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Triple combination targeting PI3K,ER,and CDK4/6 inhibits growth of ER-positive breast cancer resistant to fulvestrant and CDK4/6 or PI3K inhibitor

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Cancer Communications 2023年第6期43卷 720-725页

作者： Mikkel G.Terp martina tuttolomondo Neil Portman Sidse Ehmsen Lene E.Johansen Martin Bak Elgene Lim Henrik J.Ditzel Department of Cancer and Inflammation Research Institute of Molecular MedicineUniversity of Southern DenmarkOdenseDenmark Garvan Institute of Medical Research DarlinghurstSydneyNew SouthWalesAustralia St.Vincent’s Clinical School Faculty of MedicineUniversity of New SouthWales SydneySydneyNew South WalesAustralia Department of Oncology Institute of Clinical ResearchOdense University HospitalOdenseDenmark Department of Pathology Sydvestjysk SygehusEsbjergDenmark Academy of Geriatric Cancer Research(AgeCare) Odense University HospitalOdenseDenmark

Dear Editor,Despite the improved outcome of advanced estrogen receptor-positive(ER+)breast cancer patients treated with endocrine therapy in combination with either a cyclindependent kinase 4/6 inhibitor(CDK4/6i)or a phosphoinositide 3-kinase inhibitor(PI3Ki),the disease will eventually progress,and the optimal treatment strategy upon progression remains undefined[1-4].To address this,we developed MCF-7-and T47D-derived PIK3CAmutated breast cancer cell lines[5]resistant to combined CDK4/6i palbociclib and fulvestrant(MPF-R and TPFR)or combined PI3Ki alpelisib and fulvestrant(MAF-R and TAF-R),respectively(Supplementary Materials and Methods).Drug-sensitive isogenic cells(M-S and T-S)grown in parallel with MPF-R and TPF-R cells and the original MCF-7/S0.5 and T47D cells were analyzed for comparison.

关键词： PIK3CA breast cancer

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Machine learning applications in stroke medicine:advancements,challenges,and future prospectives

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Neural Regeneration Research 2024年第4期19卷 769-773页

作者： Mario Daidone Sergio Ferrantelli Antonino tuttolomondo Internal Medicine and Stroke Care Ward Department of Health PromotionMother and Child CareInternal Medicine and Medical SpecialtiesUniversity of Palermo Molecular and Clinical Medicine PhD Program University of Palermo

Stroke is a leading cause of disability and mortality worldwide,necessitating the development of advanced technologies to improve its diagnosis,treatment,and patient *** recent years,machine learning techniques have emerged as promising tools in stroke medicine,enabling efficient analysis of large-scale datasets and facilitating personalized and precision medicine *** abstract provides a comprehensive overview of machine learning’s applications,challenges,and future directions in stroke *** introduced machine learning algorithms have been extensively employed in all the fields of stroke *** learning models have demonstrated remarkable accuracy in imaging analysis,diagnosing stroke subtypes,risk stratifications,guiding medical treatment,and predicting patient *** the tremendous potential of machine learning in stroke medicine,several challenges must be *** include the need for standardized and interoperable data collection,robust model validation and generalization,and the ethical considerations surrounding privacy and *** addition,integrating machine learning models into clinical workflows and establishing regulatory frameworks are critical for ensuring their widespread adoption and impact in routine stroke *** learning promises to revolutionize stroke medicine by enabling precise diagnosis,tailored treatment selection,and improved *** research and collaboration among clinicians,researchers,and technologists are essential for overcoming challenges and realizing the full potential of machine learning in stroke care,ultimately leading to enhanced patient outcomes and quality of *** review aims to summarize all the current implications of machine learning in stroke diagnosis,treatment,and prognostic *** the same time,another purpose of this paper is to explore all the future perspectives these techniques can provide in combating this disabling dis

关键词： cerebrovascular disease deep learning machine learning reinforcement learning stroke stroke therapy supervised learning unsupervised learning

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Non-coding RNAs and other determinants of neuroinflammation and endothelial dysfunction:regulation of gene expression in the acute phase of ischemic stroke and possible therapeutic applications

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Neural Regeneration Research 2021年第11期16卷 2154-2158页

作者： Mario Daidone Marco Cataldi Antonio Pinto Antonino tuttolomondo Department of Health Promotion Maternal and Infant CareInternal Medicine and Medical Specialties“G.D’Alessandro”University of PalermoPiazza delle Cliniche n.2PalermoItaly

Ischemic stroke occurs under a variety of clinical conditions and has different pathogeneses,resulting in necrosis of brain *** pathogenesis is characterized by neuroinflammation and endothelial *** of the main processes triggered in the early stages of ischemic damage are the rapid activation of resident inflammatory cells(microglia,astrocytes and endothelial cells),inflammatory cytokines,and translocation of intercellular nuclear *** in stroke includes all the processes mentioned above,and it consists of either protective or detrimental effects concerning the“polarization”of these *** polarization comes out from the interaction of all the molecular pathways that regulate genome expression:the epigenetic *** recent years,new regulation mechanisms have been cleared,and these include non-coding RNAs,adenosine receptors,and the activity of mesenchymal stem/stromal cells and *** reviewed how long non-coding RNA and microRNA have emerged as an essential mediator of some neurological *** also clarified that their roles in cerebral ischemic injury may provide novel targets for the treatment of ischemic *** date,we do not have adequate tools to control pathophysiological processes associated with *** goal is to review the role of non-coding RNAs and innate immune cells(such as microglia and mesenchymal stem/stromal cells)and the possible therapeutic effects of their modulation in patients with acute ischemic stroke.A better understanding of the mechanisms that influence the“polarization”of the inflammatory response after the acute event seems to be the way to change the natural history of the disease.

关键词： acute phase cerebrovascular disease endothelial dysfunction epigenetics genetics neuroiflammation non-coding RNAs stroke

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Diabetic foot syndrome:Immune-inflammatory features as possible cardiovascular markers in diabetes

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World Journal of Orthopedics 2015年第1期6卷 62-76页

作者： Antonino tuttolomondo Carlo Maida Antonio Pinto Dipartimento Biomedico di Medicina Interna e Specialistica U.O.C di Medicina Interna e CardioangiologiaUniversità degli Studi di Palermo

Diabetic foot ulcerations have been extensively reported as vascular complications of diabetes mellitus associated with a high degree of morbidity and mortality. Diabetic foot syndrome(DFS), as defined by the World Health Organization, is an "ulceration of the foot(distally from the ankle and including the ankle) associated with neuropathy and different grades of ischemia and infection". Pathogenic events able to cause diabetic foot ulcers are *** the commonest causes of this pathogenic pathway it's possible to consider peripheral neuropathy, foot deformity, abnormal foot pressures, abnormal joint mobility, trauma, peripheral artery disease. Several studies reported how diabetic patients show a higher mortality rate compared to patients without diabetes and in particular these studies under filled how cardiovascular mortality and morbidity is 2-4 times higher among patients affected by type 2 diabetes mellitus. This higher degree of cardiovascular morbidity has been explained as due to the observed higher prevalence of major cardiovascular risk factor, of asymptomatic findings of cardiovascular diseases, and of prevalence and incidence of cardiovascular and cerebrovascular events in diabetic patients with foot complications. In diabetes a fundamental pathogenic pathway of most of vascular complications has been reported as linked to a complex interplay of inflammatory, metabolic and procoagulant variables. These pathogenetic aspects have a direct interplay with an insulin resistance, subsequent obesity, diabetes, hypertension, prothrombotic state and blood lipid disorder. Involvement of inflammatory markers such as IL-6 plasma levels and resistin in diabetic subjects as reported by tuttolomondo et al confirmed the pathogenetic issue of the a "adipo-vascular" axis that may contribute to cardiovascular risk in patients with type 2 diabetes. This "adipo-vascular axis" in patients with type 2 diabetes has been reported as characterized by lower plasma l

关键词： Diabetic foot syndrome Inflammation Cytokines Cardiovascular risk Marker

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When sepsis affects the heart: A case report and literature review

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World Journal of Clinical Cases 2015年第8期3卷 743-750页

作者： Giuseppe Clemente Antonino tuttolomondo Daniela Colomba Rosaria Pecoraro Chiara Renda Vittoriano Della Corte Carlo Maida Irene Simonetta Antonio Pinto U.O.C.di Medicina Interna e Cardioangiologia University of Palermo

A 59-year-old nursing home patient with Down syndrome was brought to the internal medicine department of our hospital due to fever, cough without expectorate, and dyspnea. A thoracic computed tomography revealed the presence of bilateral basal parenchymal opacities. Her condition deteriorated after admission and troponin reached a peak serum concentration of 16.9 ng/m L. The patient was in cardiogenic shock. In addition to fluid resuscitation, vaso-active amine infusion was administered to achieve hemodynamic stabilization. The differential diagnosis investigated possible pulmonary embolism, myocardial infarction, and myocarditis. Furthermore, a second transthoracic echocardiogram suggested Tako-Tsubo syndrome. This is a septic patient. The purpose of this manuscript is to review studies which formerly examined the possible association between high levels of troponin and mortality to see if it can be considered a positive predictive factor of fatal prognosis as the case of thrombocytopenia, already a positive independent predictive factor of multiple organ failure syndrome, and generally to characterize risk profile in a septic patient.

关键词： Sepsis Shock Hypotension Troponin Myocardial dysfunction

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