Archivio Istituzionale della Ricerca- Università del Piemonte Orientale
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Search for top squarks in final states with many light-flavor jets and 0, 1, or 2 charged leptons in proton-proton collisions at √ s =13TeV
No full textSeveral new physics models including versions of supersymmetry (SUSY) characterized by R-parity violation (RPV) or with additional hidden sectors predict the production of events with top quarks, low missing transverse momentum, and many additional quarks or gluons. The results of a search for top squarks decaying to two top quarks and six additional light-flavor quarks or gluons are reported. The search employs a novel machine learning method for background estimation from control samples in data using decorrelated discriminators. The search is performed using events with 0, 1, or 2 electrons or muons in conjunction with at least six jets. No requirement is placed on the magnitude of the missing transverse momentum. The result is based on a sample of proton-proton collisions at TeV corresponding to 138 fb−1 of integrated luminosity collected with the CMS detector at the LHC in 2016–2018. With no statistically significant excess of events observed beyond the expected contributions from the standard model, the data are used to determine upper limits on the top squark pair production cross section in the frameworks of RPV and stealth SUSY. Models with top squark masses less than 700 (930) GeV are excluded at 95% confidence level for RPV (stealth) SUSY scenarios
Search for high-mass resonances in a final state comprising a gluon and two hadronically decaying W bosons in proton-proton collisions at = 13 TeV
No full textA search for high-mass resonances decaying into a gluon, g, and two W bosons is presented. A Kaluza-Klein gluon, gKK, decaying in cascade via a scalar radion R, gKK → gR → gWW, is considered. The final state studied consists of three large-radius jets, two of which contain the products of hadronically decaying W bosons, and the third one the hadronization products of the gluon. The analysis is performed using proton-proton collision data at s = 13 TeV collected by the CMS experiment at the CERN LHC during 2016–2018, corresponding to an integrated luminosity of 138 fb−1. The masses of the gKK and R candidates are reconstructed as trijet and dijet masses, respectively. These are used for event categorization and signal extraction. No excess of data events above the standard model background expectation is observed. Upper limits are set on the product of the gKK production cross section and its branching fraction via a radion R to gWW. This is the first analysis examining the resonant WW+jet signature and setting limits on the two resonance masses in an extended warped extra-dimensional model
Safety and efficacy of P2Y12 inhibitors in acute coronary syndromes patients with KDIGO stage IV-V renal disfunction not on dialysis: a subanalysis of the CORALYS registry
No full textBackground: The impact of the most potent P2Y12i ticagrelor and prasugrel after acute coronary syndrome in patients with chronic kidney disease (CKD) remains unclear. Most evidence on dual antiplatelet therapy (DAPT) comes from real-world study but is limited to glomerular filtration rate (GFR) under 60 ml/min. Methods: Consecutive patients with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI) and severe CKD defined as GFR under 30 ml/min not on dialysis from the CORALYS registry were included. Incidence of Net Adverse Clinical Events (NACE) defined as major adverse cardiac events (cardiovascular death, myocardial infarction and unplanned revascularizations) in addition to major bleedings was our primary endpoint. Overall MACE and their single components, all bleedings, major bleedings and hospitalizations for heart failure were the secondary ones. Results: 257 patients with severe CKD not on dialysis and available data on antiplatelet regimen at discharge were included, 193 (75.1 %) were given clopidogrel while 64 (24.9 %) with ticagrelor or prasugrel. Our population was predominantly male (153, 59.5 %) with an average age 75.8 ± 10.9 years old. Over a median follow-up of 459 days, Ticagrelor and Prasugrel were associated to lower rates of NACE compared to Clopidogrel (39.9 % vs 25.0 %, p = 0.036). This was mainly driven by an excess of both CV mortality and myocardial infarction reported in the clopidogrel group. No difference was reported regarding overall bleeding events and major bleedings. At multivariate Cox regression analysis DAPT with Ticagrelor/Prasugrel resulted independently associated with a lower risk of NACE whereas left main involvement or multivessel coronary disease led to higher risk of NACE. Conclusions: In ACS patients treated with PCI with severe CKD ticagrelor and prasugrel were associated to lower risk of NACE, MACE, CV death and myocardial infarction compared to clopidogrel. No significative difference was reported in overall and major bleedings
Risk of Cardiovascular and Cerebrovascular Diseases in Patients with Myeloid Neoplasms: Results from 1.8 Million Inhabitants of Northwest Italy
No full textBackground: Myeloid neoplasms are a group of pathologies characterized by clonal hematopoiesis and genetic mutations, often associated with inflammation and cardiovascular (CV) risk. While targeted therapies have improved prognosis, they may also lead to CV adverse effects. The aim was to analyze the risk of developing cardiovascular or cerebrovascular (CVD) events in patients who received a diagnosis of myeloid neoplasm, considering four subgroups of myeloid neoplasms: Chronic Myeloid Leukemia (CML), Myeloproliferative Neoplasm (MPN), Myelodysplastic Syndromes (MDS), and Acute Myeloid Leukemia (AML).
Methods: Data was obtained from the Piedmont Longitudinal Study, including all subjects present in the census conducted in October 2011 and who were 40-80 years old. The association between myeloid neoplasms and cardiovascular and/or cerebrovascular diseases was evaluated through Competing Risks analyses, both on the entire sample and considering 40-64- and 65-80-years old subgroups.
Results: Out of 1,795,216 subjects, 1,395 received a diagnosis of myeloid neoplasm and 82,978 experienced CVDs. Patients with myeloid neoplasms exhibited different CVD risks. In the younger population, CLM resulted associated with cerebrovascular events and MDS with myocardial infarction. In the older patients, CML was associated with heart failure, AML with CVD events, MDS with cardiovascular, particularly heart failure and peripheral vascular disease, and cerebrovascular events, while MPN with cardiovascular events, especially peripheral vascular disease.
Conclusions: The results highlighted the importance of implementing a specific CVD prevention and surveillance plan for patients with myeloid neoplasms.
Impact: Study evidence underlines which myeloid neoplasm patient subgroups require increased attention and monitoring to prevent future CVD events
Corpi che invecchiano in città che cambiano. Persone anziane e vita quotidiana in contesti urbani tra senso di appartenenza ed esclusione
No full textElaborating on a qualitative research with individuals aged 65 or over and key informants in Turin, the article addresses the relationship between older people and urban spaces in a metropolitan context with a dynamic and processual reading. The contribution questions the aging-in-place approach to propose an analysis in terms of socio-spatial justice, addressing difficulties and strategies in everyday practices. The analysis highlights how cities struggle to include ageing bodies, and how this can lead to processes of exclusion of older people
Guilty by association: a newly discovered mTOR-STAT3 pathway at the ER regulates calcium-mediated apoptosis in triple negative breast cancer.
Get PDFGemcitabine-loaded ICOS-Fc decorated nanosponges: A new chemo immunotherapy combination against pancreatic cancer
No full textPancreatic cancer incidence is rising in both Europe and the USA. The late diagnosis, due to the absence of symptoms during early stages, as well as the intrinsic or acquired chemoresistance, contributed to the observed lowest 5-year relative survival rate among all cancer types. The resistance mechanisms to Gemcitabine hydrochloride (GEM), historically used as monotherapy for unresectable and metastatic pancreatic ductal adenocarcinoma (PDAC), have been widely elucidated. Recently, nanosized drug delivery systems can represent an effective strategy in overcoming poor efficacy and resistance issues, allowing site-specific delivery and improvement of drug bioavailability of encapsulated nanomedicines. Pancreatic cancer is resistant not only to chemotherapy but also to immunotherapy; therefore, identifying strategic alternatives is still necessary. Recently, the inducible T-cell co-stimulator (ICOS)/ICOS ligand (ICOSL) signaling has emerged as an interesting immunomodulatory pathway with anti-invasion activity. Interestingly, nanoparticle-based drug delivery platforms are a very promising tool since it is possible to combine chemotherapy and immunotherapy. Here, we evaluated β-cyclodextrin-based nanosponges (NS) loaded with GEM and functionalized with ICOS-Fc (ICOS-Fc-NS-GEM) as an innovative combination therapy, potentially suitable to overcome drug resistance in pancreatic cancer. NS-GEM affected viability, proliferation, and invasion in the 2D and 3D cultures of pancreatic cancer cells. Moreover, the combined formulation ICOS-Fc-NS-GEM showed an enhancement of anti-invasion properties. The MULTI-ORGAN single flow device (MIVO®) technology was exploited to confirm the anti-invasion effect, raising the system's complexity and achieving evidence closer to the in vivo scenario
P53-Induced Autophagy Degradation of NKX3-2 Improves Ovarian Cancer Prognosis
No full textNKX3-2, a transcriptional repressor factor belonging to the NK family of homeobox-containing proteins, has been widely studied for its role in promoting chondrogenic differentiation and homeostasis. NKX3-2 is upregulated in chemoresistant ovarian tumors and metastatic gastric cancer cells; however, its prognostic role and mechanistic involvement in cancer cell biology remain to be elucidated. By interrogating the TCGA database, we found that cancer patients with high NKX3-2 expression had a shorter overall survival rate than patients with low expression. In ovarian cancer patients, NKX3-2 negatively correlates with P53. Given the prominent role of the latter oncosuppressor in controlling DNA repair and cell death, here we investigate the molecular mechanism involved in this negative correlation in several ovarian cancer cell lines expressing different levels of the two proteins. We found that the high expression of endogenous or ectopic P53 reduced NKX3-2 protein expression, while its knockdown increased it. In contrast, the genetic manipulation of NKX3-2 expression did not affect P53 expression. Mechanistically, P53-mediated downregulation of NKX3-2 does not entail transcriptional activity or proteasomal clearance but occurs via P53–NKX3-2 protein–protein interaction, which in turn results in P53-induced NKX3-2 degradation via the autophagy–lysosome pathway. Remarkably, patients bearing a tumor characterized by low NKX3-2 and high MAP1LC3B expression (indicative of active autophagy) display a better prognosis. Taken together, our data indicate that NKX3-2 represents a negative prognostic factor under P53 control in ovarian cancer. From a translational point of view, identifying this novel mechanism may represent a new molecular signature capable of predicting the clinical outcome of patients, a crucial aspect of developing personalized therapeutic approaches
