Two Approaches to the Study of a Controversial Relationship: Cutaneous Photosensitivity and Anti-Ro/SS-A Autoantibodies

Background: Autoantibodies (Aabs) are the hallmark of numerous systemic autoimmune pathologies (SAPs), for instance anti-Ro/SS-A Aabs are usually found in Systemic Lupus Erythematosus (SLE) and Sjogren’s Syndrome. Cutaneous photosensitivity (CP) is found in most forms and subsets of LE and consists of a skin rash as a result of unusual reaction to sunlight. There are many theories which relate specifically the presence of circulating anti-Ro/SS-A Aabs with the CP phenomenon, though there are several studies which are in disagreement. Results: In this study we analyzed the relationship between CP and anti-Ro Aabs by means of two approaches. The first one included an in vitro model where we evaluated by flow cytometry the binding capacity of affinity-purified Aabs to autoantigens relocalized on apoptotic keratinocyte’s surface. We found that there was no relationship between the binding capacity of serum from 10 selected patients or their corresponding purified anti-Ro52 and anti-Ro60 Aabs, and the presence or absence of CP, neither with the SAPs. The in vivo model consisted of Hairless SKH:1 mice which were induced to produce anti-murine Ro52 and/or Ro60 Aabs and were subsequently irradiated with UVB light. We evaluated the skin histology and also the epidermal production of TNF-α. We found no differences between the groups in neither of the parameters evaluated. Conclusions: These results agree with some studies on the role of the Aabs in CP, considering anti-Ro Aabs not as the only responsible for the manifestation; and disagree with many other authors, who believe in the strong association between these two events.Fil: Paz, Mariela Laura. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Cela, Eliana Maiten. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Ferrari, Alejandro. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Friedrich, Adrian D.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Leoni, Juliana. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Gonzalez Maglio, Daniel Horacio. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin

Analysis of bi-atrial function using CMR feature tracking and long-axis shortening approaches in patients with diastolic dysfunction and atrial fibrillation.

OBJECTIVES Atrial function can be assessed using advancing cardiovascular magnetic resonance (CMR) post-processing methods: atrial feature tracking (FT) strain analysis or a long-axis shortening (LAS) technique. This study aimed to first compare the two FT and LAS techniques in healthy individuals and cardiovascular patients and then investigated how left (LA) and right atrial (RA) measurements are related to the severity of diastolic dysfunction or atrial fibrillation. METHODS Sixty healthy controls and 90 cardiovascular disease patients with coronary artery disease, heart failure, or atrial fibrillation, underwent CMR. LA and RA were analyzed for standard volumetry as well as for myocardial deformation using FT and LAS for the different functional phases (reservoir, conduit, booster). Additionally, ventricular shortening and valve excursion measurements were assessed with the LAS module. RESULTS The measurements for each of the LA and RA phases were correlated (p < 0.05) between the two approaches, with the highest correlation coefficients occurring in the reservoir phase (LA: r = 0.83, p < 0.01, RA: r = 0.66, p < 0.01). Both methods demonstrated reduced LA (FT: 26 ± 13% vs 48 ± 12%, LAS: 25 ± 11% vs 42 ± 8%, p < 0.01) and RA reservoir function (FT: 28 ± 15% vs 42 ± 15%, LAS: 27 ± 12% vs 42 ± 10%, p < 0.01) in patients compared to controls. Atrial LAS and FT decreased with diastolic dysfunction and atrial fibrillation. This mirrored ventricular dysfunction measurements. CONCLUSION Similar results were generated for bi-atrial function measurements between two CMR post-processing approaches of FT and LAS. Moreover, these methods allowed for the assessment of incremental deterioration of LA and RA function with increasing left ventricular diastolic dysfunction and atrial fibrillation. A CMR-based analysis of bi-atrial strain or shortening discriminates patients with early-stage diastolic dysfunction prior to the presence of compromised atrial and ventricular ejection fractions that occur with late-stage diastolic dysfunction and atrial fibrillation. KEY POINTS • Assessing right and left atrial function with CMR feature tracking or long-axis shortening techniques yields similar measurements and could potentially be used interchangeably based on the software capabilities of individual sites. • Atrial deformation and/or long-axis shortening allow for early detection of subtle atrial myopathy in diastolic dysfunction, even when atrial enlargement is not yet apparent. • Using a CMR-based analysis to understand the individual atrial-ventricular interaction in addition to tissue characteristics allows for a comprehensive interrogation of all four heart chambers. In patients, this could add clinically meaningful information and potentially allow for optimal therapies to be chosen to better target the dysfunction

Diabetic foot ulcers segmentation challenge report: benchmark and analysis

Monitoring the healing progress of diabetic foot ulcers is a challenging process. Accurate segmentation of foot ulcers can help podiatrists to quantitatively measure the size of wound regions to assist prediction of healing status. The main challenge in this field is the lack of publicly available manual delineation, which can be time consuming and laborious. Recently, methods based on deep learning have shown excellent results in automatic segmentation of medical images, however, they require large-scale datasets for training, and there is limited consensus on which methods perform the best. The 2022 Diabetic Foot Ulcers segmentation challenge was held in conjunction with the 2022 International Conference on Medical Image Computing and Computer Assisted Intervention, which sought to address these issues and stimulate progress in this research domain. A training set of 2000 images exhibiting diabetic foot ulcers was released with corresponding segmentation ground truth masks. Of the 72 (approved) requests from 47 countries, 26 teams used this data to develop fully automated systems to predict the true segmentation masks on a test set of 2000 images, with the corresponding ground truth segmentation masks kept private. Predictions from participating teams were scored and ranked according to their average Dice similarity coefficient of the ground truth masks and prediction masks. The winning team achieved a Dice of 0.7287 for diabetic foot ulcer segmentation. This challenge has now entered a live leaderboard stage where it serves as a challenging benchmark for diabetic foot ulcer segmentation

How 'dynasty' became a modern global concept : intellectual histories of sovereignty and property

The modern concept of ‘dynasty’ is a politically-motivated modern intellectual invention. For many advocates of a strong sovereign nation-state across the nineteenth and early twentieth century, in France, Germany, and Japan, the concept helped in visualizing the nation-state as a primordial entity sealed by the continuity of birth and blood, indeed by the perpetuity of sovereignty. Hegel’s references to ‘dynasty’, read with Marx’s critique, further show how ‘dynasty’ encoded the intersection of sovereignty and big property, indeed the coming into self-consciousness of their mutual identification-in-difference in the age of capitalism. Imaginaries about ‘dynasty’ also connected national sovereignty with patriarchal authority. European colonialism helped globalize the concept in the non-European world; British India offers an exemplar of ensuing debates. The globalization of the abstraction of ‘dynasty’ was ultimately bound to the globalization of capitalist-colonial infrastructures of production, circulation, violence, and exploitation. Simultaneously, colonized actors, like Indian peasant/‘tribal’ populations, brought to play alternate precolonial Indian-origin concepts of collective regality, expressed through terms like ‘rajavamshi’ and ‘Kshatriya’. These concepts nourished new forms of democracy in modern India. Global intellectual histories can thus expand political thought today by provincializing and deconstructing Eurocentric political vocabularies and by recuperating subaltern models of collective and polyarchic power.PostprintPeer reviewe

Factors Associated with Bovine Neonatal Pancytopenia (BNP) in Calves: A Case-Control Study

Bovine neonatal pancytopenia (BNP; previously known as idiopathic haemorrhagic diathesis and commonly known as bleeding calf syndrome) is a novel haemorrhagic disease of young calves which has emerged in a number of European countries during recent years. Data were retrospectively collected during June to November 2010 for 56 case calves diagnosed with BNP between 17 March and 7 June of the same year. These were compared with 58 control calves randomly recruited from herds with no history of BNP. Multivariable logistic regression analysis showed that increased odds of a calf being a BNP case were associated with its dam having received PregSure® BVD (Pfizer Animal Health) vaccination prior to the birth of the calf (odds ratio (OR) 40.78, p<0.001) and its herd of origin being located in Scotland (OR 9.71, p = 0.006). Decreased odds of a calf being a BNP case were associated with the calf having been kept outside (OR 0.11, p = 0.006). The longer that a cattle herd had been established on the farm was also associated with decreased odds of a calf in that herd being a BNP case (OR 0.97, p = 0.011)

Liberalization, globalization and the dynamics of democracy in India

In the closing decades of the twentieth century there has been an almost complete intellectual triumph of the twin principles of marketization (understood here as referring to the liberalization of domestic markets and freer international mobility of goods, services, financial capital and perhaps, more arguably, labour) and democratization . A paradigm shift of this extent and magnitude would not have occurred in the absence of some broad consensus among policymakers and (sections of) intellectuals around the globe on the desirability of such a change. There seems to be a two-fold causal nexus between marketization and democracy. The first is more direct, stemming from the fact of both systems sharing certain values and attitudes in common. But there is also a second more indirect chain from marketization to democracy, which is predicated via three sub-chains (i) from marketization to growth, (ii) from growth to overall material development welfare and (iii) from material development to social welfare and democracy. We examine each of these sub-links in detail with a view to obtaining a greater understanding of the hypothesized role of free markets in promoting democracies. In the later part of the paper we examine the socio-economic outcomes governing the quality of democracy in a specifically Indian context

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

A Stochastic Description of Dictyostelium Chemotaxis

Chemotaxis, the directed motion of a cell toward a chemical source, plays a key role in many essential biological processes. Here, we derive a statistical model that quantitatively describes the chemotactic motion of eukaryotic cells in a chemical gradient. Our model is based on observations of the chemotactic motion of the social ameba Dictyostelium discoideum, a model organism for eukaryotic chemotaxis. A large number of cell trajectories in stationary, linear chemoattractant gradients is measured, using microfluidic tools in combination with automated cell tracking. We describe the directional motion as the interplay between deterministic and stochastic contributions based on a Langevin equation. The functional form of this equation is directly extracted from experimental data by angle-resolved conditional averages. It contains quadratic deterministic damping and multiplicative noise. In the presence of an external gradient, the deterministic part shows a clear angular dependence that takes the form of a force pointing in gradient direction. With increasing gradient steepness, this force passes through a maximum that coincides with maxima in both speed and directionality of the cells. The stochastic part, on the other hand, does not depend on the orientation of the directional cue and remains independent of the gradient magnitude. Numerical simulations of our probabilistic model yield quantitative agreement with the experimental distribution functions. Thus our model captures well the dynamics of chemotactic cells and can serve to quantify differences and similarities of different chemotactic eukaryotes. Finally, on the basis of our model, we can characterize the heterogeneity within a population of chemotactic cells

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN