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The process of cervical lymph node metastasis is dependent on the phenotype of the tumor cells and their interaction with the host microenvironment and immune system; conventional research methods that focus exclusively on tumor cells are limited in their ability to elucidate the metastatic mechanism. In cancer tissues, a specialized environment called the tumor microenvironment (TME) is established around tumor cells, and inflammation in the TME has been reported to be closely associated with the development and progression of many types of cancer and with the response to anticancer therapy. In this study, to elucidate the mechanism of metastasis establishment, including the TME, in the cervical lymph node metastasis of oral cancer, we established a mouse-derived oral squamous cell carcinoma cervical lymph node highly metastatic cell line and generated a syngeneic orthotopic transplantation mouse model. In the established highly metastatic cells, epithelial-mesenchymal transition (EMT) induction was enhanced compared to that in parental cells. In the syngeneic mouse model, lymph node metastasis was observed more frequently in tumors of highly metastatic cells than in parental cells, and Cyclooxygenase-2 (COX-2) expression and lymphatic vessels in primary tumor tissues were increased, suggesting that this model is highly useful. Moreover, in the established highly metastatic cells, EMT induction was enhanced compared to that in the parent cell line, and CCL5 and IL-6 secreted during inflammation further enhanced EMT induction in cancer cells. This suggests the possibility of a synergistic effect between EMT induction and inflammation. This model, which allows for the use of two types of cells with different metastatic and tumor growth potentials, is very useful for oral cancer research involving the interaction between cancer cells and the TME in tumor tissues and for further searching for new therapeutic agents. [ABSTRACT FROM AUTHOR]

Feline norovirus (FNoV) is a potential pathogen of feline gastroenteritis and has two genogroups (GIV and GVI). Few epidemiological studies have been conducted on FNoV. We designed two enzyme-linked immunosorbent assays (ELISAs) to identify genogroup-specific FNoV antibodies for serological surveillance. Analysis of sera from cats experimentally infected with FNoV GIV or GVI and from specific-pathogen-free (SPF) cats confirmed that the two recombinant proteins used in the assay react in a genogroup-specific manner. Of the 183 samples tested, 6.6% were positive for GIV and 26.2% were positive for GVI. Antibodies to both FNoV genogroups were detected in sera collected in 2005, seven years before FNoV was first reported. [ABSTRACT FROM AUTHOR]

Objectives: To build preoperative prediction models with and without MRI for regional lymph node metastasis (r-LNM, pelvic and/or para-aortic LNM (PENM/PANM)) and for PANM in endometrial cancer using established risk factors. Methods: In this retrospective two-center study, 364 patients with endometrial cancer were included: 253 in the model development and 111 in the external validation. For r-LNM and PANM, respectively, best subset regression with ten-time fivefold cross validation was conducted using ten established risk factors (4 clinical and 6 imaging factors). Models with the top 10 percentile of area under the curve (AUC) and with the fewest variables in the model development were subjected to the external validation (11 and 4 candidates, respectively, for r-LNM and PANM). Then, the models with the highest AUC were selected as the final models. Models without MRI findings were developed similarly, assuming the cases where MRI was not available. Results: The final r-LNM model consisted of pelvic lymph node (PEN) ≥ 6 mm, deep myometrial invasion (DMI) on MRI, CA125, para-aortic lymph node (PAN) ≥ 6 mm, and biopsy; PANM model consisted of DMI, PAN, PEN, and CA125 (in order of correlation coefficient β values). The AUCs were 0.85 (95%CI: 0.77–0.92) and 0.86 (0.75–0.94) for the external validation, respectively. The model without MRI for r-LNM and PANM showed AUC of 0.79 (0.68–0.89) and 0.87 (0.76–0.96), respectively. Conclusions: The prediction models created by best subset regression with cross validation showed high diagnostic performance for predicting LNM in endometrial cancer, which may avoid unnecessary lymphadenectomies. Clinical relevance statement: The prediction risks of lymph node metastasis (LNM) and para-aortic LNM can be easily obtained for all patients with endometrial cancer by inputting the conventional clinical information into our models. They help in the decision-making for optimal lymphadenectomy and personalized treatment. Key Points: •Diagnostic performance of lymph node metastases (LNM) in endometrial cancer is low based on size criteria and can be improved by combining with other clinical information. •The optimized logistic regression model for regional LNM consists of lymph node ≥ 6 mm, deep myometrial invasion, cancer antigen-125, and biopsy, showing high diagnostic performance. •Our model predicts the preoperative risk of LNM, which may avoid unnecessary lymphadenectomies. [ABSTRACT FROM AUTHOR]

Background: Dysregulation of the terminal differentiation of bladder urothelium is associated with the pathogenesis of urinary tract disorders. Fibroblast growth factor (Fgf)7 and Fgf10 stimulate urothelial proliferation; however, their roles in cellular differentiation remain unclear. In this study, we used an organoid system to investigate the roles of these Fgfs in regulating bladder urothelium differentiation and identify their distribution patterns in the mouse bladder. Methods: Adult bladder epithelia (AdBE) isolated from adult mouse bladder tissues (AdBTs) were used to culture adult bladder organoids (AdBOs) in the presence of Fgf7 and Fgf10. The differentiation status of the cells in AdBTs, AdBEs, AdBOs, and neonatal bladder tissues (NeoBTs) was analyzed via quantitative real-time-PCR for the presence of undifferentiated cell markers (Krt5, Trp63, and Krt14) and differentiated cell markers (Krt20, Upk1a, Upk2, and Upk3a). Organoid cell proliferation was assessed by counting cell numbers using the trypan blue method. The effects of Fgf7 and Fgf10 on organoid differentiation were assessed using different doses of Fgfs, and the involvement of peroxisome proliferator-activated receptor γ (PPARγ) signaling in these processes was tested by introducing a PPARγ agonist (Rosiglitazone) and antagonist (T0070907) to the culture. The expression patterns of Fgf7 and Fgf10 were examined via in situ hybridization of AdBTs. Results: AdBOs showed higher expression of undifferentiated cell markers and lower expression of differentiated cell markers than AdBTs, NeoBTs, and AdBEs, indicating the relatively immature state of AdBOs. Differentiation of AdBOs was enhanced by Rosiglitazone and Fgf7, suggesting an interplay of intracellular signals between Fgf7 and PPARγ. Co-addition of T0070907 suppressed Fgf7-mediated differentiation, demonstrating that PPARγ is activated downstream of Fgf7 to promote cellular differentiation into umbrella cells. Furthermore, we found that Fgf7 is predominantly expressed in the umbrella cells of the urothelium, whereas Fgf10 is predominantly expressed in the urothelium and stroma of AdBTs. Conclusions: We demonstrated that unlike Fgf10, Fgf7 induces cellular differentiation via PPARγ activity and has a unique tissue distribution pattern in the adult bladder. Further studies on the Fgf7-PPARγ signaling axis would provide insights into the differentiation mechanisms toward functional umbrella cells and the pathogenesis of several urinary tract diseases. [ABSTRACT FROM AUTHOR]

Plantar fasciitis is one of the most common musculoskeletal injuries in runners and jumpers, with a higher incidence in females. However, mechanisms underlying sex-associated differences in its incidence remain unclear. This study investigated the possible differences in landing and jumping kinematics and kinetics of the foot between sexes during drop-jump activities. Twenty-six participants, including 13 males and 13 females, performed drop-jumps from a platform onto force plates. Nineteen trials including ten males and nine females were selected for inverse dynamics analysis. The patterns of stretch and tensile force generated by the plantar aponeurosis (PA) were estimated using a multi-segment foot model incorporating the PA. Our results demonstrated that dorsiflexion, angular velocity, and normalized plantarflexion moment of the midtarsal joint right after the heel landed on the floor were significantly larger in females than in males. Consequently, the PA strain rate and tensile stress tended to be larger in females than in males. Such differences in the kinematics and kinetics of the foot and the PA between sexes could potentially lead to a higher prevalence of foot injuries such as plantar fasciitis in females. [ABSTRACT FROM AUTHOR]

Herein, we report a novel strategy toward non-volatile optical memory with high-contrast, high-speed recording, and non-destructive readout capability based on the cooperative out-of-plane orientation of a fluorescent dye doped into azobenzene liquid crystalline polymer film. By employing the out-of-plane orientation switching upon irradiation with UV light and thermal heating, high-contrast turn-on fluorescence switching was successfully achieved and the optical recording was demonstrated with non-destructive fluorescence readout capability. Furthermore, the recording speed and the fluorescence on/off contrast in the present system were dramatically improved compared to the previous in-plane orientation mode. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic has had a severe impact on mental well-being. Vaccination may have played a pivotal role in enduring this mental health crisis. The present study aimed to longitudinally investigate the association between COVID-19 vaccination and mental health status among Japanese population in 2021. Longitudinal data of 17,089 individuals aged 15–79 years who participated in a nationwide online study were analyzed. Baseline and follow-up mental health statuses were assessed using the Kessler Psychological Distress Scale (K6). General linear and multivariable logistic regression models adjusted for baseline levels of mental distress were used to examine the association between vaccine receipt and follow-up levels of mental health. Mean K6 scores were lower in the vaccinated than in the non-vaccinated participants. Those who had received one or two doses of COVID-19 vaccines were associated with improved mental health at follow-up in subjects with psychological distress at baseline (odds ratio [OR] 1.31 and 1.35, respectively) and were inversely associated with deteriorated mental health status at follow-up in subjects without psychological distress at baseline (OR 0.66 and 0.70, respectively) compared with no vaccination groups, respectively. The present study would indicate that one or two doses of COVID-19 vaccinations contributed to mental well-being in Japan. This finding might provide evidence for promoting vaccination against COVID-19 and emerging infectious diseases in the future. [ABSTRACT FROM AUTHOR]

Background: Diagnosis of fetal growth restriction (FGR) entails difficulties with differentiating fetuses not fulfilling their growth potential because of pathologic conditions, such as placental insufficiency, from constitutionally small fetuses. The feasibility of placental MRI for risk stratification among pregnancies diagnosed with FGR remains unexplored. Purpose: To explore quantitative MRI features useful to identify pregnancies with unfavorable outcomes and to assess the diagnostic performance of visual analysis of MRI to detect pregnancies with unfavorable outcomes, among pregnancies diagnosed with FGR. Study Type: Retrospective. Population: Thirteen pregnancies with unfavorable outcomes (preterm emergency cesarean section or intrauterine fetal death) and 11 pregnancies with favorable outcomes performed MRI at gestational weeks 21–36. Field Strength/Sequence: A 5‐T, half‐Fourier‐acquired single‐shot turbo spin echo (HASTE), spin‐echo echo‐planar imaging (SE‐EPI) and T2 map derived from SE‐EPI. Assessment: Placental size on HASTE sequences and T2 mapping‐based histogram features were extracted. Three radiologists qualitatively evaluated the visibility of maternal cotyledon on HASTE and SE‐EPI sequences with echo times (TEs) = 60, 90, and 120 msec using 3‐point Likert scales: 0, absent; 1, equivocal; and 2, present. Statistical Tests: Welch's t‐test or Mann–Whitney U test for quantitative features between the favorable and unfavorable outcome groups. Areas under the receiver operating curves (AUCs) of the three readers' visual analyses to detect pregnancies with unfavorable outcomes. A P value of <0.05 was inferred as statistically significant. Results: Placental size (major and minor axis, estimated area of placental bed, and volume of placenta) and T2 mapping‐based histogram features (mean, skewness, and kurtosis) were statistically significantly different between the two groups. Visual analysis of HASTE and SE‐EPI with TE = 60 msec showed AUCs of 0.80–0.86 to detect pregnancies with unfavorable outcomes. Data Conclusion: Placental size, histogram features, and visual analysis of placental MRI may allow for risk stratification regarding outcomes among pregnancies diagnosed with FGR. Evidence Level: 3 Technical Efficacy: Stage 5 [ABSTRACT FROM AUTHOR]

Pleomorphic adenoma (PA) is a localized tumor that presents pleomorphic or mixed characteristics of epithelial origin and is interwoven with mucoid tissue, myxoid tissue, and chondroid masses. The literature reported that PA most often occurs in adults aged 30–60 years and is a female predilection; the exact etiology remains unclear. Epithelial–mesenchymal transition (EMT) is the transdifferentiation of stationary epithelial cells primarily activated by a core set of transcription factors (EMT-TFs) involved in DNA repair and offers advantages under various stress conditions. Data have suggested that EMTs represent the basic principle of tissue heterogeneity in PAs, demonstrating the potential of adult epithelial cells to transdifferentiate into mesenchymal cells. It has also been reported that multiple TFs, such as TWIST and SLUG, are involved in EMT in PA and that SLUG could play an essential role in the transition from myoepithelial to mesenchymal cells. Given this background, this review aims to summarize and clarify the involvement of EMT in the development of PA, chondrocyte differentiation, and malignant transformation to contribute to the fundamental elucidation of the mechanisms underlying EMT. [ABSTRACT FROM AUTHOR]

Polypoid endometriosis is a benign, rare variant of endometriosis that forms polypoid nodules mimicking malignant tumors. For three cases of polypoid endometriosis of female genital organs, this report presents characteristic MR imaging features reflecting the histopathological findings. The solid and microcystic pattern or the multilocular pattern both reflecting dilated endometrial glands, and characteristic morphology of the nodules, multilobulated or polypoid-shaped, were helpful diagnostic clues present in these three cases. Earlier reported MR findings were also recognized, including signal intensity similar to that of the endometrium on T2-weighted image and contrast enhanced T1-weighted image, hypointense rim on T2-weighted image, lack of diffusion restriction, and hyperintense foci on T1-weighted image. Two cases were diagnosed preoperatively based on MR imaging findings as polypoid endometriosis. Fertility-preserving treatment was administered for one patient. Preoperative inference of polypoid endometriosis from MR imaging can avoid overtreatment and lead to fertility preservation. [ABSTRACT FROM AUTHOR]

Purpose: Refinement of organoid technology is important for studying physiology and disease of the intestine. We aimed to optimize defined serum-free conditions for human infant small intestinal (SI) organoid culture with predetermined doses of Wnt3a and Rspo1 from surgical specimens. We further assessed whether intestinal specimens could be stored before use as a source of organoids. Methods: Different doses of Wnt3a and Rspo1 in a serum-free medium were tested to establish a condition in which surgically resected SI cells grew as organoids over multiple passages. The expression of marker genes for stem and differentiated cells was assessed by quantitative polymerase chain reaction. We also investigated the organoid-forming efficiency of cells in degenerating intestines stored at 4 °C for various intervals post-resection. Results: We determined the doses of Wnt3a and Rspo1 required for the continuous growth of infant SI organoids with multi-differentiation potential. We revealed that, despite the time-dependent loss of stem cells, tissues stored for up to 2 days preserved cells capable of generating amplifiable organoids. Conclusion: SI cells can be grown as organoids under defined conditions. This could provide a reproducible and customizable method of using surgical specimens for the study of intestinal maturation and their relevance to pediatric diseases. [ABSTRACT FROM AUTHOR]

Paradoxical reaction (PR) occurs when a drug elicits a reaction contrary to what was expected. To clarify the clinical features and genetic background of individuals susceptible to PR, we analyzed the clinical course of patients in whom psoriatic eruptions worsened or newly developed during tumor necrosis factor (TNF) antagonist administration and the role of focal infections and genetic variations. Of 125 patients who received TNF antagonist therapy for psoriasis, acrodermatitis continua of Hallopeau (ACH), generalized pustular psoriasis (GPP), or palmoplantar pustular psoriasis (PPP), eight patients with PR were surveyed at our hospital Dermatology Department between 2010 and 2021. A survey was also done on six patients who received TNF antagonist therapy for Crohn's disease, rheumatoid arthritis, ankylosing spondylitis, and hidradenitis suppurativa and were referred to our department due to PR. Additionally, Sanger sequencing analysis was performed for all exons and flanking introns of IL36RN (interleukin 36 receptor antagonist), CARD14 (caspase recruitment domain‐containing protein 14), and AP1S3 (adaptor‐related protein complex 1 subunit sigma 3). The clinical assessment of the 14 patients demonstrated an average age at PR onset of 48.4 years, a male : female ratio of 5:9, and a mean administration period until onset of 9.2 months. The clinical types of PR were plaque psoriasis, PPP, GPP, pustulosis, acne, ACH, hair loss, and exacerbation of arthralgia. Histopathology revealed psoriasiform dermatitis in three patients. One patient continued TNF antagonist therapy. All of the patients with psoriasis and GPP had dental infections, suggesting that focal infection may be a risk factor of the development of PR following TNF antagonist therapy. Gene analysis demonstrated CARD14 gene variants associated with RA, CD, AS, or PPP in four patients. In addition, all of the patients with ACH and PPP experienced PR, suggesting that these diseases may predispose patients to PR to TNF antagonist therapy. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the diagnostic performance of MRI findings for differentiating uterine leiomyoma with intraligamentous growth, or broad ligament fibroid, from subserosal leiomyoma. Methods: This study included 37 patients with surgically confirmed uterine smooth muscle tumors (36 leiomyomas and one smooth muscle tumor of uncertain malignant potential) with intraligamentous growth (IL) and size-matched control of 37 patients with subserosal leiomyoma (SS). Two radiologists independently evaluated eight preoperative MRI findings: tumor shape, degeneration, attachment to uterus, ovary elevation, ureter displacement, bladder deformation, rectal displacement, and separation of round ligament (RL) and uterine artery (UA). The diagnostic values of these findings and interobserver agreement were assessed. Receiver-operating characteristic (ROC) analysis of the number of positive MRI findings for diagnosing IL was performed. Clinical outcomes including surgical method, operation time, intraoperative blood loss, perioperative complications, and postoperative hospital stay of the two groups were compared. Results: Significant differences in tumor shape, attachment to uterus, ovary elevation, ureter displacement, and separation of RL and UA were found between IL and SS. Four of these findings, excluding ureter displacement, showed moderate to substantial interobserver agreement. When two or more of these four findings were positive, sensitivity, specificity, and area under the ROC curve were 91%, 77%, 0.90 in reader 1 and 82%, 89%, 0.91 in reader 2. The operation time was significantly longer for IL than for SS. Conclusion: Tumor shape, attachment to uterus, ovary elevation, and separation of RL and UA are useful MRI findings for differentiating intraligamentous leiomyoma from subserosal leiomyoma. [ABSTRACT FROM AUTHOR]

Submerged arc welding, which is generally used for the corner joint of box-section columns, is a welding process with a high heat input. The influence on the strength and toughness of the heat-affected zone is an important concern, especially when used with a high-performance steel that may be more susceptible to heat input. The ductility of the welded corner joint is one of the important factors to ensure safety against external forces, such as during severe earthquakes. In this study, a series of material and cyclic loading tests of the corner joint comprising SA440C high-performance steel fabricated by submerged arc welding were conducted. The experimental results indicated that the welded corner joint comprising SA440C steel is ductile enough to dissipate input energy caused by the strong ground motion from an earthquake. [ABSTRACT FROM AUTHOR]

Pustulotic arthro‐osteitis, occasionally complicated with palmoplantar pustulosis, affects patients' activities of daily living. Granulocyte and monocyte adsorption apheresis selectively removes activated granulocytes and monocytes by means of extracorporeal circulation. Although the efficacy of granulocyte and monocyte adsorption apheresis in the treatment of generalized pustular psoriasis has been proved, very few reports have assessed its efficacy in the treatment of palmoplantar pustulosis and pustulotic arthro‐osteitis. Ten pustulotic arthro‐osteitis patients with five palmoplantar skin manifestations were treated with weekly granulocyte and monocyte adsorption apheresis over 5 weeks. Skin manifestations were assessed using palmoplantar pustulosis area and severity index, and joint symptoms were assessed using a visual analog scale of joint pain, tender joint count, swollen joint count and C‐reactive protein immediately before, after and at the 3‐month follow up of the five granulocyte and monocyte adsorption apheresis sessions. Two out of five patients with skin manifestations achieved more than 50% improvement in their score (remarkably improved). However, in two patients, deterioration was noted, in one of whom the skin manifestations remained unchanged at the 3‐month follow up. In five out of the 10 patients, the joint symptoms were assessed as better than improved at the 3‐month follow up. No deterioration was noted at the 3‐month follow up. In three patients, reduction or cessation of medication for arthralgia was possible. We concluded that granulocyte and monocyte adsorption apheresis is a therapeutic option to consider when pustulotic arthro‐osteitis is recalcitrant to conventional therapy. [ABSTRACT FROM AUTHOR]

Idiopathic normal pressure hydrocephalus (iNPH) is a dementia-inducing disorder. Primary cause of iNPH is speculated to be a reduction of cerebrospinal fluid (CSF) absorption, which secondarily induces hydrocephalus, compression of brain, and reduction of CSF production. Patients are treated by surgically inserting a shunt to deliver excess CSF to the abdominal cavity. The prognosis for cognitive improvement after shunt surgery has been difficult to predict. We therefore investigated various CSF proteins, hoping to find a biomarker predictive of cognitive performance one to two years after shunt surgery. CSF proteins of 34 iNPH and 15 non-iNPH patients were analysed by Western blotting, revealing two glycan isoforms of transferrin (Tf); ‘brain-type’ Tf with N -acetylglucosaminylated glycans and ‘serum-type’ Tf with α2, 6-sialylated glycans. Brain-type Tf levels decreased in iNPH but rapidly returned to normal levels within 1–3 months after shunt surgery. This change was positively correlated with recovery from dementia, per Mini-Mental State Examination and Frontal Assessment Battery scores at 11.8 ± 7.7 months post-operation, suggesting that brain-type Tf is a prognostic marker for recovery from dementia after shunt surgery for iNPH. Histochemical staining with anti-Tf antibody and an N -acetylglucosamine-binding lectin suggests that brain-type Tf is secreted from choroid plexus, CSF-producing tissue. [ABSTRACT FROM AUTHOR]

Norovirus (NoV) infection is the most common cause of acute gastroenteritis in humans of all ages worldwide. When cats are experimentally infected with feline norovirus (FNoV), they develop symptoms of acute gastroenteritis. Therefore, FNoV infection may serve as an animal model for the disease caused by human norovirus infection. In this study, we examined whether FNoV of cats infected with genogroup GVI are protected from reinfection with the same strain. The blood anti-FNoV IgG level was inversely correlated with the viral load in stool samples and the clinical score of FNoV-infected cats, but complete prevention of reinfection was not observed. These findings were similar to the results of a reinfection experiment with NoV in human volunteers. [ABSTRACT FROM AUTHOR]

This study investigated the visual and tactile evaluation of 10 towel samples made from different fiber contents. The survey was conducted by Turkish and Japanese panelists. It was also studied how psychological manners can change their preferences. To test these facts, two kinds of trial (blind test and open test) were applied on panelists. In this way, it was observed that some of the panelists changed their first preferences from synthetic fiber-based towel to natural fiber-based towel. This fact verified that psychological manners had a great effect on Turkish consumers’ preferences, and fiber content and thickness were the most distinctive properties. Then, the preferences of the panelists were ranked and the most preferred samples were determined and compared with Japanese consumers’ preferences. It was also found that Japanese people were more consistent than Turkish people and external factors and psychological manners were not effective on their decisions. [ABSTRACT FROM AUTHOR]

An efficient and practical total synthesis of aquayamycin has been accomplished. The highly oxidized and stereochemically complex tetracyclic ring system was constructed using three key reactions: 1) highly diastereoselective 1,2-addition of C-glycosyl naphthyllithium to a cyclic ketone, 2) indium-mediated site-selective allylation-rearrangement sequence of naphthoquinone, and 3) diastereoselective intramolecular pinacol coupling. This synthetic strategy offers a novel and efficient pathway to prepare aquayamycin-type angucycline antibiotics. [ABSTRACT FROM AUTHOR]

This study investigated responsiveness of beef cattle to various environmental stimuli by subjecting 15-16 Japanese Black cows to five tests repeated twice. Within individual behavioral measures, cows were moderately (repeatability = 0.54-0.70) or highly (repeatability = 0.74-0.89) consistent in flight distance during grazing and resting in the human approach tests, maximum distance from the group pen and the number of total and different feed tub visits in the feeding-sociability trade-off test, and unwillingness to enter the restraint, movement under restraint and flight speed after release from restraint in the social isolation and restraint test. By contrast, cows were not consistent in the latency to make the first contact and the number of contacts with novel object(s) in the novelty test (repeatability = 0.24-0.39). Across behavioral measures in different tests, cows showed no consistency ( P ≥ 0.05) in any combinations of measures from the two human approach tests, the trade-off test and the social isolation and restraint test. In conclusion, human approach (particularly during resting), feeding-sociability trade-off and social isolation and restraint situations can be used for evaluating personality in Japanese Black cows, while the value of the novelty test needs to be reexamined. [ABSTRACT FROM AUTHOR]

Retinol (ROL), the alcohol form of vitamin A, is known to control cell fate decision of various types of stem cells in the form of its active metabolite, retinoic acid (RA). However, little is known about whether ROL has regulatory effects on colonic stem cells. We examined in this study the effect of ROL on the growth of murine normal colonic cells cultured as organoids. As genes involved in RA synthesis from ROL were differentially expressed along the length of the colon, we tested the effect of ROL on proximal and distal colon organoids separately. We found that organoid forming efficiency and the expression level of Lgr5, a marker gene for colonic stem cells were significantly enhanced by ROL in the proximal colon organoids, but not in the distal ones. Interestingly, neither retinaldehyde (RAL), an intermediate product of the ROL-RA pathway, nor RA exhibited growth promoting effects on the proximal colon organoids, suggesting that ROL-dependent growth enhancement in organoids involves an RA-independent mechanism. This was confirmed by the observation that an inhibitor for RA-mediated gene transcription did not abrogate the effect of ROL on organoids. This novel role of ROL in stem cell maintenance in the proximal colon provides insights into the mechanism of region-specific regulation for colonic stem cell maintenance. [ABSTRACT FROM AUTHOR]

Background: Intraepithelial lymphocytes (IELs) in the intestine play important roles in the regulation of local immune responses. Although their functions have been studied in a variety of animal experiments, in vitro studies on spatiotemporal behaviors of IELs and their interaction with intestinal epithelial cells (IECs) have been hampered due to the lack of a suitable culture system. In this study, we aimed at developing a novel co-culture system of IELs with IECs to investigate dynamic interaction between these two populations of cells in vitro.Methods: We optimized experimental conditions under which murine IELs can be efficiently maintained with IECs cultured as three-dimensional organoids. We then tested the effect of IL-2, IL-7, and IL-15 on the maintenance of IELs in this co-culture system. By time-lapse imaging, we also examined the dynamic behaviors of IELs.Results: IELs can be expanded with epithelial organoids in the presence of IL-2, IL-7, and IL-15. IELs were efficiently maintained within and outside of organoids showing a ~four-fold increase in both αβT and γδT IELs for a period of 2 weeks. Four-dimensional fluorescent imaging revealed an active, multi-directional movement of IELs along the basolateral surface of IECs, and also their inward or outward migration relative to organoid structures. Cell tracking analysis showed that αβT and γδT IELs shared indistinguishable features with regard to their dynamics.Conclusions: This novel co-culture method could serve as a unique tool to investigate the motility dynamics of IELs and their temporal and spatial interaction with IECs in vitro. [ABSTRACT FROM AUTHOR]

Regarding appropriate timings of discontinuation and resumption of biologics for psoriasis patients before and after elective surgeries, an international consensus has yet to be reached. The Japanese Dermatological Association of Guideline and Safety Manual for the use of Biologic Agents in Psoriasis 2013 states that infliximab ( IFX) and adalimumab ( ADA) should be withheld at least 4 and 2 weeks, respectively, before surgery and can be restarted as neither postoperative infection nor delayed wound healing is recognized. We experienced three generalized pustular psoriasis ( GPP) patients and one plaque-type psoriasis patient undergoing surgeries during tumor necrosis factor ( TNF)-α blocker therapy. Three GPP cases experienced uneventful post-surgical course. One psoriasis vulgaris patient on IFX had a wound healing delay with deterioration of psoriatic plaques which was restored by restarting IFX. The timing of suspension and resumption of TNF-α blockers in all cases were determined following the Japanese guideline. [ABSTRACT FROM AUTHOR]

Transferrin is an iron-transport protein which possesses N-glycans at Asn432 and Asn630 in humans. Transferrin glycoforms Tf-1 and Tf-2, previously identified in human cerebrospinal fluid, are defined as the lower and upper bands in gel electrophoresis, respectively. Importantly, the Tf-2/Tf-1 ratio is raised in idiopathic normal pressure hydrocephalus patients and is useful as a clinical marker. In order to gain insight into the relationship between transferrin glycoform and biological function, we performed comparative characterization of Tf-1, Tf-2 and serum transferrin (sTf). Mass spectrometric analyses confirmed that Tf-2 is modified with disialylated biantennary glycans at both of the two N-glycosylation sites, which are similar to the N-glycans of sTf. On the other hand, Tf-1 is site-specifically modified: Asn630 has biantennary agalacto-complex-type glycan with bisecting N-acetylglucosamine (GlcNAc) and core fucose while Asn432 is modified with complex/high mannose-type glycans and possibly single GlcNAc. Size exclusion chromatography and fluorescence correlation spectroscopy analysis revealed that the hydration volume of Tf-1 is slightly smaller than that of sTf. Our striking finding is that Tf-1 has an exposed hydrophobic surface as monitored by the fluorescence intensity and wavelength of a hydrophobic probe, 1-anilino-8-naphthalene sulfonate, whereas Tf-2 does not. These results suggest that the different N-glycan structure of Tf-1 lowers the apparent hydration volume and reveals a patch of hydrophobic surface on transferrin which is otherwise covered with sialoglycan in sTf and Tf-2. The carbohydrate deficiency in certain pathological conditions may also expose hydrophobic surface which may modulate the function and/or stability of transferrin. [ABSTRACT FROM AUTHOR]

We report 2 cases of primary central nervous system (CNS) lymphoma arising in the region of the optic nerve. For both patients, diagnosis of lymphoma was impossible without histological examination because of the rarity of the lymphoma location. The first case involved an 84-year-old woman who developed loss of vision and hypopituitarism. Intraoperative finding was optic glioma; histological diagnosis was diffuse large B cell lymphoma, however. The second case involved a 67-year-old man who developed loss of vision. The pre-surgical diagnosis was optic nerve neuritis; this was then revised to granuloma. The tumor arose in the optic nerve. Methotrexate and rituximab were administered and the patient remained in complete remission for 3 years. However, a sudden intratumoral hemorrhage occurred. Although most of the lymphoma cells obtained from the initial surgery were negative for vascular endothelial growth factor (VEGF) immunoreactivity, high levels of VEGF immunoreactivity in lymphoma cells was detected in the specimen obtained after intratumoral bleeding at recurrence, and correlation between VEGF reactivity and tumor recurrence was suggested. To date, primary CNS lymphomas with intracerebral hemorrhage have been reported in 3 cases only, and a correlation between intratumoral hemorrhage and the degree of VEGF expression has been suggested. VEGF also might have predictive significance for recurrence. [ABSTRACT FROM AUTHOR]

Biologics such as tumor necrosis factor ( TNF) inhibitors are highly effective for treating severe psoriasis, and an increasing number of patients benefit from them. However, subsidiary subjects have arisen in the course of treatment which may directly impact the continued use of these drugs in a given case. In this article, we report two cases of psoriasis vulgaris refractory to treatment with both adalimumab and infliximab. We measured the serum drug concentration and absorbance value of antidrug antibodies using the sandwich enzyme-linked immunoassay method. Antibodies to adalimumab and infliximab were detected in both patients. The low drug concentration and adverse clinical response observed corroborated these findings. Dosage and concomitant medication are considered to be important factors influencing the development of antibody formation. Therapeutic drug monitoring and measurement of antidrug antibodies will assist in maintaining a clinical response and in optimizing the response of patients being treated with biological therapies. The use of concomitant immunosuppressive medication should be considered for patients who will be treated with their second TNF inhibitor after having developed antidrug antibodies against their first TNF inhibitor. [ABSTRACT FROM AUTHOR]

ABSTRACT Nephrogenic systemic fibrosis is a fibrosing disorder that affects patients with advanced renal dysfunction and is associated with gadolinium-based contrast media. As the number of reports increase, it is becoming clear that its clinical course and symptoms are various. We describe a 14-year-old boy and 71-year-old man with nephrogenic systemic fibrosis and review the Japanese cases documented thus far. In Japan, there are only 10 cases definitely associated with gadolinium, whereas over 500 cases have been recorded worldwide. We found a remarkable difference in clinical signs among Japanese cases. Some cases showed keratotic papules or plaques on the extremities. This group tended to develop symptoms after a shorter interval following gadolinium exposure. The remainder of the cases presented glossy and smooth surfaces, with symptoms tending to develop after a longer interval following their last gadolinium exposure. The discrepancies between the actual and the estimated number of patients, and the various clinical manifestations can be explained by the comparatively smaller dosage of gadolinium-based contrast agents commonly administrated in Japan, in contrast to the higher dosages administrated in the USA and Europe. [ABSTRACT FROM AUTHOR]

Background: Failure of skull base reconstruction is a life-threatening issue. This study describes surgical techniques utilising various types of galeal flaps and reports on outcome of these procedures for skull base reconstruction. Method: Clinical records of 136 patients (75 men, 61 women; mean age, 50.0 years) who required skull base reconstruction with galeal flaps were reviewed retrospectively. Patients had undergone skull base surgeries with simultaneous reconstruction for benign tumours in 77 patients, malignant tumours in 53, and other lesions in 6. We repaired dural defects using a fascial patch, and covered the skull base defects using various types of galeal flap according to the size and location of the skull base defects. Routine spinal drainage was not used in any patients. Findings: Reconstruction was performed as planned in all patients. We utilised a galea frontalis flap in 17 patients, temporoparietal galeal flap in 95, temporoparietal galeal flap with calvarial bone in 9, and bipedicled temporoparietal galeal flap in 15. Postoperative complications included scalp wound necrosis in 8 patients (5.9%), transient leakage of cerebrospinal fluid in 3 (2.2%), and intracranial infection in 2 (1.5%). Necrosis of the galeal flaps was not encountered. Conclusions: Galea is a well-vascularised tissue with homogenous thickness. Since the galeal layer covers the entire head area, various types of galeal flap can be elevated to cover any size and location of skull base defect. [ABSTRACT FROM AUTHOR]

We report a case of cutaneous infection due to Scedosporium apiospermum in a 75-year-old immunocompromised male patient who had received long-term corticosteroid and immunosuppressant therapy for the treatment of nephrotic syndrome. The patient came to our department complaining of erythema with a number of pustules on the dorsal surface of the right hand. S. apiospermum was identified from a culture taken from the pus. After unsuccessful treatment with topical ketoconazole, oral itraconazole and oral terbinafine, the lesion quickly resolved with the daily administration of 400 mg voriconazole. No recurrence was observed despite discontinuation of voriconazole due to drug-induced hepatitis. Voriconazole holds out the promise of an effective treatment for invasive Scedosporium infection. [ABSTRACT FROM AUTHOR]

Background: Vitamin D3ointment and corticosteroid ointment are both used for the treatment of palmoplantar pustulosis (PPP). However, to date there is no systematic study of the efficacy of combination therapy for the treatment of PPP.Objective: We compared the efficacy of a topical combination therapy with vitamin D3and a topical corticosteroid with that of topical corticosteroid alone in the treatment of PPP.Method: We evaluated left-right comparison study of the efficacy of a combination therapy consisting of maxacalcitol ointment and betamethasone butyrate propionate ointment (BBP), and monotherapy with BBP alone in 27 patients with PPP for 8 weeks.Results: The improvement in the symptom (erythema, pustules/vesicles, hyperkeratosis/scales) scores was high for the combination therapy. In particular, the improvement rate for pustules/vesicles at week 8 after the combination therapy was significantly higher than for the monotherapy (p < 0.05).Conclusion: This combination regimen demonstrated that not only topical corticosteroids, but also topical vitamin D3ointment, is useful for the treatment of PPP. [ABSTRACT FROM AUTHOR]

Correction to: Abdominal Radiology https://doi.org/10.1007/s00261-021-03042-7 The original version of this article unfortunately contained a mistake in Fig. 7 Receiver operating characteristic (ROC) curves of the number of positive imaging findings for intraligamentous leiomyoma among four imaging findings: tumor shape deformity, lower attachment to the uterus, ovary elevation, and separation of round ligament and uterine artery Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. [Extracted from the article]

We report a case of acute generalized exanthematous pustulosis (AGEP) induced by ampicillin/cloxacillin sodium (ABPC/MCIPC) in a pregnant woman. AGEP is caused mostly by drugs. Among them, β-lactam antibiotics account for a high proportion of the cases, predominantly by amoxicillin. To our knowledge, this is only the second case ever reported in the Japanese language published work of AGEP induced by ABPC/MCIPC. [ABSTRACT FROM AUTHOR]

Lichen sclerosus is a chronic inflammatory skin disorder that has a predilection for the anogenital area. Topical corticosteroid is occasionally effective; however, continuous treatment is often required and recurrence after its stoppage is frequent. Herein, we report a case of vulvar lichen sclerosus in a 5-year-old girl, which was refractory to topical corticosteroids. After 14 weeks of treatment with 0.03% tacrolimus ointment once daily, the lesions completely resolved without side-effects. Of interest, the number of milia within the plaque of lichen sclerosus was reduced in tandem with the improvement of lichen sclerosus. This is the first report of topical low-concentration tacrolimus treatment showing a dramatic effect in the treatment of childhood vulvar lichen sclerosus. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is an increasingly severe chronic metabolic disease that is occurring at an alarming rate worldwide. Various diabetic models, including non-obese diabetic mice and chemically induced diabetic models, are used to characterize and explore the mechanism of the disease's pathophysiology, in hopes of detecting and identifying novel potential therapeutic targets. However, this is accompanied by disadvantages, such as specific conditions for maintaining the incidence, nonstable hyperglycemia induction, and potential toxicity to other organs. Murine MAFA and MAFB, two closely-linked islet-enriched transcription factors, play fundamental roles in glucose sensing and insulin secretion, and maintenance of pancreatic β-cell, respectively, which are highly homologous to human protein orthologs. Herein, to induce the diabetes mellitus model at a specific time point, we generated Pdx1-dependent Mafb-deletion mice under Mafa knockout condition (A0BΔpanc), via tamoxifen-inducible Cre-loxP system. After 16 weeks, metabolic phenotypes were characterized by intraperitoneal glucose tolerance test (IPGTT), urine glucose test, and metabolic parameters analysis. The results indicated that male A0BΔpanc mice had obvious impaired glucose tolerance, and high urine glucose level. Furthermore, obvious renal lesions, impaired islet structure and decreased proportion of insulin positive cells were observed. Collectively, our results indicate that A0BΔpanc mice can be an efficient inducible model for diabetes research. [ABSTRACT FROM AUTHOR]