Despite their crucial role in health and disease, our knowledge of immune cells within human tissues remains limited. We surveyed the immune compartment of 16 tissues from 12 adult donors by ...single-cell RNA sequencing and VDJ sequencing generating a dataset of ~360,000 cells. To systematically resolve immune cell heterogeneity across tissues, we developed CellTypist, a machine learning tool for rapid and precise cell type annotation. Using this approach, combined with detailed curation, we determined the tissue distribution of finely phenotyped immune cell types, revealing hitherto unappreciated tissue-specific features and clonal architecture of T and B cells. Our multitissue approach lays the foundation for identifying highly resolved immune cell types by leveraging a common reference dataset, tissue-integrated expression analysis, and antigen receptor sequencing.
Aims
Aggressive meningioma remains incurable with neither chemo‐ nor targeted therapies proven effective, largely due to unidentified genetic alterations and/or aberrant oncogenic pathways driving ...the disease progression. In this study, we examined the expression and function of Forkhead box M1 (FOXM1) transcription factor during meningioma progression.
Methods
Human meningioma samples (n = 101) were collected, followed by Western blotting, quantitative PCR, immunohistochemical and progression‐free survival (PFS) analyses. For in vitro assays, FOXM1 was overexpressed or knocked‐down in benign (SF4433 and SF4068) or malignant (SF3061 and IOMM‐Lee) human meningioma cell lines respectively. For in vivo studies, siomycin A (a FOXM1 inhibitor)‐pretreated or control IOMM‐Lee cells were implanted subcutaneously in nude mice.
Results
FOXM1 expression was increased in higher grades of meningioma and correlated with the mitotic index in the tumour tissue. Moreover, FOXM1 was increased in recurrent meningioma compared with the matched primary lesions. The patients who had higher FOXM1 expression had shorter PFS. In the subsequent in vitro assays, knockdown of FOXM1 in malignant meningioma cell lines resulted in decreased tumour cell proliferation, angiogenesis and invasion, potentially via regulation of β‐catenin, cyclin D1, p21, interleukin‐8, vascular endothelial growth factor‐A, PLAU, and epithelial‐to‐mesenchymal transition‐related genes, whereas overexpression of FOXM1 in benign meningioma cell lines had the opposite effects. Last, suppression of FOXM1 using a pharmacological inhibitor, siomycin A, decreased tumour growth in an in vivo mouse model.
Conclusions
Our data demonstrate that FOXM1 is a key transcription factor regulating oncogenic signalling pathways in meningioma progression, and a promising therapeutic target for aggressive meningioma.
Although perforation of the colon is known as one of the main complications of endoscopic submucosal dissection (ESD) for colorectal tumor management, factors predictive of perforation have not been ...fully evaluated. This study aimed to determine the factors associated with perforation during colorectal ESD.
Patients with colorectal tumors undergoing ESD were enrolled and their records were reviewed retrospectively. Age, sex, co-morbidity, medication history, procedure time, resection method, tumor size, location, gross morphology, the presence of fibrosis, and histologic findings were included as possible risk factors. In the cases where perforation had occurred, factors associated with the duration of hospitalization were analyzed.
One hundred eight lesions in 108 patients were eligible for inclusion in the study (68 patients were male; mean patient age was 63.01 ± 10.71 years). Mean tumor size was 27.59 ± 10.10 mm (range: 8 - 53 mm). Laterally spreading tumor was the most common type (75 %), followed by the protruding type (25 %). Procedure time was 61.95 ± 41.90 minutes (range: 5 - 198 minutes). Complete en bloc resection was achieved for 85 lesions (78.7 %). Perforation occurred in 22 patients (20.4 %). Multivariate analysis confirmed that tumor size odds ratio (OR): 1.084; 95 % confidence interval (CI): 1.015 - 1.158; P = 0.017 and the presence of fibrosis (OR: 4.551; 95 %CI: 1.092 - 18.960; P = 0.037) were independent risk factors for perforation. All cases of perforation were managed with nonsurgical treatment. Younger age and abdominal pain appeared to be related to prolonged hospitalization.
Tumor size and fibrosis are important factors related to complications during colorectal ESD. Younger age and development of abdominal pain can predict the hospital course in patients with perforation after ESD.
The recent manufacturing trend toward mass customization and further personalization of products requires factories to be smarter than ever before in order to: (1) quickly respond to customer ...requirements, (2) resiliently retool machinery and adjust operational parameters for unforeseen system failures and product quality problems, and (3) retrofit old systems with upcoming new technologies. Furthermore, product lifecycles are becoming shorter due to unbounded and unpredictable customer requirements, thereby requiring reconfigurable and versatile manufacturing systems that underpin the basic building blocks of smart factories. This study introduces a modular factory testbed, emphasizing transformability and modularity under a distributed shop-floor control architecture. The main technologies and methods, being developed and verified through the testbed, are presented from the four aspects of rapid factory transformation: self-layout recognition, rapid workstation and robot reprogramming, inter-layer information sharing, and configurable software for shop-floor monitoring.
Aims
Atopic dermatitis (AD) is an inflammatory skin disease. Probiotics have been reported to modulate immune responses and thus are now being suggested as potential treatments for allergies. In this ...study, we investigated the inhibitory effects of Lactobacillus sakei probio 65 isolated from Kimchi on artificially inducing AD in NC/Nga mice.
Methods and Results
Oral administration of viable or heat‐inactivated Lact. sakei probio 65 improved the condition of skin and reduced scratching frequency. Serum levels of IgE and cutaneous T‐cell‐attracting chemokine (CTACK) were significantly decreased by this therapy. Dead Lact. sakei probio 65 also decreased IL‐4 and IL‐6 serum concentrations. Moreover, both live and dead Lact. sakei probio 65 inhibited the expression of Thymus and activation‐regulated chemokine and CTACK in AD‐like skin lesions. The increased levels of Foxp3 expression in the lesional skin and ears were also suppressed by Lact. sakei probio 65. In addition, Lact. sakei probio 65 inhibited β‐hexosaminidase release and the secretion of IL‐4, TNF‐α and IL‐6 from RBL‐2H3 cells.
Conclusions
Oral treatment with both viable and heat‐inactivated Lact. sakei probio 65 inhibits skin inflammation and AD‐like skin lesions, as well as mast cell activation.
Significance and Impact of the Study
Lactobacillus sakei probio 65 has an inhibitory effect on atopic dermatitis‐like skin lesions and may represent an effective new anti‐inflammatory agent.
In the past 4 years, incidences of endemic or epidemic respiratory diseases associated with canine influenza H3N2 virus in Asian dogs have been reported in countries such as South Korea and China. ...Canine species were considered to be the new natural hosts for this virus. However, at the beginning of 2010, influenza-like respiratory signs, such as dyspnoea, were also observed among cats as well as in dogs in an animal shelter located in Seoul, South Korea. The affected cats showed 100 % morbidity and 40 % mortality. We were able to isolate a virus from a lung specimen of a dead cat, which had suffered from the respiratory disease, in embryonated-chicken eggs. The eight viral genes isolated were almost identical to those of the canine influenza H3N2 virus, suggesting interspecies transmission of canine influenza H3N2 virus to the cat. Moreover, three domestic cats infected with intranasal canine/Korea/GCVP01/07 (H3N2) all showed elevated rectal temperatures, nasal virus shedding and severe pulmonary lesions, such as suppurative bronchopneumonia. Our study shows, for the first time, that cats are susceptible to canine influenza H3N2 infection, suggesting that cats may play an intermediate host role in transmitting the H3N2 virus among feline and canine species, which could lead to the endemic establishment of the virus in companion animals. Such a scenario raises a public health concern, as the possibility of the emergence of new recombinant feline or canine influenza viruses in companion animals with the potential to act as a zoonotic infection cannot be excluded.
We present the first demonstration of THz driven bunch compression and timing stabilization of a relativistic electron beam. Quasi-single-cycle strong field THz radiation is used in a shorted ...parallel-plate structure to compress a few-fC beam with 2.5 MeV kinetic energy by a factor of 2.7, producing a 39 fs rms bunch length and a reduction in timing jitter by more than a factor of 2 to 31 fs rms. This THz driven technique offers a significant improvement to beam performance for applications like ultrafast electron diffraction, providing a critical step towards unprecedented timing resolution in ultrafast sciences, and other accelerator applications using femtosecond-scale electron beams.
Summary
Bone disorder is a common complication of chronic kidney disease (CKD). The clinical usefulness of bone mineral density (BMD) in CKD is not well known. Our study shows that low BMD is ...associated with physical activity and dietary Na/K intake ratio and can predict poor renal outcome in non-dialysis CKD.
Purpose
Despite evidence of a link between bone mineral disorders and chronic kidney disease (CKD), the clinical implications of bone mineral density (BMD) in CKD are not well established. We investigated risk factors and renal outcomes of low BMD in CKD.
Methods
We analyzed data from the KNOW-CKD. BMD measured by dual-energy x-ray absorptiometry was classified by
T
score: normal (
T
score ≥ − 1.0), osteopenia (− 1.0 >
T
score > − 2.5), and osteoporosis (
T
score ≤ − 2.5) of the lumbar spine, hip, or femoral neck. Logistic regression analysis to assess risk factors of low BMD (
T
score < − 1.0) and Cox proportional hazards models to estimate risk of incident end-stage renal disease (ESRD).
Results
Low BMD was prevalent (osteopenia 33%; osteoporosis 8%) in 2128 adults with CKD (age 54 ± 12 years; male 61%). Over a median follow-up of 4.3 years, there were 521 cases of incident ESRD. Lower BMD was associated with female sex, older age, low eGFR, low BMI, and lifestyle factors of physical activity (odds ratio (OR) = 0.62, 95% confidence interval (0.49–0.77)) and spot urine Na/K ratio (1.07 (1.00–1.15)). In adjusted Cox models, low BMD was associated with increased incident ESRD (hazard ratio (HR) = 1.14 (0.92–1.41) for osteopenia; 1.43 (1.01–2.04) for osteoporosis,
P
for trend < 0.05) compared with the reference of normal BMD. The association between low BMD and ESRD was similar according to
T
score discordance classification.
Conclusions
Low BMD was associated with modifiable lifestyle factors including low physical activity and high dietary Na/K intake ratio. The presence of low BMD is associated with poor renal outcomes in non-dialysis CKD.
Background and purpose
The rate at which the chance of a good outcome of endovascular stroke therapy (EVT) decays with time when eligible patients are selected by baseline diffusion‐weighted magnetic ...resonance imaging (DWI‐MRI) and whether ischaemic core size affects this rate remain to be investigated.
Methods
This study analyses a prospective multicentre registry of stroke patients treated with EVT based on pretreatment DWI‐MRI that was categorized into three groups: small Diffusion‐Weighted Imaging Alberta Stroke Program Early Computed Tomography Score (DWI‐ASPECTS) (8–10), moderate (5–7) and large (<5) cores. The main outcome was a good outcome at 90 days (modified Rankin Scale 0–2). The interaction between onset‐to‐groin puncture time (OTP) and DWI‐ASPECTS categories regarding functional outcomes was investigated.
Results
Ultimately, 985 patients (age 69 ± 11 years; male 55%) were analysed. Potential interaction effects between the DWI‐ASPECTS categories and OTP on a good outcome at 90 days were observed (Pinteraction = 0.06). Every 60‐min delay in OTP was associated with a 16% reduced likelihood of a good outcome at 90 days amongst patients with large cores, although no associations were observed amongst patients with small to moderate cores. Interestingly, the adjusted rates of a good outcome at 90 days steeply declined between 65 and 213 min of OTP and then remained smooth throughout 24 h of OTP (Pnonlinearity = 0.15).
Conclusions
Our study showed that the probability of a good outcome after EVT nonlinearly decreased, with a steeper decline at earlier OTP than at later OTP. Discrepant effects of OTP on functional outcomes by baseline DWI‐ASPECTS categories were observed. Thus, different strategies for EVT based on time and ischaemic core size are warranted.
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