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Hypoxia may promote tumor progression, and hypoxically altered noncoding RNA (ncRNA) expression may play a role in metastasis. Canine oral melanoma (COM) frequently metastasizes, and ncRNA expression under hypoxia may be clinically significant. We aimed to elucidate ncRNA fragments whose expression is altered by hypoxia in COM-derived primary KMeC and metastatic LMeC cell lines using next-generation sequencing to validate these results in qRT-PCR, and then compare expression between metastatic and non-metastatic COM. The NGS analysis and subsequent qRT-PCR validation were performed using hypoxic and normoxic KMeC and LMeC cells, and clinical samples [tumor tissue, plasma, and plasma-derived extracellular vesicles] obtained from dogs with metastatic or non-metastatic melanoma were analyzed with qRT-PCR. Y RNA was significantly decreased in metastatic LMeC cells versus primary KMeC cells in hypoxic and normoxic conditions. The expression of Y RNA was decreased in dogs with metastatic melanoma versus those with non-metastatic melanoma for all clinical sample types, reflecting the pattern found with hypoxia. Receiver operating characteristic analysis demonstrated that Y RNA level is a promising biomarker for discriminating metastatic from non-metastatic melanoma in plasma [area under the curve (AUC) = 0.993, p

We examined a 6-week consumption effect of astaxanthin- and tocotrienol-containing foods on ocular function pre- and post-visual display terminal (VDT) work in a randomized, placebo-controlled, parallel-group study including 60 healthy adults. For 6 weeks, participants consumed astaxanthin (9 mg/day) + tocotrienol (50 mg/day)- or placebo-containing foods. The astaxanthin + tocotrienol group had significantly better corrected post-VDT visual acuity (VA) in the dominant eye than the placebo group according to the measured value and change from pre-VDT after 6 weeks of astaxanthin + tocotrienol consumption (p

IntroductionThe Mishima Islands in Kagoshima Prefecture, Japan, are remote islands designated as medically underserved. Supporting the people living in such remote islands requires a multifaceted examination of the livelihoods of the residents, including their health, work, and living environment.MethodsStudents from the faculties of nursing, veterinary science, agriculture, and engineering participated in a 3-day virtual fieldwork session held synchronously from the campus of Kagoshima University and on a remote island in the Mishima Mura island group in Kagoshima Prefecture, Japan. Coursework and post-course surveys were analyzed to determine student engagement and learning. In particular, the analysis considered learning in relation to interprofessional learning and community-based learning.Results and discussionStudents expressed being able to conduct fieldwork online, collaborate with students from multiple faculties and graduate schools, and apply their expertise. These outcomes were reflected in the five-point Likert scale evaluation responses, highlighting a sense of accomplishment and satisfaction. Virtual fieldwork can contribute to student learning by introducing new concepts and allowing them to consider development issues in remote areas from multiple perspectives.

Canine oral melanoma (COM) is a common and highly aggressive disease with the potential to model human melanomas. Dysregulated microRNAs represent an interesting line of research for COM because they are implicated in tumor progression. One example is miR-450b, which has been investigated for its molecular mechanisms and biological functions in multiple human cancers, but not human or canine melanoma. Here, we aimed to investigate miR-450b as a potential diagnostic biomarker of COM and its functional roles in metastatic and non-metastatic forms of the disease. We investigated the expression of miR-450b and its target mRNA genes in clinical (tumor tissue and plasma) samples and metastatic and primary-tumor cell lines. Knockdown and overexpression experiments were performed to determine the influence of miR-450b on cell proliferation, migration, colony formation, and apoptosis. miR-450b was significantly upregulated in COM and differentiated between metastatic and non-metastatic tumors, and its potential as a biomarker of metastatic and non-metastatic COM was further confirmed in ROC analysis. miR-450b knockdown promoted cell proliferation, migration, and clonogenicity and inhibited apoptosis, whereas its overexpression yielded the reverse pattern. miR-450b directly binds 3’ UTR of PAX9 mRNA and modulates its function leading to BMP4 downregulation and MMP9 upregulation at the transcript level. Furthermore, we surmised that miR-450b activates the Wnt signaling pathway based on gene ontology and enrichment analyses. We concluded that miR-450b has the potential as a diagnostic biomarker and could be a target candidate for COM treatment.

To investigate the crack growth behavior in a cladded structure, a numerical simulation method based on the extended finite element method (XFEM) was developed. This method employs 8-node hexahedral continuum elements enriched only with the Heaviside step function, which can model planar crack independently of finite elements. For a crack across the interface of dissimilar materials in cladded structures, stress intensity factors along the crack front are evaluated by the domain integral method. Crack front shapes are updated by using Paris’ law and then smoothed by cubic Bézier curves in each region. In addition, fatigue crack propagation analyses for cladded compact tension [C(T)] specimens were performed. The relationships between crack length and load cycles as well as the transition of propagating crack front shapes were compared with experimental results and validated. Furthermore, sensitivity analyses were performed to explore the influence on the crack propagation behaviors of analysis parameters and conditions. The developed method was shown to provide an appropriate approximation of fatigue crack growth behaviors in cladded C(T) specimens.

Hypoxia contributes to tumor progression and metastasis, and hypoxically dysregulated RNA molecules may, thus, be implicated in poor outcomes. Canine oral melanoma (COM) has a particularly poor prognosis, and some hypoxia-mediated miRNAs are known to exist in this cancer; however, equivalent data on other hypoxically dysregulated non-coding RNAs (ncRNAs) are lacking. Accordingly, we aimed to elucidate non-miRNA ncRNAs that may be mediated by hypoxia, targeting primary-site and metastatic COM cell lines and clinical COM tissue samples in next-generation sequencing (NGS), with subsequent qPCR validation and quantification in COM primary and metastatic cells and plasma and extracellular vesicles (EVs) for any identified ncRNA of interest. The findings suggest that a number of non-miRNA ncRNA species are hypoxically up- or downregulated in COM. We identified one ncRNA, the long ncRNA fragment ENSCAFT00000084705.1, as a molecule of interest due to its consistent downregulation in COM tissues, hypoxically and normoxically cultured primary and metastatic cell lines, when compared to the oral tissues from healthy dogs. However, this molecule was undetectable in plasma and plasma EVs, suggesting that its expression may be tumor tissue-specific, and it has little potential as a biomarker. Here, we provide evidence of hypoxic transcriptional dysregulation for ncRNAs other than miRNA in COM for the first time and suggest that ncRNA ENSCAFT00000084705.1 is a molecule of interest for future research on the role of the transcriptome in the hypoxia-mediated progression of this aggressive cancer.

Abstract Organic thin-film transistors (OTFTs) are promising building blocks of flexible printable electronic devices. Similar to inorganic FETs, OTFTs are heterostructures consisting of metals, insulators, and semiconductors, in which nanoscale interfaces between different components should be precisely engineered. However, OTFTs use noble metals, such as gold, as electrodes, which has been a bottleneck in terms of cost reduction and low environmental loading. In this study, we demonstrate that graphite-based carbon electrodes can be deposited and patterned directly onto an organic single-crystalline thin film via electrostatic spray coating. The present OTFTs exhibited reasonably high field-effect mobilities of up to 11 cm2 V−1 s−1 for p-type and 1.4 cm2 V−1 s−1 for n-type with no significant deterioration during electrostatic spray processes. We also demonstrate two significant milestones from the viewpoint of material science: a complementary circuit, an inverter consisting of p- and n-type OTFTs, and an operatable metal-free OTFT composed of fully carbon-based materials. These results constitute a key step forward in the further development of printed metal-free integrated circuits.

The COVID-19 pandemic required people to adapt rapidly to the digital transformation of society for social survival, which highlighted the divide between those who can and cannot digitalize. Previous studies investigated factors promoting adaptation to digitalization; however, outcomes from adaptation to a digitalized society have not been sorted into a parsimonious model, even though there should be several multifaceted outcomes (e.g., usefulness, economic profit, and social outcome), each of which is promoted by different factors. If the effects of individual background factors can be revealed, including the technical-environment and survival-relevant personality in relation to each outcome, it would help in the creation of a society where more people play an active role by adapting to digitalization. This study aimed to construct such a model by identifying major outcomes gained in a digitalized society and investigating individual factors that contribute to the degree of gain of each of these outcomes. Five dimensions were identified by online surveys and factor analysis: Socialization (outcomes derived from new social connections created online), Space–time (freedom from time and space constraints), Economics (monetary outcome by using digital services), and Information (ease and amount of acquisition of information) were the positive outcomes, whereas Loneliness (feelings of not being able to keep up with digitization) was identified as a negative outcome. We determined that technical-environmental factors (e.g., familiarity with digital techniques and the amount of money that can be used for digitalization) facilitated gain in four positive outcomes. Notably, leadership and conscientiousness facilitated the Socialization gain while etiquette suppressed it. These factors’ effects would reflect the importance of a personality trait prioritizing construction and maintenance of social relationships. This study implies that material outcomes (i.e., Space–time, Economics, and Information) are promoted by technical-environmental support, whereas social outcomes may additionally require motivation and a positive attitude for purposeful social engagement.

Abstract The hyperscanning technique, that is, simultaneous measurement of neural signals in more than one person, is a powerful research tool for understanding humans’ social interactions. In recent years, many studies have investigated interpersonal neural synchronization during various types of communication processes. However, there has been little focus on the impact of the presence of others without explicit social interaction, despite the mere presence of others having been suggested as influencing behavior. In this study, we clarify whether neural signals during a self-paced, repeated, addition task are synchronized when another individual is adjacent without direct interaction. Twenty pairs of participants were measured using a hyperscanning approach with near-infrared spectroscopy. The results show that interpersonal neural synchronization of the task-related signal in the left forehead region was enhanced under the condition of being adjacent to another participant. By contrast, a significant decrease in neural synchronization in the center of the forehead region, where increased neural synchronization is often reported in explicit communication, was observed. Thus, the results indicate that the adjacency of others modulates interpersonal neural synchronization in the task-related signal, and the effect on cognitive processing is different from that of explicit social interaction.

In this paper, smooth and notched bar tensile tests of austenitic stainless steel 304 are performed, covering four different multi-axial stress states and six different strain rate conditions, to investigate the effect of the stress triaxiality and strain rate on fracture strain. Test data show that the measured true fracture strain tends to decrease with increasing stress triaxiality and strain rate. The test data are then quantified using the Johnson-Cook (J-C) fracture strain model incorporating combined effects of the stress triaxiality and strain rate. The determined J-C model can predict true fracture strain overall conservatively with the difference less than 20%. The conservatism in the strain-based acceptance criteria in ASME B&PV Code, Section III, Appendix FF is also discussed.

Case summary An 8-year-old neutered male domestic shorthair cat was presented for further investigation of anorexia, vomiting and lethargy. Abdominal ultrasonography and contrast-enhanced CT revealed choledocholithiasis with suspected bacterial peritonitis and non-visualisation of the gallbladder. During surgery, the common bile duct was noted to be perforated, and a cholelith was found in the abdominal cavity. No gallbladder was confirmed during surgery. Three months postoperatively, the cat underwent CT cholangiography and absence of the gallbladder with a vestigial duplicated gallbladder was diagnosed. Relevance and novel information Gallbladder agenesis is extremely rare in cats, with only one previous report, but several dogs have been diagnosed based on CT cholangiography and laparoscopy. This report describes gallbladder agenesis concurrent with choledocholithiasis in an adult cat and represents the first report of CT cholangiography in a cat with gallbladder agenesis.

Hepatocellular carcinomas (HCC) are common tumors, whereas hepatocellular adenomas (HCA) are rare, benign tumors in dogs. The aberrant expression of noncoding RNAs (ncRNAs) plays a pivotal role in HCC tumorigenesis and progression. Among ncRNAs, micro RNAs have been widely researched in human HCC, but much less widely in canine HCC. However, Y RNA-derived fragments have yet to be investigated in canine HCC and HCA. This study targeted canine HCC and HCA patients. We used qRT-PCR to determine Y RNA expression in clinical tissues, plasma, and plasma extracellular vesicles, and two HCC cell lines (95-1044 and AZACH). Y RNA was significantly decreased in tissue, plasma, and plasma extracellular vesicles for canine HCC versus canine HCA and healthy controls. Y RNA was decreased in 95-1044 and AZACH cells versus normal liver tissue and in AZACH versus 95-1044 cells. In plasma samples, Y RNA levels were decreased in HCC versus HCA and Healthy controls and increased in HCA versus Healthy controls. Receiver operating characteristic analysis showed that Y RNA could be a promising biomarker for distinguishing HCC from HCA and healthy controls. Overall, the dysregulated expression of Y RNA can distinguish canine HCC from HCA. However, further research is necessary to elucidate the underlying Y RNA-related molecular mechanisms in hepatocellular neoplastic diseases. To the best of our knowledge, this is the first report on the relative expression of Y RNA in canine HCC and HCA.

Of intracranial tumors, primary central nervous system lymphoma (PCNSL) is rare in dogs. Herein, we describe our experience with two dogs (a 3-year-old intact female toy poodle and a 5-year-old spayed female toy poodle) that developed neurological symptoms. Magnetic resonance imaging (MRI) revealed intracranial disseminated lesions. Cerebrospinal fluid (CSF) examination revealed pleocytosis and B-cell monoclonal proliferation in both cases. PCNSL or secondary central nervous system lymphoma (SCNSL) was diagnosed on the basis of MRI findings and CSF examinations. Nimustine (ACNU) is a nitrosourea alkylating agent, a class of drugs that includes lomustine. Nimustine is mainly used to treat human intracranial neoplasia because of its high permeability across the blood-brain barrier. The dogs in this study were treated with combined chemotherapy comprising nimustine and prednisolone, which achieved complete or nearly complete remission of neurological symptoms and long-term survival (>2583 days and 1218 days), but with problematic adverse effects. We determined that the dose of nimustine for canine PCNSL or SCNSL with intravenous infusion was 25–30 mg/m2 every 3–4 weeks for a total of four times; however, the data were insufficient to determine the optimal regimen.

Heart failure cause hypoperfusion-induced damage to abdominal organs due to decreased cardiac output (CO). Using a model dog with heart failure caused by rapid ventricular pacing (RVP), we have previously demonstrated that a decrease in CO reduces pancreatic blood flow (PBF). Furthermore, we have revealed that pancreatic acinar cell atrophy, which is a change in the pre-stage of pancreatitis was caused. However, the mechanism by which pancreatic acinar cell atrophy was caused in RVP dogs remains unknown. This study aimed to clarify the association between cardiac function, PBF, and histopathological changes in pancreatic acinar cells by administrating pimobendan, which increase CO, to RVP dogs. RVP dogs were divided into the control group (no medication, n = 5) and the pimobendan group (pimobendan at 0.25 mg/kg BID, n = 5). Non-invasive blood pressure measurement, echocardiography, and contrast-enhanced ultrasonography for PBF measurement were performed before initiating RVP and at 4 weeks after initiating RVP (4 weeks). At 4 weeks, the decreases in CO, mean blood pressure and PBF due to RVP were suppressed in pimobendan group. Furthermore, histopathological examination showed no changes in pancreatic acinar cells in the pimobendan group. Overall, it was clarified that the decrease in PBF due to cardiac dysfunction was a direct cause of pancreatic acinar cell atrophy. This suggests that maintaining PBF is clinically important for treating dogs with heart failure. In addition, these findings offer a reliable basis for developing new therapeutic strategies for heart failure in dogs, that is, pancreatic protection.

Abstract Background Toceranib phosphate (TOC) could be made widely available for treating tumors in dogs if evidence shows that TOC inhibits recurrence after surgery. Objectives To investigate how postoperative adjuvant treatment with TOC modulates the tumor microenvironment (TME), by assessing effects on angiogenic activity, tumor‐infiltrating regulatory T cells (Tregs), and intratumoral hypoxia. Animals Ninety‐two client‐owned dogs were included: 28 with apocrine gland anal sac adenocarcinoma, 24 with small intestinal adenocarcinoma, 22 with lung adenocarcinoma, and 18 with renal cell carcinoma. Methods Retrospective, multicenter study comparing time to progression (TTP) between 42 dogs treated by surgery and TOC and 50 dogs treated by surgery alone. Differences were analyzed in the expression of vascular endothelial growth factor receptor‐2 (VEGFR2) and the number of Foxp3+ Tregs and hypoxia‐inducible factor (HIF)‐1α+ cells in tumor tissues sampled at the first and second (recurrence) surgeries. Results Median TTP for dogs treated by surgery and TOC (360 days) was higher than that for dogs treated by surgery alone (298 days; hazard ratio, 0.82; 95% confidence interval [CI], 0.65‐0.96; P = .02). In dogs treated by surgery and TOC, VEGFR2 expression and the number of Tregs and HIF‐1α+ cells were significantly lower in tissues sampled at the second surgery than in those sampled after the first surgery. In dogs treated by surgery alone, significant differences were found between samples from the 2 surgeries. Conclusions and Clinical Importance Toceranib phosphate could prove to be a useful postoperative adjuvant treatment because of its modulation of the TME.

Hemorrhagic diseases are common in dogs. Current coagulation assays do not model all aspects of in vivo hemostasis and may not predict bleeding risk. The Total-Thrombus Analysis System (T-TAS) is a novel hemostasis assay system in which whole blood flows through microfluidic channels at defined shear rates to provide qualitative and quantitative evaluation of platelet function (PL-chip) and coagulation function (AR-chip). The present study evaluated the T-TAS in dogs with hereditary bleeding disorders and with acquired hemorrhagic syndromes (Group 1), and healthy controls (Group 2). Hereditary defects included von Willebrand's disease (VWD; n = 4), hemophilia A (n = 2), and canine Scott syndrome (n = 2). Acquired hemorrhagic disorders included neoplastic hemoperitoneum (n = 2) and acute hemorrhagic diarrhea syndrome (n = 1). Citrate anticoagulated samples were collected from diseased dogs (Group 1, n = 11) and controls (Group 2, n = 11) for coagulation screening tests, fibrinogen analyses, D-dimer concentration, antithrombin activity, von Willebrand Factor antigen, PFA-100 closure time (PFA-CT), and thromboelastography (TEG). Citrate and hirudin anticoagulated samples were used for T-TAS analyses at two shear rates. Qualitative thrombus formation in each chip was recorded using the T-TAS video camera. Numeric parameters, derived from the instrument software, included occlusion start time (OST; time to 10 kPa), occlusion time (OT; time to 60 kPa (PL-chip) or 80 kPa (AR-chip)), and area under the pressure curve (AUC). Correlations between continuous variables were evaluated by Spearman's rank. Continuous variables were compared between groups by Student's t-test or the Mann-Whitney U-test. Alpha was set at 0.05. In combined analyses of all dogs, significant correlations were identified between T-TAS variables, between the PFA-CT and PL-chip parameters and between TEG variables and AR-chip parameters. The prothrombin time correlated with the AR-chip AUC at both shear rates. In Group 1 dogs, the AR-chip AUC at low shear was significantly reduced compared with Group 2 dogs. Aberrant thrombus formation was seen in video images recorded from dogs with VWD and hemophilia A. The T-TAS AR-chip analysis distinguished dogs with bleeding risk compared to healthy controls. Initial evaluations of the T-TAS suggest it may aid characterization of hemostasis in patients at-risk of bleeding and assist with delineating bleeding phenotypes.

The assessment of retinal nerve fiber layer defects (RNFLDs) is a useful part of glaucoma care. Here, we obtained en-face images of retinal layers below the inner limiting membrane (ILM) with swept source-optical coherence tomography (SS-OCT), and measured RNFLD angle with new software.This study included 105 eyes of 105 normal tension glaucoma (NTG) patients (age, 59.8 ± 13.2). Exclusion criteria were best-corrected visual acuity < 0.5, axial length > 28 mm, non-glaucoma ocular disease, and systemic disease affecting the visual field. We obtained 12 x 9 mm 3D volume scans centered on the macula with SS-OCT (DRI OCT-1, Topcon), and from these scans, created 3 averaged en-face images, each comprising 7 horizontal en-face images (total thickness: 18.2 μm). We labeled these averaged images, according to their depth below the ILM, as en-face images 1 (shallowest), 2 (middle) and 3 (deepest). In each image, a circle was drawn centered on the disc, with a radius of half the distance between the centers of the disc and macula. The investigator marked points where the edge of the RNFLD intersected this circle, and RNFLD angle (RNFLDA) was calculated with new software. Finally, we analyzed the association between RNFLDA, cpRNFLT, weighted RGC count (wrgc) and Humphrey field analyzer (HFA)-measured mean deviation (MD) and hemifield total deviation (TD), both overall and in each hemifield.En-face image 2 had the highest interclass reproducibility for measuring RNFLDA (intra-rater intraclass correlation coefficient (ICC): 0.988, inter-rater ICC: 0.962). The correlation coefficients with RNFLDA were: HFA MD, -0.60; superior TD, -0.73; inferior TD, -0.69; overall cpRNFLT, -0.27; superior hemifield cpRNFLT, -0.39; and inferior hemifield cpRNFLT, -0.53 (all p

We tested the hypotheses that hypoxic stimulation enhances growth potentials of canine lymphoma cells by activating hypoxia-inducible factor 1α (HIF-1α), and that the hypoxia-activated prodrug (TH-302) inhibits growth potentials in the cells. We investigated how hypoxic culture affects the growth rate, chemoresistance, and invasiveness of canine lymphoma cells and doxorubicin (DOX)-resistant lymphoma cells, and influences of TH-302 on survival rate of the cells under hypoxic conditions. Our results demonstrated that hypoxic culture upregulated the expression of HIF-1α and its target genes, including ATP-binding cassette transporter B1 (ABCB1), ATP-binding cassette transporter G2 (ABCG2), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and survivin, and enhanced the growth rate, DOX resistance, and invasiveness of the cells. Additionally, TH-302 decreased the survival rate of the cells under hypoxic condition. Our studies suggest that hypoxic stimulation may advance the tumorigenicity of canine lymphoma cells, favoring malignant transformation. Therefore, the data presented may contribute to the development of TH-302-based hypoxia-targeting therapies for canine lymphoma.

MicroRNA (miRNA) in tissue and liquid samples have been shown to be associated with many diseases including inflammation. We aimed to identify inflammation-related miRNA expression level in the bovine mastitis milk. Expression level of inflammation-related miRNA in milk from mastitis-affected and normal cows was analyzed using qPCR. We found that expression level of miR-21, miR-146a, miR-155, miR-222, and miR-383 was significantly upregulated in California mastitis test positive (CMT+) milk. We further analyzed these miRNA using a chip-based QuantStudio Digital PCR System. The digital PCR results correlated with those of qPCR, demonstrating upregulation of miR-21, miR-146a, miR-155, miR-222, and miR-383 in CMT+ milk. In conclusion, we identified miRNA that are upregulated in CMT+ milk. These miRNA exhibited sensitivity and specificity greater than 80% for differentiating between CMT+ milk and normal milk. Our findings suggest that inflammation-related miRNA expression level in the bovine milk was affected by mastitis, and miRNA in milk have potential for use as biomarkers of bovine mastitis.

Bradyarrhythmia is usually a spontaneously subsiding complication of cervical spinal cord injury. However, in severe cases, it can lead to cardiac arrest. We report a case of cervical spinal cord injury, complicated by right-sided infective endocarditis after the placement of a temporary pacing catheter in the right ventricle for severe bradyarrhythmia that led to cardiac arrest. Although the patient׳s condition was successfully treated by pacing catheter removal and pharmacological therapy, right-sided infective endocarditis would be a fatal complication in cases of cervical spinal cord injury where cardiac pacing is required for long-term refractory severe bradyarrhythmia.

Rules prescribe human behavior and our attempts to choose appropriate behavior under a given rule. Cognitive control, a mechanism to choose and evaluate actions under a rule, is required to determine the appropriate behavior within the limitations of that rule. Consequently, such cognitive control increases mental workload. However, the workload caused by a cognitive task might be different when an additional rule must be considered in choosing the action. The present study was a functional near-infrared spectroscopy (fNIRS) investigation of an experimental task, in which the difficulty of an operation and existence of an additional rule were manipulated to dissociate the influence of that additional rule on cognitive processing. Twenty healthy Japanese volunteers participated. The participants performed an experimental task, in which the player caught one of five colored balls from the upper part of a computer screen by operating a mouse. Four task conditions were prepared to manipulate the task difficulty, which was defined in terms of operational difficulty. In turn, operational difficulty was determined by the width of the playable space and the existence of an additional rule, which reduced the score when a red ball was not caught. The 52-channel fNIRS data were collected from the forehead. Two regions of interest (ROIs) associated with the bilateral lateral prefrontal cortices (LPFCs) were determined, and a three-way repeated-measures analysis of variance (ANOVA) was performed using the task-related signal changes from each ROI. The fNIRS results revealed that bilateral LPFCs showed large signal changes with the increase in mental workload. The ANOVA showed a significant interaction between the existence of an additional rule and the location of the ROIs; that is, the left lateral prefrontal area showed a significant increase in signal intensity when the additional rule existed, and the participant occasionally decided to avoid catching a ball to successfully catch the red-colored ball. Thus, activation of the left LPFC corresponded more closely to the increase in cognitive control underlying the behavioral change made to cope with the additional rule.

Atherosclerotic lesions were observed in male and ovariectomized female Microminipig (MMP) fed a high fat and cholesterol diet with sodium cholate (HFCD/SC) for 3 months. HFCD/SC induced hypercholesterolemia accompanied by an increase in serum total cholesterol (T-Cho), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and cholesterol ester (CE). Unlike the mouse or rabbit, a dominant LDL-C fraction in the intact MMP, similar to that in humans, was observed by serum lipoprotein analysis. HFCD/SC increased body weight gain. At the end of the experiment, computed tomography scans of conscious animals showed that HFCD/SC had decreased liver attenuation values (Hounsfield unit) and increased subcutaneous and abdominal fat, suggesting the induction of fatty liver and obesity. HFCD/SC induced atherosclerotic lesions in systemic arteries, including the external and internal iliac arteries, abdominal aorta, coronary artery, and cerebral arterial circle. Atherosclerosis and pathological findings induced by HFCD/SC in MMP were similar to those in humans. The MMP is a potentially suitable tool for investigating human atherosclerosis. Keywords:: atherosclerosis, cholesterol, diet, life-style, Microminipig

Dabigatran and rivaroxaban are novel oral anticoagulants that specifically inhibit thrombin and factor Xa, respectively. The aim of this study is to elucidate antithrombotic properties of these anticoagulant agents under arterial and venous shear conditions. Whole blood samples treated with dabigatran or rivaroxaban at 250, 500, and 1000 nM, with/without aspirin and AR-C66096, a P2Y12 antagonist, were perfused over a microchip coated with collagen and tissue thromboplastin at shear rates of 240 and 600 s(-1). Fibrin-rich platelet thrombus formation was quantified by monitoring flow pressure changes. Dabigatran at higher concentrations (500 and 1000 nM) potently inhibited thrombus formation at both shear rates, whereas 1000 nM of rivaroxaban delayed, but did not completely inhibit, thrombus formation. Dual antiplatelet agents weakly suppressed thrombus formation at both shear rates, but intensified the anticoagulant effects of dabigatran and rivaroxaban. The anticoagulant effects of dabigatran and rivaroxaban were also evaluated under static conditions using thrombin generation (TG) assay. In platelet-poor plasma, dabigatran at 250 and 500 nM efficiently prolonged the lag time (LT) and moderately reduce peak height (PH) of TG, whereas rivaroxaban at 250 nM efficiently prolonged LT and reduced PH of TG. In platelet-rich plasma, however, both anticoagulants efficiently delayed LT and reduced PH of TG. Our results suggest that dabigatran and rivaroxaban may exert distinct antithrombotic effects under flow conditions, particularly in combination with dual antiplatelet therapy.

This study provides an insight into the effectiveness of an optical network unit (ONU) sleep technique, where a subcomponent of the ONU is powered down during the absence of input traffic. The approach contributes to the realisation of advanced power efficiency over a wide range of input throughputs in situations where downstream traffic exceeds upstream traffic in recent residential networks. A numerical simulation showed that power-saving effectiveness could be achieved for an Mbit/s downstream throughput without latency implications in the Tx sleep mode.

Background/Aim: Atherosclerosis is known as a major risk factor for cardiovascular disease, and development of an animal model of atherosclerosis is required to investigate its clinical pathogenesis. We studied the optimal amount of cholesterol in the diet and the optimal experimental period for development of a Microminipig model of atherosclerosis for the evaluation of a hydroxymethylglutaryl-CoA reductase (HMGCR) inhibitor (atorvastatin). Materials and Methods: Eighteen male animals (3-4 months old) were divided into 3 groups. Group 1 consisted of control animals receiving a normal chow diet, Group 2 animals received a high fat (12% w/w) and low cholesterol (0.1% w/w) diet (HFLCD), and Group 3 animals received HFLCD+statin for 12 weeks. Animals received statin at 3 mg/kg body weight per day. HFLCD did not down-regulate the hepatic expression of HMGCR mRNA. Results: HFLCD increased body, omentum, and mesenteric adipose tissue weight, and induced hypercholesterolemia and atherosclerotic lesions in the abdominal aorta. HFLCD+statin inhibited hypercholesterolemia and atherosclerotic lesions, but not obesity. Conclusion: A microminipig atherosclerosis model induced by HFLCD can be used in the evaluation of HMGCR inhibitors for the treatment of hypercholesterolemia and atherosclerosis. [ABSTRACT FROM AUTHOR]

A 36-day-old Japanese Black calf exhibited wheezing associated with dyspnea from birth. Arterial blood gas analysis revealed a low oxygen partial pressure of 51 mmHg, low oxygen saturation of 83%, and high carbon dioxide partial pressure of 58.8 mmHg. Computed tomography, endoscopy, and ultrasonography showed cyst formation under the epiglottis. When the cyst was aspirated under ultrasonic guidance to secure the airway, 30 ml of viscous white turbid content was aspirated. The cyst shrank immediately after aspiration, but the wheezing and respiratory symptoms resumed 7 days after aspiration. Therefore, the cyst was surgically removed from the ventral side of the neck. No cyst remodeling was observed 30 days after surgical removal. [ABSTRACT FROM AUTHOR]

Background/Aim: Canine mammary gland tumors (MGTs), as a potential model of human breast cancer, have a well-defined histological classification system. MicroRNA (miRNA) expression is a key part of the molecular signatures of both MGTs and human breast cancer, although the signatures alone do not yet provide a sufficient basis for definitive diagnosis. In this study, we investigated the association between miRNA expression patterns and histological classification. Materials and Methods: Mammary gland tissue was collected from healthy dogs (n=7) and dog patients (n=80). Further samples (n=5) were obtained from established MGT cell lines. We targeted miRNAs differentially expressed in metastatic tumor tissue versus non-metastatic and normal tissue. A subset of samples was analyzed using small RNA next generation sequencing (NGS) with subsequent qPCR. Results: Six differentially expressed miRNAs were selected from the NGS analysis and submitted for large-scale qPCR. The large-scale qPCR analysis revealed greater alternations in miRNA expression. Large-scale analysis, based on 79 samples, revealed a hierarchical clustering based on selected miRNAs that did not strikingly match the histopathological subtype classification. Conclusion: We successfully investigated the large-scale miRNA expression pattern in canine MGT and provided the whole miRNA expression. The selected miRNA demonstrated that there is no straightforward mapping between molecular signatures and histological classification of canine MGTs at the miRNA level. [ABSTRACT FROM AUTHOR]

In snowy cold regions such as Hokkaido, slopes can collapse owing to the frost heave phenomenon, freeze-thaw actions in winter, or snowmelt in spring. Kitami City in Hokkaido recently suffered from such slope failures when the extremely shallow layer eroded and slid after snowmelt in the early spring of 2020. The depth of this slope failure was about 0.20 to 0.25 m, which was very shallow compared with general surface failures. In this research, we conducted a site investigation of the road slope and collected undisturbed soil samples from a non-collapsed area near the slope failure to conduct a constant pressure direct shear test. For the direct shear tests, specimens with natural water content at the time of sampling and forcibly saturated specimens were used. The results of the slope stability analysis with the strength parameters obtained from the direct shear test showed that the slope failure was caused by snowmelt penetration, mainly due to a decrease in cohesion. [ABSTRACT FROM AUTHOR]

Background: Functional foods and electric fields (EFs) have been previously reported as interventions for insomnia other than medications. As for functional foods, gamma-aminobutyric acid (GABA) and lafma have been reported to be related to sleep. EFs have also been reported to have a sleep-related, anti-stress effect in mouse model experiments. However, the effects of combining these two methods on the human body remain poorly studied. Objective: Thus, this study aimed to investigate the cointervention effect of sleep-promoting functional food intake and EF application on sleep quality in healthy participants. Methods: Fifteen healthy participants were divided into three groups. The Food and Placebo groups were given active tablets containing food mixture of GABA and lafma, and placebo tablets, respectively, for 4 weeks. Meanwhile, the Food plus EF group used an EF therapy device during sleep in addition to the active food tablets. Sleep quality was evaluated using electroencephalography and sleep questionnaires. Results: Sleep efficiency (SE) was significantly higher in the Food group and the Food plus EF group than the Placebo group at 4 weeks. The Food plus EF group also had a significantly higher SE involving sleep latency. Conclusions: Food mixture containing known sleep-promoting ingredients such as GABA and lafma can improve sleep quality, and the improvement effect can be enhanced when administered in combination with an EF. [ABSTRACT FROM AUTHOR]

Background/Aim: The reproducibility of athero - sclerotic lesions was evaluated after the production of clonedmicrominipigs and their offspring. Materials and Methods: Cloned-microminipig-parents were produced by microminipigsomatic cell nuclei. These parents were crossbred and delivered males (F1-offspring) were divided into two groups: normal chow diet (NcD)-fed and high-fat/high-cholesterol diet (HcD)-fed groups. One of the F1-offsprings was subjected to cloning, and delivered males (F1-clones) were fed with HcD. After 8 weeks, all animals were necropsied for patho - physiological studies compared to non-cloned-microminipigs. Results: HcD-fed F1-offspring and F1-clones, but not NcDfed F1-offspring, exhibited increased serum lipid levels and systemic atherosclerosis, which were comparable to those of HcD-fed non-cloned-microminipigs. Homogeneity of variance analysis demonstrated that standard deviation values of serum lipoprotein and aortic atherosclerosis area from HcD-fed animals decreased in F1-offspring and F1-clones. Conclusion: HcD-induced atherogenesis was highly reproducible in F1- offsprings and F1-clones, indicating that the atherosclerosisprone genomic background was preserved in the clonedmicrominipigs, which can be used for studies on human atherosclerosis and related diseases. [ABSTRACT FROM AUTHOR]

In dogs, pancreatic acinar cell injury is thought to be caused by decreased pancreatic blood flow due to heart failure. In previous our report, it demonstrated that decreased heart function causes a significant decrease in pancreatic blood flow in heart failure dog model caused by rapid ventricular pacing (RVP). However, the types of histopathological changes remain unclear. We aimed to verify the types of histopathological changes occurring in the pancreatic tissue due to decreased heart function. After RVP for 4 weeks, atrophy of pancreatic acinar cells, characterized by a decrease in zymogen granules, was observed in all areas of the pancreas. In conclusion, the result of this study suggests that attention should be paid to ischemia/hypoperfusion injury in the pancreas. [ABSTRACT FROM AUTHOR]

Background/Aim: The number of vertebrae in swine varies from 19 to 23 and is associated with body size. Nuclear receptor subfamily 6 group A member 1 (NR6A1) is considered a strong candidate for affecting the number of vertebrae in swine. Wild boars, which uniformly have 19 vertebrae, have the wild type allele while multi-vertebrae European commercial pigs have the mutated allele. Our aim was to confirm the factor of the miniaturization. Materials and Methods: We examined vertebrae number and NR6A1 polymorphism in the Microminipig and three domestic breeds that vary in body size. Results: The Microminipig had 19 or less vertebrae and a wild type NR6A1 genotype. Three domestic breeds had more than 21 vertebrae while the largest vertebrae number was observed in multi-vertebrae-fixed Large White. Heterozygous genotypes were observed in the middle-sized indigenous pig while homozygous NR6A1 mutations were observed in European commercial breeds. Conclusion: NR6A1 could be a useful index for both miniaturizing and increasing pig body size. [ABSTRACT FROM AUTHOR]

Background/Aim: An appropriate animal model is essential to investigate the relationship between inflammation, atherosclerosis, and thrombogenesis, and the development of preventive measures and therapies for atherosclerosis. Materials and Methods: Atherosclerosis was induced in Microminipigs (MMPs) using a high-fat diet. We assessed high mobility group box 1 (HMGB1) expression levels and measured thrombus formation using a Total Thrombus Formation Analysis System (T-TAS). MMPs were divided into a normal diet (control) group and four high-fat diet groups, with differing amounts of cholesterol. After 8 weeks, blood was collected for analysis. Results: HMGB1 levels increased with increasing dietary cholesterol, and a thrombus formation time. Conclusion: T-TAS is useful in the assessment of thrombogenesis in MMPs and HMGB1 is associated with thrombus formation. [ABSTRACT FROM AUTHOR]

Background: There are various types of sleep disorders, such as insomnia, hypersomnia, and rhythm disorder, which are attributed to diverse and complex background factors. Recently, many studies have reported that lactic acid bacteria, bifidobacteria, and lactoferrin, are related to fatigue and sleep. Considering these factors, we prepared test food samples containing lactic acid bacteria ingredients (fermentation products, living bacteria, and ground bacteria) derived from the lactic acid bacterium strain Lactobacillus helveticus MIKI-020 (LBH MIKI-020) and theanine, which is known to have a relaxing effect. We then tested and observed the effects of lactic acid bacteria on the quality of sleep. Methods: In this placebo-controlled, double-blinded, randomized crossover study, we randomly selected 40 male and female subjects (aged 20-64 years) to consume four-weeks test food (lactic acid bacteria ingredients -containing) tablets and placebo control food. The physical examination and laboratory test, sleep electroencephalography, Oguri-Shirakawa-Azumi sleep questionnaire (OSA sleep questionnaire), Pittsburgh Sleep Quality Index (PSQI), and Visual Analogue Scale (VAS) questionnaire were measured. Results: Sleep electroencephalography: the intergroup comparison in changes of the sleep efficiency (SE) until the 4th week showed a significant increase (improvements) compared with the placebo control food group. Furthermore, SE was compared within the group. In the test food group, the SE increased (improved) significantly in 4 weeks. OSA sleep questionnaire: in intragroup analyses between 0 and 4 weeks, significant increases (improvements) were found in the test food group. PSQI: in intragroup comparisons between week 0 and week 4, significant decreases (improvements) were found in the test food group. VAS questionnaire: the intergroup comparison in changes of Feeling of physical fatigue, Motivation (liveliness), and Calmness until the 4th week showed significant decreases (improvements) compared with placebo control food group. Conclusion: The sleep efficiency (SE) and Feeling of physical fatigue, Motivation (liveliness), and Calmness were improved by continuous consumption of test food (lactic acid bacteriacontaining food). Among various sleep disorders, a large population in Japan has trouble with sleeping quality. Accordingly, consumption of lactic acid bacteria-containing foods can be a safe and effective method to improve sleep quality. [ABSTRACT FROM AUTHOR]