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Objective: To identify the efficacy and tolerability of Proteoglycan F in patients with primary knee OA.Design: A 24-week randomized, placebo-controlled, double-blind clinical trial with two arms: (1) Proteoglycan F (received 10 ​mg proteoglycan daily, for 24 weeks) and (2) control group (received placebo). Knee symptoms and joint cartilage status (evaluated by ultrasound and MRI of knee joints), quality of life, serum cytokine levels (IL-1β and TNF-α), and safety evaluation were measured before, during, and after the treatment. Results: After 24-week treatment, pain reduction (in the KOOS pain score) of at least 20% and at least 50% (NRS scale) compared to baseline in the PGF group was significantly higher than those in the control group. The PGF group had greater reductions in the total scores of subchondral bone marrow edema, and bone cocoon under cartilage on knee MRI (classification according to WORMs), which were −2.27 (-4.0; −0.51) and −1.77 (-3.08; −0.46), respectively (p ​

Abstract Extramedullary hematopoietic effusion (EHE) is one of the extremely rare phenomena associated with extramedullary hematopoiesis, which is caused by serous effusions, including pleural effusion, and may be related to hematologic disorders and neoplasms. Herein, we present the case of an 81‐year‐old man with EHE accompanying Waldenström's macroglobulinemia (WM). The patient complained of anemia and dyspnea. The chest X‐ray and computed tomography showed a massive left pleural effusion, and the aspirates revealed infiltration of the immature myeloid cells and megakaryocytes, in addition to the lymphoma cells. To our knowledge, this is the first report of EHE in WM.

Numerous wind displays have been developed to provide wind sensation in virtual reality applications. However, in previous studies, wind displays required the production of physical wind using a wind source. To release cold or hot wind, previous wind displays required large equipment for making the air temperature changes. In this study, we propose to induce pseudo-wind perception, perceiving wind even in the absence of physical wind, using visuo-audio-haptic cross-modal effects. We provide audio-visual stimuli with a head-mounted display and headphones, and vibrotactile and thermal stimuli to the skin using belt-type devices, instead of physical wind. We found that vibrotactile and thermal stimuli based on the measurement of skin displacement and temperature exposed to the wind are suitable for the tactile sensation of wind. We also found that thermal and audio-visual stimuli can induce wind sensation of cold wind, and that vibro-thermal stimuli in addition to audio-visual stimuli are effective for the wind sensation and realness of the experience of hot wind. In future, inducing variable types of wind sensations will be pursued as a research direction regarding pseudo-wind perception.

Abstract The wound healing response is one of most primitive and conserved physiological responses in the animal kingdom, as restoring tissue integrity/homeostasis can be the difference between life and death. Wound healing in mammals is mediated by immune cells and inflammatory signaling molecules that regulate tissue resident cells, including local progenitor cells, to mediate closure of the wound through formation of a scar. Proteoglycan 4 (PRG4), a protein found throughout the animal kingdom from fish to elephants, is best known as a glycoprotein that reduces friction between articulating surfaces (e.g. cartilage). Previously, PRG4 was also shown to regulate the inflammatory and fibrotic response. Based on this, we asked whether PRG4 plays a role in the wound healing response. Using an ear wound model, topical application of exogenous recombinant human (rh)PRG4 hastened wound closure and enhanced tissue regeneration. Our results also suggest that rhPRG4 may impact the fibrotic response, angiogenesis/blood flow to the injury site, macrophage inflammatory dynamics, recruitment of immune and increased proliferation of adult mesenchymal progenitor cells (MPCs) and promoting chondrogenic differentiation of MPCs to form the auricular cartilage scaffold of the injured ear. These results suggest that PRG4 has the potential to suppress scar formation while enhancing connective tissue regeneration post-injury by modulating aspects of each wound healing stage (blood clotting, inflammation, tissue generation and tissue remodeling). Therefore, we propose that rhPRG4 may represent a potential therapy to mitigate scar and improve wound healing.

Abstract This study investigated the effects of salmon nasal cartilage proteoglycan (PG), which shows anti‐inflammatory properties, on obesity induced by high‐fat diet (HFD) in a mouse model. Mice were fed either a HFD or normal diet (ND), with or without PG, for 8–12 weeks. After 12 weeks, the body weight of mice fed with PG‐free HFD was 54.08 ± 4.67 g, whereas that of mice fed with HFD containing PG was 41.83 ± 4.97 g. The results suggest that the increase in body weight was attenuated in mice fed with HFD containing PG. This effect was not observed in mice fed with ND. The PG administration suppressed the elevation of serum lipids (the level of serum lipids ranged between 54% and 69% compared to 100% in mice fed with PG‐free HFD) and the upregulated mRNA expression of sterol regulatory element‐binding protein‐1c (SREBP‐1c), which is a transcription factor that acts as a master regulator of lipogenic gene expression in the liver (the expression level was 77.5% compared to 100% in mice fed with PG‐free HFD). High leptin levels in mice fed with PG‐free HFD were observed during fasting (average at 14,376 ng/ml), and they did not increase after refeeding (average of 14,263 ng/ml), whereas serum leptin levels in mice fed with HFD containing PG were low during fasting (average of 6481 ng/ml) and increased after refeeding (average 13,382 ng/ml). These results suggest that PG feeding has an anti‐obesity effect and that the regulation of SREBP‐1c and leptin secretion play a role in this effect.

Alzheimer's disease (AD) is characterized by progressive cognitive decline, and the number of affected individuals has increased worldwide. However, there are no effective treatments for AD. Therefore, it is important to prevent the onset of dementia. Oxidative stress and endoplasmic reticulum (ER) stress are increased in the brains of AD patients, and are postulated to induce neuronal cell death and cognitive dysfunction. In this study, Centella asiatica, a traditional Indian medicinal herb, were fractionated and compared for their protective effects against glutamate and tunicamycin damage. Araliadiol was identified as a component from the fraction with the highest activity. Further, murine hippocampal cells (HT22) were damaged by glutamate, an oxidative stress inducer. C. asiatica and araliadiol suppressed cell death and reactive oxygen species production. HT22 cells were also injured by tunicamycin, an ER stress inducer. C. asiatica and araliadiol prevented cell death by mainly inhibiting PERK phosphorylation; additionally, C. asiatica also suppressed the expression levels of GRP94 and BiP. In Y-maze test, oral administration of araliadiol (10 mg/kg/day) for 7 days ameliorated the arm alternation ratio in mice with scopolamine-induced cognitive impairment. These results suggest that C. asiatica and its active component, araliadiol, have neuroprotective effects, which may prevent cognitive dysfunction.

Other iatrogenic immunodeficiency lymphoproliferative disorders (oii-LPD) are defined as lymphoid proliferations or lymphomas that occur in patients taking immunosuppressive agents (ISA) for autoimmune disorders (AID). Although methotrexate and tumor necrosis factor-alpha inhibitors cause oii-LPD, the association between corticosteroids and lymphomagenesis remains unknown. Herein, we present the case of a 51-year-old woman with oii-LPD caused by corticosteroid use for autoimmune hemolytic anemia (AIHA). The diagnosis of AIHA was made in May 2016, and AIHA had been well-controlled for 5 years with oral prednisolone (PSL). During a regular follow-up visit in March 2022, an abnormal increase in atypical lymphoid cells in the peripheral blood was found. The bone marrow biopsy specimens showed local aggregations of large cells that were identified as lymphoplasmacytic cells and plasma cells, and that were positive for cluster of differentiation (CD)19 and CD20, with apparent nucleoli among the diffuse infiltration of atypical small lymphocytes. The large cells were partially positive for the Epstein–Barr encoding region in situ hybridization and latent membrane protein 1, which confirmed Epstein–Barr virus (EBV)-affected lymphomagenesis. To our knowledge, this is the first report of an oii-LPD case shown to be induced by corticosteroid use for AID.

Any change in the light-source spectrum modifies the color information of an object. The spectral distribution of the light source can be optimized to enhance specific details of the obtained images; thus, using information-enhanced images is expected to improve the image recognition performance via machine vision. However, no studies have applied light spectrum optimization to reduce the training loss in modern machine vision using deep learning. Therefore, we propose a method for optimizing the light-source spectrum to reduce the training loss using neural networks. A two-class classification of one-vs-rest among the classes, including enamel as a healthy condition and dental lesions, was performed to validate the proposed method. The proposed convolutional neural network-based model, which accepts a 5 × 5 small patch image, was compared with an alternating optimization scheme using a linear-support vector machine that optimizes classification weights and lighting weights separately. Furthermore, it was compared with the proposed neural network-based algorithm, which inputs a pixel and consists of fully connected layers. The results of the five-fold cross-validation revealed that, compared to the previous method, the proposed method improved the F1-score and was superior to the models that were using the immutable standard illuminant D65.

The 5-year survival rate for pancreatic cancer has improved (10%) but remains worse than that for other cancers. Early pancreatic cancer diagnosis is challenging, and delayed diagnosis can delay treatment, which impairs survival. Practitioners do not promptly refer cases to a general hospital, causing delayed discovery. Herein, we aimed to examine the usefulness of the Pancreatic Cancer Project in Matsue, whose objective is to detect pancreatic cancer in patients presenting at any medical institution in Matsue City. Clinical data were extracted from medical records, and abdominal ultrasonography and tumor marker blood level assessments were performed (n = 234; median age, 71 [range, 41–94] years; 51% male). Cases with abnormal abdominal ultrasonography or blood test findings were referred for specialist imaging and followed up. The pancreatic cancer detection rate was 6.0% (n = 14); all cases were referred to a general hospital by practitioners within 1 month. Patients had stage IA (n = 1), IIA (n = 6), IIB (n = 2), III (n = 1), and IV (n = 4) disease. Overall, pancreatic cancer could be detected at an earlier stage (I–II), but referral to a general hospital by visiting practitioners should be prompt. The Pancreatic Cancer Project in Matsue may help improve the detection and prognosis of pancreatic cancer.

The perception of the relationship between humans and nature is important for promoting not only pro-environmental behaviors but also psychological well-being. The present research explored how people’s self-construal would moderate the relationship between the need to belong, the desire for social acceptance and connectedness and perceived nature relatedness. Two studies using community samples with diverse demographic characteristics in two different cultures (Study 1: the United States; Study 2: Singapore) obtained consistent findings. The results showed that independent self-construal, which emphasizes separateness from others in the social contexts, moderated the relationship between the need to belong and nature relatedness. Specifically, the need to belong was negatively associated with nature relatedness among people with a stronger independent self-construal, while this pattern was not significant among those with a weaker independent self-construal. No evidence for the moderating role of interdependent self-construal was found in the two studies. These findings highlighted the importance of non-nature experience in understanding people’s perception of human–nature relationships.

Dialectical thinking refers to a constellation of beliefs that consist of expectation of change, tolerance of contradiction, and holism. The current research explored whether dialectical thinking would affect people’s anticipation of climate change, which has been propagated globally. Study 1 compared the responses between Chinese participants, representing people from cultures that promote dialectical thinking, and North American participants, representing people from cultures that promote linear thinking. The results showed that Chinese participants demonstrated a stronger non-linear pattern regarding the anticipation of climate change as compared with American participants, in which Chinese participants were more likely to anticipate a stable trend but less likely to anticipate an increasing trend for global warming. Study 2 with a manipulation of dialectical and linear thinking was conducted and provided some generally supportive evidence for the causal relation between dialectical beliefs and the anticipation of climate change. Implications for cross-cultural environmental research and international climate change education programs were discussed.

Cultural psychology has great potential to expand its research frameworks to more applied research fields in business such as marketing and organizational studies while going beyond basic psychological processes to more complex social practices. In fact, the number of cross-cultural business studies has grown constantly over the past 20 years. Nonetheless, the theoretical and methodological closeness between cultural psychology and these business-oriented studies has not been fully recognized by scholars in cultural psychology. In this paper, we briefly introduce six representative cultural constructs commonly applied in business research, which include (1) individualism vs. collectivism, (2) independence vs. interdependence, (3) analytic vs. holistic cognition, (4) vertical vs. horizontal orientation, (5) tightness vs. looseness, and (6) strong vs. weak uncertainty avoidance. We plot the constructs on a chart to conceptually represent a common ground between cultural psychology and business research. We then review some representative empirical studies from the research fields of marketing and organizational studies which utilize at least one of these six constructs in their research frameworks. At the end of the paper, we recommend some future directions for further advancing collaboration with scholars in the field of marketing and organizational studies, while referring to theoretical and methodological issues.

Adsorption parameters such as the distribution coefficient are required to predict the release behavior of contaminants using advection-dispersion models. However, for potentially contaminant-releasing materials (PCMs) such as dredged sludge and coal ash, these parameters cannot be obtained by conventional adsorption tests. This study developed a method to determine adsorption parameters for PCMs from a set of batch tests conducted in parallel as a function of the liquid-solid ratio (LS-parallel test). This LS-parallel test was performed on sandy soil derived from marine sediment using liquid-solid ratios from 1 to 300 L/kg. The water-contact time was also changed from 10 min to 28 d to elucidate the kinetics or equilibrium of contaminants released from the sample. Adsorption parameters were successfully obtained if the substance was under adsorption control. A column percolation test was performed to confirm the effectiveness of the obtained parameters. Good agreements were observed for SO42− and B, but discrepancies remained for other substances such as F− and As suggesting that improvements are necessary in both the LS-parallel test procedure and the advection-dispersion model.

Contexts of face perception are diverse. They range from the social environment to body postures, from the expresser’s gaze direction to the tone of voice. In extending the research on contexts of face perception, we investigated people’s perception of tears on a face. The act of shedding tears is often perceived as an expression of sad feelings aroused by experiencing loss, disappointment, or helplessness. Alternatively, tears may also represent the excessive intensity of any emotion, such as extreme fear during an unexpected encounter with a giant bear and extreme happiness when you win a competition. Investigating these competing interpretations of tears, we found that the addition of tears to different facial expressions made the expressions conceptually closer to sad expressions. In particular, the results of the similarity analysis showed that, after the addition of tears, patterns of ratings for anger, fear, disgust, and neutral facial expressions became more similar to those for sadness expressions. The effect of tears on the ratings of basic emotions and their patterns in facial expressions are discussed.

Despite significant recent advances in the development of immune checkpoint inhibitors, the treatment of advanced colorectal cancer involving metastasis to distant organs remains challenging. We conducted a phase I study to investigate the safety and immunogenicity of Wilms’ tumor (WT1) class I/II peptides-pulsed dendritic cell DC vaccination for patients with advanced colorectal cancer. Standard treatment comprising surgical resection and chemotherapy was followed by one course of seven biweekly administrations of 1–2 × 107 DCs with 1–2 KE of OK-432 (streptococcal preparation) in three patients. Clinical efficacy was confirmed based on WT1 expression using immunohistochemistry on paraffin-embedded tissues and immune monitoring using tetramer analysis and enzyme-linked immunosorbent spot (ELISPOT) assays. WT1 expression with human leukocyte antigen (HLA)-class I molecules was detected in surgical resected tissues. Adverse reactions to DC vaccinations were tolerable under an adjuvant setting. WT1-specific cytotoxic T cells were detected by both modified WT1-peptide/HLA-A*24:02 tetramer analysis and/or interferon-γ-producing cells through the use of ELISPOT assays after the first DC vaccination. Immunity acquired from DC vaccination persisted for two years with prolonged disease-free and overall survival. The present study indicated that DC vaccination targeting WT1 demonstrated the safety and immunogenicity as an adjuvant therapy in patients with resectable advanced colorectal cancer.

Background and Objective. 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) inhibits proinflammatory cytokines in microglial cells and monocytes. However, it is unclear whether 1,25(OH)2D3 inhibits proinflammatory cytokines in muscle cells. This study was conducted to investigate whether 1,25(OH)2D3 inhibits the production of proinflammatory cytokines, resulting in inhibition of the protein expression of E3 ubiquitin ligases and muscle protein loss. Materials and Methods. C2C12 myoblasts were proliferated in Dulbecco’s modified Eagle medium (DMEM) containing 10% fetal bovine serum, and myoblasts were differentiated into myotubes in DMEM containing 2% horse serum. Myotubes were treated with 1,25(OH)2D3 for 24 h, followed by lipopolysaccharide (LPS) stimulation for 48 h. Results. Interleukin (IL)-6 protein concentrations were higher in the culture supernatant following LPS stimulation compared to that without LPS stimulation (p < 0.001). However, the IL-6 concentration was significantly lower in C2C12 myotubes following 1,25(OH)2D3 treatment than in C2C12 myotubes without 1,25(OH)2D3 treatment (p < 0.001). The myosin heavy chain (MHC), muscle atrophy F-box, and muscle ring-finger protein-1 protein levels did not significantly differ (P = 0.324, 0.552, and 0.352, respectively). We could not compare tumor necrosis factor α (TNFα) protein levels because they were below the limit of detection of our assay in many supernatant samples, including in LPS-stimulated samples. Conclusions. 1,25(OH)2D3 inhibited increases in IL-6 protein concentrations in muscle cells stimulated by LPS, suggesting that 1,25(OH)2D3 inhibits inflammation in muscle cells. The findings suggest that 1,25(OH)2D3 can prevent or improve sarcopenia, which is associated with IL-6. The TNFα protein content could not be measured, and MHC was not decreased despite LPS stimulation of C2C12 myotubes. Further studies are needed to examine the effects of higher doses of LPS stimulation on muscle cells and use more sensitive methods for measuring TNFα protein to investigate the preventive effects of 1,25(OH)2D3 on increased TNFα and muscle proteolysis.

Up-flow column percolation tests are used at laboratory scale to assess the leaching behavior of hazardous substance from contaminated soils in a specific condition as a function of time. Monitoring the quality of these test results inter or within laboratory is crucial, especially if used for Environment-related legal policy or for routine testing purposes. We tested three different sandy loam type soils (Soils I, II and III) to determine the reproducibility (variability inter laboratory) of test results and to evaluate the difference in the test results within laboratory. Up-flow column percolation tests were performed following the procedure described in the ISO/TS 21268-3. This procedure consists of percolating solution (calcium chloride 1 mM) from bottom to top at a flow rate of 12 mL/h through softly compacted soil contained in a column of 5 cm diameter and 30 ± 5 cm height. Eluate samples were collected at liquid-to-solid ratio of 0.1, 0.2, 0.5, 1, 2, 5 and 10 L/kg and analyzed for quantification of the target elements (Cu, As, Se, Cl, Ca, F, Mg, DOC and B in this research). For Soil I, 17 institutions in Japan joined this validation test. The up-flow column experiments were conducted in duplicate, after 48 h of equilibration time and at a flow rate of 12 mL/h. Column percolation test results from Soils II and III were used to evaluate the difference in test results from the experiments conducted in duplicate in a single laboratory, after 16 h of equilibration time and at a flow rate of 36 mL/h. Overall results showed good reproducibility (expressed in terms of the coefficient of variation, CV, calculated by dividing the standard deviation by the mean), as the CV was lower than 30% in more than 90% of the test results associated with Soil I. Moreover, low variability (expressed in terms of difference between the two test results divided by the mean) was observed in the test results related to Soils II and III, with a variability lower than 30% in more than 88% of the cases for Soil II and in more than 96% of the cases for Soil III. We also discussed the possible factors that affect the reproducibility and variability in the test results from the up-flow column percolation tests. The low variability inter and within laboratory obtained in this research indicates that the ISO/TS 21268-3 can be successfully upgraded to a fully validated ISO standard.

[This corrects the article DOI: 10.1371/journal.pone.0159822.].

To recycle silica byproducts and to moderate the heat-island phenomenon, a porous ceramic was prepared by mixing waste silica powder with clay, and then firing the resultant mixture. By exploiting the high water-absorption capacity of the resulting ceramic, a greening material in which the porous ceramic was covered with moss was produced. The suppression effect of the temperature increase caused by solar-radiant heat on the moss-covered ceramic, was investigated quantitatively using the following procedure. First, the surface temperature change of the water-absorbing moss-covered sample during solar-radiant heat reception, and the amount of water that evaporated from the sample were measured simultaneously. Then, the heat of evaporation was estimated from measurements of the rate of water evaporation. Next, to investigate how much the sample temperature was reduced by heat of water evaporation, the temperature change of the sample when the heat of water evaporation was absorbed from the sample, was simulated by performing Finite Element Method (FEM) analysis. The summary of the results was as follows. (1) The primary factor of the temperature-reduction-effects on the moss-covered sample was action of heat of water evaporation. Therefore, the moss-covered sample did not exhibit much of the suppression ability of the temperature increase caused by solar-radiant heat, when the sample did not contain sufficient water. (2) This analytical method enabled us to simulate with a relatively high accuracy, the temperature change of a water-absorbing sample during solar-radiant-heat reception. Especially, the method enabled us to investigate visibly the influence of water evaporation-heat on the sample temperature, in addition to the influences of the emissivity of the sample, and the apparent specific heat and thermal conductivity changes due to water content in the sample.