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Indoor position fingerprint-based location estimation methods have been widely used by applications on smartphones. In these localization estimation methods, it is very popular to use the RSSI (Received Signal Strength Indication) of signals to represent the position fingerprint. This paper proposes the design of a particle filter for reducing the estimation error of the machine learning-based indoor BLE location fingerprinting method. Unlike the general particle filter, taking into account the distance, the proposed system designs improved likelihood functions, considering the coordinates based on fingerprint points using mean and variance of RSSI values, combining the particle filter with the k-NN (k-Nearest Neighbor) algorithm to realize the reduction in indoor positioning error. The initial position is estimated by the position fingerprinting method based on the machine learning method. By comparing the fingerprint method based on k-NN with general particle filter processing, and the fingerprint estimation method based on only k-NN or SVM (Support Vector Machine), experiment results showed that the proposed method has a smaller minimum error and a better average error than the conventional method.

Staphylococcus aureus grows in the skin of patients with atopic dermatitis and the associated symptoms are induced by membrane vesicles (MVs). This study explored the effects of slightly acidic electrolyzed water (SAEW) on the expression of virulence factors of S. aureus and MV-induced inflammation to uncover the potential of SAEW as a new treatment method for atopic dermatitis. Expression levels of genes related to virulence factors in S. aureus was assessed and S. aureus-derived MVs were characterized. Moreover, expression level of MV-induced Type I allergic reaction-related genes in RBL2H3 cells was also assessed. Significantly decreased staphylococcal enterotoxin A production and decreased virulence factor-related gene expression were observed after culturing S. aureus in broth supplemented with SAEW at ratios of 1, 2, and 5 per broth. MVs prepared by culturing S. aureus in SAEW-supplemented broth exhibited altered particle size and markedly reduced staphylococcal enterotoxin A content under all addition conditions; moreover, those obtained at a ratio of 1:5 (broth:SAEW) exhibited a reduction in the expression of several proteins associated with hemolytic activity and free iron uptake. The MVs prepared in SAEW-supplemented broth also exhibited remarkably reduced allergy-related gene expression levels in rat cell lines derived from basophilic leukemia-2H3 cells. Overall, SAEW is expected to suppress atopic dermatitis symptoms through the alteration of the properties of S. aureus-derived MVs.

ObjectivesOn phenotypic and neuroanatomical grounds, music exposure might potentially affect the clinical expression of behavioural variant frontotemporal dementia (bvFTD). However, this has not been clarified.Methods14 consecutive patients with bvFTD fulfilling consensus diagnostic criteria were recruited via a specialist cognitive clinic. Earlier life musical experience, current musical listening habits and general socio-emotional behaviours were scored using a bespoke semi-quantitative musical survey and standardised functional scales, completed with the assistance of patients’ primary caregivers. Associations of musical scores with behavioural scales were assessed using a linear regression model adjusted for age, sex, educational attainment and level of executive and general cognitive impairment.ResultsGreater earlier life musical experience was associated with significantly lower Cambridge Behavioural Inventory (Revised) scores (β ± SE = −17.2 ± 5.2; p = 0.01) and higher Modified Interpersonal Reactivity Index (MIRI) perspective-taking scores (β ± SE = 2.8 ± 1.1; p = 0.03), after adjusting for general cognitive ability. Number of hours each week currently spent listening to music was associated with higher MIRI empathic concern (β ± SE = 0.7 ± 0.21; p = 0.015) and MIRI total scores (β ± SE = 1.1 ± 0.34; p = 0.014).DiscussionMusical experience in earlier life and potentially ongoing regular music listening may ameliorate socio-emotional functioning in bvFTD. Future work in larger cohorts is required to substantiate the robustness of this association, establish its mechanism and evaluate its clinical potential.

Background Although the close relationship between cancer and venous thromboembolism (VTE) has been identified, risk stratification for VTE in Japanese patients with cancer remains unclear.

Background Atrial fibrillation (AF) progression is closely related to heart failure occurrence, and catheter ablation carries a beneficial effect for heart failure prevention. Recently, particular attention has been given to left atrial (LA) function and functional reserve in the pathogenesis linking AF and heart failure, although its significance and reversibility is not well studied. Methods and Results We prospectively investigated 164 patients with AF with normal left ventricular systolic function and free from heart failure who underwent first catheter ablation and pre‐/postprocedural echocardiography. Conventional and speckle‐tracking echocardiography were performed at rest and during passive leg lifting to assess LA size, LA reservoir strain (LARS), and functional reserve calculated as passive leg lifting‐LARS – rest‐LARS. Patients were categorized into 3 AF subtypes: paroxysmal AF (N=95), persistent AF (PeAF; N=50), and long‐standing persistent AF (LS‐PeAF; N=19). The PeAF and LS‐PeAF groups had larger LA size and reduced LARS compared with the paroxysmal AF group (all P

Abstract Objective Loeys–Dietz syndrome (LDS) is a heritable disorder of connective tissue closely related to Marfan syndrome (MFS). LDS is caused by loss‐of‐function variants of genes that encode components of transforming growth factor‐β (TGF‐β) signaling; nevertheless, LDS type 1/2 caused by TGFBR1/2 pathogenic variants is frequently found to have paradoxical increases in TGF‐β signaling in the aneurysmal aortic wall. Here, we present a Japanese LDS family having a novel SMAD3 variant. Methods The proband was tested via clinical, genetic, and histological analyses. In vitro analysis was performed for pathogenic evaluation. Results The novel heterozygous missense variant of SMAD3 [c.1262G>A, p.(Cys421Tyr)], located just upstream of the C‐terminal Ser423‐X‐Ser425 phosphorylation motif, was found in this instance of LDS type 3. This variant led to reduced phospho‐SMAD3 (Ser423/Ser425) levels and transcription activity in vitro; however, a paradoxical upregulation of TGF‐β signaling was evident in the aortic wall. Conclusions Our results revealed the presence of TGF‐β paradox in this case with the novel loss‐of‐function SMAD3 variant. The precise mechanism underlying the paradox is unknown, but further research is warranted to clarify the influence of the SMAD3 variant type and location on the LDS3 phenotype as well as the molecular mechanism leading to LDS3 aortopathy.

Background and purposeSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with an increased rate of cerebrovascular events including ischemic stroke and intracerebral hemorrhage. The mechanisms underlying cerebral endothelial susceptibility and response to SARS-CoV-2 are unknown yet critical to understanding the association of SARS-CoV-2 infection with cerebrovascular events.MethodsEndothelial cells were isolated from human brain and analyzed by RNA sequencing. Human umbilical vein and human brain microvascular cells were used in both monolayer culture and endothelialized within a 3-dimensional printed vascular model of the middle cerebral artery. Gene expression levels were measured by quantitative polymerase chain reaction and direct RNA hybridization. Recombinant SARS-CoV-2 S protein and S protein-containing liposomes were used to measure endothelial binding by immunocytochemistry.ResultsACE2 (angiotensin-converting enzyme-2) mRNA levels were low in human brain and monolayer endothelial cell culture. Within the 3-dimensional printed vascular model, ACE2 gene expression and protein levels were progressively increased by vessel size and flow rates. SARS-CoV-2 S protein-containing liposomes were detected in human umbilical vein endothelial cells and human brain microvascular endothelial cells in 3-dimensional middle cerebral artery models but not in monolayer culture consistent with flow dependency of ACE2 expression. Binding of SARS-CoV-2 S protein triggered 83 unique genes in human brain endothelial cells including upregulation of complement component C3.ConclusionsBrain endothelial cells are susceptible to direct SARS-CoV-2 infection through flow-dependent expression of ACE2. Viral S protein binding triggers a unique gene expression profile in brain endothelia that may explain the association of SARS-CoV-2 infection with cerebrovascular events.

Abstract Background Although weight loss in heart failure (HF) is a detrimental condition known as cachexia, weight gain caused by fluid retention should also be considered harmful. However, studies with sufficient number of patients examining the impact of weight change and its interval on in‐hospital mortality in HF have not been conducted thus far. We sought to elucidate the association of weight change with in‐hospital mortality in patients with HF. Methods This retrospective observational study used data from the Diagnosis Procedure Combination database, a nationwide inpatient health claims database in Japan. In total, 48 234 patients repeatedly hospitalized for HF (median 82 [74–87] years; 46.4% men) between 2010 and 2018 were included. Weight change was derived from body weight at the first and second admissions. Results The median weight change and interval between two hospitalizations were −3.1 [−8.3 to −1.8] % and 172 [67–420] days, with 66.9% of overall cohort experiencing any weight loss. As a result of multivariable‐adjusted logistic regression analysis, weight loss +5.0% were associated with increased in‐hospital mortality (adjusted odds ratio [OR] [95% confidence interval]: 1.46 [1.31–1.62], P

Introduction Granulomas are chronic inflammatory lesions having well-defined borders and comprising mainly macrophages and other inflammatory cells (1). Differentiation of macrophages into epithelioid cells and multinucleated giant cells is often [...], Sarcoidosis is a disease of unknown etiology in which granulomas form throughout the body and is typically treated with glucocorticoids, but there are no approved steroid-sparing alternatives. Here, we investigated the mechanism of granuloma formation using single-cell RNA-Seq in sarcoidosis patients. We observed that the percentages of triggering receptor expressed on myeloid cells 2-positive (TREM2- positive) macrophages expressing angiotensin- converting enzyme (ACE) and lysozyme, diagnostic makers of sarcoidosis, were increased in cutaneous sarcoidosis granulomas. Macrophages in the sarcoidosis lesion were hypermetabolic, especially in the pentose phosphate pathway (PPP). Expression of the PPP enzymes, such as fructose-1,6-bisphosphatase 1 (FBP1), was elevated in both systemic granuloma lesions and serum of sarcoidosis patients. Granuloma formation was attenuated by the PPP inhibitors in in vitro giant cell and in vivo murine granuloma models. These results suggest that the PPP may be a promising target for developing therapeutics for sarcoidosis.

O artigo objetiva refletir e fundamentar a problemática do fenômeno bullying, visto como uma violência que afeta o desenvolvimento social e cognitivo da criança, sendo analisado como um problema legal, escolar, familiar e social que acomete o desenvolvimento da vítima como um todo, gerando consequências graves e, muitas vezes, irreversíveis, bem como as formas de prevenção e contenção. Para tanto, utilizou-se o método materialista histórico-dialético, com abordagem interpretativa, baseada, principalmente, em obras de diversos autores da área da Educação, do Direito e da Psicologia. Sendo assim, o tema escolhido é justificável, pois alerta para a ampliação da violência nas escolas brasileiras, ao longo dos últimos anos, prioritariamente, nas escolas públicas, manifestada por tendência à naturalização dos atos violentos, que, por vezes, acaba sendo considerado evento corriqueiro, o que indica a banalização da violência. Nesse sentido, o texto busca aprofundar o conhecimento sobre a violência nas escolas no sentido de compreender a origem do fenômeno, considerando fatores externos e internos e a eficácia das formas de combate e prevenção. Com efeito, considera-se, portanto, a violência como reflexo das vulnerabilidades sociais atreladas à exclusão social e às formas de combate ao bullying dentro da gestão escolar.

Ischemic injury to white matter tracts is increasingly recognized to play a key role in age-related cognitive decline, vascular dementia, and Alzheimer's disease. Knowledge of the effects of ischemic axonal injury on cortical neurons is limited yet critical to identifying molecular pathways that link neurodegeneration and ischemia. Using a mouse model of subcortical white matter ischemic injury coupled with retrograde neuronal tracing, we employed magnetic affinity cell sorting with fluorescence-activated cell sorting to capture layer-specific cortical neurons and performed RNA-sequencing. With this approach, we identified a role for microtubule reorganization within stroke-injured neurons acting through the regulation of tau. We find that subcortical stroke-injured Layer 5 cortical neurons up-regulate the microtubule affinity-regulating kinase, Mark4, in response to axonal injury. Stroke-induced up-regulation of Mark4 is associated with selective remodeling of the apical dendrite after stroke and the phosphorylation of tau in vivo. In a cell-based tau biosensor assay, Mark4 promotes the aggregation of human tau in vitro. Increased expression of Mark4 after ischemic axonal injury in deep layer cortical neurons provides new evidence for synergism between axonal and neurodegenerative pathologies by priming of tau phosphorylation and aggregation.