by computed tomography (12/24) or magnetic resonance cholangiopancreatography (12/24). In univariate analyses, a large number of stones (P = 0.01), long procedure time (P = 0.005), and performance of the pancreatic duct guidewire placement method (P-GW) for selective bile duct cannulation (P = 0.01) were the factors involved in residual stones. In multiple logistic regression analysis, performing P-GW was retained as the only independent factor of residual stones (adjusted odds ratio, 3.44; 95% CI, 1.19–9.88; P = 0.02). Conclusions When removing bile duct stones with a pancreatic guidewire in place, paying attention to residual stones is necessary.

Abstract Background Vascular abnormalities in neurofibromatosis type 1 (NF1) are rare, but are the second leading cause of death in persons with NF1. In NF1 vasculopathy (NF-V), fatal bleeding due to a spontaneous arterial rupture sometimes occurs. Ruptured extracranial arteries in patients with NF1 often involve thoracic vessels, such as the intercostal and subclavian arteries; very few reports exist regarding the abdominal region. Herein, we present the first case of intraperitoneal bleeding due to spontaneous pancreatic arcade artery (PAA) rupture associated with NF1, successfully treated by transcatheter arterial embolization (TAE) combined with stent-graft placement and partial intra-aortic balloon occlusion (IABO). Case presentation A 40-year-old woman complained of back and abdominal pain. Upon admission, her blood pressure was 85/41 mmHg and heart rate was 129 beats/min. Computed tomography (CT) showed large intraperitoneal bleeding due to PAA rupture. After CT scanning, her systolic blood pressure decreased to 50 mmHg. Therefore, we performed emergency TAE with partial IABO. She was treated by TAE of the anterior superior pancreaticoduodenal artery, anterior inferior pancreaticoduodenal artery, and inferior pancreaticoduodenal artery. However, even after TAE, minor extravasation around the superior mesenteric artery continued, and her vital signs remained unstable. Stent-graft placement was selected to stop the haemorrhage, preserving normal blood flow of the superior mesenteric artery trunk. Excellent patency of the stent graft was confirmed on follow-up CT, and she was discharged on postoperative day 56. Conclusion PAA rupture associated with NF1 can be successfully treated by TAE combined with partial intra-aortic balloon occlusion, and stent-graft placement.

Background Several studies have previously demonstrated the survival benefit of both EGFR‐TKI treatment and chemotherapy in patients with non‐small cell lung cancer (NSCLC) harboring EGFR mutations. The aim of the present study was to clarify the factors influencing the treatment sequence after failure of EGFR‐TKI therapy, focusing on the number of organs with metastasis (hereafter, metastatic organs). Methods Between January 2010 and December 2016, consecutive patients with EGFR‐mutated NSCLC who were started on first‐line EGFR‐TKI were reviewed. The factors influencing withholding systemic chemotherapy and the post‐progression survival (PPS) after failure of EGFR‐TKI were investigated. Results A total of 393 patients were started on first‐line EGFR‐TKI during the study period. After excluding patients maintained on EGFR‐TKI or who received osimertinib targeting secondary EGFR T790M, 297 patients were included in the analysis. Among these, 180 (60.6%) received chemotherapy after failure of EGFR‐TKI (TKI‐Ct group), while the remaining 117 (39.4%) received no chemotherapy (TKI‐only group). Multivariate analysis identified older age (≥75 years: odds ratio [OR] = 0.25, 95% confidence interval [CI]: 0.11–0.43, P

BackgroundMacrophage migration inhibitory factor (MIF) is a multifunctional cytokine that promotes neurogenesis and neuroprotection. MIF is predominantly expressed in astrocytes in the brain. The serum MIF level and microsatellites/single nucleotide polymorphisms (SNPs) in the MIF gene promoter region are known to be associated with schizophrenia (SCZ). Interestingly, previous studies reported that hypoxia, an environmental risk factor for SCZ, induced MIF expression through binding of the hypoxia inducible factor (HIF)-1 to the hypoxia response element (HRE) in the MIF promoter.MethodsWe investigated the involvement of MIF in SCZ while focusing on the HIF pathway. First, we conducted an association study of the SNP rs17004038 (C>A) in the HRE of the MIF promoter between 1758 patients with SCZ and 1507 controls. Next, we investigated the effect of hypoxia on MIF expression in primary cultured astrocytes derived from neonatal mice forebrain.ResultsSNP rs17004038 was significantly associated with SCZ (p = 0.0424, odds ratio = 1.445), indicating that this SNP in the HRE of the MIF promoter was a genetic risk factor for SCZ. Hypoxia induced MIF mRNA expression and MIF protein production and increased HIF-1 binding to the MIF promoter, while the activity of the MIF promoter was suppressed by mutations in the HRE and by deletion of the HRE in astrocytes.ConclusionThese results suggest that SNP rs17004038 in the HRE of the MIF promoter was significantly associated with SCZ and may be involved in the pathophysiology of SCZ via suppression of hypoxia and HIF pathway-induced MIF expression.

The ocular mucosal tissues are exposed to potentially harmful foreign antigens in the air and tear fluid. The tear duct-associated lymphoid tissue (TALT) may contribute to immune surveillance in the eye region. Follicle-associated epithelium (FAE) of TALTs is classified as stratified squamous epithelium and consists of squamous epithelial cells arranged in layers on the basement membrane. In contrast, most mucosa-associated lymphoid tissue is covered by a monolayer of epithelium containing microfold (M) cells. Therefore, antigen uptake and the presence of M cells in TALT are not fully understood. The present study found that a small population of FAE cells in the TALT expressed intestinal M-cell markers, namely Sox8, Tnfaip2, GP2, and OPG. This cell population was identified as functional M cells because of their uptake capacity of luminal nanoparticles. In addition, RANKL, which is essential for M-cell differentiation, was expressed by stroma-like cells at the subepithelial region and its receptor RANK by the FAE in the TALT. The administration of RANKL markedly increased the number of Sox8+ M cells. In contrast, deficiency in OPG, an endogenous inhibitor of RANKL, increased the number of M cells in the TALT. These data demonstrate that the RANKL-RANK axis is essential for M-cell differentiation in the TALT. Furthermore, immunization via eye drops elicited the production of antigen-specific antibodies in tears, which was enhanced by RANKL administration. Thus, TALT M cells play an important role in the immunosurveillance of the eye region.

Prednisolone is a frequently prescribed steroid with a bitter, unpalatable taste that can result in treatment refusal. Oral suspensions or powder dosage forms are often prescribed, particularly to pediatric patients, as they improve swallowability and ease of dose adjustment. Consequently, the bitterness of prednisolone is more apparent in these dosage forms. Few studies have investigated prednisolone’s bitterness. Thus, in this study, 50 adults evaluated the bitterness of prednisolone using the generalized Labeled Magnitude Scale (gLMS), in comparison with quinine, a standard bitter substance. Overall, prednisolone-saturated solution demonstrated the same extent (mean gLMS score: 46.8) of bitterness as 1 mM quinine solution (mean gLMS score: 40.1). Additionally, large individual differences were observed in the perception of the bitterness of prednisolone and quinine. Perceived flavors of some drugs are reportedly associated with bitter-taste receptor (TAS2Rs) polymorphisms. Therefore, we investigated the relationship between subjects’ genetic polymorphisms of TAS2R19, 38, and 46, and their sensitivity to bitterness. Although a relationship between TAS2R19 polymorphisms and the perception of quinine bitterness was observed, no significant relationship was found between the perceived bitterness of prednisolone and the investigated genes. Ultimately, the results show that despite individual differences among subjects, the cause of prednisolone’s strong bitterness is yet to be elucidated.

Abstract Background Precise staging is indispensable to select the appropriate treatment strategy for gastric cancer (GC); however, the diagnostic accuracy of conventional modalities needs to be improved. This study investigated the clinical significance of the preoperative neutrophil-to-lymphocyte ratio (NLR) for the prediction of pathological lymph node metastasis (pN+) in GC. Methods This was a retrospective study of 429 patients with GC who underwent curative gastrectomy. The predictive ability of NLR for pN+ was examined in comparison with that of computed tomography. Results The preoperative NLR ranged from 0.6 to 10.8 (median, 2.0), and the optimal cut-off value for predicting pN+ was 1.6 according to the receiver operating characteristic curve with the maximal Youden index. Multivariate analysis identified a NLR ≥ 1.6 (odds ratio (OR) 3.171; 95% confidence interval (CI) 1.448–7.235, p = 0.004) and cN+ (OR 2.426; 95% CI 1.221–4.958, p = 0.011) to be independent factors associated with pN+ in advanced GC (cT2-T4). On the other hand, a NLR ≥ 1.6 was not useful for predicting pN+ in early GC (cT1). In advanced GC, a NLR ≥ 1.6 detected pN+ with a higher sensitivity (84.9%) and negative predictive value (NPV) (63.9%) than conventional modalities (50.0 and 51.7%, respectively). When the subjects were limited to those with advanced GC with cN0, the sensitivity and NPV of a NLR ≥ 1.6 for pN+ increased further (90.7 and 81.0%, respectively). Conclusion The preoperative NLR may be a useful complementary diagnostic tool for predicting pN+ in advanced GC because of its higher sensitivity and NPV than conventional modalities.

Background Although non‐small cell lung cancers (NSCLCs) harboring EGFR mutations initially respond well to EGFR‐tyrosine kinase inhibitors (TKIs), they typically progress after approximately one year. The EGFR T790M mutation is the most common resistance mechanism. NSCLCs with T790M respond well to osimertinib; however, the heterogeneity of NSCLCs may limit the efficacy. Some patients exhibit a mixed response (MR), in which some lesions shrink and others progress, but little is known of the incidence and characteristics of such a response. We sought to determine the frequency and clinical course in MR patients. Methods We retrospectively reviewed the records of patients who had received osimertinib for NSCLC with EGFR T790M. Results Between April and December 2016, 48 patients were administered osimertinib. Seven patients (15%) exhibited one of two MR types: (i) progressive lesions that did not include the re‐biopsy site (5 patients), and (ii) progressive lesions that included the re‐biopsy site (2 patients). The most frequent progressive sites were liver and lung metastases (4 patients). Three patients continued osimertinib following an MR, one of whom had received local therapy for liver metastasis and achieved disease control on osimertinib for an additional four months. Conclusion An MR was detected in 15% of NSCLC patients with T790M. This finding suggests that several different resistance mechanisms are active within a single patient who develops resistance to EGFR‐TKIs. Osimertinib is basically effective for tumors that acquire resistance to EGFR‐TKIs as a result of T790M mutation. Therefore, additional local therapy may be beneficial for patients who develop an MR to osimertinib.

Objective: Regional differences in cardiac magnetic resonance, which can reveal catecholamine-induced myocardial injury in patients with pheochromocytoma, have not yet been assessed using 3T magnetic resonance imaging. We evaluated these differences using myocardial T1-mapping and strain analysis. Design and Methods: We retrospectively reviewed 16 patients newly diagnosed with catecholamine-producing tumors (CPT group) and 16 patients with essential hypertension (EH group), who underwent cardiac magnetic resonance imaging between May 2016 and March 2018. We acquired 3T magnetic resonance cine and native T1-mapping images and performed feature-tracking-based strain analysis in the former. Results: Global cardiac function, morphology, global strain and peak strain rate were similar, but end-diastolic wall thickness differed between groups (CPT vs EH: 10.5 ± 1.7 vs 12.6 ± 2.8 mm; P < 0.05). Basal, but not apical, circumferential strain was significantly higher in the CPT than the EH group (19.4 ± 3.2 vs 16.8 ± 3.6 %; P < 0.05). Native T1 values were significantly higher in CPT than in EH patients, in both the basal septum (1307 ± 48 vs 1241 ± 45 ms; P < 0.01) and the apical septum (1377 ± 59 vs 1265 ± 58 ms; P < 0.01) mid-walls. In the CPT, but not in the EH group, native T1 value s in the apical wall were significantly higher than those in the basal wall (P < 0.01). Conclusion: 3T magnetic resonance-based T1-mapping can sensitively detect subclinical catecholamine-induced myocardial injury; the influence of catecholamines may be greater in the apical than in the basal wall.

Through advising in language learning, this study describes two Japanese secondary school students’ (Ai and Yu: both pseudonyms) longitudinal trajectories of socioculturally mediated emotions in four dimensions. To investigate types of emotions, the research integrates multiple qualitative methods and Plutchik’s wheel of emotions, thus acknowledging both contextually complex and longitudinally dynamic aspects of emotions. Throughout a year of 19 advisory sessions, the amount of time spent was 1,263 minutes (Ai’s 12 sessions = 891 minutes; Yu’s 7 sessions = 372 minutes), and the number of emotional incidences identified was 358 (201 for Ai; 157 for Yu). Among multiple findings, the most notable was that both participants experienced convergence of emotions: the one process from diversified to less diversified emotions was caused by longitudinal dynamics of emotions in Ai’s case and by contextual complexity of emotions in Yu’s case. The study concludes by suggesting a tentative four-dimensional model of emotions to capture trajectories of advisees’ emotions from multiple perspectives. This model can help advisors to understand advisees’ emotionality and, therefore, to implement emotional support appropriately and continuously.

In vertebrates, the development of lymphocytes from undifferentiated haematopoietic precursors takes place in so-called primary lymphoid organs, such as the thymus. Therein, lymphocytes undergo a complex differentiation and selection process that culminates in the generation of a pool of mature T cells that collectively express a self-tolerant repertoire of somatically diversified antigen receptors. Throughout this entire process, the microenvironment of the thymus in large parts dictates the sequence and outcome of the lymphopoietic activity. In vertebrates, direct genetic evidence in some species and circumstantial evidence in others suggest that the formation of a functional thymic microenvironment is controlled by members of the Foxn1/4 family of transcription factors. In teleost fishes, both Foxn1 and Foxn4 contribute to thymopoietic activity, whereas Foxn1 is both necessary and sufficient in the mammalian thymus. The evolutionary history of Foxn1/4 genes suggests that an ancient Foxn4 gene lineage gave rise to the Foxn1 genes in early vertebrates, raising the question of the thymopoietic capacity of the ancestor common to all vertebrates. Recent attempts to reconstruct the early events in the evolution of thymopoietic tissues by replacement of the mouse Foxn1 gene by Foxn1-like genes isolated from various chordate species suggest a plausible scenario. It appears that the primordial thymus was a bi-potent lymphoid organ, supporting both B cell and T cell development; however, during the course of vertebrate, evolution B cell development was gradually diminished converting the thymus into a site specialized in T cell development.

Background: The clinical results of total hip arthroplasty (THA) with a cementless prosthesis have been constantly improving due to progress in the area of stem design and surface finish. Cementless Spotorno stem (CLS stem; Zimmer, Warsaw, USA) is a double-tapered rectangular straight stem. The purpose of this study is to investigate the mean 10 year results of CLS stem and to evaluate the pressfit stability of CLS stem. Methods: One hundred and eighty-six consecutive patients (194 hips) were evaluated at more than five years after THA using CLS stems. The mean follow-up period was 111 months. The radiographic stability of the femoral stem was determined by Engh's criteria. The ascertained period of spot welds was noted by Gruen zones on the femoral side. The presence of stress shielding, and subsidence was also evaluated. Results: A stable stem with bony on growth was identified in all cases. The mean period of expression of spot welds was 10.8 months in zone 2, 9.9 months in zone 3, 8.5 months in zone 5, and 8.8 months in zone 6. Stress shielding of more than grade 2 was observed in only three hips, which was non-progressive at one year after surgery. Subsidence of more than 2 mm was not observed in any of the hips. Conclusions: Excellent stability of CLS stem has been maintained without abnormal bone reaction at the proximal femur. CLS stem is considered to achieve not only press-fit stability at trochanteric and subtrochanteric level, but bony fixation by osseointegration within one year after THA. [ABSTRACT FROM AUTHOR]

Pheochromocytomas (PHEOs) are relatively rare catecholamine-producing tumors derived from adrenal medulla. Tumor microenvironment (TME) including neoangiogenesis has been explored in many human neoplasms but not necessarily in PHEOs. Therefore, in this study, we examined tumor infiltrating lymphocytes (CD4 and CD8), tumor associated macrophages (CD68 and CD163), sustentacular cells (S100p), and angiogenic markers (CD31 and areas of intratumoral hemorrhage) in 39 cases of PHEOs in the quantitative fashion. We then compared the results with pheochromocytoma of the adrenal gland scaled score (PASS), grading system for pheochromocytoma and paraganglioma (GAPP) and the status of intra-tumoral catecholamine-synthesizing enzymes (TH, DDC, and PNMT) as well as their clinicopathological factors. Intratumoral CD8 (p = 0.0256), CD31 (p = 0.0400), and PNMT (p = 0.0498) status was significantly higher in PHEOs with PASS

Objectives We conducted a subanalysis of data from the multicentre, retrospective observational Nivolumab Japan Real World (CA209-9CR) study to evaluate nivolumab effectiveness and safety in elderly patients (aged ≥75 years) with advanced/metastatic non-small cell lung cancer.Materials and methods Medical record data of patients initiating nivolumab treatment between April 2016 and December 2016 were collected using electronic data capture from 23 cancer hospitals in Japan between March 2017 and August 2018. Nivolumab treatment data were collected to investigate the treatment patterns by age group (

Pheochromocytomas and paragangliomas (PHEO/PGL) are rare but occasionally life-threatening neoplasms, and are potentially malignant according to WHO classification in 2017. However, it is also well known that histopathological risk stratification to predict clinical outcome has not yet been established. The first histopathological diagnostic algorithm for PHEO, “PASS”, was proposed in 2002 by Thompson et al. Another algorithm, GAPP, was then proposed by Kimura et al. in 2014. However, neither algorithm has necessarily been regarded a ‘gold standard’ for predicting post-operative clinical behavior of tumors. This is because the histopathological features of PHEO/PGL are rather diverse and independent of their hormonal activities, as well as the clinical course of patients. On the other hand, recent developments in wide-scale genetic analysis using next-generation sequencing have revealed the molecular characteristics of pheochromocytomas and paragangliomas. More than 30%–40% of PHEO/PGL are reported to be associated with hereditary genetic abnormalities involving > 20 genes, including SDHXs, RET, VHL, NF1, TMEM127, MAX, and others. Such genetic alterations are mainly involved in the pathogenesis of pseudohypoxia, Wnt, and kinase signaling, and other intracellular signaling cascades. In addition, recurrent somatic mutations are frequently detected and overlapped with the presence of genetic alterations associated with hereditary diseases. In addition, therapeutic strategies specifically targeting such genetic abnormalities have been proposed, but they are not clinically applicable at this time. Therefore, we herein review recent advances in relevant studies, including histopathological and molecular analyses, to summarize the current status of potential prognostic factors in patients with PHEO/PGL.

Flow Accelerated Corrosion (FAC) is a pipe wall thinning phenomenon to be monitored and managed in the power plants with high priority. Its management has been conducted with conservative evaluation of the thinning rate and the residual lifetime of the piping based on the wall thickness measurements. However, noticeable case of the wall thinning was occurred in branch and junction piping (tee tube). It is a problem to manage the section beneath the reinforcing plate of the tee tube; the region where measurement is difficult to conduct with ordinary ultrasonic testing device. In this study, numerical analysis for the tee tube was conducted, and the wall thinning profile due to the FAC was evaluated by calculating the mass transfer coefficient. In the case of the union flow, local wall thinning profile was found near the junction where is covered by the reinforcing plate. This profile showed the tendency of increase in association with increasing of the flow amount from the branch pipe. And, the profiles also have smooth decay tendency from the junction to downstream of the main pipe. Therefore, the amount of the wall thinning beneath the reinforcing plate can be predicted from the location where is deviated from the plate.

This paper presents a detailed experimental study on the dispersion behaviour of a horizontal water jet with atomization. The study mainly focuses on flow structure of the water jet such as a spread angle and a flying distance. The experiments were conducted by using a flow visualization method. Dimensionless numbers (Reynolds number and Weber number) were introduced to determine evaluation condition on a map of the jet flow pattern. The experimental results were compared with existing theoretical model. The jet spread angle was increased by the atomization at the interface between the water jet and surrounding air, and its angle were correlated with non-dimensional numbers. It was also found that the experimental data of the jet flying distance agree with the theoretical model under the low velocity condition. However, the experimental data showed shorter flying distance compared with the theoretical model due to the atomization under the high velocity condition.

Living in temporary housing is a risk factor for psychological distress after a natural disaster. As temporary housing is an essential resource for those affected by disasters, investigation of factors which potentially mediate living in temporary housing and psychological distress is needed. This is a cohort study in general population of areas affected by the Great East Japan Earthquake in 2011. Data were obtained from self-report questionnaires in annual health checks between 2014 and 2016 regarding residential situation (e.g., prefabricated or privately-rented temporary housing), psychological distress, sleep disturbances, social support, and covariates. Mediation effects of sleep disturbances and social support on the relationship between temporary housing and psychological distress were evaluated using a cross-lagged panel model during three time points. Among 3,116 participants in 2014, approximately 12% lived in prefabricated or privately-rented temporary housing. Living in prefabricated (β = 0.046, p = 0.031) and privately-rented temporary housing (β = 0.043, p = 0.042) predicted later psychological distress. There was no mediation effect by sleep disturbances (prefabricated temporary housing: β = 0.001, p = 0.620; privately-rented temporary housing: β = −0.001, p = 0.467) or social support (prefabricated temporary housing: β

Steam is widely used as a medium for thermal energy transport in industry, such as in heat supply and drying processes. It is therefore important to evaluate precisely the steam flow rate at the demand end from the viewpoint of energy management. The state of steam in the steam piping of industrial facilities without the superheating process is usually wet steam resulting from causes such as heat loss, heat supply, and work. It is well known that steam wetness often causes measurement error of the steam flow meter. However, there has been no established standard for estimating the measurement error since it is difficult to evaluate the effects of steam wetness quantitatively in plants and factories. A clamp-on ultrasonic steam flow meter is suitable for use in factories since pipe processing is unnecessary. We conducted experiments to clarify characteristics of the measurement error of a clamp-on ultrasonic flow meter owing to steam wetness considering the influence of pipe diameter. The total mass flow rate of the steam through the test section was measured using a calibrated Coriolis flow meter downstream of the condenser to obtain a reference value. The measurement error of the clamp-on ultrasonic flow meter was estimated by comparison with the reference value. The flow rate difference between these two flow meters was found to increase with increasing steam wetness. Moreover, the clamp-on ultrasonic flow meter measurement was almost the same as the flow rate of only the gas phase in the wet steam flow. From the experimental results, we proposed a correction method for measurement using the clamp-on ultrasonic flow meter in a wet steam flow by correcting the density in the flow rate calculation. Moreover, we clarified the applicability of the clamp-on ultrasonic flow meter in piping of various diameters.

Removability is one of the important features of biliary covered self-expandable metal stents (CSEMS). In this study, we evaluated the diagnostic ability of washing cytology of removed CSEMS. For 14 removed CSEMS that had been placed for the biliary strictures (12 malignant, 2 benign), the surface of CSEMS was washed with saline, and pathological examination of the washing liquid as cytology (CSEMS washing cytology) was performed. The specimen sampling rates and sensitivity for malignancy of CSEMS washing cytology were 92.9 % and 41.7 %, respectively. Sensitivity according to the primary disease was 60.0 % for bile duct cancer and 20 % for pancreatic cancer. Sensitivities based on the methods of stent removal were 16.7 % and 66.7 % for removal through the channel of the scope and with the scope, respectively. Therefore, it is possible that sensitivity of CSEMS washing cytology is higher in bile duct cancer and for removal with the scope. In conclusion, CSEMS washing cytology may have potential as a pathological diagnostic method.

The largest outbreak of dengue fever in Tanzania is ongoing. Dengue virus type 1 was diagnosed in a traveler who returned from Tanzania to Japan. In phylogenetic analysis, the detected strain was close to the Singapore 2015 strain, providing a valuable clue for investigating the dengue outbreak in Tanzania.

Endoscopic transpapillary gallbladder drainage (ETGBD) for acute cholecystitis is challenging. We evaluated the influence of pre-procedural imaging and cystic duct cholangiography on ETGBD. Patients who underwent ETGBD for acute cholecystitis were retrospectively examined. The rate of gallbladder contrast on cholangiography, the accuracy of cystic duct direction and location by computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP), and the relationship between pre-procedural imaging and the technical success of ETGBD were investigated. A total of 145 patients were enrolled in this study. Gallbladder contrast on cholangiography was observed in 29 patients. The accuracy of cystic duct direction and location (proximal or distal, right or left, and cranial or caudal) by CT were, respectively, 79%, 60%, and 58% by CT and 68%, 55%, and 58% by MRCP. Patients showing gallbladder contrast on cholangiography underwent ETGBD with a significantly shorter procedure time and a lower rate of cystic duct injury. No other factors affecting procedure time, technical success, and cystic duct injury were identified. Pre-procedural evaluation of cystic duct direction and location by CT or MRCP was difficult in patients with acute cholecystitis. Patients who showed gallbladder contrast on cholangiography showed a shorter procedure time and a lower rate of cystic duct injury.

A lymphocele is one of the complications of systematic pelvic or para-aortic lymphadenectomy. Although most patients are entirely asymptomatic, our patient exhibited an obstructive ileus at the jejunum compressed by a lymphocele. We report here a case of a subsequent para-aortic lymphocele treated with autologous peripheral blood injection. A 68-year-old woman with sigmoid colon cancer (T3N2bM1a) underwent laparoscopic sigmoidectomy. After 4 courses of chemotherapy (CapeOX + Bmab), para-aortic lymphadenectomy was additionally performed. One month later, an obstructive ileus occurred suddenly due to a lymphocele. A drainage catheter was placed into the lymphocele and a total of 35 mL of autologous peripheral blood was injected in 4 divided doses through the catheter. The volume of the lymphocele gradually reduced and the ileus improved after blood injection. This is the first report of a successful case of a subsequent para-aortic lymphocele treated with autologous peripheral blood injection without any complications.

Abstract This study explored decreased tumor suppressor microRNA (miRNA) plasma levels in pancreatic cancer (PCa) patients to clarify their potential as novel biomarkers and therapeutic targets. We used the microRNA array-based approach to select candidates by comparing plasma levels between PCa patients and healthy volunteers. Six down-regulated miRNAs (miR-107, miR-126, miR-451, miR-145, miR-491-5p, and miR-146b-5p) were selected. Small- and large-scale analyses using samples from 100 PCa patients and 80 healthy volunteers revealed that miR-107 was the most down-regulated miRNA in PCa patients compared with healthy volunteers (P

Background and study aims Biliary plastic stents are generally substituted for gallbladder stents in endoscopic transpapillary gallbladder stenting (EGBS), there is no sufficient evidence about what type of plastic stent is suitable. We examined outcomes of EGBS using standard biliary stents and a novel stent for acute cholecystitis and evaluated the efficacy of the novel stent. Patients and methods Seventy patients with acute cholecystitis in whom EGBS was performed were evaluated retrospectively. We performed EGBS in 23 patients using the novel stent (novel stent group) and 47 patients using standard biliary stents (pigtail: 35, straight: 12) (control group). In the two groups, we examined outcomes of EGBS. Results There were no significant differences in patient backgrounds or rates of technical success, clinical success, or early adverse events (AE) between the novel stent group and the control groups. However, rates of late AEs were 4.3 % in the novel stent group (liver abscess: 1) and 40.4 % in the control group (stent migration: 15, recurrence of cholecystitis: 4), indicating a significantly higher rate in the control group (P = 0.004). The rate of stent migration was significantly higher in the control group (P = 0.006). Multivariate analysis identified a straight type stent as the risk factor for stent migration (odds ratio: 8.81, 95 % confidence interval: 1.66 – 46.83). Conclusions The novel stent had significantly lower rates of late AEs and stent migration. Thus, for long-term stent placement, the novel stent was more effective than traditional biliary stents.