The scale-free topology of market investments

We propose a network description of large market investments, where both stocks and shareholders are represented as vertices connected by weighted links corresponding to shareholdings. In this framework, the in-degree ($k_{in}$) and the sum of incoming link weights ($v$) of an investor correspond to the number of assets held (\emph{portfolio diversification}) and to the invested wealth (\emph{portfolio volume}) respectively. An empirical analysis of three different real markets reveals that the distributions of both $k_{in}$ and $v$ display power-law tails with exponents $\gamma$ and $\alpha$. Moreover, we find that $k_{in}$ scales as a power-law function of $v$ with an exponent $\beta$. Remarkably, despite the values of $\alpha$, $\beta$ and $\gamma$ differ across the three markets, they are always governed by the scaling relation $\beta=(1-\alpha)/(1-\gamma)$. We show that these empirical findings can be reproduced by a recent model relating the emergence of scale-free networks to an underlying Paretian distribution of `hidden' vertex properties.Comment: Final version accepted for publication on Physica

Plexiform architecture in gastrointestinal stromal tumors is not restricted to succinate dehydrogenase-deficient cases

Accumulating evidence reveals the heterogeneous features of gastrointestinal stromal tumors (GISTs), primarily distinguished by their various molecular triggers defining well characterized subgroups. The identification of the pathogenetic group a given GIST belongs to, in combination with the currently adopted GIST prognosticators, is pivotal for the correct management of GIST patients. Epidemiological, anatomical and morphological features are more or less strictly associated with the various possible GIST molecular pathogenesis; therefore, they can concur to addressing molecular analysis or even influence the identification of GIST subsets by themselves. This is particularly true in a cost/benefit perspective aimed at cutting the expenses of pathology labs. Under these circumstances, a correct classical pathological analysis still appears a fundamental step to achieve an optimal GIST characterization.We herein report a gastric epithelioid PDGFRA-mutant GIST displaying the multinodular/plexiform architecture distinctive of succinate dehydrogenase (SDH)-deficient GISTs. Immunohistochemistry and molecular analysis led to the correct tumor characterization. The reported case constitutes a valuable contribution to GIST pathology in that it demonstrates that multinodular/plexiform architecture is not restricted to SDH-deficient GISTs, but can be found also in PDGFRA-mutant ones; this is an event to be aware of, given the predilection for gastric location and epithelioid morphology shared by these two GIST subgroups, only the latter of which includes imatinib-sensitive cases. Keywords: Gastrointestinal stromal tumor, Platelet-derived growth factor receptor alpha, Multinodular architecture, Plexiform architecture, Succinate dehydrogenas

Base-Excision Repair Mutational Signature in Two Sebaceous Carcinomas of the Eyelid

: Personalized medicine aims to develop tailored treatments for individual patients based on specific mutations present in the affected organ. This approach has proven paramount in cancer treatment, as each tumor carries distinct driver mutations that respond to targeted drugs and, in some cases, may confer resistance to other therapies. Particularly for rare conditions, personalized medicine has the potential to revolutionize treatment strategies. Rare cancers often lack extensive datasets of molecular and pathological information, large-scale trials for novel therapies, and established treatment guidelines. Consequently, surgery is frequently the only viable option for many rare tumors, when feasible, as traditional multimodal approaches employed for more common cancers often play a limited role. Sebaceous carcinoma of the eyelid is an exceptionally rare cancer affecting the eye's adnexal tissues, most frequently reported in Asia, but whose prevalence is significantly increasing even in Europe and the US. The sole established curative treatment is surgical excision, which can lead to significant disfigurement. In cases of metastatic sebaceous carcinoma, validated drug options are currently lacking. In this project, we set out to characterize the mutational landscape of two sebaceous carcinomas of the eyelid following surgical excision. Utilizing available bioinformatics tools, we demonstrated our ability to identify common features promptly and accurately in both tumors. These features included a Base-Excision Repair mutational signature, a notably high tumor mutational burden, and key driver mutations in somatic tissues. These findings had not been previously reported in similar studies. This report underscores how, in the case of rare tumors, it is possible to comprehensively characterize the mutational landscape of each individual case, potentially opening doors to targeted therapeutic options

The scale-free topology of market investments

We propose a network description of large market investments, where both stocks and shareholders are represented as vertices connected by weighted links corresponding to shareholdings. In this framework, the in-degree ($k_{in}$) and the sum of incoming link weights ($v$) of an investor correspond to the number of assets held (\emph{portfolio diversification}) and to the invested wealth (\emph{portfolio volume}) respectively. An empirical analysis of three different real markets reveals that the distributions of both $k_{in}$ and $v$ display power-law tails with exponents $\gamma$ and $\alpha$. Moreover, we find that $k_{in}$ scales as a power-law function of $v$ with an exponent $\beta$. Remarkably, despite the values of $\alpha$, $\beta$ and $\gamma$ differ across the three markets, they are always governed by the scaling relation $\beta=(1-\alpha)/(1-\gamma)$. We show that these empirical findings can be reproduced by a recent model relating the emergence of scale-free networks to an underlying Paretian distribution of `hidden' vertex properties.

Preparation of adipose tissue stromal vascular fraction by mechanical digestion for point of care application in veterinary medicine.

Preparation of adipose tissue stromal vascular fraction by mechanical digestion for point of care application in veterinary medicine. OBJECTIVES: Mesenchymal Stem Cells (MSCs) derived from adipose tissue have a growing role in the therapy of a variety of animals diseases, including wound healing, tendonitis, bone defects, osteoarticular pathologies and neurodegenerative diseases. As a matter of fact, fat tissue represents a complex source of cells as well as bioactive factors able to contribute to the healing of injured tissues. The term Stromal Vascular Fraction (SVF) has been introduced in recent years to describe the mixed cell population (endothelial cells, pericytes, smooth muscle cells, stromal progenitor cells) isolated from fat tissue. We evaluated the feasibility of a simple procedure for the preparation of a SVF derived from fat in the dog, to be used “point of care” ”, i.e. shortly after the collection of the biological sample and after a minimal manipulation. A key concept of the approach we propose, is that fat tissue is a source of MSCs but also of other cell types able, for example, to promote the formation of blood vessels and to modulate the different phases of tissue healing. MATERIALS AND METHODS: SVF was prepared by mechanical treatment of 2 grams of subcutaneous and visceral fat. A mechanical digestion was performed inside a 50 ml test tube using a set of 6 mm diameter sterile steel balls obtaining tissue fragments ranging from 1 mm3 to 4 mm3. The tissue fragments were cultured either on plastic surface or inside a three-dimensional scaffold prepared with Platelet Rich Plasma, thrombin and culture medium. Cell cultures were maintained until passage four for cells grown on plastic surface, or for 10-12 days for cells grown inside the three-dimensional matrix. RNA was collected to analyze the expression of markers typical for MSCs as well as endothelial cells and pericytes. RESULTS: The fragments released in the surrounding environment a high number of actively proliferating cells that populated the plastic surface or the three-dimensional gel in different culture conditions. Noteworthy, complex multicellular structures connecting different tissue fragments were often observed, thus suggesting the ability of the cells to respond to chemotactic signaling. The histological examination of the cultured fragments demonstrated that the tissue maintained its structural organization for at least 10-12 days. In addition, the cells released by tissue fragments adhered to the culture plate and were able to differentiate into adipocytes and osteoblasts. RT- PCR analysis demonstrated that cells expressing phenotypes of MSCs and endothelial cells are present in cell cultures. CONCLUSIONS: Although incomplete, the preliminary characterization of the cells obtained by the in-vitro culture of SVF, let us hypothesize that the cell population include MSCs maintaining their typical features. The safeguard of the tissue architecture and the long-lasting maintenance of its vitality guarantee a positive evaluation of the efficacy and efficiency of the proposed mechanical treatment

Gastrointestinal juvenile-like (inflammatory/hyperplastic) mucosal polyps in neurofibromatosis type 1 with no concurrent genetic or clinical evidence of other syndromes

Gastrointestinal \u201cjuvenile-like (inflammatory/hyperplastic) mucosal polyps\u201d (JLIHMPs) have been proposed as a neurofibromatosis type 1 (NF1)-specific gastrointestinal manifestation. Juvenile polyposis syndrome (JPS) has also been reported in a NF1 patient, harboring concurrent NF1 and SMAD4 germline mutations. Additionally, NF1-like cafe-au-lait spots have been described in biallelic mismatch repair deficiency, another condition featuring gastrointestinal polyps. The SMAD4 and BMPR1A genes that are involved in 50\u201360% of JPS cases have not been investigated in the ~ 20 published cases of NF1-associated JLIHMPs with the exception of the abovementioned patient with concomitant JPS and NF1. NF1 defects have been found in the only two cases exhaustively tested. Therefore, JLIHMP has been questioned as an independent, NF1-specific entity. Incidental associations between NF1 and gastrointestinal polyposes at risk for gastrointestinal carcinoma should not be overlooked, given their implications in terms of clinical surveillance. We describe two patients featuring JLIHMPs in clinically/genetically proven NF1, in the absence of SMAD4 and BMPR1A mutations. In one case, the intervening mucosa was markedly inflamed, unlike JPS. We suggest that JLIHMP probably represents a gastrointestinal lesion specific to NF1

Role of p16/INK4a in gastrointestinal stromal tumor progression

Because the p16 locus is involved consistently in chromosomal losses found in malignant gastrointestinal stromal tumors (GISTs), we studied p16 in a series of 21 GISTs with complete follow-up using immunohistochemical analysis, semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and methylation-specific PCR (MSP). A fraction of cells of more than 20% with low or absent p16 immunostaining was detected in 12 GISTs, including all showing malignancy. RT-PCR revealed decreased p16 transcription in all except 2 p16 protein-deficient GISTs. By MSP, 7 cases showed p16 promoter methylation (all hypoexpressing p16; 6 malignant). A fraction of p16-deficient cells of more than 20% was associated with clinical malignancy (P = .003; log-rank test). The percentage of cells underexpressing p16, size, cellularity, mitotic count, and coagulative necrosis were associated with malignancy by Cox proportional hazards univariate analysis; only the former factor was selected by multivariate analysis (P = .039). Thus, p16 down-regulation, partly due to p16 promoter methylation, is implied in GIST progression. Furthermore, p16 immunohistochemical assessment seems a promising method for GIST prognostication