Human Adipose-Derived Stem Cells Suppress Elastase-Induced Murine Abdominal Aortic Inflammation and Aneurysm Expansion Through Paracrine Factors

Abdominal aortic aneurysm (AAA) is a potentially lethal disease associated with immune activation-induced aortic degradation. We hypothesized that xenotransplantation of human adipose-derived stem cells (hADSCs) would reduce aortic inflammation and attenuate expansion in a murine AAA model. Modulatory effects of ADSCs on immune cell subtypes associated with AAA progression were investigated using human peripheral blood mononuclear cells (hPBMNCs) cocultured with ADSCs. Murine AAA was induced through elastase application to the abdominal aorta in C57BL/6 mice. ADSCs were administered intravenously, and aortic changes were determined by ultrasonography and videomicrometry. Circulating monocytes, aortic neutrophils, CD28− T cells, FoxP3+ regulatory T cells (Tregs), and CD206+ M2 macrophages were assessed at multiple terminal time points. In vitro, ADSCs induced M2 macrophage and Treg phenotypes while inhibiting neutrophil transmigration and lymphocyte activation without cellular contact. Intravenous ADSC delivery reduced aneurysmal expansion starting from day 4 [from baseline: 54.8% (saline) vs. 16.9% (ADSCs), n = 10 at baseline, n = 4 at day 4, p < 0.001], and the therapeutic effect persists through day 14 (from baseline: 64.1% saline vs. 24.6% ADSCs, n = 4, p < 0.01). ADSC administration increased aortic Tregs by 20-fold (n = 5, p < 0.01), while decreasing CD4+CD28− (-28%), CD8+CD28− T cells (-61%), and Ly6G/C+ neutrophils (-43%, n = 5, p < 0.05). Circulating CD115+CXCR1−LY6C+-activated monocytes decreased in the ADSC-treated group by day 7 (-60%, n = 10, p < 0.05), paralleled by an increase in aortic CD206+ M2 macrophages by 2.4-fold (n = 5, p < 0.05). Intravenously injected ADSCs transiently engrafted in the lung on day 1 without aortic engraftment at any time point. In conclusion, ADSCs exhibit pleiotropic immunomodulatory effects in vitro as well as in vivo during the development of AAA. The temporal evolution of these effects systemically as well as in aortic tissue suggests that ADSCs induce a sequence of anti-inflammatory cellular events mediated by paracrine factors, which leads to amelioration of AAA progression

Maximising data to optimise animal disease early warning systems and risk assessment tools within Europe

Timely and reliable data and information availability and sharing is essential for early warning, prevention and control of transboundary diseases. While there are a growing number of global datasets capable of providing information for use in early warning systems and risk assessment (RA) tools, there are currently time-consuming data cleansing and harmonisation activities which need to be carried out before they can be reliably used and combined. Thus, using global datasets as they stand can lead to errors in RA parameterisation and results due to inherent biases in the data, e.g. missing disease prevalence data treated as a zero may inadvertently penalise those countries which do report disease outbreaks as opposed to those countries which are affected by a pathogen but do not report outbreak data. It is therefore of great importance that data are clearly provided and easy to understand and that data providers strive for greater harmonisation of database standards. In this paper the datasets utilised in the SPARE (’Spatial risk assessment framework for assessing exotic disease incursion and spread through Europe’) project are described and discussed in terms of key criteria: accessibility, availability, completeness, consistency and quality. It is evident that most databases exist as information portals and not exclusively for RA purposes. Another striking issue from this assessment is the need for enhanced data sharing specifically with regards to data on illegal seizures, arthropod vector/wildlife abundance, intra-country livestock movement and national animal disease surveillance. It is hoped that the outcomes of this work will promote discussion and exchange between data providers, including the development of standardised data exchange protocols. The transformation of datasets to a common format is a considerable challenge but recommendations could and should be made on the standardisation of datasets and reporting in order to achieve a unified approach across Europe

Video and Synthetic MRI Pre-training of 3D Vision Architectures for Neuroimage Analysis

Transfer learning represents a recent paradigm shift in the way we build artificial intelligence (AI) systems. In contrast to training task-specific models, transfer learning involves pre-training deep learning models on a large corpus of data and minimally fine-tuning them for adaptation to specific tasks. Even so, for 3D medical imaging tasks, we do not know if it is best to pre-train models on natural images, medical images, or even synthetically generated MRI scans or video data. To evaluate these alternatives, here we benchmarked vision transformers (ViTs) and convolutional neural networks (CNNs), initialized with varied upstream pre-training approaches. These methods were then adapted to three unique downstream neuroimaging tasks with a range of difficulty: Alzheimer's disease (AD) and Parkinson's disease (PD) classification, "brain age" prediction. Experimental tests led to the following key observations: 1. Pre-training improved performance across all tasks including a boost of 7.4% for AD classification and 4.6% for PD classification for the ViT and 19.1% for PD classification and reduction in brain age prediction error by 1.26 years for CNNs, 2. Pre-training on large-scale video or synthetic MRI data boosted performance of ViTs, 3. CNNs were robust in limited-data settings, and in-domain pretraining enhanced their performances, 4. Pre-training improved generalization to out-of-distribution datasets and sites. Overall, we benchmarked different vision architectures, revealing the value of pre-training them with emerging datasets for model initialization. The resulting pre-trained models can be adapted to a range of downstream neuroimaging tasks, even when training data for the target task is limited

Cardiac magnetic resonance T1 and extracellular volume mapping with motion correction and co-registration based on fast elastic image registration

10.1007/s10334-017-0668-2Magnetic Resonance Materials in Physics, Biology and Medicine311115-12

Deletions in VANGL1 are a risk factor for antibody-mediated kidney disease

We identify an intronic deletion in VANGL1 that predisposes to renal injury in high risk populations through a kidney-intrinsic process. Half of all SLE patients develop nephritis, yet the predisposing mechanisms to kidney damage remain poorly understood. There is limited evidence of genetic contribution to specific organ involvement in SLE.(1,2) We identify a large deletion in intron 7 of Van Gogh Like 1 (VANGL1), which associates with nephritis in SLE patients. The same deletion occurs at increased frequency in an indigenous population (Tiwi Islanders) with 10-fold higher rates of kidney disease compared with non-indigenous populations. Vangl1 hemizygosity in mice results in spontaneous IgA and IgG deposition within the glomerular mesangium in the absence of autoimmune nephritis. Serum transfer into B cell-deficient Vangl1(+/-) mice results in mesangial IgG deposition indicating that Ig deposits occur in a kidney-intrinsic fashion in the absence of Vangl1. These results suggest that Vangl1 acts in the kidney to prevent Ig deposits and its deficiency may trigger nephritis in individuals with SLE

Autonomous indoor wayfinding for individuals with cognitive impairments

<p>Abstract</p> <p>Background</p> <p>A challenge to individuals with cognitive impairments in wayfinding is how to remain oriented, recall routines, and travel in unfamiliar areas in a way relying on limited cognitive capacity. While people without disabilities often use maps or written directions as navigation tools or for remaining oriented, this cognitively-impaired population is very sensitive to issues of abstraction (e.g. icons on maps or signage) and presents the designer with a challenge to tailor navigation information specific to each user and context.</p> <p>Methods</p> <p>This paper describes an approach to providing distributed cognition support of travel guidance for persons with cognitive disabilities. A solution is proposed based on passive near-field RFID tags and scanning PDAs. A prototype is built and tested in field experiments with real subjects. The unique strength of the system is the ability to provide unique-to-the-user prompts that are triggered by context. The key to the approach is to spread the context awareness across the system, with the context being flagged by the RFID tags and the appropriate response being evoked by displaying the appropriate path guidance images indexed by the intersection of specific end-user and context ID embedded in RFID tags.</p> <p>Results</p> <p>We found that passive RFIDs generally served as good context for triggering navigation prompts, although individual differences in effectiveness varied. The results of controlled experiments provided more evidence with regard to applicabilities of the proposed autonomous indoor wayfinding method.</p> <p>Conclusions</p> <p>Our findings suggest that the ability to adapt indoor wayfinding devices for appropriate timing of directions and standing orientation will be particularly important.</p

Two-year Clinical Outcomes of Patients with Long Segments Drug-Eluting Stents: Comparison of Sirolimus-Eluting Stent with Paclitaxel-Eluting Stent

Limited data are available on the long-term clinical efficacy of drug-eluting stent (DES) in diffuse long lesions. From May 2006 to May 2007, a total of 335 consecutive patients (374 lesions) were underwent percutaneous coronary intervention with implantation of long DES (≥ 30 mm) in real world practice. Eight-month angiographic outcomes and 2-yr clinical outcomes were compared between SES (n = 218) and PES (n = 117). Study endpoints were major adverse cardiac events including cardiac death, myocardial infarction, target-lesion revascularization, target-vessel revascularization and stent thrombosis. Baseline characteristics were similar in the two groups as were mean stent length (44.9 ± 15.2 mm in SES and 47.4 ± 15.9 in PES, P = 0.121). Late loss at 8 months follow-up was significantly lower in SES than in PES group (0.4 ± 0.6 mm in SES vs 0.7 ± 0.8 mm in PES, P = 0.007). Mean follow-up duration was 849 ± 256 days, and 2-yr cumulative major adverse cardiac events were significantly lower in the SES than in the PES group (5.5% in SES vs 15.4% in PES, P = 0.003). In conclusion, long-term DES use in diffuse long coronary lesions is associated with favorable results, with SES being more effective and safer than PES in this real-world clinical experience

A global view of the OCA2-HERC2 region and pigmentation

Mutations in the gene OCA2 are responsible for oculocutaneous albinism type 2, but polymorphisms in and around OCA2 have also been associated with normal pigment variation. In Europeans, three haplotypes in the region have been shown to be associated with eye pigmentation and a missense SNP (rs1800407) has been associated with green/hazel eyes (Branicki et al. in Ann Hum Genet 73:160–170, 2009). In addition, a missense mutation (rs1800414) is a candidate for light skin pigmentation in East Asia (Yuasa et al. in Biochem Genet 45:535–542, 2007; Anno et al. in Int J Biol Sci 4, 2008). We have genotyped 3,432 individuals from 72 populations for 21 SNPs in the OCA2-HERC2 region including those previously associated with eye or skin pigmentation. We report that the blue-eye associated alleles at all three haplotypes were found at high frequencies in Europe; however, one is restricted to Europe and surrounding regions, while the other two are found at moderate to high frequencies throughout the world. We also observed that the derived allele of rs1800414 is essentially limited to East Asia where it is found at high frequencies. Long-range haplotype tests provide evidence of selection for the blue-eye allele at the three haplotyped systems but not for the green/hazel eye SNP allele. We also saw evidence of selection at the derived allele of rs1800414 in East Asia. Our data suggest that the haplotype restricted to Europe is the strongest marker for blue eyes globally and add further inferential evidence that the derived allele of rs1800414 is an East Asian skin pigmentation allele

Economic and Environmental Impacts of Harmful Non-Indigenous Species in Southeast Asia

10.1371/journal.pone.0071255PLoS ONE88-POLN