Haploidentical Hematopoietic Stem Cell Transplantation: Step-by-Step Progress

n/

Brain fitness, “Tête bien faite”, enazione. Dalla pedagogia del contenuto alla pedagogia del contenitore

The aim of this paper is to propose a pedagogy of the container to integrate to a pedagogy of the content and information. A new framework is provided concerning with the fitness of the child brain in his relationship with the caregiver within a more aware and strategic interaction which triggersimportant developments and structural-anatomical modifications of the brain in order to achieve a more explicit learning in the future ages of life. This pedagogy uses the species-specific processing of the human organism following the Middle Age statement: Omnis recipitur per modum recipientis, everything receives to the extent of its capacity of receiving. We support this claim adding the idea of a dynamic perceptual and cognitive receiving in which the container tends tomodify its capacity according to the amount and quality of motor and cognitive learnings and stimulations to which it is exposed during childhood.This kind of pedagogy have to be integrated with a most representational and cognitive perspective, but maintining a strong senory-motor and enactive bodily-grounded perspective. The contemporary development of neurosciences allow us to rethink the mind not only like a container for contents, but as container able to structural modifications and with a complex management of the neurophysiological processing that will support the parallel functional information processing. Thus mind is not only a container in which one can pass down knowledge, but a dynamical organ with an its own particular fitness and plasticity. The hebbian plasticity and the new framework of homeostaticsynaptic plasticity (Turrigiano 2012) help us to provide a consistent account of a new kind of education of the erlier childhood and of all periods of the life. A paradigm that can be integrate with the Edgar Morin (1999) theory of the Tête bien faite, in which the neuro-biological perspective opens to the a bio-anthropological and socio-cultural complexity framework.Lo scopo del presente contributo è di proporre una pedagogia del contenitore da integrare alla classica pedagogia del contenuto in relazione alla fitness cui il caregiver può sottoporre il neonato con una interazione strategica e consapevole innescando sviluppi e modificazioni strutturalianatomiche del suo cervello che saranno importanti per l’apprendimento più consapevole degli annifuturi. Essa sfrutta il processing specie-specifico dell’organismo umano rielaborando in ottica pedagogica la sentenza medievale per cui: Omnis recipitur per modum recipientis. Cui si aggiunge l’idea che il ricevente non è statico, ma modifica e amplifica se stesso e le proprie capacità a seconda degli stimoli che riceve nella propria formazione e dell’apprendimento motorio e non solo cognitivo che egli compie.Questa pedagogia si andrà poi intrecciando a quella più rappresentazionale- cognitiva mantenendo stabile una forte base senso-motoria ed enattiva di tipo bodily grounded. Lo sviluppo odierno delle neuroscienze e delle scienze cognitive permettono di ripensare la mente non solo come un organo che incamera contenuti, ma come un apparato complesso di gestione delle stesse modalità e reti di presa in carico di questi contenuti. Occorre dunque educare la mente e formarla non solo per ricevere e trasferire informazioni, ma anche per predisporsi al meglio a questo trasferimento. La teoria della plasticità sinaptica permette di ipotizzare una forma di educazione precoce del bambino cheabbia di mira la strutturazione di un cervello ben fatto in grado in seguito di diventare la testa ben fatta teorizzata da Edgar Morin

Jack of all trades: thymosin α1 and its pleiotropy

n/

LOB-Based Deep Learning Models for Stock Price Trend Prediction: A Benchmark Study

The recent advancements in Deep Learning (DL) research have notably influenced the finance sector. We examine the robustness and generalizability of fifteen state-of-the-art DL models focusing on Stock Price Trend Prediction (SPTP) based on Limit Order Book (LOB) data. To carry out this study, we developed LOBCAST, an open-source framework that incorporates data preprocessing, DL model training, evaluation and profit analysis. Our extensive experiments reveal that all models exhibit a significant performance drop when exposed to new data, thereby raising questions about their real-world market applicability. Our work serves as a benchmark, illuminating the potential and the limitations of current approaches and providing insight for innovative solutions

Treg/Tcon Immunotherapy and High Dose Marrow Irradiation Ensure Full Control of Leukemia Relapse in Haploidentical Transplantation

Allogeneic hematopoietic stem cell transplantation (HSCT) is the most powerful therapy for patients with high risk of relapse. In spite of that, no matter the donor source or conditioning regimen used, leukemia relapse is still the leading cause of HSCT failure. In HLA-haploidentical HSCT, we recently applied a clinical protocol consisting of total body irradiation (TBI)-based conditioning regimen and a peripheral blood CD34+ cell graft combined with the adoptive transfer of naturally occurring regulatory T cells (Tregs) and conventional T cells (Tcons). No post-transplant pharmacologic GvHD prophylaxis was given. Such protocol was associated with low GvHD and relapse rate (Martelli et al., Blood 2014). To further reduce leukemia relapse in Treg/Tcon-based haploidentical HSCT (Treg/Tcon haplo-HSCT) we used high dose hyper-fractionated TBI (HF-TBI) in the conditioning regimen. We also extended Treg/Tcon haplo-HSCT to patients that are unfit (because of previous comorbidities) and/or too old to withstand high intensity regimens. In these patients the extra-hematologic toxicity of irradiation was reduced with the use of targeted total marrow and lymph node irradiation (TMLI). 40 patients with high risk acute leukemia (36 AML, 4 ALL) received Treg/Tcon haplo-HSCT. All but 3 patients were transplanted in complete remission. 12 younger patients (median age: 28, range: 20-43) received HF-TBI, while 28 older or unfit patients (59, 40-70) received TMLI in the conditioning regimen. HF-TBI (14.4 Gy) was administered in 12 fractions, 3 times a day for 4 days. TMLI was administered by means of Helical Tomotherapy HI-ART (9 fractions, 2 times a day for 4.5 days). Irradiation was followed by chemotherapy with Thiotepa, Fludarabine, and Cyclophosphamide. 2 × 106/kg freshly isolated CD4+CD25+FOXP3+ Tregs were transferred 4 days before the infusion of 1 × 106/kg Tcons and a mega-dose of CD34+ hematopoietic stem cells. No post-transplant pharmacologic GvHD prophylaxis was given. 38/40 patients engrafted. 12 (31%) developed aGvHD grade ³2 (10 are alive and off-therapy). 6 (16%) died because of transplant related complications (2 because of aGvHD, 2 infections, 1 veno-occlusive disease, 1 intracranial hemorrhage). Strikingly, despite the high risk diseases, no patient relapsed after a median follow up of 13 months (range 1-36, Fig. A). Further, only 1 patient developed cGvHD. Thus, cGvHD/Leukemia-free survival was 82% (Fig. B). Treg adoptive transfer allows for the safe infusion of an otherwise lethal dose of donor alloreactive Tcons in the absence of any other form of immune suppression. Our results demonstrate that the potent graft versus leukemia effect of Treg/Tcon adoptive transfer was boosted by high dose marrow irradiation. Thus, this study proves that the right combination of haploidentical Treg/Tcon immunotherapy plus a powerful conditioning regimen can fully eradicate leukemia

AI-based Data Preparation and Data Analytics in Healthcare: The Case of Diabetes

The Associazione Medici Diabetologi (AMD) collects and manages one of the largest worldwide-available collections of diabetic patient records, also known as the AMD database. This paper presents the initial results of an ongoing project whose focus is the application of Artificial Intelligence and Machine Learning techniques for conceptualizing, cleaning, and analyzing such an important and valuable dataset, with the goal of providing predictive insights to better support diabetologists in their diagnostic and therapeutic choices.Comment: The work has been presented at the conference Ital-IA 2022 (https://www.ital-ia2022.it/

Long-Term Outcome After Adoptive Immunotherapy With Natural Killer Cells: Alloreactive NK Cell Dose Still Matters

Recently, many reports were published supporting the clinical use of adoptivelytransferred natural killer (NK) cells as a therapeutic tool against cancer, including acutemyeloid leukemia (AML). Our group demonstrated promising clinical response usingadoptive immunotherapy with donor-derived alloreactive KIR-ligand-mismatched NK cellsin AML patients. Moreover, the antileukemic effect was correlated with the dose of infusedalloreactive NK cells (“functional NK cell dose”). Herein, we update the results of ourprevious study on a cohort of adult AML patients (median age at enrollment 64) infirstmorphological complete remission (CR), not eligible for allogeneic stem celltransplantation. After an extended median follow-up of 55.5 months, 8/16 evaluablepatients (50%) are still off-therapy and alive disease-free. Overall survival (OS) and disease-free survival (DFS) are related with the dose of infused alloreactive NK cells (≥2×105/kg