University of Bari Aldo Moro
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Can Focused Ultrasound Overcome the Failure of Chemotherapy in Treating Pediatric Diffuse Intrinsic Pontine Glioma Due to a Blood–Brain Barrier Obstacle?
No full textBackground: The blood–brain barrier (BBB) plays an important role in regulating homeostasis of the central nervous system (CNS), and it is an obstacle for molecules with a molecular weight higher than 500 Da seeking to reach it, making many drugs ineffective simply because they cannot be delivered to where they are needed. As a result, crossing the BBB remains the rate-limiting factor in brain drug delivery during the treatment of brain diseases, specifically tumors such as diffuse intrinsic pontine glioma (DIPG), a highly aggressive pediatric tumor with onset in the pons Varolii, the middle portion of the three contiguous parts of the brainstem, located above the medulla and below the midbrain. Methods: Currently, radiotherapy (RT) relieves DIPG symptoms but chemotherapy drugs do not lead to significant results as they do not easily cross the BBB. Focused ultrasound (FUS) and microbubbles (MBs) can temporarily open the BBB, facilitating radiotherapy and the entry of drugs into the CNS. A patient-derived xenograft DIPG model exposed to high-intensity focalized ultrasound (HIFU) or low-intensity focalized ultrasound (LIFU) combined with MBs was treated with doxorubicin, panobinostat, olaparib, ONC201 (Dordaviprone®) and anti-PD1. Panobinostat has also been used in children with diffuse midline glioma, a broad class of brain tumors to which DIPG belongs. Results: Preliminary studies were performed using FUS to temporarily open the BBB and allow a milder use of radiotherapy and facilitate the passage of drugs through the BBB. The data collected show that after opening the BBB with FUS and MBs, drug delivery to the CNS significantly improved. Conclusions: FUS associated with MBs appears safe and feasible and represents a new strategy to increase the uptake of drugs in the CNS and therefore enhance their effectiveness. This review reports pre-clinical and clinical studies performed to demonstrate the usefulness of FUS in patients with DIPG treated with some chemotherapy. The papers reviewed were published in PubMed until the end of 2024 and were found using a combination of the following keywords: diffuse intrinsic pontine glioma (DIPG), DIPG H3K27-altered, blood–brain barrier and BBB, focused ultrasound (FUS) and radiotherapy (RT)
Pharmacological therapy of non-dystrophic myotonias
Get PDFObjectives. Non-dystrophic myotonias (NDM) are rare diseases due to mutations in the voltage-gated sodium (Nav1.4) and chloride (ClC-1) channels expressed in skeletal muscle fibers. We provide an up-to-date review of pharmacological treatments available for NDM patients and experimental studies aimed at identifying alternative treatments and at better understanding the mechanisms of actions. Methods. Literature research was performed using PubMed and ClinicalTrial.gov. Results. Today, the sodium channel blocker mexiletine is the drug of choice for treatment of NDM. Alternative drugs include other sodium channel blockers and the carbonic anhydrase inhibitor acetazolamide. Preclinical studies suggest that activators of ClC-1 channels or voltage-gated potassium channels may have antimyotonic potential. Conclusions. An increasing number of antimyotonic drugs would help to design a precision therapy to address personalized treatment of myotonic individuals
Leveraging explainable AI to predict soil respiration sensitivity and its drivers for climate change mitigation
Get PDFGlobal warming is one of the most pressing and critical problems facing the world today. It is mainly caused by the increase in greenhouse gases in the atmosphere, such as carbon dioxide (CO2). Understanding how soils respond to rising temperatures is critical for predicting carbon release and informing climate mitigation strategies. Q10, a measure of soil microbial respiration, quantifies the increase in CO2 release caused by a Celsius rise in temperature, serving as a key indicator of this sensitivity. However, predicting Q10 across diverse soil types remains a challenge, especially when considering the complex interactions between biochemical, microbiome, and environmental factors. In this study, we applied explainable artificial intelligence (XAI) to machine learning models to predict soil respiration sensitivity (Q10) and uncover the key factors driving this process. Using SHAP (SHapley Additive exPlanations) values, we identified glucose-induced soil respiration and the proportion of bacteria positively associated with Q10 as the most influential predictors. Our machine learning models achieved an accuracy of, precision of, an AUC-ROC of, and an AUC-PRC of, ensuring robust and reliable predictions. By leveraging t-SNE (t-distributed Stochastic Neighbor Embedding) and clustering techniques, we further segmented low Q10 soils into distinct subgroups, identifying soils with a higher probability of transitioning to high Q10 states. Our findings not only highlight the potential of XAI in making model predictions transparent and interpretable, but also provide actionable insights into managing soil carbon release in response to climate change. This research bridges the gap between AI-driven environmental modeling and practical applications in agriculture, offering new directions for targeted soil management and climate resilience strategies
Spain
No full textThis is the 5th edition of The International Review of Constitutional Reform (ISBN: 978-1-7374527-8-2).
The International Review of Constitutional Reform (IRCR) is a first-of-its-kind scholarly effort to gather jurisdictional reports--written by scholars and judges, often in collaboration--on all forms of constitutional revision around the world over the past year.
This edition contains more than 100 jurisdictional reports. Each report explains and contextualizes events in constitutional reform over the previous year in a given jurisdiction. Constitutional reform is defined broadly to include constitutional amendment, constitutional dismemberment, constitutional mutation, constitutional replacement and other events in constitutional reform, including the judicial review of constitutional amendments
Association Between Decision-Making Styles, Personality Traits, and Socio-Demographic Factors in Women Choosing Voluntary Pregnancy Termination: A Cross-Sectional Study
No full textPersonality traits, decision-making styles, and socio-demographic information help understand the characteristics of women requesting voluntary termination of pregnancy (VTP) and monitor the timing and quality of this service However, our current data do not allow for an in-depth exploration of additional, less evident factors that might influence the decision. The aim was to characterise a sample of women requesting VTP in terms of socio-demographic, personality, and decision-making style variables, and to examine the associations among these factors. We conducted a cross-sectional study administering the General Decision-Making Style (GDMS) test, the Big Five Questionnaire (BFQ) and the Personality Inventory for DSM-5 (PID-5) to women requesting VTP certification. BFQ scores were generally high, especially for "Conscientiousness" and "Openness". "Agreeableness" and "Openness" scores were lower in women with low vs. high education (diff = -8.2 [-13.9, -2.4] and diff = -7.5 [-15.0, -0.1]); "Extraversion" was higher in employed women. PID-5 scores for "Detachment" and "Psychoticism" were higher in medium vs. high education (diff = 1.6 [0.05, 3.2] and diff = 1.9 [0.1, 3.8]), but not at pathological level; "Negative affect" was lower in women with children (diff = -1.6 [-3.1, -0.2]). GDMS scores were not associated with socio-demographic factors. "Avoidant" and "Spontaneous" styles were negatively associated with "Conscientiousness" and "Emotional Stability"; "Rational" style was positively associated with "Conscientiousness" and "Disinhibition". High BFQ and low PID-5 scores suggest no personality dysfunction in women undergoing VTP. No predominant decision-making style emerged, but associations between personality traits, decision-making, and socio-demographic factors such as educational level, employment and parity, were observed
Very high energy observations of the Seyfert galaxy NGC 4151 with MAGIC
No full textSeyfert galaxies are emerging as a promising source class of high-energy neutrinos. The Seyfert galaxies NGC 4151 and NGC 1068 have respectively come up as the most promising counterparts of a 3σ and of a 4.2σ neutrino excesses detected by IceCube in the TeV energy range. Constraining the very high energy (VHE) emission associated with the neutrino signal is crucial to unveiling the mechanism and site of neutrino production. In this work, we present the first results of the VHE observations (∼29 hours) of NGC 4151 with the MAGIC telescopes. We detected no gamma-ray excess in the direction of NGC 4151, and we derived constraining upper limits on the VHE gamma-ray flux. The integral flux upper limit (at the 95% confidence level) above 200 GeV is f = 2.3 × 10−12 cm−2 s−1. Comparison of the MAGIC and IceCube measurements suggests the presence of a gamma-ray obscured accelerator, and it allowed us to constrain the gamma-ray optical depth and the size of the neutrino production site
DOES NON-CONVENTIONAL WATER USE IMPACT THE PERFORMANCE OF IRRIGATION COMMUNITIES IN WATER-SCARCE REGIONS?
No full textIrrigation Communities (ICs) are crucial for sustainable water management in arid regions like the Mediterranean. To address water scarcity, many ICs have integrated non-conventional water (NCW) sources, such as reclaimed
and desalinated water. This study examines the impact of NCW on IC performance using benchmarking, principal component analysis, and cluster analysis across 19 ICs in Murcia, Spain, from 2019 to 2021. Results show significant variability: top-performing ICs excel in operational and financial aspects but struggle with productivity, while larger, modernized ICs achieve high water efficiency despite supply variability and deficit irrigation. Regression analysis confirms that NCW enhances water supply reliability and overall IC performance but increases
costs, particularly through desalination, which reduces gross margins. Despite these challenges, NCW is vital for regional water security. Achieving long-term sustainability will require technological improvements, renewable energy adoption, and supportive governance to reduce costs and enhance resilience against water scarcity
Modelli scolastici nell’Oltremare italiano: oltre la retorica degli italiani «bravi gente»
No full textIl saggio intende approfondire le ragioni educative e politiche sottese allo sviluppo dell’istruzione nelle colonie africane italiane nel corso degli anni Trenta del secolo scorso, alla luce del coevo contesto internazionale. L’obiettivo del contributo è mostrare la fragilità, in termini fattuali, del mito coloniale divisivo degli italiani «brava gente», che si sarebbero distinti dalle altre potenze imperialistiche europee per un approccio più umano e tollerante nei confronti dei popoli assoggettati. Lo studio della documentazione conservata presso l’Archivio Centrale di Stato a Roma ha permesso di verificare la presenza di un ordinamento scolastico coloniale teso a preservare l’esistenza di due diversi livelli di istruzione: il primo, dotato di carattere elitario e riservato agli alunni europei, il secondo, invece, suddiviso a sua volta in tre gradi distinti, riservato agli
indigeni. L’analisi del progetto di riforma per l’istruzione dei sudditi coloniali, avviato
sul finire degli anni Trenta, pur non comportando conseguenze pratiche rilevanti, in
considerazione dell’approssimarsi del secondo conflitto mondiale, si rivela di grande
interesse euristico perché ha svelato quali fossero gli intenti formativi ed educativi propri
del regime fascista in colonia, in una fase storica nella quale era stato promulgato il
razzismo di Stato. In particolare, come emerge dall’analisi delle carte prodotte dal
Ministero dell’Africa Italiana, l’istruzione coloniale aveva l’obiettivo di avviare i giovani
indigeni principalmente allo svolgimento di attività agricole nel territorio dell’Africa
Orientale Italiana, educandoli, parimenti, alla subalternità nei confronti delle autorità
italiane
Napoli, Archivio di Stato, Regia Camera della Sommaria, Dipendenze, II serie, 74/194
No full textEdizione in forma di tabella di un registro di introito dei diritti di fondaco e piazza di Barletta (VII ind., probabilmente 1459-1460), conservato nell'Archivio di Stato di Napoli (Sommaria, Dipendenze, II ser., 74/194
Search for the lepton-flavour-violating decays B0→ K*0τ±e∓
No full textA first search at LHCb for the lepton-flavour-violating decays B0 → K*0τ±e∓ is presented. The analysis is performed using a sample of proton-proton collision data, collected with the LHCb detector at a centre-of-mass energy of 13 TeV between 2016 and 2018, corresponding to an integrated luminosity of 5.4 fb−1. No significant signal is observed, and upper limits on the branching fractions are determined to be BB0→K∗0τ−e+<5.97.1×10−6 and BB0→K∗0τ+e−<4.95.9×10−6 at the 90% (95%) confidence level. These results correspond to the current most stringent upper limits for b → sτl transitions