Thymic Epithelial Neoplasms: Focusing on the Epigenetic Alterations

Thymic Epithelial Neoplasms (TENs) represent the most common tumors of the thymus gland. Epigenetic alterations are generally involved in initiation and progression of various cancer entities. However, little is known about the role of epigenetic modifications in TENs. In order to identify relevant studies, a literature review was conducted using the MEDLINE and LIVIVO databases. The search terms thymoma, thymic carcinoma, thymic epithelial neoplasm, epigenetics, DNA methylation, HDAC and miRNA were employed and we were able to identify forty studies focused on TENs and published between 1997 and 2021. Aberrant epigenetic alterations seem to be involved in the tumorigenesis of thymomas and thymic carcinomas, with numerous studies reporting on non-coding RNA clusters and altered gene methylation as possible biomarkers in different types of TENs. Interestingly, Histone Deacetylase Inhibitors have shown potent antitumor effects in clinical trials, thus possibly representing effective epigenetic therapeutic agents in TENs. Additional studies in larger patient cohorts are, nevertheless, needed to verify the clinical utility and safety of novel epigenetic agents in the treatment of patients with TENs.     

Single-shot 3D hand pose estimation using radial basis function networks trained on synthetic data

Pattern Analysis and Applications - In this work, we present a novel framework to perform single-shot hand pose estimation using depth data as input. The method follows a coarse to fine strategy...     

The Role of Leptin in Childhood Immune Thrombocytopenia (ITP): An Anti-Inflammatory Agent?

To investigate the effect of leptin in childhood ITP, we measured plasma leptin in 39 children with acute ITP, after treatment and in remission, and in 33 healthy age/BMI-matched controls. We also cultured ITP and control peripheral blood mononuclear cells (PBMCs) with recombinant leptin to assess its direct effect on pro/anti-inflammatory cytokine gene expression. A significant increase in leptin was observed in children with active disease compared to controls. A significant inverse correlation of leptin with platelet count was also observed in children with acute ITP. Leptin remained high after treatment with IVIg, whereas steroid treatment lowered leptin below control levels. In remission, leptin was in the control range. Cytokine gene expression was significantly increased in children with acute ITP compared with controls, with highest expression for IFN-γ and IL-10. IVIg/steroid treatment significantly decreased IFN-γ and IL-10 expression. In remission, IFN-γ and IL-10 expression remained low. Addition of leptin to PBMCs isolated from patients in remission resulted in a significant increase in IL-10 gene expression compared to controls. Further experiments with purified T-cells and monocytes identified monocytes as the source of leptin-induced IL-10. We suggest that leptin acts as an active anti-inflammatory agent in childhood ITP by promoting IL-10 secretion by monocytes.     

Effects of birch phenolics on a grazing and a browsing mammal: A comparison of hares

Mountain hares (Lepus timidus L.) commonly have high proportions of birch (Betula spp.) in their winter diets, whereas European hares (Lepus europaeus) do not. The effects of a birch extract added to laboratory diets offered to mountain hares and European hares on the digestibility and sodium balance were measured. The extract added contained total phenolics equivalent in amount to that occurring in diets containing 0, 40, 60 and 80% dry matter of birch twigs. Increasing dietary phenolic concentration led to reduced voluntary food intake and apparent protein digestibility in both hare species. No effects on apparent dry matter digestibility were observed. The highest concentration of birch extract caused severe sodium losses via the urine by European hares but not by mountain hares. The effects of the birch extract within the digestive system appear to be similar in the two hare species, whereas the mountain hare appears to be better adapted to the toxic effects that disrupted sodium balance in the European hare. These preliminary results suggest that detoxification rather than digestive abilityper se may contribute to different mammalian herbivores' feeding strategies.     

CMOS tuners for mobile TV

Digital video reception is emerging as the latest feature toward multimedia-enriched handheld devices. Mobile battery-operated devices require small-size tuners that consume low power and are amenable to single-chip integration with the baseband demodulator. Following an overview of the system and circuit-level implementation challenges of mobile TV standards such as DVB-H and T-DMB, this article presents a dual-band direct conversion tuner for DVB-H. Architecture and circuit trade-offs are discussed, and detailed measurements are presented. The tuner occupies 9.7 mm² and achieves a 4 dB NF at both UHF and L-band, eliminating the need for an external LNA. By using a fractional-TV synthesizer both 470-890 MHz and 1.4-1.8 GHz bands are supported, while achieving an integrated phase noise of less than -41 dBc. Sixth-order low-pass filters support channel bandwidths from 4 to 10 MHz     

Interferon Lambda Regulates Cellular and Humoral Immunity in Pristane-Induced Lupus

A pivotal role of type I interferons in systemic lupus erythematosus (SLE) is widely accepted. Type III interferons (IFN-λ) however, the most recently discovered cytokines grouped within the interferon family, have not been extensively studied in lupus disease models yet. Growing evidence suggests a role for IFN-λ in regulating both innate and adaptive immune responses, and increased serum concentrations have been described in multiple autoimmune diseases including SLE. Using the pristane-induced lupus model, we found that mice with defective IFN-λ receptors (Ifnlr1^−/−) showed increased survival rates, decreased lipogranuloma formation and reduced anti-dsDNA autoantibody titers in the early phase of autoimmunity development compared to pristane-treated wild-type mice. Moreover, Ifnlr1^−/− mice treated with pristane had reduced numbers of inflammatory mononuclear phagocytes and cNK cells in their kidneys, resembling untreated control mice. Systemically, circulating B cells and monocytes (CD115⁺Ly6C⁺) were reduced in pristane-treated Ifnlr1^−/− mice. The present study supports a significant role for type III interferons in the pathogenesis of pristane-induced murine autoimmunity as well as in systemic and renal inflammation. Although the absence of type III interferon receptors does not completely prevent the development of autoantibodies, type III interferon signaling accelerates the development of autoimmunity and promotes a pro-inflammatory environment in autoimmune-prone hosts.     

The EPH/Ephrin System in Gynecological Cancers: Focusing on the Roots of Carcinogenesis for Better Patient Management

Gynecological cancers represent some of the most common types of malignancy worldwide. Erythropoietin-producing hepatocellular receptors (EPHs) comprise the largest subfamily of receptor tyrosine kinases, binding membrane-bound proteins called ephrins. EPHs/ephrins exhibit widespread expression in different cell types, playing an important role in carcinogenesis. The aim of the current review was to examine the dysregulation of the EPH/ephrin system in gynecological cancer, clarifying its role in ovarian, endometrial, and cervical carcinogenesis. In order to identify relevant studies, a literature review was conducted using the MEDLINE and LIVIVO databases. The search terms ephrin, ephrin receptor, ovarian cancer, endometrial cancer, and cervical cancer were employed and we were able to identify 57 studies focused on gynecological cancer and published between 2001 and 2021. All researched ephrins seemed to be upregulated in gynecological cancer, whereas EPHs showed either significant overexpression or extensive loss of expression in gynecological tumors, depending on the particular receptor. EPHA2, the most extensively studied EPH in ovarian cancer, exhibited overexpression both in ovarian carcinoma cell lines and patient tissue samples, while EPHB4 was found to be upregulated in endometrial cancer in a series of studies. EPHs/ephrins were shown to exert their role in different stages of gynecological cancer and to influence various clinicopathological parameters. The analysis of patients’ gynecological cancer tissue samples, most importantly, revealed the significant role of the EPH/ephrin system in the development and progression of gynecological cancer, as well as overall patient survival. In conclusion, the EPH/ephrin system represents a large family of biomolecules with promising applications in the fields of diagnosis, prognosis, disease monitoring, and treatment of gynecological cancer, with an established important clinical impact.     

Assessment and Implications of Intraspecific and Phenological Variability in Monoterpenes of Scots Pine (<Emphasis Type="Italic">Pinus sylvestris</Emphasis>) Foliage

Scots pine populations contain individuals with widely differing amounts and composition of monoterpenes and exist as one of two chemotypes: with or without Δ³-carene. We investigated the significance for ecological studies of two types of variation in monoterpenes: (1) the inherent variability in the concentration of monoterpenes or their relative amounts in needles of seedlings, saplings, and mature trees; and (2) phenological variation in developing needles. The relative composition of needle monoterpenes in 5-year-old saplings changed during the needle development period until the final composition was reached upon needle maturity. Changes in composition depended on chemotype. Needles of the “no-Δ³-carene” chemotype had higher absolute concentrations of α-pinene, β-pinene, camphene, and total monoterpenes than “Δ³-carene” chemotype. For the “Δ³-carene” chemotype, the relative concentration of Δ³-carene during the needle growing season and immediately after emergence of seedlings was higher compared to that reached at needle maturity. Repeated removal of single needles (at weekly intervals during growth) from 5-year-old saplings did not influence the composition of monoterpenes. Within a natural Scots pine dominated woodland, 18% of mature Scots pines (N = 574) belonged to the “no-Δ³-carene” chemotype. Chemotypic variation within populations means that the statistical power with which differences in monoterpene concentrations can be detected is lower when sampling from the whole population compared to sampling within chemotypes. Reduction of this background variation and accounting for chiral variation if present, would significantly aid efficiency, interpretation, and understanding of processes in chemical and ecological research. One method for achieving this is the screening of plants for chemotypes before the establishment of experiments or field sampling regimes. We present a summary of suitable analytical methods for needle tissue that facilitates this prior screening.     

Coupling the cross-entropy with the line sampling method for risk-based design optimization

An algorithm for risk-based optimization (RO) of engineering systems is proposed, which couples the Cross-entropy (CE) optimization method with the Line Sampling (LS) reliability method. The CE-LS algorithm relies on the CE method to optimize the total cost of a system that is composed of the design and operation cost (e.g., production cost) and the expected failure cost (i.e., failure risk). Guided by the random search of the CE method, the algorithm proceeds iteratively to update a set of random search distributions such that the optimal or near-optimal solution is likely to occur. The LS-based failure probability estimates are required to evaluate the failure risk. Throughout the optimization process, the coupling relies on a local weighted average approximation of the probability of failure to reduce the computational demands associated with RO. As the CE-LS algorithm proceeds to locate a region of design parameters with near-optimal solutions, the local weighted average approximation of the probability of failure is refined. The adaptive refinement procedure is repeatedly applied until convergence criteria with respect to both the optimization and the approximation of the failure probability are satisfied. The performance of the proposed optimization heuristic is examined empirically on several RO problems, including the design of a monopile foundation for offshore wind turbines.