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In recent years, a new generation of optical intensity interferometers has emerged, leveraging the existing infrastructure of Imaging Atmospheric Cherenkov Telescopes (IACTs). The MAGIC telescopes host the MAGIC-SII system (Stellar Intensity Interferometer), implemented to investigate the feasibility and potential of this technique on IACTs. After the first successful measurements in 2019, the system was upgraded and now features a real-time, dead-time-free, 4-channel, GPU-based correlator. These hardware modifications allow seamless transitions between MAGIC's standard very-high-energy gamma-ray observations and optical interferometry measurements within seconds. We establish the feasibility and potential of employing IACTs as competitive optical Intensity Interferometers with minimal hardware adjustments. The measurement of a total of 22 stellar diameters are reported, 9 corresponding to reference stars with previous comparable measurements, and 13 with no prior measurements. A prospective implementation involving telescopes from the forthcoming Cherenkov Telescope Array Observatory's Northern hemisphere array, such as the first prototype of its Large-Sized Telescopes, LST-1, is technically viable. This integration would significantly enhance the sensitivity of the current system and broaden the UV-plane coverage. This advancement would enable the system to achieve competitive sensitivity with the current generation of long-baseline optical interferometers over blue wavelengths. [ABSTRACT FROM AUTHOR]

Gamma-ray bursts (GRBs) are explosive transient events occurring at cosmological distances, releasing a large amount of energy as electromagnetic radiation over several energy bands. We report the detection of the long GRB 201216C by the MAGIC telescopes. The source is located at z  = 1.1 and thus it is the farthest one detected at very high energies. The emission above 70 GeV of GRB 201216C is modelled together with multiwavelength data within a synchrotron and synchrotron self-Compton (SSC) scenario. We find that SSC can explain the broad-band data well from the optical to the very-high-energy band. For the late-time radio data, a different component is needed to account for the observed emission. Differently from previous GRBs detected in the very-high-energy range, the model for GRB 201216C strongly favours a wind-like medium. The model parameters have values similar to those found in past studies of the afterglows of GRBs detected up to GeV energies. [ABSTRACT FROM AUTHOR]

MAXI J1820+070 is a low-mass X-ray binary with a black hole (BH) as a compact object. This binary underwent an exceptionally bright X-ray outburst from 2018 March to October, showing evidence of a non-thermal particle population through its radio emission during this whole period. The combined results of 59.5 h of observations of the MAXI J1820+070 outburst with the H.E.S.S. MAGIC and VERITAS experiments at energies above 200 GeV are presented, together with Fermi -LAT data between 0.1 and 500 GeV, and multiwavelength observations from radio to X-rays. Gamma-ray emission is not detected from MAXI J1820+070, but the obtained upper limits and the multiwavelength data allow us to put meaningful constraints on the source properties under reasonable assumptions regarding the non-thermal particle population and the jet synchrotron spectrum. In particular, it is possible to show that, if a high-energy (HE) gamma-ray emitting region is present during the hard state of the source, its predicted flux should be at most a factor of 20 below the obtained Fermi -LAT upper limits, and closer to them for magnetic fields significantly below equipartition. During the state transitions, under the plausible assumption that electrons are accelerated up to ∼500 GeV, the multiwavelength data and the gamma-ray upper limits lead consistently to the conclusion that a potential HE and very-HE gamma-ray emitting region should be located at a distance from the BH ranging between 1011 and 1013 cm. Similar outbursts from low-mass X-ray binaries might be detectable in the near future with upcoming instruments such as CTA. [ABSTRACT FROM AUTHOR]

Epidemiological and experimental studies suggest that diesel exhaust particles (DEP) may play an active role in the increased respiratory mortality and morbidity. We have shown that DEP augmented the production of inflammatory cytokines by human airway epithelial cells in vitro. ICAM-1 has been shown to play an important role in the local accumulation of inflammatory cells. We studied the effect of DEP on ICAM-1 gene expression and surface expression in human bronchial epithelial cell line BEAS-2B. DEP (5–50 μg/ml) showed a stimulatory effect on ICAM-1 mRNA levels as evaluated by reverse transcription-polymerase chain reaction (RT-PCR). Flow cytometric analysis demonstrated an increased ICAM-1 expression on the epithelial cell surfaces. The soluble form of ICAM-1 molecules was also increased by the stimulation of DEP. In vitro neutrophil attachment onto DEP-stimulated epithelial cells was augmented, which was partially blocked by anti-ICAM-1 neutralizing antibody. Finally, these events were significantly inhibited by pretreatment with anti-oxidants pyrrolidine dithiocarbamate and N-acetyl cysteine, and p38 mitogen activated protein kinase (MAPK) inhibitor SB203580. These findings suggested that DEP induced up-regulation of ICAM-1 gene, and this process might be largely dependent on oxidant-mediated NF-κB activation and p38-MAPK pathways. [ABSTRACT FROM AUTHOR]

Summary: Humanized non‐obese diabetic/severe combined immunodeficiency/interleukin‐2 receptor‐γ‐null (NOD/SCID/IL2rγnull) [humanized (huNSG)] mice engrafted with human hematopoietic cells have been used for investigations of the human immune system. However, the epigenetic features of the human regulatory T (Treg) cells of huNSG mice have not been studied. The objective of this study was to clarify the characteristics of human Treg cells in huNSG mice, especially in terms of the epigenetic aspects. We compared the populations, inhibitory molecule expression and suppressive capacity of human Treg cells in spleens harvested from the huNSG mice 120 days after the engraftment of human umbilical cord blood CD34+ cells with human peripheral blood mononuclear cells (PBMCs). Histone modifications and enhancer of zeste homolog 2 (Ezh2), an H3K27 methyltransferase, of human Treg cells were quantified in huNSG mice and human PBMCs. The effect of Ezh2 inhibitor on human Treg cells exposed to interleukin (IL)‐6 was also compared between them. Human Treg cells in the spleens of huNSG mice showed an increased proportion among CD4+ T cells, higher expressions of forkhead box protein 3 (FoxP3), cytotoxic T lymphocyte antigen 4 (CTLA‐4) and glucocorticoid‐induced tumor necrosis factor‐related protein (GITR), a higher production of IL‐10 and enhanced suppressive capacity when compared with those in human PBMCs. H3K27me3 and Ezh2 were specifically up‐regulated in human Treg cells of huNSG mice in comparison with those of human PBMCs. The decrease in Treg cells induced by IL‐6 exposure was attenuated in huNSG mice when compared with human PBMCs, while the difference between them was cancelled by addition of Ezh2 inhibitor. In conclusion, huNSG mice exhibit functionally augmented human Treg cells owing to enzymatic up‐regulation of H3K27me3. [ABSTRACT FROM AUTHOR]

Endoscopic submucosal dissection (ESD) has evolved into a viable treatment modality for superficial esophageal cancer. ESD offers a distinct advantage given the ability to perform en bloc resection enabling accurate histopathologic assessment. Data from published literature has established ESD as the preferred option in the treatment of superficial squamous cell carcinoma with complete resection rates of 78–100%, and a low rate recurrence of 0–2.6%. En bloc resection for esophageal SCC is curative for tumors with M1 (intrapethelial) or M2 (invasion into the lamina propria) involvement with no lymphovascular invasion. Tumors that contain lymphovascular invasion or submucosal invasion greater than 200 μm should be treated as advanced carcinomas due to the increased risk of lymph node metastasis. In contrast, the role of ESD in Barrett’s esophagus is more limited due to the high rate of efficacy of EMR. A randomized control trial comparing EMR and ESD strategies found a higher R0 resection rate for ESD, but no significant difference in complete remission from neoplasia at 3 month follow up. Endoscopic ultrasound (EUS) has a limited role in the evaluation of superficial esophageal cancer. Alternatively, detailed endoscopic assessment along with magnification endoscopy or narrow band imaging, may provide greater utility than EUS. The most common adverse events of ESD in the esophagus include perforation and stricture. Perforation can often be managed by defect closure along with non-operative conservative management. Steroid administration with either topical or local injection can be effective management in stricture prevention. Continued refinement of ESD technique and innovation will overcome some of the current limitations of ESD and enable curative resection of superficial esophageal cancer as an alternative to invasive surgery. [ABSTRACT FROM AUTHOR]

Background Mycosis fungoides ( MF) classically presents from patch stage to plaque stage over a number of years and finally progresses to tumour stage with nodal or visceral involvement. The mechanism of progression remains incompletely elucidated. Chemokines and their receptors are known to be involved in disease mechanisms, with CXCL12 and CXCR4 playing a critical role in carcinogenesis, invasion and cancer cell migration in various carcinomas. Objectives To investigate the expression of CXCL12 and CXCR4 in different cutaneous stages of MF. Methods Formalin-fixed, paraffin-embedded skin samples from 40 patients with MF (21 patch stage, 10 plaque stage, nine tumour stage) and 30 non-neoplastic control skin samples were analysed. CXCL12 and CXCR4 were assessed by quantitative reverse-transcription polymerase chain reaction and immunohistochemical staining. Results The expression level of mRNA for CXCL12 in plaque-stage MF was significantly higher than in control skin ( P = 0·0035), or patch-stage ( P = 0·0108) or tumour-stage disease ( P = 0·0089). The CXCR4 mRNA expression level in plaque-stage disease was significantly higher than in control skin ( P = 0·0090) or patch-stage disease ( P = 0·0387). CXCL12- and CXCR4-positive cell rates in patch-stage and plaque-stage MF were significantly higher than those in control skin ( P < 0·0001). CXCL12- and CXCR4-positve cell rates in tumour-stage MF were significantly lower than those in patch- and plaque-stage disease ( P = 0·0274 and P = 0·0492, respectively). Conclusions Our data suggest that neoplastic T cells in MF are exposed to the microenvironment, given the abundance of CXCL12 during its progression, and also that neoplastic T cells express CXCR4, especially in the pretumour stage. We reveal that the CXCL12- CXCR4 axis plays a critical role in MF progression. [ABSTRACT FROM AUTHOR]

The article presents the study which evaluated the medication adherence for oral and topical remedies of Japanese dermatological patients using the translated version of the Morisky Medication Adherence Scale-8 (MMAS-8) and other socioeconomic background factors. In the study, information like smoking habit, alcohol use, and frequency of hospital visits were collected. Based on the results, lower adherence in both oral and topical drug groups was observed in younger subjects.

Background Onychomycosis is often caused by dermatophytes, but the role of nondermatophytes is underestimated due to the difficulty of identifying them by conventional direct microscopy and culture. Objectives This study aims to detect nondermatophytes, as well as dermatophytes, in the nail samples of patients with onychomycosis using a polymerase chain reaction (PCR)-based culture-independent method. Materials and methods The nested PCR assay targeting the sequence of the 28S ribosomal RNA gene was used to amplify fungal DNAs from 50 microscopy-positive nail specimens. Newly designed primer sets for dermatophyte universal, Trichophyton rubrum, T. mentagrophytes, Aspergillus spp., Scopulariopsis brevicaulis, Fusarium solani, F. oxysporum, F. verticillioides, Candida albicans and C. tropicalis were used after confirmation of their specificity. Results Forty-seven cases (94%) were positive for fungal DNA, among which dermatophytes were detected in 39 cases (83·0%): T. rubrum in 35 cases (74·5%) and T. mentagrophytes in eight cases (17·0%). Surprisingly, nondermatophytes were detected in 18 cases (38·3%), both dermatophytes and nondermatophytes in 10 cases (21·3%) and nondermatophytes alone in eight cases (17·0%). Aspergillus spp. alone was observed in five cases (10·6%). Conclusions This study indicates that most of the affected nail plates of patients with onychomycosis were positive for specific fungal DNAs, and suggests that nondermatophytes detected at high rates may be involved in the pathogenesis of onychomycosis. [ABSTRACT FROM AUTHOR]

Contemporary mushroom factories are places where there is a substantial risk of the occurrence of respiratory allergy. The aims of this investigation were to estimate its causative agents and to evaluate the contribution of innate immune response in mushroom workers who cultivate Hypsizigus marmoreus (Bunashimeji). Cross-sectional and follow-up studies were performed in the factory. We investigated CD1b, CD3, CD4, CD8, CD14, CD45RO, CD62L and CD161 expression in peripheral blood mononuclear cells (PBMC) by flow cytometry, and serum levels of interleukin (IL-2), IL-4, granulocyte-macrophage colony stimulating factor (GM-CSF), IL-13 and interferon (IFN)- γ by enzyme-linked immunosorbent assay (ELISA). Co-culture experiments of PBMC with spore extracts were also performed. Percentages of CD1b+ monocytes, natural killer (NK), NK T and CD4+ T cells were increased in the workers compared with controls. Increases in Th2 type cells, Th2/Th1 ratio and serum IL-13 and decreased IFN- γ were detected, indicating a Th2-biased status of the workers. The follow-up study showed that monocytes and NK cells increased soon after employment while CD4+ T, Th2 and NK T cells increased gradually as employment time lengthened. Serum precipitating antibody to the mushroom antigen could be detected at a later stage. Co-cultivation of PBMC with the spore extracts induced much higher CD1b expression, and suppressed secretion of Th1 cytokine in culture supernatants. These results indicate that the mushroom antigen contains highly immunogenic substances which stimulate PBMC into a Th2-biased in vivo status, and innate immune cells might also play a critical role in developing respiratory allergy in mushroom workers. [ABSTRACT FROM AUTHOR]

SUMMARY In sarcoidosis, a T helper 1 (Th1) response is an essential event and the up-regulation of interleukin-12 (IL-12) has been detected in affected disease sites. In order to investigate the clinical usefulness of circulating IL-12, we measured the serum concentrations of IL-12 by ELISA and performed immunohistochemistry using specific MoAbs for IL-12 in the lungs and scalene lymph nodes of patients with sarcoidosis. The serum concentration of IL-12 p40 was detectable in all 45 patients with pulmonary sarcoidosis and 18 normal controls, whereas that of IL-12 p70 was undetectable. The serum concentrations of IL-12 p40 in pulmonary sarcoidosis were significantly higher than those of the normal controls, especially in cases with abnormal intrathoracic findings detected by chest roentogenogram. The serum concentrations of interferon-γ (IFN-γ ) also increased compared with those of normal controls and there was a significant positive correlation between the serum concentrations of IL-12 p40 and IFN-γ . Furthermore, serum angiotensin-converting enzyme (ACE) and lysozyme, which are known to be useful markers for disease activity in sarcoidosis, correlated well with the serum concentrations of IL-12 p40. The positive 67 Ga scan group (for lung field) had significantly elevated serum IL-12 p40 levels compared with those of the negative group. No bioactivity of IL-12 p70 was detected in three sarcoid cases sera by using the IL-12 responsive cell line. Finally, the immunohistochemical approach revealed that IL-12 p40 was expressed in the epithelioid cells and macrophages of sarcoid lungs and lymph nodes. We concluded that the production of IL-12 p40 was far greater in the sera and we have demonstrated this to be a useful clinical marker for disease activity and the Th1 response in pulmonary sarcoidosis. [ABSTRACT FROM AUTHOR]

sICAM-1 has been elevated in sera of specific inflammatory diseases, and circulating sICAM-1 concentrations reflect disease activity in these diseases. We measured circulating sICAM-1 concentrations and serum angiotensin-converting enzyme (SACE) activity in patients with sarcoidosis. Patients with sarcoidosis had significantly increased circulating sICAM-1 concentrations (62.8 ± 33.5 U/ml) and SACE activity (23.7 ± 7.4 U/l) compared with controls (circulating sICAM-1 50.9 ± 12.1 U/ml, and SACE I3.5 ± 3 8U/l). Successive measurements showed that circulating sICAM-1 values changed in parallel with disease activity in sarcoidosis. In the progressive disease group (progressed or without change for 2 years or more), circulating sICAM-1 values (102.2 ± 35 3 U/ml) at the time of diagnosis were significantly increased compared with those in the regressive disease group (disappeared or regressed within 2 years) (46.4 ± 12.6 U/ml), However, there was no significant difference in SACE activity of the regressive and progressive disease groups. Fifteen patients with a high value of circulating sICAM-1 (< 75 U/ml, mean of controls + 2 s.d.) all had progressive disease, while only 15 of 44 patients with a high value of SACE had progressive disease. Circulating sICAM-1 will be a useful blood marker to predict outcome and to monitor disease activity in sarcoidosis. [ABSTRACT FROM AUTHOR]

ICAM-l plays an important role in inflammatory diseases. We analysed ICAM-l expression on BAL fluid cells and measured soluble ICAM-l (sICAM-I) concentrations in sent and BAL fluids from patients with extrinsic allergic alveolitis (EAA). We found significantly increased cellular ICAM-1 expression on BAL fluid lymphocytes and alveolar marcrophages, and significantly increased values of circulating and BAL fluid sICAM-l in EAA patients compared with controls. Successive measurement shows prompt decrease of both sICAM-l values in EAA patients during periods when antigen exposure was prevented. In BAL fluids from EAA patients sICAM-l values significantly correlated to neutrophil and ICAM-1+ lymphocyte counts. In EAA patients, circulating and BAL fluid sICAM-1 values has significant negative correlations to values of carbon monoxide diffusing capacity and to time intervals between last episode and sample collection. However, these values had significant positive correlation to values of alveolar arterial oxygen pressure difference. In EAA, antigen exposure appears to induce cellular ICAM-l expression on BAL fluid cells, and also appears to up-regulate shedding of ICAM-l in the alveolar lining fluid and in the circulation. The sICAM values appear to reflect disease activity of EAA. [ABSTRACT FROM AUTHOR]

ICAM-I plays an important role in inflammatory diseases. To assess level of soluble ICAM-I in the circulation and inflamed lesions, we measured levels of soluble ICAM-1 in the circulation and bronchoalvcolar lavage fluid (BALF) of patients with idiopathic pulmonary fibrosis (IPF) and with pulmonary sarcoidosis (PS) and of healthy volunteers (HV), and we also analysed ICAM-I expression of BALF cells in some patients and HV. IPF patients had significantly higher levels of circulating ICAM-I than HV, while PS patients did not. By contrast, significantly increased levels of BALF soluble ICAM-I were found in PS patients compared with those of HV, but not in IPF patients. There were no significant differences in the proportions of ICAM-1+ BALF lymphocytes in IPF patients, PS patients and HV, whereas significantly increased proportions of ICAM-I + pulmonary alveolar macrophages were found in PS patients compared with those of HV, but not in IPF patients. There was a significant positive correlation of BALF soluble ICAM-I levels to BALF lymphocyte proportions in PS patients. Although the source of BALF soluble ICAM-l is unclear, BALF soluble ICAM-1 appears to reflect the grade of local activity of sarcoidosis. An interesting discrepancy between soluble ICAM-1 levels in the circulation and BALF was found in IPF patients, and this might be an important clue to an understanding of this disorder. [ABSTRACT FROM AUTHOR]