Complexity in action: Untangling latent relationships between land quality, economic structures and socio-spatial patterns in Italy

Land quality, a key economic capital supporting local development, is affected by biophysical and anthropogenic factors. Taken as a relevant attribute of economic systems, land quality has shaped the territorial organization of any given region influencing localization of agriculture, industry and settlements. In regions with long-established human-landscape interactions, such as the Mediterranean basin, land quality has determined social disparities and polarization in the use of land, reflecting the action of geographical gradients based on elevation and population density. The present study investigates latent relationships within a large set of indicators profiling local communities and land quality on a fine-grained resolution scale in Italy with the aim to assess the potential impact of land quality on the regional socioeconomic structure. The importance of land quality gradients in the socioeconomic configuration of urban and rural regions was verified analyzing the distribution of 149 socioeconomic and environmental indicators organized in 5 themes and 17 research dimensions. Agriculture, income, education and labour market variables discriminate areas with high land quality from areas with low land quality. While differential land quality in peri-urban areas may reflect conflicts between competing actors, moderate (or low) quality of land in rural districts is associated with depopulation, land abandonment, subsidence agriculture, unemployment and low educational levels. We conclude that the socioeconomic profile of local communities has been influenced by land quality in a different way along urban-rural gradients. Policies integrating environmental and socioeconomic measures are required to consider land quality as a pivotal target for sustainable development. Regional planning will benefit from an in-depth understanding of place-specific relationships between local communities and the environment

The European MAPPYACTS Trial: Precision Medicine Program in Pediatric and Adolescent Patients with Recurrent Malignancies

Precision Medicine; Pediatric and Adolescent Patients; Recurrent MalignanciesMedicina de Precisión; Pacientes pediátricos y adolescentes; Neoplasias malignas recurrentesMedicina de precisió; Pacients pediàtrics i adolescents; Neoplasmes malignes recurrentsMAPPYACTS (NCT02613962) is an international prospective precision medicine trial aiming to define tumor molecular profiles in pediatric patients with recurrent/ refractory malignancies in order to suggest the most adapted salvage treatment. From February 2016 to July 2020, 787 patients were included in France, Italy, Ireland, and Spain. At least one genetic alteration leading to a targeted treatment suggestion was identified in 436 patients (69%) with successful sequencing; 10% of these alterations were considered “ready for routine use.” Of 356 patients with follow-up beyond 12 months, 107 (30%) received one or more matched targeted therapies—56% of them within early clinical trials—mainly in the AcSé-ESMART platform trial (NCT02813135). Overall, matched treatment resulted in a 17% objective response rate, and of those patients with ready for routine use alterations, it was 38%. In patients with extracerebral tumors, 76% of actionable alterations detected in tumor tissue were also identified in circulating cell-free DNA (cfDNA)

Computational evidence for an early, amplified systemic inflammation program in polytrauma patients with severe extremity injuries

Extremity and soft tissue injuries contribute significantly to inflammation and adverse in-hospital outcomes for trauma survivors; accordingly, we examined the complex association between clinical outcomes inflammatory responses in this setting using in silico tools. Two stringently propensity-matched, moderately/severely injured (Injury Severity Score > 16) patient sub-cohorts of ~30 patients each were derived retrospectively from a cohort of 472 blunt trauma survivors and segregated based on their degree of extremity injury severity (above or below 3 on the Abbreviated Injury Scale). Serial blood samples were analyzed for 31 plasma inflammatory mediators. In addition to standard statistical analyses, Dynamic Network Analysis (DyNA) and Principal Component Analysis (PCA) were used to model systemic inflammation following trauma. Patients in the severe extremity injury sub-cohort experienced longer intensive care unit length of stay (LOS), total LOS, and days on a mechanical ventilator, with higher Marshall Multiple Organ Dysfunction (MOD) Scores over the first 7 days post-injury as compared to the mild/moderate extremity injury sub-cohort. The higher severity cohort had statistically significant elevated lactate, base deficit, and creatine phosphokinase on first blood draw, along with significant changes in multiple circulating inflammatory mediators. DyNA pointed to a sustained role for type 17 immunity in both sub-cohorts, along with IFN-γ in the severe extremity injury group. DyNA network complexity increased over 7 days post-injury in the severe injury group, while generally decreasing over this same time period in the mild/moderate injury group. PCA suggested a more robust activation of multiple pathways in the severe extremity injury group as compared to the mild/moderate injury group. These studies thus point to the possibility of self-sustaining inflammation following severe extremity injury vs. resolving inflammation following less severe extremity injury

Modulation of microRNA editing, expression and processing by ADAR2 deaminase in glioblastoma.

Background: ADAR enzymes convert adenosines to inosines within double-stranded RNAs, including microRNA (miRNA) precursors, with important consequences on miRNA retargeting and expression. ADAR2 activity is impaired in glioblastoma and its rescue has anti-tumoral effects. However, how ADAR2 activity may impact the miRNome and the progression of glioblastoma is not known. Results: By integrating deep-sequencing and array approaches with bioinformatics analyses and molecular studies, we show that ADAR2 is essential to edit a small number of mature miRNAs and to significantly modulate the expression of about 90 miRNAs in glioblastoma cells. Specifically, the rescue of ADAR2 activity in cancer cells recovers the edited miRNA population lost in glioblastoma cell lines and tissues, and rebalances expression of onco-miRNAs and tumor suppressor miRNAs to the levels observed in normal human brain. We report that the major effect of ADAR2 is to reduce the expression of a large number of miRNAs, most of which act as onco-miRNAs. ADAR2 can edit miR-222/221 and miR-21 precursors and decrease the expression of the corresponding mature onco-miRNAs in vivo and in vitro, with important effects on cell proliferation and migration. Conclusions: Our findings disclose an additional layer of complexity in miRNome regulation and provide information to better understand the impact of ADAR2 editing enzyme in glioblastoma. We propose that ADAR2 is a key factor for maintaining edited-miRNA population and balancing the expression of several essential miRNAs involved in cancer

A multi-objective evolutionary algorithm fitness function for case-base maintenance.

Case-Base Maintenance (CBM) has two important goals. On the one hand, it aims to reduce the size of the case-base. On the other hand, it has to improve the accuracy of the CBR system. CBM can be represented as a multi-objective optimization problem to achieve both goals. Multi-Objective Evolutionary Algorithms (MOEAs) have been recognised as appropriate techniques for multi-objective optimisation because they perform a search for multiple solutions in parallel. In the present paper we introduce a fitness function based on the Complexity Profiling model to perform CBM with MOEA, and we compare its results against other known CBM approaches. From the experimental results, CBM with MOEA shows regularly good results in many case-bases, despite the amount of redundant and noisy cases, and with a significant potential for improvement

Retrospective evaluation and prospective value-add: a review of R&D investment in Australia

This paper describes a lead project currently underway through Australia’s Sustainable Built Environment National Research Centre evaluating diffusion mechanisms and impacts of R&D investment in the Australian built environment. Through a retrospective analysis of R&D investment trends and industry outcomes, and a prospective assessment of industry futures using strategic foresighting, a future-focussed industry R&D roadmap and pursuant policy guidelines will be developed. This research aims to build new understandings and knowledge relevant to R&D funding strategies, research team formation and management, dissemination of outcomes and industry uptake. Each of these issues are critical due to: the disaggregated nature of the built environment industry; intense competition; limited R&D investment; and new challenges (e.g. IT, increased environmental expectations). This paper details the context within which this project is being undertaken and the research design. Findings of the retrospective analysis of past R&D investment in Australia will be presented at this conference

16S rRNA gene profiling and genome reconstruction reveal community metabolic interactions and prebiotic potential of medicinal herbs used in neurodegenerative disease and as nootropics.

The prebiotic potential of nervine herbal medicines has been scarcely studied. We therefore used anaerobic human fecal cultivation to investigate whether medicinal herbs commonly used as treatment in neurological health and disease in Ayurveda and other traditional systems of medicine modulate gut microbiota. Profiling of fecal cultures supplemented with either Kapikacchu, Gotu Kola, Bacopa/Brahmi, Shankhapushpi, Boswellia/Frankincense, Jatamansi, Bhringaraj, Guduchi, Ashwagandha or Shatavari by 16S rRNA sequencing revealed profound changes in diverse taxa. Principal coordinate analysis highlights that each herb drives the formation of unique microbial communities predicted to display unique metabolic potential. The relative abundance of approximately one-third of the 243 enumerated species was altered by all herbs. Additional species were impacted in an herb-specific manner. In this study, we combine genome reconstruction of sugar utilization and short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb by quantitative mass spectrometry to enhance the interpretation of resulting microbial communities and discern potential drivers of microbiota restructuring. Collectively, our results indicate that gut microbiota engage in both protein and glycan catabolism, providing amino acid and sugar substrates that are consumed by fermentative species. We identified taxa that are efficient amino acid fermenters and those capable of both amino acid and sugar fermentation. Herb-induced microbial communities are predicted to alter the relative abundance of taxa encoding SCFA (butyrate and propionate) pathways. Co-occurrence network analyses identified a large number of taxa pairs in medicinal herb cultures. Some of these pairs displayed related culture growth relationships in replicate cultures highlighting potential functional interactions among medicinal herb-induced taxa