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The Epstein-Barr virus (EBV) is associated with various lymphoproliferative disorders (LPDs). Additionally, EBV infection has correlated with diverse autoimmune diseases. However, the association between EBV and systemic small vessel vasculitis (SVV) remains controversial. Here, we report a case of SVV with pauci-immune glomerulonephritis accompanied by an EBV-positive polymorphic B-cell LPD, not otherwise specified. The intricate distinction between EBV-positive B-cell LPD and SVV was difficult, as both diseases demonstrated similar clinical presentations. Lymph node and kidney biopsies facilitated the accurate diagnosis of these two conditions. The administration of high-dose prednisolone, combined with rituximab, proved efficacious, with no instances of relapse over the subsequent 2-year period. This case indicates an association between EBV-positive B-cell LPD and SVV. The diligent execution of biopsies is a crucial diagnostic and interpretive strategy, generating precise comprehension of this condition and guiding its appropriate therapeutic management., (© Japan College of Rheumatology 2025. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Interstitial lung disease (ILD) is a serious complication of connective tissue diseases (CTDs). The heterogeneity of ILDs reflects differences in pathogenesis among diseases. This study aimed to clarify the characteristics of CTD-ILDs via a detailed analysis of the bronchoalveolar lavage fluid (BALF) and blood immune cells. BALF and blood samples were collected from 39 Japanese patients with newly diagnosed ILD: five patients with Sjögren's syndrome (SS), eight patients with dermatomyositis (DM), six patients with rheumatoid arthritis (RA), six patients with systemic sclerosis, four patients with anti-neutrophil cytoplasmic antibody-associated vasculitis, and 10 patients with idiopathic interstitial pneumonia. We performed single-cell RNA sequencing to analyze the gene expression profiles in these patients' immune cells. In patients with SS, B cells in the BALF were increased and genes associated with the innate and acquired immunity were enriched in both the BALF and blood. In contrast, patients with DM showed an upregulation of genes associated with viral infection in both the BALF and blood. In patients with RA, neutrophils in the BALF tended to increase, and their gene expression patterns changed towards inflammation. These disease-specific characteristics may help us understand the pathogenesis for each disease and discover potential biomarkers., Competing Interests: Author KB was employed by the company Aimed Analytics GmbH. WF receives fundings from Nippon Boehringer Ingelheim Co., Ltd. and GlaxoSmithKline Consumer Healthcare Japan K.K., grants from Takeda Pharmaceutical Company Limited, and speaking fees from Asahi Kasei Pharma Corporation, Astellas Pharma Inc., Mitsubishi Tanabe Pharma Corporation, and Chugai Pharmaceutical Co., Ltd. TT receives speaking fees from Asahi Kasei Pharma Corporation, Chugai Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., and Novartis Pharma K.K. AO receives speaking fees from AbbVie GK, Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Ono Pharmaceutical Co., Ltd., DAIICHI SANKYO COMPANY, LIMITED, Astellas Pharma Inc., AstraZeneca, Mitsubishi Tanabe Pharma Corporation, Pfizer Japan Inc., Asahi Kasei Pharma Corporation, Novartis Pharma K.K., Gilead Sciences, Inc., Janssen Pharmaceutical K.K., GlaxoSmithKline Consumer Healthcare Japan K.K., and Eli Lilly Japan K.K. TS receives consulting fees from Asahi Kasei Pharma and speaking fees from Asahi Kasei Pharma Corporation, Astellas Pharma Inc., AbbVie GK, GlaxoSmithKline Consumer Healthcare Japan K.K., Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K. Nippon Boehringer Ingelheim Co., Ltd., and Pfizer Japan Inc. MW receives speaking fees from Asahi Kasei Pharma Corporation, Astellas Pharma Inc., AbbVie GK, Gilead Sciences, Inc., GlaxoSmithKline Consumer Healthcare Japan K.K., Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., and Pfizer Japan Inc. MK receives speaking fees from AbbVie GK, Asahi Kasei Pharma Corporation, Astellas Pharma Inc., GlaxoSmithKline Consumer Healthcare Japan K.K., Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Eli Lilly Japan K.K., Nippon Boehringer Ingelheim Co., Ltd., and Pfizer Japan Inc. WF receives speaking fees from Asahi Kasei Pharma Corporation, Astellas Pharma Inc., AbbVie GK, Gilead Sciences, Sawai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., and Pfizer Japan Inc. and represents committees supported by Astellas Pharma Inc. and AYUMI Pharmaceutical Corporation. KY receives supports for attending meetings from Shionogi Pharma Co., Ltd. KT receives grants from Chugai-Roche, Boehringer-Ingelheim, Ono Pharmaceutical, and Taiho Pharmaceutical, consulting fees from Ono Pharmaceutical, lecture fees from Eli Lilly, Ono Pharmaceutical, AstraZeneca, Chugai-Roche, Boehringer-Ingelheim, MSD-Merck, and Daiichi-Sankyo, and serves on the board member of Japan Lung Cancer Society. YuK receives grants from Asahi Kasei Pharma Corporation, AbbVie GK, AYUMI Pharmaceutical Corporation., Gilead Sciences, Inc., Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Ltd., and Nippon Boehringer Ingelheim Co., Ltd. and speaking fees from Asahi Kasei Pharma Corporation, Astellas Pharma Inc., AbbVie GK, AYUMI Pharmaceutical Corporation., GlaxoSmithKline Consumer Healthcare Japan K.K., Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K.K. Pfizer Japan Inc., and Mylan Inc. Author KB was employed by the company Aimed Analytics GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hirano, Sakashita, Fujii, Baßler, Tsuji, Kadoya, Omoto, Hiraoka, Imabayashi, Kaneko, Sofue, Maehara, Seno, Wada, Kohno, Fukuda, Yamada, Takayama and Kawahito.)

Objectives: To evaluate the effectiveness and safety of two different intravenous methylprednisolone (IVMP) pulse doses in patients with severe microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA)., Methods: We emulated a target trial using observational data from the nationwide registry in Japan. Patients with severe glomerulonephritis or diffuse alveolar haemorrhage were selected and pseudo-randomized into three groups using propensity score-based overlap weighting as follows: non-IVMP, IVMP 0.5 g/day and IVMP 1.0 g/day. The primary outcome was all-cause mortality, and the secondary outcomes were composite all-cause mortality and kidney failure, severe relapse and serious infection from 2 to 48 weeks after treatment initiation. To estimate the treatment effects, the Cox proportional hazard model and Fine-Gray subdistribution hazard model were used., Results: In this emulated target trial, of 201 eligible patients (MPA, 175; GPA, 26), 6 (3%) died, 4 (2.0%) had kidney failure, 11 (5.5%) had severe relapse, and 40 (19.9%) had severe infections. Hazard ratios (HR) for IVMP 0.5 g/day and IVMP 1.0 g/day pulse groups compared with non-IVMP pulse were as follows: all-cause mortality 0.46 (95% CI: 0.07, 2.81) and 0.07 (95% CI: 0.01, 0.41), respectively; all-cause mortality/kidney failure 1.18 (95% CI: 0.26, 5.31) and 0.59 (95% CI: 0.08, 4.52), respectively; subdistribution HRs for severe relapse were 1.26 (95% CI: 0.12, 13.70) and 3.36 (95% CI: 0.49, 23.29), respectively; and for serious infection 1.88 (95% CI: 0.76, 4.65) and 0.94 (95% CI: 0.28, 3.13), respectively., Conclusion: IVMP 1.0 g/day pulse may improve 48-week mortality in patients with severe MPA/GPA., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Backgrounds: Iris nodules are frequently noted as clinical manifestations of neurofibromatosis type 1 but the other intraocular manifestations are rare. The purpose of this study is to present a patient with a phthisic eye who underwent enucleation for a cosmetic reason after 15-year follow-up and also to review 14 patients with enucleation described in the literature., Case Presentation: A 17-year-old man with neurofibromatosis type 1 from infancy underwent the enucleation of phthisic left eye and also had the resection of eyelid subcutaneous mass lesions on the left side for a cosmetic reason. He had undergone four-time preceding surgeries for eyelid and orbital mass reduction on the left side in childhood and had developed total retinal detachment 10 years previously. Pathologically, the enucleated eye showed massive retinal gliosis positive for both S-100 and glial fibrillary acidic protein (GFAP) in the area with involvement of the detached retinal neuronal layer, together with a more fibrotic lesion along the choroid which were, in contrast, negative for both S-100 and GFAP. The choroid, ciliary body, and iris did not show apparent neurofibroma while episcleral neurofibroma was present., Literature Review: In review of enucleated eyes of 14 patients in the literature, buphthalmic eyes with early-onset glaucoma on the unilateral side was clinically diagnosed in 9 patients who frequently showed varying extent of hemifacial neurofibromatosis which involved the eyelid and orbit on the same side. Pathologically, neurofibromas in varying extent were found in the choroid of 12 patients. One patient showed choroidal malignant melanoma on the left side and fusiform enlargement of the optic nerve on the right side suspected of optic nerve glioma. The phthisic eye in another patient showed massive retinal gliosis similar to the present patient., Conclusions: In summary of the 15 patients with neurofibromatosis type 1, including the present patient, buphthalmic or phthisic eyes with no vision were enucleated for cosmetic reasons and showed choroidal neurofibroma in most patients and massive retinal gliosis in two patients including the present patient., (© 2024. The Author(s).)

Objectives: To identify the optimal dose of intravenous cyclophosphamide (IVCY) for induction therapy for anti-neutrophil cytoplasmic antibody-associated vasculitis., Methods: We retrospectively assessed patients with antibody-associated vasculitis who received IVCY every 2-3 weeks during the remission induction phase. The associations of the IVCY dose with infection-free survival and relapse-free survival were analysed using a Cox regression model. We compared patients in three categories: very low-dose (VLD), low-dose (LD), and conventional dose (CD) (<7.5 mg/kg, 7.5-12.5 mg/kg, and >12.5 mg/kg, respectively). The non-linear association between IVCY dose and the outcomes was also evaluated., Results: Of the 80 patients (median age 72 years), 12, 42, and 26 underwent the VLD, LD, and CD regimens, respectively, of whom 4, 3, and 7 developed infection or died. The adjusted hazard ratios for infection or death were 4.3 (95% confidence interval (CI) 0.94-19.8) for VLD and 5.1 (95% CI 1.21-21.3) for CD, compared with LD. We found the hazard ratio for infection or death increased when the initial IVCY dose exceeded 9 mg/kg. Relapse-free survival did not differ clearly., Conclusion: Low-dose IVCY (7.5-12.5 mg/kg) may result in fewer infections and similar relapse rates compared with the conventional regimen (>12.5 mg/kg)., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

High-density lipoprotein (HDL) nanoparticles promote endothelial cell (EC) function and suppress inflammation, but their utility in treating EC dysfunction has not been fully explored. Here, we describe a fusion protein named ApoA1-ApoM (A1M) consisting of apolipoprotein A1 (ApoA1), the principal structural protein of HDL that forms lipid nanoparticles, and ApoM, a chaperone for the bioactive lipid sphingosine 1-phosphate (S1P). A1M forms HDL-like particles, binds to S1P, and is signaling competent. Molecular dynamics simulations showed that the S1P-bound ApoM moiety in A1M efficiently activated EC surface receptors. Treatment of human umbilical vein ECs with A1M-S1P stimulated barrier function either alone or cooperatively with other barrier-enhancing molecules, including the stable prostacyclin analog iloprost, and suppressed cytokine-induced inflammation. A1M-S1P injection into mice during sterile inflammation suppressed neutrophil influx and inflammatory mediator secretion. Moreover, systemic A1M administration led to a sustained increase in circulating HDL-bound S1P and suppressed inflammation in a murine model of LPS-induced endotoxemia. We propose that A1M administration may enhance vascular endothelial barrier function, suppress cytokine storm, and promote resilience of the vascular endothelium.

Visual motion signals can produce self-motion perception known as vection in observers. Vection can be generated by illusory motions in the form of global expantion in still images as well as by visual motion signals. The perception of vection can be enhanced by flickering images at a rate of 5 Hz. This study examined the illusory motion and vection induced by a printed static image under flickering ambient light at rates up to 100 Hz. The perception of illusory motion and vection were enhanced by flickering ambient lights at 50, 75, and 100 Hz. The enhancement effect was higher for the flicker rates expected to be detectable by humans. The findings of this study suggest that alternating bright and dark signals to the cone receptors and primary visual cortex trigger perceptions of illusory motions., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Dandy-Walker syndrome (DWS) is a well-known developmental anomaly. An occipital meningocele (OMC) is recognized as a malformation that is relatively often associated with DWS, but the association of DWS with OMC has been reported in approximately 40 cases. We present herein a rare clinical course of DWS with OMC, in which the sac was small at birth and became progressively larger., Case Description: A 5-day-old baby boy was referred to our hospital due to OMC. He was born at 33 gestational weeks due to premature rupture of the membranes. He was diagnosed as having DWS associated with OMC. The OMC was covered with skin and its maximum diameter at birth was 3 cm. Magnetic resonance imaging showed an occipital bone defect and continuity of the fourth ventricle, posterior fossa cyst, and OMC sac. The aqueduct was patent, and no hydrocephalus was found. The OMC sac increased progressively with moderate hydrocephalus and reached 7 cm at the age of 54 days when his weight was 2508 g. A cystoperitoneal shunt and repair were performed after sinus venography by contrast computed tomography (CT). At the age of 1 year and 8 months, he had moderate developmental disabilities., Conclusion: In most cases reported, the OMC was relatively small, and large and giant sizes were reported in only six cases. Almost all cases remained the same size as at birth and underwent surgical intervention as early as possible. It was possible to understand the relationship between the occipital bone defect and abnormal running of sinuses such as the superior sagittal sinus, torcular Herophili, and transverse sinus preoperatively from the CT venography (CTV) image. CTV may be an effective and important method for safely performing repair and shunt., Competing Interests: There are no conflicts of interest, (Copyright: © 2023 Surgical Neurology International.)

Humans exhibit colour vision variations due to genetic polymorphisms, with trichromacy being the most common, while some people are classified as dichromats. Whether genetic differences in colour vision affect the way of viewing complex images remains unknown. Here, we investigated how people with different colour vision focused their gaze on aesthetic paintings by eye-tracking while freely viewing digital rendering of paintings and assessed individual impressions through a decomposition analysis of adjective ratings for the images. Gaze-concentrated areas among trichromats were more highly correlated than those among dichromats. However, compared with the brief dichromatic experience with the simulated images, there was little effect of innate colour vision differences on impressions. These results indicate that chromatic information is instructive as a cue for guiding attention, whereas the impression of each person is generated according to their own sensory experience and normalized through one's own colour space.

Sphingosine-1-phosphate (S1P), the circulating HDL-bound lipid mediator that acts via S1P receptors (S1PR), is required for normal vascular development. The role of this signaling axis in vascular retinopathies is unclear. Here, we show in a mouse model of oxygen-induced retinopathy (OIR) that endothelial overexpression of S1pr1 suppresses while endothelial knockout of S1pr1 worsens neovascular tuft formation. Furthermore, neovascular tufts are increased in Apom -/- mice which lack HDL-bound S1P while they are suppressed in Apom TG mice which have more circulating HDL-S1P. These results suggest that circulating HDL-S1P activation of endothelial S1PR1 suppresses neovascular pathology in OIR. Additionally, systemic administration of ApoM-Fc-bound S1P or a small-molecule Gi-biased S1PR1 agonist suppressed neovascular tuft formation. Circulating HDL-S1P activation of endothelial S1PR1 may be a key protective mechanism to guard against neovascular retinopathies that occur not only in premature infants but also in diabetic patients and aging people., (© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)

Belimumab is a therapeutic medication that inhibits the B-cell-activating factor (BAFF) used for systemic lupus erythematosus (SLE); however, the response sometimes varies among individuals, even when patients are stratified based on general clinical characteristics. Therefore, we focused on immunological phenotypic changes with belimumab, investigated their association with subsequent clinical courses, and sought to identify relevant immunological indicators to stratify patients who would benefit from belimumab. We assessed changes in B and T cell phenotypes, as well as BAFF-related factors, such as levels of BAFF and a proliferation-inducing ligand, and expression of three BAFF receptors: BAFF receptor (BAFF-R), B-cell maturation antigen (BCMA), transmembrane activator and cyclophilin ligand interactor (TACI), in 19 patients with SLE who were treated with belimumab before and 3 months after treatment. First, to visualize patterns in complex and diverse data, we summarized B cell changes such as subsets and BAFF receptor expressions into two axes, the first and second principal components (PC1 and PC2), and characterized broad phenotypic changes by cluster analysis. Next, we evaluated whether the B cell changes represented by PC1 and PC2 were associated with other concurrent phenotypic changes, baseline factors, and treatment response at 6 months. We found that lower PC2, indicating increased BAFF-R expression and decreased percentage of naïve B cells, was associated with a subsequent therapeutic response at 6 months (odds ratio 5.3, 95% confidence interval 1.2-24, p = .031). Furthermore, higher percentages of effector memory CD3+CD4+ T cells at baseline were associated with lower PC2 and therapeutic response. Further analysis revealed that increased PC1, as reflected by increased BCMA and TACI expression and an increase in the percentage of class-switched memory B cells, was associated with both T and B cell activation. Although belimumab is a B-cell targeted therapy, it can also influence T-cell phenotypes. Thus, early B cell changes could be used to predict treatment response, and their changes could be predicted from baseline T cell phenotypes, indicating the importance of B and T cell interactions.

Background: Allergen immunotherapy (AIT) is the only treatment that has modified the natural history of allergic diseases. However, since its overall effect on the immune system has not been elucidated, AIT is either absolutely or relatively contraindicated in patients with rheumatic autoimmune diseases (RADs). Therefore, there have been no long-term observations of patients with RADs receiving AIT; thus, the effectiveness and safety of AIT in these patients remain unclear., Methods: This was a single-center retrospective observational study. RAD patients receiving AIT for allergic rhinitis at our institution were selected. Changes in the activity of RAD patients were investigated for 2 years from baseline, including those who discontinued AIT. The effectiveness of AIT was also investigated using the Japan Allergic Rhinitis Standard Quality of Life Questionnaire., Results: Thirteen patients with RADs were enrolled in the study. All patients received sublingual immunotherapy, of which four discontinued AIT owing to adverse events. Among all patients, the symptoms of RADs in three patients worsened during the observation period; however, none of them were causally related to AIT. Most of the adverse events associated with AIT were mild, in which only one patient required drug intervention due to worsening rhinitis symptoms. In the nine patients who were able to continue AIT, their eye and nasal symptom scores showed a significant improvement from 1.67 (1.5-2.0) at baseline to 0.67 (0-1.17) in the 2nd year of treatment (p = 0.0141)., Conclusions: AIT is a safe and effective treatment modality for patients with allergic rhinitis complicated by RADs., (© 2022. The Author(s).)

Many potential applications of artificial intelligence involve making real-time decisions in physical systems while interacting with humans. Automobile racing represents an extreme example of these conditions; drivers must execute complex tactical manoeuvres to pass or block opponents while operating their vehicles at their traction limits 1 . Racing simulations, such as the PlayStation game Gran Turismo, faithfully reproduce the non-linear control challenges of real race cars while also encapsulating the complex multi-agent interactions. Here we describe how we trained agents for Gran Turismo that can compete with the world's best e-sports drivers. We combine state-of-the-art, model-free, deep reinforcement learning algorithms with mixed-scenario training to learn an integrated control policy that combines exceptional speed with impressive tactics. In addition, we construct a reward function that enables the agent to be competitive while adhering to racing's important, but under-specified, sportsmanship rules. We demonstrate the capabilities of our agent, Gran Turismo Sophy, by winning a head-to-head competition against four of the world's best Gran Turismo drivers. By describing how we trained championship-level racers, we demonstrate the possibilities and challenges of using these techniques to control complex dynamical systems in domains where agents must respect imprecisely defined human norms., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Attention contains three functional network subcomponents of alerting, orienting, and executive control. The attention network test (ANT) is usually used to measure the efficiency of three attention subcomponents. Previous researches have focused on examining the unimodal attention with visual or auditory ANT paradigms. However, it is still unclear how an auditory stimulus influences the visual attention networks. This study investigated the effects of bilateral auditory stimuli (Experiment 1) and ipsilateral auditory stimulus (Experiment 2) on the visual attention subcomponents. We employed an ANT paradigm and manipulated the target modality types, including visual and audiovisual modalities. The participants were instructed to distinguish the direction of the central arrow surrounded by distractor arrows. In Experiment 1, we found that the simultaneous bilateral auditory stimuli reduced the efficiency of visual alerting and orienting, but had no significant effect on the efficiency of visual executive control. In Experiment 2, the ipsilateral auditory stimulus reduced the efficiency of visual executive control, but had no significant effect on the efficiency of visual alerting and orienting. We also observed a reduced relative multisensory response enhancement (rMRE) effect in cue condition relative to no cue condition (Experiment 1), and an increased rMRE effect in congruent condition compared with incongruent condition (Experiment 2). These results firstly provide evidence for the alerting, orienting and executive control effects in audiovisual condition. And the bilateral and ipsilateral auditory stimuli have different effects on the subcomponents of visual attention., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Changing the speed, size and material properties of optic flow can significantly alter the experience of vection (i.e. visually induced illusions of self-motion). Until now, there has not been a systematic investigation of the effects of luminance contrast, averaged luminance and stimulus spatial frequency on vection. This study examined the vection induced by horizontally oriented gratings that continuously drifted downwards at either 20° or 60°/s. Each of the visual motion stimuli tested had one of: (a) six different levels of luminance contrast; (b) four different levels of averaged luminance; and (c) four different spatial frequencies. Our experiments showed that vection could be significantly altered by manipulating each of these visual properties. Vection strength increased with the grating's luminance contrast (in Experiment 1), its averaged luminance (in Experiment 2), and its spatial frequency (in Experiment 3). Importantly, interactions between these three factors were also found for the vection induced in Experiment 4. While simulations showed that these vection results could have been caused by effects on stimulus motion energy, differences in perceived grating visibility, brightness or speed may have also contributed to our findings., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Vection has been reported to be enhanced by wind, as long as the wind is a normal temperature and not hot. However, here we report that a hot wind can facilitate vection, as long as it is natural and consistent with the visual stimulus. We created a fire-corridor stimulus that was consistent with a hot wind and a control stimulus composed of cubes, which were irrelevant to a hot wind. We compared the vection strength induced by a fire-corridor (fire condition) visual stimulus with that induced by geometric cubes (no-fire condition) visual stimulus. There were three wind type conditions: a normal temperature wind, hot wind, and no wind. The results showed that a normal temperature wind facilitated vection and that a hot wind (but not a normal wind) highly enhanced vection when a fire-corridor stimulus was presented. These results suggest that vection is highly affected and modulated by high-level cognitive processes.

We proposed a method for extracting the optical flow suitable for visualization, pseudo-flow (P-flow), from a natural movie [Exp. Brain Res.237, 3321 (2019)EXBRAP0014-481910.1007/s00221-019-05674-0]. The P-flow algorithm comprises two stages: (1) extraction of a local motion vector field from two successive frames and (2) tracking of vectors between two successive frame pairs. In this study, we show that while P-flow takes a feature (vector) tracking approach, it is also classified as a gradient-based approach that satisfies the brightness constancy constraint. We also incorporate interpolation and a corner detector to address the shortcomings associated with the two approaches.

To create a self-motion (vection) situation in three-dimensional computer graphics (CG), there are mainly two ways: moving a camera toward an object ("camera moving") or by moving the object and its surrounding environment toward the camera ("object moving"). As both methods vary considerably in the amount of computer calculations involved in generating CG, knowing how each method affects self-motion perception should be important to CG-creators and psychologists. Here, we simulated self-motion in a virtual three-dimensional CG-world, without stereoscopic disparity, which correctly reflected the lighting and glare. Self-motion was induced by "camera moving" or by "object moving," which in the present experiments was done by moving a tunnel surrounding the camera toward the camera. This produced two retinal images that were virtually identical in Experiment 1 and very similar in Experiments 2 and 3. The stimuli were presented on a large plasma display to 15 naive participants and induced substantial vection. Three experiments comparing vection strength between the two methods found weak but significant differences. The results suggest that when creating CG visual experiences, "camera-moving" induces stronger vection., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

We report an extremely rare case of a 27-year-old woman presenting with ischemic stroke as an initial manifestation of moyamoya disease in the first trimester of pregnancy. We conducted an artificial abortion when her neurological symptoms rapidly became refractory to optimal antithrombotic treatments. The progression of neurologic deficits stopped immediately after abortion, resulting in recovery to independence, with slight motor aphasia and right hemiparesis due to improved cerebral flow. We highlight rapid artificial abortion combined with antithrombotic treatment for patients of moyamoya disease with pregnancy-associated ischemic stroke as an appropriate treatment to correct hemodynamic instability and suppress the progression of neurological symptoms., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Inflammatory colorectal polyps (ICRPs) are frequently observed in miniature dachshunds in Japan and treated by prednisolone and immunosuppressive drugs such as cyclosporine and leflunomide. The purpose of this retrospective study was to compare the treatment efficacy, such as response rate, response interval, recurrence rate, and adverse events between cyclosporine and leflunomide. While the response rates were significantly higher in dogs treated with leflunomide, no significant differences were observed in the response interval or recurrence rate. Two of the 11 dogs treated with leflunomide showed hematological or gastrointestinal adverse events, while no dog treated with cyclosporine showed any adverse events. A case-controlled prospective study to compare the treatment efficacy of leflunomide with that of cyclosporine should be conducted.

Bronchopulmonary dysplasia (BPD) is a devastating lung condition that develops in premature newborns exposed to prolonged mechanical ventilation and supplemental oxygen. Significant morbidity and mortality are associated with this costly disease and effective therapies are limited. Mesenchymal stem/stromal cells (MSCs) are multipotent cells that can repair injured tissue by secreting paracrine factors known to restore the function and integrity of injured lung epithelium and endothelium. Most preclinical studies showing therapeutic efficacy of MSCs for BPD are administered either intratracheally or intravenously. The purpose of this study was to examine the feasibility and effectiveness of human cord tissue-derived MSC administration given via the intranasal route. Human umbilical cord tissue MSCs were isolated, characterized, and given intranasally (500 000 cells per 20 μL) to a hyperoxia-induced rat model of BPD. Lung alveolarization, vascularization, and pulmonary vascular remodeling were restored in animals receiving MSC treatment. Gene and protein analysis suggest the beneficial effects of MSCs were attributed, in part, to a concerted effort targeting angiogenesis, immunomodulation, wound healing, and cell survival. These findings are clinically significant, as neonates who develop BPD have altered alveolar development, decreased pulmonary vascularization and chronic inflammation, all resulting in impaired tissue healing. Our study is the first to report the intranasal delivery of umbilical cord Wharton's jelly MSCs in experimental BPD is feasible, noninvasive, and an effective route that may bear clinical applicability., (© 2019 The Authors. Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

In some phenomena of visual perception, the motion direction of visual stimuli can affect perception. In particular, asymmetries between oblique directions and cardinal (horizontal and vertical) directions have been reported and are known as oblique effects (e.g., contrast sensitivity and motion threshold). In this study, we investigated how vection strength depends on motion direction. Participants observed random-dot optical flow in a circular field and rated the perceived vection strength. Dot movement was systematically controlled using the following angles: 0° (up), 30°, 45°, 60°, 90°, 120°, 135°, 150°, and 180° (down). We found that vection strength depended on motion direction and was weaker in the oblique directions than cardinal directions. Thus, the effect of motion direction on vection strength was variable, as seen in the shape of the oblique effect., (© The Author(s) 2020.)

Objective: To assess risk factors for cytomegalovirus (CMV) disease with CMV re-activation in patients with rheumatic disease. Methods: The clinical data of consecutive patients with rheumatic disease who experienced CMV re-activation were examined. We evaluated the difference in various baseline factors at the first detection of CMV pp65 antigenemia on the development of CMV disease using logistic regression models. The changes of laboratory data in the 4 weeks before CMV re-activation were also assessed. Results: We identified 80 patients (median age [interquartile range] = 65.0 years [51.5-74.0]) with CMV re-activation. Oral candidiasis, serum albumin ≤30 g/L, and CMV pp65-positive cell count >5.6/10 5 polymorphonuclear leukocyte cells were found to be associated with CMV disease (odds ratio [OR] [95% CI] = 9.99 [2.02-49.50], 11.4 [1.94-67.40] and 6.80 [1.63-28.30], respectively). Moreover, decreases in serum albumin level and blood lymphocyte count in the 4 weeks before CMV re-activation also predicted CMV disease (OR [95% CI] = 2.02 [1.07-3.8] and 1.96 [1.09-3.54], respectively). Conclusion: In CMV re-activation patients with rheumatic disease, the presence of oral candidiasis, high CMV pp65 positive cell count, and hypoalbuminemia are possible risk factors for CMV disease.

This study examined the contributions of low-, mid- and high-level visual motion information to vection. We compared the vection experiences induced by hand-drawn and computer-generated animation clips to those induced by versions of these movies that contained only their pure optic flow. While the original movies were found to induce longer and stronger vection experiences than the pure optic flow, vection onsets were not significantly altered by removing the mid- and high-level information. We conclude that low-level visual motion information appears to be important for vection induction, whereas mid- and higher-level display information appears to be important for sustaining and strengthening this vection after its initial induction.

Realistic appearance and complexity in the visual field are known to affect the strength of vection (visually induced self-motion perception). Although surface properties of materials are, therefore, expected to be visual features that influence vection, to date, the results have been mixed. Here, we used computer graphics to simulate self-motion through rendered 3D tunnels constructed from nine different materials (bark, ceramic, fabric, fur, glass, leather, metal, stone, and wood). There are three ways in which the new stimuli are changed from those found in previous studies: (1) as they move, their appearances interactively change with the 3D structures of the simulated world, as do all the lighting effects and 3D geometric appearances, (2) they are colored, (3) and their components covered a large portion of the visual field. The entire inner surface of each tunnel was composed from one of the nine materials, and optic flow was evoked when an observer virtually moved through the tunnel. Bark, fabric, leather, stone, and wood effectively induced strong vection, whereas, ceramic, glass, fur, and metal did not. Regression analyses suggested that low-level image features such as the lighting and amplitude of spatial frequency were the main factors that modulated vection strength. Additionally, subjective impressions of the nine surface materials showed that the perceived depth, smoothness, and rigidity were related to the perceived vection strength. Overall, our results indicate that surface properties of materials do indeed modulate vection strength.

The present study investigated whether vection could be modified by an object grasping movement. Twenty-five university students were asked to do one of the following four types of left-hand movements while they were viewing a radial optic flow: (1) grasping the hand-gripper strongly; (2) holding the hand-gripper; (3) clenching fist strongly; and (4) open hand without having anything in their left hands (normal hand condition). The participants' tasks were to keep pressing a button with their right hands while they were perceiving vection. After each trial, they estimated the subjective strength of vection on a 101-point scale. The result showed that the vection was inhibited by strongly grasping the hand-gripper task more than by the other hand movements. Vection could be weakened by the object grasping movement. It might be suggested that vection could be inhibited by the presence of an object being grasped and also by the grasping movement itself. We speculated that the mechanism underlying this inhibition might be related to cognitive pressure, attentional load, power and muscle tonus, and multisensory and proprioception interactions.

Aim: To examine the efficacy of abatacept in patients with rheumatoid arthritis (RA) using magnetic resonance imaging (MRI) of bilateral hands., Method: This prospective study included 35 RA patients. MRI of bilateral hands was performed at baseline and after 12 months of treatment with intravenous abatacept. MRI images were scored for synovitis, osteitis, erosion and joint space narrowing (JSN) according to the RA MRI Scoring System (RAMRIS). The primary endpoint was the change in RAMRIS score from baseline. Repair of erosion was defined as a negative change in the erosion score that was greater than the smallest detectable changes (SDCs)., Results: Thirty-one patients completed the study. Median synovitis and osteitis scores showed statistically significant reductions at Month 12 when compared to baseline (synovitis score, -5.5 [P < 0.0001]; osteitis score, -0.5 [P = 0.03]). However, median erosion and JSN scores did not significantly change. At Month 12, 83% of patients showed no progression of erosion scores and repair of erosion was observed in 11% of patients. All patients with repair of erosion achieved functional remission (Health Assessment Questionnaire-Disability Index ≤ 0.5). The Simplified Disease Activity Index response rate at Month 1 was identified as an independent factor predicting changes in the erosion scores at Month 12., Conclusion: Abatacept treatment reduced synovitis and osteitis scores and did not worsen erosion and JSN scores at Month 12. Over 10% of patients experienced repair of erosion., (© 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

We examined whether vection strength could be modulated by altering the exposure duration to optic flow. Experiment 1 sourced 150 different video clips from various Japanese animation works which simulated self-motion. Despite large differences in the content of these video clips, we found a significant positive correlation between their play durations and their ratings of vection magnitude. Experiment 2 examined this relationship further using more tightly controlled visual motion stimuli. Vection was induced by presenting the motion of the same expanding grating stimulus for 8, 16, 32, or 64 seconds. While vection onset latencies remained constant across these four conditions, vection magnitude/strength was found to increase systematically with the exposure duration. As predicted by a recent computational model of vection, we conclude that subjective vection strength does depend on the exposure duration to optic flow.