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The present study provides a reflection on the agent-based intelligence of urban spatial environments through the comparison of a formal quantitative approach, i.e., space syntax, and a qualitative experimentation based on the spatial cognition approach. Until recently, space syntax was adopted by urban planners and designers to support urban design and planning decisions, based on an analysis of the urban physical environment. Researchers in the cognitive science field have increased their attempts to address space syntax techniques to better understand the relationships of cognitive spatial agents with the spatial features of urban environments. In this context, the experimental approach focuses on the qualities of the environment as interacted, perceived and interpreted by cognitive agents and reflects on the role which it plays in affecting spatial decisions and route choices. The present paper aimed to explore the extent to which possible integration between the different approaches can provide insights on agent-based decisions in actions and behavioural processes in space for useful perspectives in urban analysis and planning. Findings suggest relevant correlations between the experimentation results and space syntax predictions when a correspondence of some aspects can be found. Conversely, interesting qualitative insights from the spatial cognition approach are pointed out to enrich the configurational analysis. The potential and constraints of each approach and the ways of combining these are presented. Evidence supports the suitability of the proposal outlined in the present paper within the framework of urban planning practice.

The concept of ecosystem services (ES) arises as a formal outcome of historical processes of understanding and interpreting settlements as complex ecological systems. Because of a straightforward, bottom-up demand for environment enhancement, this concept increasingly occurs in discourses, in narratives, in the demands of common people, triggering a new urban environmental awareness. This is now often arising spontaneously in the protocols of participatory plan processes, especially when planning for the future of complex environments such as city areas. The present study tries to elicit reflections around the significance of ES issues awareness in the case study of Bari (Italy), which is experiencing an inclusive and participatory process of construction of shared knowledge for the new master plan. Starting from an initial campaign of civic walks (CWs) along the urban neighborhoods and a subsequent semi-structured interview to the community, the paper carries out comparative analyses using problem-structuring methods (PMs), in order to evaluate and reflect on community behaviors and expectations about ES. Then the paper ends by emphasizing the role of structured knowledge-raising approaches, as critical activities to enhance ecosystem awareness in planning settlements as complex ecological systems.

In a modern pandemic outbreak, where collective threats require global strategies and local operational defence applications, data-driven solutions for infection tracing and forecasting epidemic trends are crucial to achieve sustainable and socially resilient cities. Indeed, the need for monitoring, containing, and mitigating the ongoing COVID-19 pandemic has generated a great deal of interest in Digital Proximity Tracing Technology (DPTT) on smartphones, as well as their function and effectiveness and insights of population acceptance. This paper introduces and compares different Data-Driven Epidemic Intelligence Strategies (DDEIS) developed on DPTTs. It aims to clarify to what extent DDEIS could be effective and both technologically and socially suitable in reaching the objective of a swift return to normality for cities, guaranteeing public health safety and minimizing the risk of epidemic resurgence. It assesses key advantages and limits in supporting both individual decision-making and policy-making, considering the role of human behaviour. Specifically, an online survey carried out in Italy revealed user preferences for DPTTs and provided preliminary data for an SEIR (Susceptible–Exposed–Infectious–Recovered) epidemiological model. This was developed to evaluate the impact of DDEIS on COVID-19 spread dynamics, and results are presented together with an evaluation of potential drawbacks.

The endocannabinoid system (ES) is a cell-signalling system widely distributed in biological tissues that includes endogenous ligands, receptors, and biosynthetic and hydrolysing machineries. The impairment of the ES has been associated to several pathological conditions like behavioural, neurological, or metabolic disorders and infertility, suggesting that the modulation of this system may be critical for the maintenance of health status and disease treatment. Lifestyle and environmental factors can exert long-term effects on gene expression without any change in the nucleotide sequence of DNA, affecting health maintenance and influencing both disease load and resistance. This potentially reversible “epigenetic” modulation of gene expression occurs through the chemical modification of DNA and histone protein tails or the specific production of regulatory non-coding RNA (ncRNA). Recent findings demonstrate the epigenetic modulation of the ES in biological tissues; in the same way, endocannabinoids, phytocannabinoids, and cannabinoid receptor agonists and antagonists induce widespread or gene-specific epigenetic changes with the possibility of trans-generational epigenetic inheritance in the offspring explained by the transmission of deregulated epigenetic marks in the gametes. Therefore, this review provides an update on the epigenetics of the ES, with particular attention on the emerging role in reproduction and fertility.

The endocannabinoid system (ECS) is a lipid cell signaling system involved in the physiology and homeostasis of the brain and peripheral tissues. Synaptic plasticity, neuroendocrine functions, reproduction, and immune response among others all require the activity of functional ECS, with the onset of disease in case of ECS impairment. Estrogens, classically considered as female steroid hormones, regulate growth, differentiation, and many other functions in a broad range of target tissues and both sexes through the activation of nuclear and membrane estrogen receptors (ERs), which leads to genomic and non-genomic cell responses. Since ECS function overlaps or integrates with many other cell signaling systems, this review aims at updating the knowledge about the possible crosstalk between ECS and estrogen system (ES) at both central and peripheral level, with focuses on the central nervous system, reproduction, and cancer.

Autism Spectrum Disorders (ASD) are principally diagnosed by three core behavioural symptoms, such as stereotyped repertoire, communication impairments and social dysfunctions. This complex pathology has been linked to abnormalities of corticostriatal and limbic circuits. Despite experimental efforts in elucidating the molecular mechanisms behind these abnormalities, a clear etiopathogenic hypothesis is still lacking. To this aim, preclinical studies can be really helpful to longitudinally study behavioural alterations resembling human symptoms and to investigate the underlying neurobiological correlates. In this regard, the BTBR T + Itpr3 tf /J (BTBR) mice are an inbred mouse strain that exhibits a pattern of behaviours well resembling human ASD-like behavioural features. In this study, the BTBR mice model was used to investigate neurochemical and biomolecular alterations, regarding Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF), together with GABAergic, glutamatergic, cholinergic, dopaminergic and noradrenergic neurotransmissions and their metabolites in four different brain areas, i.e. prefrontal cortex, hippocampus, amygdala and hypothalamus. In our results, BTBR strain reported decreased noradrenaline, acetylcholine and GABA levels in prefrontal cortex, while hippocampal measurements showed reduced NGF and BDNF expression levels, together with GABA levels. Concerning hypothalamus, no differences were retrieved. As regarding amygdala, we found reduced dopamine levels, accompanied by increased dopamine metabolites in BTBR mice, together with decreased acetylcholine, NGF and GABA levels and enhanced glutamate content. Taken together, our data showed that the BTBR ASD model, beyond its face validity, is a useful tool to untangle neurotransmission alterations that could be underpinned to the heterogeneous ASD-like behaviours, highlighting the crucial role played by amygdala.

CAR T-cell therapy has emerged as a potentially transformative immunotherapy for certain B-cell malignancies including relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Unhindered and appropriate access for eligible patients is essential to enable optimal outcomes and depends on effective interplay of stakeholders and processes along the patient’s therapeutic journey. In Italy, CAR T-cell therapies have been awarded innovation status by the Italian Medicines Agency (AIFA) and were integrated into routine patient care under specific criteria. However, our analysis indicates that fewer than one in five DLBCL patients eligible under the EMA authorization, or around one in three DLBCL patients eligible under the AIFA criteria, received treatment with a licensed CAR T-cell therapy product in 2020. This publication describes key patient access barriers to CAR T-cell therapies in Italy and provides recommendations on potential solutions at the health system level.

In the last decade, the bacterial pathogen Xylella fastidiosa has devastated olive trees throughout Apulia region (Southern Italy) in the form of the disease called “Olive Quick Decline Syndrome” (OQDS). This study describes changes in the metabolic profile due to the infection by X. fastidiosa subsp. pauca ST53 in artificially inoculated young olive plants of the susceptible variety Cellina di Nardò . The test plants, grown in a thermo-conditioned greenhouse, were also co-inoculated with some xylem-inhabiting fungi known to largely occur in OQDS-affected trees, in order to partially reproduce field conditions in terms of biotic stress. The investigations were performed by combining NMR spectroscopy and MS spectrometry with a non-targeted approach for the analysis of leaf extracts. Statistical analysis revealed that Xylella -infected plants were characterized by higher amounts of malic acid, formic acid, mannitol, and sucrose than in Xylella -non-infected ones, whereas it revealed slightly lower amounts of oleuropein. Attention was paid to mannitol which may play a central role in sustaining the survival of the olive tree against bacterial infection. This study contributes to describe a set of metabolites playing a possible role as markers in the infections by X. fastidiosa in olive.

Glyphosate is widely used worldwide as a potent herbicide. Due to its ubiquitous use, it is detectable in air, water and foodstuffs and can accumulate in human biological fluids and tissues representing a severe human health risk. In plants, glyphosate acts as an inhibitor of the shikimate pathway, which is absent in vertebrates. Due to this, international scientific authorities have long-considered glyphosate as a compound that has no or weak toxicity in humans. However, increasing evidence has highlighted the toxicity of glyphosate and its formulations in animals and human cells and tissues. Thus, despite the extension of the authorization of the use of glyphosate in Europe until 2022, several countries have begun to take precautionary measures to reduce its diffusion. Glyphosate has been detected in urine, blood and maternal milk and has been found to induce the generation of reactive oxygen species (ROS) and several cytotoxic and genotoxic effects in vitro and in animal models directly or indirectly through its metabolite, aminomethylphosphonic acid (AMPA). This review aims to summarize the more relevant findings on the biological effects and underlying molecular mechanisms of glyphosate, with a particular focus on glyphosate's potential to induce inflammation, DNA damage and alterations in gene expression profiles as well as adverse effects on reproduction and development.

Neoplastic transformation is accompanied by critical changes in cell mechanical properties, including reduced cell elasticity. By leveraging such mechanical flaw, exposure to low intensity therapeutic ultrasounds (LITUS) has been proposed as a tool for selective killing of cancer cells. Here, we have developed dynamic models to address the morpho-mechanical differences between prostate cancer and non-tumoral counterparts and studied the effects of LITUS on cell viability. We show that LITUS exposure (1 MHz) leads to cancer-selective cytoskeletal disruption associated to loss of nuclear envelope integrity, DNA damage marked by γH2AX and 53BP1 foci, and release of DNA into the cytosol with activation of the cGAS–STING signaling cascade. Mechanistically, the LINC complex, which connects the cytoskeleton to nucleoskeleton and chromosomes, is critical to mediate nuclear rupture triggered by LITUS. Accordingly, genetic ablation of the LINC component SUN2 tuned down DNA damage and cGAS–STING signaling while the inactivation of the endosomal sorting complex (ESCRT), required for the transport machinery that preserves the nuclear envelope integrity, enhanced cell killing by LITUS. In conclusion, LITUS induce cancer cell DNA damage and an innate immune response, this suggesting LITUS treatment as a mechanobiology-driven anti-neoplastic strategy.