Bridging therapeutic opportunities: a survey by the Italian molecular tumor board workgroup of Alliance Against Cancer

Background: Molecular tumor boards (MTBs) match molecular alterations with targeted anticancer drugs upon failure of the available therapeutic options. Special and local needs are most likely to emerge through the comparative analysis of MTB networks, but these are rarely reported. This manuscript summarizes the state-of-art of 16 active Italian MTBs, as it emerges from an online survey curated by Alliance Against Cancer (ACC).Main text: Most MTBs (13/16) are exclusively supported through local Institutional grants and meet regularly. All but one adopts a fully virtual or a mixed face-to-face/virtual calling/attendance meeting model. It appears that the ACC MTB initiative is shaping a hub-and-spoke virtual MTB network reminiscent of non-redundant, cost-effective health-care organization models. Unfortunately, public awareness of MTB opportunities presently remains insufficient. Only one center has a website. Dedicated e-mail addresses are for the exclusive use of the MTB staff. More than half of ACC members consider a miscellanea of most or all solid and hematological malignancies, and more than one-third consider neoplasms arising at any anatomical location. The average number of Staff Members in MTBs is 9. More than 10 staff members simultaneously attend MTB meetings in 13 MTBs. A medical oncologist is invariably present and is in charge of introducing the clinical case either with (45%) or without previous discussion in organ-specific multidisciplinary Boards. All but two MTBs take charge of not only patients with no standard-of-care (SoC) therapy option, but also cases receiving NGS profiling in SoC settings, implying a larger number of yearly cases. All MTBs run targeted NGS panels. Three run whole-exome and/or RNAseq approaches. ESCAT-ESMO and/or Onco-KB levels of evidence are similarly used for diagnostic reporting. Most MTBs (11) provide a written diagnostic report within 15 days. Conclusions are invariably communicated to the patient by the medical oncologist.Conclusions: MTB networking is crucial not only for molecular diagnosis and therapy assignment, but also for healthcare governance. Survey results show that MTBs review therapeutic opportunities at the crossover between standard-of-care with off-label, the former task being much beyond their scope. Societal and scientific implications of this beyond-the-scope MTB function may be relevant for healthcare in Italy and abroad

Loss of miR-204 expression is a key event in melanoma

Cutaneous melanoma (CM) is a malignancy with increasing occurrence. Its microRNA repertoire has been defined in a number studies, leading to candidates for biological and clinical relevance: miR-200a/b/c, miR-203, miR-205, miR-204, miR-211, miR-23b and miR-26a/b. Our work was aimed to validate the role of these candidate miRNAs in melanoma, using additional patients cohorts and in vitro cultures. miR-26a, miR-204 and miR-211 were more expressed in normal melanocytes, while miR-23b, miR-200b/c, miR-203 and miR-205 in epidermis and keratinocytes. None of the keratinocyte-related miRNAs was associated with any known mutation or with clinical covariates in melanoma. On the other hand, the loss of miR-204 was enriched in melanomas with NRAS sole mutation (Fisher exact test, P = 0.001, Log Odds = 1.67), and less frequent than expected in those harbouring CDKN2A mutations (Fisher exact test, P = 0.001, Log Odds − 1.09). Additionally, miR-204 was associated with better prognosis in two independent melanoma cohorts and its exogenous expression led to growth impairment in melanoma cell lines. Thus, miR-204 represents a relevant mechanism in melanoma, with potential prognostic value and its loss seems to act in the CDKN2A pathway, in cooperation with NRAS

Data decoding aided channel estimation techniques for OFDM systems in vehicular environment

L'oggetto del presente lavoro di tesi è costituito dallo studio e sviluppo di algoritmi di inseguimento di canale per sistemi basati su una modulazione di tipo Orthogonal Frequency Division Multiplexing (OFDM), con riferimento allo standard IEEE802.11p per comunicazioni mobili di tipo Wireless Local Area Network (WLAN), tra veicolo e veicolo e tra veicolo e infrastruttura. La caratteristica principale dei sistemi wireless in ambiente veicolare µe la presenza dell'effetto Doppler dovuto alla velocità relativa tra trasmettitore e ricevitore che rende il canale wireless tempo variante

Implementação de um servidor de nomes distribuído tolerante a falhas

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Implementação de um servidor de nomes distribuído tolerante a falhas

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Architetture padane

Dopo la mostra Giovanni Chiaramonte "Interno perduto" organizzata dal Laboratorio "Ricerca Emilia" della Facolt\ue0 di Architettura \u201cAldo Rossi\u201d di Cesena per documentare la distruzione causata in Emilia dal terremoto di maggio, in diretta continuit\ue0 si apre il 6 marzo una seconda esposizione, intitolata Architetture padane per investigare come \ue8 stata gestita l'emergenza in questi mesi e per raccontare la storia di questo territorio. Architetture padane \ue8 il titolo che Aldo Rossi con Luigi Ghirri diede ad una importante mostra sulla sua opera presentata al pubblico nel 1984 alla Casa del Mantegna a Mantova. Si \ue8 ritenuto indispensabile ripartire da quella significativa esperienza, che \ue8 stata capace di cogliere la verit\ue0 di un territorio connotato da valori architettonici precisi e identitari, relazionati con il paesaggio a salvaguardia di una antica tradizione, fondata \u2013 come scriveva il Maestro \u2013 sulla \u201ccommistione tra campagna e citt\ue0, tra terra e acqua\u201d. Questa nuova mostra cesenate ripartendo da quelle posizioni vuole evidenziare la necessit\ue0 di porre al centro delle pratiche della ricostruzione in Emilia questa conoscenza, portando un contributo culturale col fine di evitare che il dopo terremoto sia pi\uf9 devastante del terremoto stesso. Il rischio di dimenticare la storia di queste terre e di cancellare irrimediabilmente architetture storiche e segni antropici \ue8 altissimo. Curata dal Dottorato di ricerca in Architettura per il Laboratorio "Ricerca Emilia", la mostra si divide in 3 sezioni principali: \u201cPaesaggio e Storia\u201d, \u201cDistruzione\u201d, \u201cEmergenza\u201d. Come incipit diretto, nella sezione \u201cPaesaggio e Storia\u201d sono esposti alcuni disegni originali del progetto Fiera Catena di Aldo Rossi e Gianni Braghieri presentati alla mostra mantovana del 1984, oltre ad una importante documentazione cartografica proveniente dalla collezione comunale di Mirandola che descrive il territorio emiliano e le sue origini. Uno straordinario modello ligneo della citt\ue0 di Mirandola risalente al XVI secolo chiude questa prima parte dell'esposizione. Nella sezione \u201cDistruzione\u201d una serie di documenti ripercorre i danni causati dal sisma alle architetture emiliane: oltre alla campagna fotografica aerea di Nazario Spadoni, grafici e schede di sintesi descrivono il patrimonio architettonico danneggiato dal terremoto. Infine la terza sezione presenta in anteprima alcuni tra i pi\uf9 importanti progetti per la ricostruzione in Emilia: tra gli altri, la chiesa temporanea di Paolo Zermani, la chiesa di Medolla di Marazzi Architetti, il centro polisportivo di San Felice sul Panaro di Architetcure for humanity con Rizoma architetture, il municipio temporaneo di Novi di Zamboni Associati e Politecnica, le tre proposte progettuali elaborate per il complesso scolastico di Cavezzo su invito di Renzo Piano

Epigenetic silencing of selected hypothalamic neuropeptides in narcolepsy with cataplexy

Narcolepsy with cataplexy is a sleep disorder caused by deficiency in the hypothalamic neuropeptide hypocretin/orexin (HCRT), unanimously believed to result from autoimmune destruction of hypocretin-producing neurons. HCRT deficiency can also occur in secondary forms of narcolepsy and be only temporary, suggesting it can occur without irreversible neuronal loss. The recent discovery that narcolepsy patients also show loss of hypothalamic (corticotropin-releasing hormone) CRH-producing neurons suggests that other mechanisms than cell-specific autoimmune attack, are involved. Here, we identify the HCRT cell-colocalized neuropeptide QRFP as the best marker of HCRT neurons. We show that if HCRT neurons are ablated in mice, in addition to Hcrt, Qrfp transcript is also lost in the lateral hypothalamus, while in mice where only the Hcrt gene is inactivated Qrfp is unchanged. Similarly, postmortem hypothalamic tissues of narcolepsy patients show preserved QRFP expression, suggesting the neurons are present but fail to actively produce HCRT. We show that the promoter of the HCRT gene of patients exhibits hypermethylation at a methylation-sensitive and evolutionary-conserved PAX5:ETS1 transcription factor-binding site, suggesting the gene is subject to transcriptional silencing. We show also that in addition to HCRT, CRH and Dynorphin (PDYN) gene promoters, exhibit hypermethylation in the hypothalamus of patients. Altogether, we propose that HCRT, PDYN, and CRH are epigenetically silenced by a hypothalamic assault (inflammation) in narcolepsy patients, without concurrent cell death. Since methylation is reversible, our findings open the prospect of reversing or curing narcolepsy