Distributed Utility Estimation with Heterogeneous Relative Information

In this letter, we consider a scenario where a set of agents, interconnected by a network topology, aim at computing an estimate of their own utility, importance or value, based on pairwise relative information having heterogeneous nature. In more detail, the agents are able to measure the difference between their value and the value of some their neighbors, or have an estimate of the ratio between their value and the value the remaining neighbors. This setting may find application in problems involving information provided by heterogeneous sensors (e.g., differences and ratios), as well as in scenarios where estimations provided by humans have to be merged with sensor measurements. Specifically, we develop a distributed algorithm that lets each agent asymptotically compute a utility value. To this end, we first characterize the task at hand in terms of a least-squares minimum problem, providing a necessary and sufficient condition for the existence of a unique global minimum, and then we show that the proposed algorithm asymptotically converges to a global minimum. This letter is concluded by numerical analyses that corroborate the theoretical findings

Epigallocatechin-3-gallate inhibits doxorubicin-induced inflammation on human ovarian tissue

Chemotherapy protocol can destroy the reproductive potential of young cancer patients. Doxorubicin (DOX) is a potent anthracycline commonly used in the treatment of numerous malignancies. The purpose of the study was to evaluate the ovarian toxicity of DOX via inflammation and the possible protective effect of the green tea polyphenol epigallocatechin-3-gallate (EGCG). Ovarian tissue of three patients was cultured with 1 \ub5g/ml DOX and/or 10 \ub5g/ml EGCG for 24 and 48 h. Levels of inflammatory factors were determined by quantitative Real-Time PCR, western blot, zimography, and multiplex bead-based immunoassay. Morphological evaluation, damaged follicle count and TUNEL assay were also performed. DOX influenced inflammatory responses by inducing a significant increase in the expression of pro-inflammatory cytokines, such as tumor necrosis factor-\u3b1 (TNF-\u3b1) and cyclooxigenase-2 (COX-2), of inflammatory interleukins (IL), such as interleukin-6 (IL-6) and interleukin-8 (IL-8), and the inflammatory proteins mediators metalloproteinase-2 and metalloproteinase-9 (MMP2 and MMP9). IL-8 secretion in the culture supernatants and MMP9 activity also significantly raised after DOX treatment. Moreover, a histological evaluation of the ovarian tissue showed morphological damage to follicles and stroma after DOX exposure. EGCG significantly reduced DOX-induced inflammatory responses and improved the preservation of follicles. DOX-induced inflammation could be responsible for the ovarian function impairment of chemotherapy. EGCG could have a protective role in reducing DOX-mediated inflammatory responses in human ovarian tissue

Self-assembly of glycoprotein nanostructured filaments for modulating extracellular networks at long range

The intriguing capability of branched glycoprotein filaments to change their hierarchical organization, mediated by external biophysical stimuli, continues to expand understanding of self-assembling strategies that can dynamically rearrange networks at long range. Previous research has explored the corresponding biological, physiological and genetic mechanisms, focusing on protein assemblies within a limited range of nanometric units. Using direct microscopy bio-imaging, we have determined the morpho-structural changes of self-assembled filament networks of the zona pellucida, revealing controlled levels of structured organizations to join distinct evolved stages of the oocyte (Immature, Mature, and Fertilized). This natural soft network reorganizes its corresponding hierarchical network to generate symmetric, asymmetric, and ultimately a state with the lowest asymmetry of the outer surface roughness, and internal pores reversibly changed from elliptical to circular configurations at the corresponding stages. These elusive morpho-structural changes are regulated by the nanostructured polymorphisms of the branched filaments by self-extension/-contraction/-bending processes, modulated by determinate theoretical angles among repetitive filament units. Controlling the nanoscale self-assembling properties by delivering a minimum number of activation bio-signals may be triggered by these specific nanostructured polymorphic organizations. Finally, this research aims to guide this soft biomaterial into a desired state to protect oocytes, eggs, and embryos during development, to favour/prevent the fertilization/polyspermy processes and eventually to impact interactions with bacteria/virus at multiscale levels.The intriguing capability of branched glycoprotein filaments to change their hierarchical organization, mediated by external biophysical stimuli, continues to expand understanding of self-assembling strategies that can dynamically rearrange networks at long range

Factors leading to dissemination of cutaneous anthrax: an international ID-IRI study

Background: Although anthrax is a rare zoonotic infection, it still causes significant mortality and morbidity. In this multicenter study, which is the largest anthrax case series ever reported, we aimed to describe the factors leading to dissemination of cutaneous anthrax. Methods: Adult patients with cutaneous anthrax from 16 referral centers were pooled. The study had a retrospective design, and included patients treated between January 1, 1990 and December 1, 2019. Probable, and confirmed cases based upon CDC anthrax 2018 case definition were included in the study. A descriptive statistical analysis was performed for all variables. Results: A total of 141 cutaneous anthrax patients were included. Of these, 105 (74%) patients had probable and 36 (26%) had confirmed diagnosis. Anthrax meningitis and bacteremia occurred in three and six patients, respectively. Sequelae were observed in three patients: cicatricial ectropion followed by ocular anthrax (n = 2) and movement restriction on the left hand after surgical intervention (n = 1). One patient had gastrointestinal anthrax. The parameters related to poor outcome (p < 0.05) were fever, anorexia, hypoxia, malaise/fatigue, cellulitis, fasciitis, lymphadenopathy, leukocytosis, high CRP and creatinine levels, longer duration of antimicrobial therapy, and combined therapy. The last two were seemingly the consequences of dissemination rather than being the reasons. The fatality rate was 1.4%. Conclusions: Rapid identification of anthrax is crucial for prompt and effective treatment. Systemic symptoms, disseminated local infection, and high inflammatory markers should alert the treating physicians for the dissemination of the disease. © 2022 The Author

Denominator identities for finite-dimensional Lie superalgebras and Howe duality for compact dual pairs

We provide formulas for the denominator and superdenominator of a basic classical type Lie superalgebra for any set of positive roots. We establish a connection between certain sets of positive roots and the theory of reductive dual pairs of real Lie groups. As an application of our formulas, we recover the Theta correspondence for compact dual pairs. Along the way we give an explicit description of the real forms of basic classical type Lie superalgebras.Comment: Latex, 75 pages. Minor corrections. Final version, to appear in the Japanese Journal of Mathematic

synchronous angiosarcoma melanoma and morphea of the breast skin 14 years after radiotherapy for mammary carcinoma

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Spirometry: A practical lifespan predictor of global health and chronic respiratory and non-respiratory diseases

Objectives. 1. To review and discuss available evidence supporting that spirometry is an overlooked global health marker, that could be used regularly through the lifespan to monitor human health and predict risk of chronic respiratory and other chronic non-communicable diseases (NCDs). 2. To discuss the challenges and opportunities that this proposal faces.Summary of key data. First, spirometry is essential to assess and monitor respiratory health. Second, spirometry adds prognostic value to other well-accepted health markers used in clinical practice, such as blood pressure, body mass index, glucose and blood lipids, by identifying individuals at risk, not only of respiratory diseases, but also of other NCDs, particularly cardiovascular and metabolic disorders. Conclusion. Although we acknowledge that research gaps still exist, we propose that spirometry assessed during childhood, adolescence and early and late adulthood can be a reproducible, non-invasive, safe and affordable global health marker to identify individuals in the general population at risk of respiratory and non-respiratory NCDs. In this context, spirometry may act as the caged canaries that miners used to carry into mines to alert them of dangerous accumulations of gases, thus providing an early warning and save lives

Efficient Delivery of MicroRNA and AntimiRNA Molecules Using an Argininocalix[4]arene Macrocycle

MicroRNAs (miRNAs) are short non-coding RNA molecules acting as gene regulators by repressing translation or by inducing degradation of the target RNA transcripts. Altered expression of miRNAs may be involved in the pathogenesis of many severe human diseases, opening new avenues in the field of therapeutic strategies, i.e., miRNA targeting or miRNA mimicking. In this context, the efficient and non-toxic delivery of premiRNA and antimiRNA molecules might be of great interest. The aim of the present paper is to determine whether an argininocalix[4]arene is able to efficiently deliver miRNA, premiRNA, and antimiRNA molecules to target cells, preserving their biological activity. This study points out that (1) the toxicity of argininocalix[4]arene 1 is low, and it can be proposed for long-term treatment of target cells, being that this feature is a pre-requisite for the development of therapeutic protocols; (2) the delivery of premiRNA and antimiRNA molecules is efficient, being higher when compared with reference gold standards available; and (3) the biological activity of the premiRNAs and antimiRNAs is maintained. This was demonstrated using the argininocalix[4]arene 1 in miRNA therapeutic approaches performed on three well-described experimental model systems: (1) the induction of apoptosis by antimiR-221 in glioma U251 cells; (2) the induction of apoptosis by premiR-124 in U251 cells; and (3) the inhibition of pro-inflammatory IL-8 and IL-6 genes in cystic fibrosis IB3-1 cells. Our results demonstrate that the argininocalix[4]arene 1 should be considered a very useful delivery system for efficient transfer to target cells of both premiRNA and antimiRNA molecules, preserving their biological activity

Multiplexed detection of pancreatic cancer by combining a nanoparticle-enabled blood test and plasma levels of Acute-Phase Proteins

The development of new tools for the early detection of pancreatic ductal adenocarcinoma (PDAC) represents an area of intense research. Recently, the concept has emerged that multiplexed detection of different signatures from a single biospecimen (e.g., saliva, blood, etc.) may exhibit better diagnostic capability than single biomarkers. In this work, we develop a multiplexed strategy for detecting PDAC by combining characterization of the nanoparticle (NP)-protein corona, i.e., the protein layer that surrounds NPs upon exposure to biological fluids and circulating levels of plasma proteins belonging to the acute phase protein (APPs) family. As a first step, we developed a nanoparticle-enabled blood (NEB) test that employed 600 nm graphene oxide (GO) nanosheets and human plasma (HP) (5% vol/vol) to produce 75 personalized protein coronas (25 from healthy subjects and 50 from PDAC patients). Isolation and characterization of protein corona patterns by 1-dimensional (1D) SDS-PAGE identified significant differences in the abundance of low-molecular-weight corona proteins (20–30 kDa) between healthy subjects and PDAC patients. Coupling the outcomes of the NEB test with the circulating levels of alpha 2 globulins, we detected PDAC with a global capacity of 83.3%. Notably, a version of the multiplexed detection strategy run on sex-disaggregated data provided substantially better classification accuracy for men (93.1% vs. 77.8%). Nanoliquid chromatography tandem mass spectrometry (nano-LC MS/MS) experiments allowed to correlate PDAC with an altered enrichment of Apolipoprotein A-I, Apolipoprotein D, Complement factor D, Alpha-1-antichymotrypsin and Alpha-1-antitrypsin in the personalized protein corona. Moreover, other significant changes in the protein corona of PDAC patients were found. Overall, the developed multiplexed strategy is a valid tool for PDAC detection and paves the way for the identification of new potential PDAC biomarkers