Blockade of the co-inhibitory molecule PD-1 unleashes ILC2-dependent antitumor immunity in melanoma.

Group 2 innate lymphoid cells (ILC2s) are essential to maintain tissue homeostasis. In cancer, ILC2s can harbor both pro-tumorigenic and anti-tumorigenic functions, but we know little about their underlying mechanisms or whether they could be clinically relevant or targeted to improve patient outcomes. Here, we found that high ILC2 infiltration in human melanoma was associated with a good clinical prognosis. ILC2s are critical producers of the cytokine granulocyte-macrophage colony-stimulating factor, which coordinates the recruitment and activation of eosinophils to enhance antitumor responses. Tumor-infiltrating ILC2s expressed programmed cell death protein-1, which limited their intratumoral accumulation, proliferation and antitumor effector functions. This inhibition could be overcome in vivo by combining interleukin-33-driven ILC2 activation with programmed cell death protein-1 blockade to significantly increase antitumor responses. Together, our results identified ILC2s as a critical immune cell type involved in melanoma immunity and revealed a potential synergistic approach to harness ILC2 function for antitumor immunotherapies

A window into the mind-brain-body interplay: Development of diagnostic, prognostic biomarkers, and rehabilitation strategies in functional motor disorders

Background and aims: Functional motor disorders (FMD) present a prevalent, yet misunderstood spectrum of neurological conditions characterized by abnormal movements (i.e., functional limb weakness, tremor, dystonia, gait impairments), leading to substantial disability and diminished quality of life. Despite their high prevalence, FMD often face delayed diagnosis and inadequate treatment, resulting in significant social and economic burdens. The old concept of psychological factors as the primary cause (conversion disorder) has been abandoned due to the need for more evidence about their causal role. According to a predictive coding account, the emerging idea is that symptoms and disability may depend on dysfunctions of a specific neural system integrating interoception, exteroception, and motor control. Consequently, symptoms are construed as perceptions of the body's state. Besides the main pathophysiological features (abnormal attentional focus, beliefs/expectations, and sense of agency), the lived experience of symptoms and their resulting disability may depend on an altered integration at the neural level of interoception, exteroception, and motor control. Methods and materials: Our proposal aims to elucidate the pathophysiological mechanisms of FMD through a three-stage research approach. Initially, a large cohort study will collect behavioral, neurophysiological, and MRI biomarkers from patients with FMD and healthy controls, employing eXplainable Artificial Intelligence (XAI) to develop a diagnostic algorithm. Subsequently, validation will occur using patients with organic motor disorders. Finally, the algorithm's prognostic value will be explored post-rehabilitation in one subgroup of patients with FMD. Results: Data collection for the present study started in May 2023, and by May 2025, data collection will conclude. Discussion: Our approach seeks to enhance early diagnosis and prognostication, improve FMD management, and reduce associated disability and socio-economic costs by identifying disease-specific biomarkers. Trial registration: This trial was registered in clinicaltrials.gov (NCT06328790)

Effetti legati alla morfologia nella stima della Radiazione Solare globale e dell’Evapotraspirazione potenziale

Nel presente lavoro vengono messi a confronto due algoritmi per la stima della radiazione solare esoatmosferica e delle principali componenti del bilancio radiativo al suolo in funzione delle caratteristiche della vegetazione, della morfologia delle superfici considerate (pendenza ed esposizione) e in condizioni di cielo sereno. Attraverso la stima della radiazione solare netta, definita mediante gli algoritmi di calcolo presentati (Kumar et al., 1997; Allen et al., 2006), si giunge alla valutazione dell’evapotraspirazione potenziale utilizzando l’equazione di Penman-Monteith. In tal modo è possibile evidenziare gli effetti legati alla morfologia nella stima della radiazione solare e dell’evapotraspirazione potenziale. Inoltre, il confronto tra le mappe ed i profili di radiazione ottenuti mostrano le differenze tra i due approcci di calcolo, dovute fondamentalmente alla differente struttura degli algoritmi. I risultati sono stati messi a confronto con dati misurati da diverse stazioni meteorologiche distribuite sul territorio lucano fornendo una stima quantitativa dell'errore associato ai due algoritmi. Il confronto ha evidenziato che i due metodi di calcolo producono risultati simili se applicati alla scala annuale, mentre alla scala giornaliera le approssimazioni presenti nel metodo di Kumar et al. (1997) producono errori non trascurabili per cui risulta più affidabile il modello proposto da Allen et al. (2006). Le analisi evidenziano il ruolo della morfologia (pendenza ed esposizione dei versanti) nella determinazione della radiazione solare globale e conseguentemente dell'evapotraspirazione potenziale a scala locale

Updating flood annual maxima in Southern Italy

Recent studies have highlighted concerns about the impact of climate change on the hydrological cycle and extremes. Analysis of long hydrological series or modeled data in Europe has revealed conflicting trends. The lack of continuous observations and significant alterations in some watersheds pose challenges for quantifying the effects of climate change, particularly in Southern Italy. The objective of this study is to update flood time-series in Southern Italy from 1920 to 2021 using direct and indirect measurements. Missing data were reconstructed using specific flood rating curves or daily flow rates to estimate equivalent flood peaks. The resulting series were analyzed using the nonparametric Mann-Kendall test to provide a preliminary description on flood trends in Southern Italy over the past 50 years

Aggregation of Cesium Perfluorooctanoate on Poly(ethylene glycol) Oligomers in Water

The interaction of cesium perfluorooctanoate (CsPFO) with poly(ethylene glycol) (PEG) of different molecular weight (300 e MW e 20000 Da) has been investigated at 298.15 K by isothermal titration calorimetry (ITC), density, viscosity, and conductivity measurements. Calorimetric titrations exhibited peculiar trends analogous to those already observed for sodium dodecyl sulfate (SDS). Micelles of the perfluorosurfactant, as compared to those of SDS, yield complexes with the polymer of similar thermodynamic stability but are able to interact with shorter PEG oligomers. The average number of surfactant molecules bonded per polymer chain at the saturation is about twice that observed for SDS. ITC data at 308.15 K indicate a larger thermodynamic stability of the aggregates but an almost constant stoichiometry. The peculiar thermal effects and the viscosity trend observed during the titration of an aqueous PEG solution with the surfactant appear consistent with a conformational change of the polymer. The PEG chain would evolve from a strained to an expanded conformation, induced by the growing of the surfactant micellar clusters bonded to the polymer, as suggested in a previous study of the PEG/SDS/H2O system