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DEVELOPMENT OF A NEW SCORE BASED ON IMAGE DEFINED RISK FACTORS TO STANDARDIZE SURGICAL RISK IN NEUROBLASTOMA RESECTION - A SIOPEN COLLABORATIVE STUDY
No full textBackground and aims: Image Defined Risk Factors (IDRFs) assess surgical risk in neuroblastoma (NB) and guide neoadjuvant therapy. Despite chemotherapy IDRFs may persist in 70 % of cases. Several studies have suggested that not all IDRFs hold equal significance and that the presence of an IDRF does not inherently signify unresectability. This current study seeks to stratify and assign a score to each IDRF based on its impact on surgical risk. Methods: This collaborative study entailed retrospective collection of patient data from NB operations conducted between 2016 and 2020, together with the computation of a Surgical Complexity Index (SCI) for every patient. The SCI values obtained were correlated with preoperatively identified IDRFs. Mann–Whitney statistical test was employed to assign a relevance score to the association between individual IDRFs and SCI. Results: 14 centers contributed 427 neuroblastoma index cases meeting study inclusion criteria. 303 patients had 1 or more IDRFs. ..
Nutraceuticals and Supplements in Management of Prediabetes and Diabetes
Full text linkDysglycemia is a condition preceding diabetes mellitus. The two situations inherent in this condition are called impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). If one of these situations is found in the patient, after the advice of an appropriate diet and physical activity, the addition of nutraceuticals or supplements can be considered, which can stop or delay the progression to diabetes mellitus over time. The purpose was to compile a systematic review about the use of nutraceuticals for treating diabetes and prediabetes and to offer a valuable resource for colleagues working on this crucial subject, thereby improving patient health. The added value of the paper compared to other reviews is that it was written by experts appointed by five different scientific societies dealing with diabetes, nutrition, and complications
Automated Synthesis of Certified Neural Networks: Initial Results and Open Research Lines
Full text linkCertifying machine learning systems has become more and more important, especially when they are deployed in safety critical domains. In this paper, we sum up the work in [1] that combines Deep Learning with Formal Methods for the automated synthesis of certified neural networks and we discuss current open research lines
The effect of occlusion on the visual working memory pointer-system
No full textTo access its online representations, visual working memory (VWM) relies on a pointer-system that creates correspondence between objects in the environment with their memory representations. This pointer-system allows VWM to modify its representations using a process called updating. When the pointer is invalidated, however, VWM triggers a process called resetting in which the no longer relevant representation and pointer are replaced. Past studies used the contralateral delay activity (CDA) to differentiate between updating and resetting and found that resetting is followed by a drop in the CDA amplitude. The current study aimed to investigate the effects of occlusion on VWM representations and the resetting process across four experiments. Experiment 1 examined whether resetting occurs with occluded changes and compared the CDA of occluded versus visible objects. The results indicated a decline in CDA amplitude during occlusion, but it was unclear if resetting occurred when the change was occluded due to the lack of time-locked changes. To better isolate the resetting process, Experiment 2 used a brief occluder appearances (100 ms) and observed a CDA drop likely due to an ERP response to the sudden stimulus appearance. This drop occurred earlier than the resetting CDA drop and appeared even in conditions that did not trigger resetting, which indicates that it might be an ERP response to the short and sudden appearance of a stimulus. Experiment 3 further isolated this ERP response, confirming the early CDA drop as a reaction to the occluder's onset and offset. Experiment 4, which included occluders that did not flash to avoid ERP responses, found a CDA drop indicating that resetting can occur with inferred changes. These findings suggest that VWM maintains representations of occluded objects, and can update or reset these representations based on inferred changes, with brief stimuli eliciting ERP responses that affect CDA amplitude
Structural study of Lindqvist polyoxovanadate-peptide conjugates
Full text linkPolyoxometalates (POMs) are inorganic molecular clusters that exhibit significant biological activity against various pathologies, including cancer. Despite their therapeutic potential, the clinical application of POMs is limited by challenges such as low selectivity and toxicity. To overcome these limitations, conjugation with targeting moieties such as biomolecules and peptides has emerged as a promising strategy to enhance their selectivity. Within this context, the use of spacers can reduce intramolecular interactions between the POM surface and targeting molecules, thereby maintaining their accessibility for biological recognition. In this study, the Lindqvist hexavanadate cluster is functionalized with the antagonist peptide demobesin-1 (DB), both with and without spacers, to evaluate the impact of this modification on peptide conformation and biological activity. Our findings provide valuable insights into the optimization of POM-based therapeutic agents with improved selectivity and reduced toxicity
Childhood BMI trajectories and sociodemographic factors in an Italian pediatric population
Full text linkChildhood obesity is a growing global concern due to its long-term health consequences. Yet, more research relying on multiple time-point BMI measurements is warranted to gain further insight into obesity’s temporal trends. We aimed to identify BMI trajectories in children aged 2–10 years and evaluate their association with sociodemographic factors. This retrospective cohort study utilized data from the PEDIANET registry, containing sociodemographic, clinical, and prescribing information on patients assisted by Italian family pediatricians, linked to the corresponding area deprivation index. 29,576 children with at least 10 years of follow-up, born at term with normal birthweight, and at least three plausible BMI measurements were identified. BMI z-score trajectories were calculated using Group-Based Trajectory Modeling, and mixed multinomial logistic regression was used to assess their association with the sociodemographic factors. A secondary analysis examined BMI trajectories from a..
Ritorno al futuro: il perimetro di sicurezza nazionale cibernetica
No full textL'evoluzione degli ordinamenti giuridici ha avuto un impatto significativo sulla funzione di pubblica sicurezza, ridefinendo i concetti e le pratiche correlate. Le categorie tradizionali della teoria generale della sicurezza, quali i principi di precauzione e prevenzione, e il ricorso a concetti giuridici indeterminati per legittimare il potere esercitato, manifestano la complessità nel rispondere alle nuove sfide e la necessità di trovare criteri di bilanciamento del potere e degli interessi coinvolti. La sicurezza, considerata come un concetto olistico e poliedrico, si è ampliata per includere la dimensione della cybersicurezza, un ambito sempre più centrale nelle moderne politiche di sicurezza, ampliando anche il potere amministrativo di tutela in via preventiva. Uno degli strumenti nuovi attraverso cui si esplica questa funzione antica è il perimetro di sicurezza nazionale cibernetica. Esso rappresenta uno strumento cruciale per proteggere gli interessi strategici del paese, individuando i soggetti inclusi a cui imporre obblighi preventivi e successivi per la tutela delle funzioni e dei servizi essenziali dello Stato. La natura del potere esercitato in questo contesto, le peculiarità del procedimento e gli effetti sull’attività dei soggetti inclusi, sollevano importanti questioni riguardanti le garanzie e le tutele necessarie per bilanciare la sicurezza nazionale con i diritti individuali e collettivi
3D bioprinting for the production of a perfusable vascularized model of a cancer niche
Full text linkThe ever-growing need for improved in vitro models of human tissues to study
both healthy and diseased states is advancing the use of techniques such as 3D
Bioprinting. We here present our results on the development of a vascularized
and perfusable 3D tumor mimic for studies of the early steps of Neuroblastoma
metastatic spread. We used a multi-material and sacrificial bioprinting approach
to fabricate vascularized 3D cell-laden structures and developed a customized
perfusion system enabling maintenance of growth and viability of the constructs
for up to 3 weeks. Cell phenotypes and densities in co-culture for both the bulk of
the construct and the endothelialization of the vascular channels were optimized
to better replicate in vivo conditions and ideally simulate tumor progression. We
proved the formation of an endothelium layer lining the vascular channel after
14 days of perfused culture. Cells in the bulk of the construct reflected
Neuroblastoma growth and its tendency to recruit endothelial cells
contributing to neovascularization. We also collected preliminary evidence of
Neuroblastoma cells migration towards the vascular compartment, recapitulating
the first stages of metastatic dissemination
Neoadjuvant nivolumab and chemotherapy in early estrogen receptor-positive breast cancer: a randomized phase 3 trial
No full textPatients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) primary breast cancer (BC) have low pathological complete response (pCR) rates with neoadjuvant chemotherapy. A subset of ER+/HER2- BC contains dense lymphocytic infiltration. We hypothesized that addition of an anti-programmed death 1 agent may increase pCR rates in this BC subtype. We conducted a randomized, multicenter, double-blind phase 3 trial to investigate the benefit of adding nivolumab to neoadjuvant chemotherapy in patients with newly diagnosed, high-risk, grade 3 or 2 (ER 1 to = 1%: 44.3% versus 20.2% respectively). There were no new safety signals identified. Of the five deaths that occurred in the nivolumab arm, two were related to study drug toxicity; no deaths occurred in the placebo arm. Adding nivolumab to neoadjuvant chemotherapy significantly increased pCR rates in high-risk, early-stage ER+/HER2- BC, particularly among patients with higher stromal tumor-infiltrating lymphocyte levels or programmed death ligand 1 expression, suggesting a new treatment paradigm that emphasizes the role of immunotherapy and T cell immunosurveillance in luminal disease. Clinical trials.gov identifier: NCT0410906