15 research outputs found

    miRNA:mRNA interplay in the malignant evolution of miniGIST to overt GIST

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    Gastrointestinal Stromal Tumor (GIST) is the most common mesenchymal tumor that occurs throughout the digestive tract and is thought to arise from the gastrointestinal (GI) pacemakers, the Interstitial Cells of Cajal (ICC). Different from most sarcomas for which premalignant lesions are not known, premalignant GIST counterparts have been identified. These entities, named miniGIST, share with overt GIST histological and molecular features, namely the presence of oncogenic mutations affecting the tyrosine kinases KIT or PDGFRA. MiniGISTs are remarkably common (about 1/3 of unselected elderly subjects carry miniGIST in their GI tract) whilst GIST are quite rare, indicating that a very minute fraction of miniGIST actually progress to clinically relevant tumors. This indicates that KIT/PDGFRA oncogenic mutations are insufficient to convey malignancy. The aim of this work was to address the molecular mechanisms that sustain miniGIST to overt GIST malignant evolution, focusing on particular on the role of miRNAs. By performing combined miRNA and mRNA NGS profilings of a large set of miniGISTs and overt GISTs we identified a set of miRNAs potentially involved in the transcriptional perturbation during GIST progression. We made a step ahead by in vitro validating the role of hsa-miR-485-5p loss in determining the BIRC5 gene upregulation in overt GIST. Overall, our work laid down the bases for the elucidation of the role of miRNA:mRNA interaction in the malignant evolution of GIST

    Pulsed light beams in vacuum with superluminal and negative group velocities

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    Gouy's phase of transversally limited pulses can create a strong anomalous dispersion in vacuum leading to highly superluminal and negative group velocities. As a consequence, a focusing pulse can diverge beyond the focus before converging into it. A simple experiment is proposed.Comment: 4 pages, 5 figure

    Tumor genotype, location and malignant potential shape the immunogenicity of primary, untreated Gastrointestinal Stromal Tumors

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    Intratumoral immune infiltrate was recently reported in Gastrointestinal Stromal Tumors (GIST). However, what tumor-intrinsic factors dictate GIST immunogenicity is still largely undefined. To shed light on this issue a large cohort (82 samples) of primary untreated GIST, representative of major clinicopathological variables, was investigated by an integrated immunohistochemical, transcriptomic and computational approach. Our results indicate that tumor genotype, location and malignant potential concur to shape the immunogenicity of primary na\uefve GIST. Immune infiltration was greater in overt GIST than in lesions with limited malignant potential (miniGIST), in KIT/PDGFRA mutated than in KIT/PDGFRA wild-type tumors and in PDGFRA versus KIT mutated GIST. Within the KIT mutated subset, a higher degree of immune colonization was detected in the intestine. Immune hot tumors showed expression patterns compatible with a potentially proficient but curbed antigen-specific immunity, hinting at sensitivity to immunomodulatory treatments. Poorly infiltrated GIST, primarily KIT/PDGFRA wild-type intestinal tumors, showed activation of Hedgehog and WNT/\u3b2-catenin immune excluding pathways. This finding discloses a potential therapeutic vulnerability, as the targeting of these pathways might prove effective by both inhibiting pro-oncogenic signals and fostering anti-tumor immune responses. Finally, an intriguing anticorrelation between immune infiltration and ANO1/DOG1 expression was observed, suggesting an immunomodulatory activity for anoctamin-1

    Current hospital policies on breastfeeding: a survey from Italy

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    Abstract Background The availability of an appropriate newborn feeding policy is an essential component of the promotion of breastfeeding in health facilities. The Italian Society of Neonatology (SIN) and the Italian Society of Paediatrics (SIP) have run an online survey among Maternity Hospitals to explore the existing breastfeeding policies and their characteristics. Methods Between February and April 2023, an online survey was carried out among 110 Italian maternity hospitals with a Neonatal Intensive Care Unit (NICU). Results Forty-nine Maternity Hospitals completed the online questionnaire. Twenty out of 49 (40.8%) reported to have a breastfeeding policy. When a policy is available, its quality appears to be suboptimal because of lack of inclusion of a family representative in the policy working group, limited options for translating breastfeeding policy into minority languages, lack of periodic assessment of their implementation. Conclusion Currently, only a limited number of Italian Maternity Hospitals have developed a breastfeeding policy. Additional efforts are needed for their improvement as well as implementation

    Quadruple-negative GIST is a sentinel for unrecognized Neurofibromatosis Type 1 syndrome

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    The majority of Gastrointestinal Stromal Tumors (GISTs) are driven by KIT, PDGFRA or, less commonly, BRAF mutations, and SDH gene inactivation is involved in a limited fraction of gastric lesions. However, about 10% of GISTs are devoid of any of such alterations and are poorly responsive to standard treatments. This study aims to shed light on the molecular drivers of quadruple-negative GISTs

    ESA’s Lidar Missions Aeolus and EarthCARE

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    ESAs Earth Explorer Aeolus was launched in August 2018. Aboard the first spaceborne wind lidar ALADIN (Atmospheric LAser Doppler INstrument) was switched on in early September 2018 and demonstrated the capability to provide atmospheric wind profiles globally from particle and molecular backscatter. In doing so, it will contribute to the improvement in numerical weather prediction (NWP) and the understanding of global dynamics. At the same, it is a major step for powerful and frequency stabilized ultraviolet (UV) lasers for space applications. In parallel, ESA and its partners continue the development of this technology by setting up further ground tests based on Aeolus, and preparing the next milestone with ATLID (ATmospheric LIDar) for the Earth Cloud, Aerosol and Radiation Explorer (EarthCARE) mission. ATLID is currently fully integrated and getting prepared for its on-ground testing

    ESA’s Lidar Missions Aeolus and EarthCARE

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    ESAs Earth Explorer Aeolus was launched in August 2018. Aboard the first spaceborne wind lidar ALADIN (Atmospheric LAser Doppler INstrument) was switched on in early September 2018 and demonstrated the capability to provide atmospheric wind profiles globally from particle and molecular backscatter. In doing so, it will contribute to the improvement in numerical weather prediction (NWP) and the understanding of global dynamics. At the same, it is a major step for powerful and frequency stabilized ultraviolet (UV) lasers for space applications. In parallel, ESA and its partners continue the development of this technology by setting up further ground tests based on Aeolus, and preparing the next milestone with ATLID (ATmospheric LIDar) for the Earth Cloud, Aerosol and Radiation Explorer (EarthCARE) mission. ATLID is currently fully integrated and getting prepared for its on-ground testing

    Traumatic brain injury : integrated approaches to improve prevention, clinical care, and research

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    Rahul Raj on työryhmän InTBIR Participants Investigators jäsen.Peer reviewe
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