Toward the European Health Data Space: The IMPaCT-Data secure infrastructure for EHR-based precision medicine research.

BACKGROUND: Art. 50 of the proposal for a Regulation on the European Health Data Space (EHDS) states that "health data access bodies shall provide access to electronic health data only through a secure processing environment, with technical and organizational measures and security and interoperability requirements". OBJECTIVE: To identify specific security measures that nodes participating in health data spaces shall implement based on the results of the IMPaCT-Data project, whose goal is to facilitate the exchange of electronic health records (EHR) between public entities based in Spain and the secondary use of this information for precision medicine research in compliance with the General Data Protection Regulation (GDPR). DATA AND METHODS: This article presents an analysis of 24 out of a list of 72 security measures identified in the Spanish National Security Scheme (ENS) and adopted by members of the federated data infrastructure developed during the IMPaCT-Data project. RESULTS: The IMPaCT-Data case helps clarify roles and responsibilities of entities willing to participate in the EHDS by reconciling technical system notions with the legal terminology. Most relevant security measures for Data Space Gatekeepers, Enablers and Prosumers are identified and explained. CONCLUSION: The EHDS can only be viable as long as the fiduciary duty of care of public health authorities is preserved; this implies that the secondary use of personal data shall contribute to the public interest and/or to protect the vital interests of the data subjects. This condition can only be met if all nodes participating in a health data space adopt the appropriate organizational and technical security measures necessary to fulfill their role.

Notch Partners in the Long Journey of T-ALL Pathogenesis.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological disease that arises from the oncogenic transformation of developing T cells during T-lymphopoiesis. Although T-ALL prognosis has improved markedly in recent years, relapsing and refractory patients with dismal outcomes still represent a major clinical issue. Consequently, understanding the pathological mechanisms that lead to the appearance of this malignancy and developing novel and more effective targeted therapies is an urgent need. Since the discovery in 2004 that a major proportion of T-ALL patients carry activating mutations that turn NOTCH1 into an oncogene, great efforts have been made to decipher the mechanisms underlying constitutive NOTCH1 activation, with the aim of understanding how NOTCH1 dysregulation converts the physiological NOTCH1-dependent T-cell developmental program into a pathological T-cell transformation process. Several molecular players have so far been shown to cooperate with NOTCH1 in this oncogenic process, and different therapeutic strategies have been developed to specifically target NOTCH1-dependent T-ALLs. Here, we comprehensively analyze the molecular bases of the cross-talk between NOTCH1 and cooperating partners critically involved in the generation and/or maintenance and progression of T-ALL and discuss novel opportunities and therapeutic approaches that current knowledge may open for future treatment of T-ALL patients.

IL-7R is essential for leukemia-initiating cell activity of T-cell acute lymphoblastic leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy resulting from the dysregulation of signaling pathways that control intrathymic T-cell development. Relapse rates are still significant, and prognosis is particularly bleak for relapsed patients. Therefore, development of novel therapies specifically targeting pathways controlling leukemia-initiating cell (LIC) activity is mandatory for fighting refractory T-ALL. The interleukin-7 receptor (IL-7R) is a crucial T-cell developmental pathway that is commonly expressed in T-ALL and has been implicated in leukemia progression; however, the significance of IL-7R/IL-7 signaling in T-ALL pathogenesis and its contribution to disease relapse remain unknown. To directly explore whether IL-7R targeting may be therapeutically efficient against T-ALL relapse, we focused on a known Notch1-induced T-ALL model, because a majority of T-ALL patients harbor activating mutations in NOTCH1, which is a transcriptional regulator of IL-7R expression. Using loss-of-function approaches, we show that Il7r-deficient, but not wild-type, mouse hematopoietic progenitors transduced with constitutively active Notch1 failed to generate leukemia upon transplantation into immunodeficient mice, thus providing formal evidence that IL-7R function is essential for Notch1-induced T-cell leukemogenesis. Moreover, we demonstrate that IL-7R expression is an early functional biomarker of T-ALL cells with LIC potential and report that impaired IL-7R signaling hampers engraftment and progression of patient-derived T-ALL xenografts. Notably, we show that IL-7R-dependent LIC activity and leukemia progression can be extended to human B-cell acute lymphoblastic leukemia (B-ALL). These results have important therapeutic implications, highlighting the relevance that targeting normal IL-7R signaling may have in future therapeutic interventions, particularly for preventing T-ALL (and B-ALL) relapse.

Fratricide-resistant CD1a-specific CAR T cells for the treatment of cortical T-cell acute lymphoblastic leukemia.

Relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL) has a dismal outcome, and no effective targeted immunotherapies for T-ALL exist. The extension of chimeric antigen receptor (CAR) T cells (CARTs) to T-ALL remains challenging because the shared expression of target antigens between CARTs and T-ALL blasts leads to CART fratricide. CD1a is exclusively expressed in cortical T-ALL (coT-ALL), a major subset of T-ALL, and retained at relapse. This article reports that the expression of CD1a is mainly restricted to developing cortical thymocytes, and neither CD34+ progenitors nor T cells express CD1a during ontogeny, confining the risk of on-target/off-tumor toxicity. We thus developed and preclinically validated a CD1a-specific CAR with robust and specific cytotoxicity in vitro and antileukemic activity in vivo in xenograft models of coT-ALL, using both cell lines and coT-ALL patient-derived primary blasts. CD1a-CARTs are fratricide resistant, persist long term in vivo (retaining antileukemic activity in re-challenge experiments), and respond to viral antigens. Our data support the therapeutic and safe use of fratricide-resistant CD1a-CARTs for relapsed/refractory coT-ALL.

Environmental consequences of wheat-based crop rotation in potato farming systems in galicia, Spain.

Intensive agricultural farming systems have negative impacts on the ecosystem. Therefore, the use of crop rotation emerges as an opportunity to improve the environmental sustainability of agricultural systems. In the region of Galicia in north-western Spain, potato and wheat are important commodities and essential foods in the diet. Hence, it is interesting to investigate the environmental profile of these crops to improve the understanding of local agrosystems. This study evaluated three agricultural crops managed under a crop rotation system and following a conventional arable farming: the main rotation crop, which is the potato in the first year (cP), followed by a second year of commercial wheat (cW) and autochthonous Galician wheat (GcW) in the third year. The Life Cycle Assessment (LCA) methodology was performed using four types of functional units: in terms of productivity (kg-1); land management (ha-1∙year-1); a financial function (euros €-1 of income from sales) and energetic value (MJ-1). The environmental indicators selected are Climate Change (CC), Particulate Matter (PM), Terrestrial Acidification (TA), Freshwater Eutrophication (FE), Marine Eutrophication (ME), Human Toxicity (HT), Land Use (LU) and Fossil Depletion (FD). The figures show that the GcW has the lowest environmental impact when the functional units refer to land management, financial function and energetic value. However, if analysed in terms of productivity, cP is presented as the best crop due to its comparatively higher yield, reaching a production ratio 10 times higher than wheat. In the specific case of wheat, compared to a previous study in the same region, the environmental impacts are lower when grown in a crop rotation system in contrast to monoculture. This article demonstrates the relevance of using LCA for diverse stakeholders (e.g., farmers, consumers and researchers) to understand the environmental impacts of regional agricultural systems. In addition, it serves as a basis for future work aimed at comparing rotational agricultural systems in this region, integrating economic and social aspects.

Facts and Challenges in Immunotherapy for T-Cell Acute Lymphoblastic Leukemia.

T-cell acute lymphoblastic leukemia (T-ALL), a T-cell malignant disease that mainly affects children, is still a medical challenge, especially for refractory patients for whom therapeutic options are scarce. Recent advances in immunotherapy for B-cell malignancies based on increasingly efficacious monoclonal antibodies (mAbs) and chimeric antigen receptors (CARs) have been encouraging for non-responding or relapsing patients suffering from other aggressive cancers like T-ALL. However, secondary life-threatening T-cell immunodeficiency due to shared expression of targeted antigens by healthy and malignant T cells is a main drawback of mAb-or CAR-based immunotherapies for T-ALL and other T-cell malignancies. This review provides a comprehensive update on the different immunotherapeutic strategies that are being currently applied to T-ALL. We highlight recent progress on the identification of new potential targets showing promising preclinical results and discuss current challenges and opportunities for developing novel safe and efficacious immunotherapies for T-ALL.

Dietary recommendations in Spain -affordability and environmental sustainability?

Global food demand is increasing due to population growth and dietary transitions, resulting from rising incomes, are associated with increased prevalence of non-communicable diseases. Improving the sustainability of the food sector is also critical for achieving the Sustainable Development Goals. This study assesses for the first time the greenhouse gases emissions (Carbon Footprint - CF), the water footprint (WF) and the cost of three omnivorous diets recommended in Spain due to their health benefits: the Mediterranean diet (MD), the Southern European Atlantic diet (SEAD) and the Spanish dietary guidelines (NAOS). Analysis was conducted using standard Life Cycle Assessment and WF methods together with current Spanish food price data. The dietary energy recommendation of the SEAD is greater than that of MD and NAOS (11 and 15% respectively), and SEAD also has greater animal source food content than the other two diets. SEAD has a concomitantly higher CF, WF and cost scores in comparison with MD (+30%, +23% and +21% respectively) and NAOS (+15%, +9% and +21% respectively). Adjusting recommendations to meet the suggested Spanish adult dietary energy of 2228 kcal.capita-1.day-1 changed the environmental profiles of the diets and the NAOS has the highest environmental impact. However, the isocaloric diets had approximately the same cost. Analysis of the WF of the diets identified the major contribution of precipitation (the green WF) to the overall WF (88% of the total) and the significant contribution of animal-source foods to dietary WF. Regardless of the dietary scenario, better scores were identified for the Spanish recommendations analysed than those reported for other healthy diets identified in Europe. Differences in the recommended intake levels of certain food groups, cooking techniques and the origin of food products are behind these results. Environmental indicators should be considered alongside nutrition and health metrics when defining national dietary guidelines. Supporting citizens to follow healthy and environmentally-friendly dietary recommendations through, among other things, information campaigns and nutritional education programmes is essential. It is recommended the incorporation not only of health, but also of environmental indicators of these dietary options in the national dietary guidelines, as well as implementation of information campaigns and nutritional education programs among citizens to promote their adhesion since balanced dietary habits rich on plant-based products and low on animal-based ones involve multiple health and environmental benefits.

Assessing the environmental sustainability of glucose from wheat as a fermentation feedstock.

In recent years, the need to substitute fossil fuels with renewable biomass has been a key driver in the development of the biorefinery concept. One of the possible routes towards the development of bioproducts under this scheme is through a sugar intermediate. Sugars, such as glucose, can be produced through starch crops, for instance wheat. While there are many environmental assessment studies that consider sugar as a platform for biofuel production, the main focus is on the end product of the value chain (typically bioethanol), but not on sugars as the basic feedstock. Taking the bottom-up perspective as a roadmap, the assessment of technological, economic and environmental barriers in the biorefinery scheme must take into account the sustainability of sugar production with the aim of improving its current framework or finding novel technologies. This study investigates the environmental sustainability of wheat cultivation and grain processing in different European countries by applying the life cycle assessment (LCA) methodology with a cradle to gate approach. Moreover, 1 kg of glucose at the factory gate has been considered as a functional unit for reporting the environmental results. The chosen impact categories are climate change (CC), particular matter (PM), human toxicity (HT), freshwater eutrophication (FE), terrestrial eutrophication (TE), acidification (AC) and abiotic depletion (AD). Mass and economic allocations are evaluated as the processing of grain wheat generates different valuable by-products, namely wheat bran, gluten meal and gluten feed. The results show that agricultural activities play an important role in the environmental impacts, predominantly due to the production of agrochemicals and field emissions derived from fertilisation. In addition, the choice of allocation has a greater environmental influence (both positive or negative) on the by-products than the main product under investigation.

Decentralised schemes for integrated management of wastewater and domestic organic waste: the case of a small community.

This study assesses from an environmental perspective two different configurations for the combined treatment of wastewater and domestic organic waste (DOW) in a small and decentralised community having a population of 2000. The applied schemes consist of an upflow anaerobic blanket (UASB) as core treatment process. Scheme A integrates membranes with the anaerobic treatment; while in Scheme B biological removal of nutrients in a sequencing batch reactor (SBR) is applied as a post treatment to UASB effluent. In energy-related categories, the main contributor is electricity consumption (producing 18-50% of the impacts); whereas in terms of eutrophication-related categories, the discharge of the treated effluent arises as a major hotspot (with 57-99% of the impacts). Scheme B consumes 25% more electricity and produces 40% extra sludge than Scheme A, resulting in worse environmental results for those energy categories. However, the environmental impact due to the discharge of the treated effluent is 75% lower in eutrophication categories due to the removal of nutrients. In addition, the quality of the final effluent in Scheme B would allow its use for irrigation (9.6 mg N/L and 2 mg P/L) if proper tertiary treatment and disinfection are provided, expanding its potential adoption at a wider scale. Direct emissions due to the dissolved methane in the UASB effluent have a significant environmental impact in climate change (23-26%). Additionally, the study shows the environmental feasibility of the use of food waste disposers for DOW collection in different integration rates.

Carbon and water footprint of pork supply chain in Catalonia: From feed to final products.

A systematic tool to assess the Carbon Footprint (CF) and Water Footprint (WF) of pork production companies was developed and applied to representative Catalan companies. To do so, a cradle-to-gate environmental assessment was carried out by means of the LCA methodology, taking into account all the stages involved in the pork chain, from feed production to the processing of final products, ready for distribution. In this approach, the environmental results are reported based on eight different functional units (FUs) according to the main pork products obtained. With the aim of ensuring the reliability of the results and facilitating the comparison with other available reports, the Product Category Rules (PCR) for Catalan pork sector were also defined as a basis for calculations. The characterization results show fodder production as the main contributor to the global environmental burdens, with contributions higher than 76% regardless the environmental indicator or the life cycle stage considered, which is in agreement with other published data. In contrast, the results in terms of CF and WF lay above the range of values reported elsewhere. However, major discrepancies are mainly due to the differences in the co-products allocation criteria. In this sense, economic/physical allocation and/or system expansion have been mostly considered in literature. In contrast, no allocation was considered appropriate in this study, according to the characteristics of the industries and products under assessment; thus, the major impacts fall on the main product, which derives on comparatively higher environmental burdens. Finally, due to the relevance of fodder production in the overall impact assessment results, strategies to reduce greenhouse gases (GHG) emissions as well as water use associated to this stage were proposed in the pork supply chain.

Traditional Atlantic Diet and Its Effect on Health and the Environment: A Secondary Analysis of the GALIAT Cluster Randomized Clinical Trial.

Importance: The universal call to action for healthier and more sustainable dietary choices is the framework of the United Nations's Sustainable Development Goals. The Atlantic diet, originating from the northwest of the Iberian Peninsula, represents an example of a traditional diet that aligns with these principles. Objective: To explore a 6-month intervention based on the Atlantic diet's effects on metabolic and environmental health, assessing metabolic syndrome (MetS) incidence and the carbon footprint. Design, Setting, and Participants: The Galician Atlantic Diet study was a 6-month randomized clinical trial designed to assess the effects of this regional traditional diet on families' eating habits. The study was conducted from March 3, 2014, to May 29, 2015, at a local primary health care center in the rural town of A Estrada in northwestern Spain and involved a multisectoral collaboration. Families were randomly selected from National Health System records and randomized 1:1 to an intervention or control group. This secondary analysis of the trial findings was performed between March 24, 2021, and November 7, 2023. Interventions: Over 6 months, families in the intervention group received educational sessions, cooking classes, written supporting material, and foods characteristic of the Atlantic diet, whereas those randomized to the control group continued with their habitual lifestyle. Main Outcomes and Measures: The main outcomes were MetS incidence, defined per National Cholesterol Education Program Adult Treatment Panel III guidelines, and carbon footprint emissions as an environmental metric using life cycle assessment with daily dietary intake as the functional unit. Results: Initially, 250 families were randomized (574 participants; mean [SD] age, 46.8 [15.7] years; 231 males [40.2%] and 343 females [59.8%]). The intervention group included 126 families (287 participants) and the control group, 124 families (287 participants). Ultimately, 231 families completed the trial. The intervention significantly reduced the risk of incident cases of MetS (rate ratio, 0.32; 95% CI, 0.13-0.79) and had fewer MetS components (proportional odds ratio, 0.58; 95% CI, 0.42-0.82) compared with the control condition. The intervention group did not have a significantly reduced environmental impact in terms of carbon footprint emissions compared with the control group (-0.17 [95% CI, -0.46 to 0.12] kg CO2 equivalents/person/d). Conclusions and Relevance: These findings provide important evidence that a family-focused dietary intervention based on a traditional diet can reduce the risk of incident MetS. Further research is needed to understand the underlying mechanisms and determine the generalizability to other populations, taking into account regional cultural and dietary variations. Trial Registration: ClinicalTrials.gov Identifier: NCT02391701.

Notch1 and IL-7 receptor signalling in early T-cell development and leukaemia.

Notch receptors are master regulators of many aspects of development and tissue renewal in metazoans. Notch1 activation is essential for T-cell specification of bone marrow-derived multipotent progenitors that seed the thymus, and for proliferation and further progression of early thymocytes along the T-cell lineage. Deregulated activation of Notch1 significantly contributes to the generation of T-cell acute lymphoblastic leukaemia (T-ALL). In addition to Notch1 signals, survival and proliferation signals provided by the IL-7 receptor (IL-7R) are also required during thymopoiesis. Our understanding of the molecular mechanisms controlling stage-specific survival and proliferation signals provided by Notch1 and IL-7R has recently been improved by the discovery that the IL-7R is a transcriptional target of Notch1. Thus, Notch1 controls T-cell development, in part by regulating the stage- and lineage-specific expression of IL-7R. The finding that induction of IL-7R expression downstream of Notch1 also occurs in T-ALL highlights the important contribution that deregulated IL-7R expression and function may have in this pathology. Confirming this notion, oncogenic IL7R gain-of-function mutations have recently been identified in childhood T-ALL. Here we discuss the fundamental role of Notch1 and IL-7R signalling pathways in physiological and pathological T-cell development in mice and men, highlighting their close molecular underpinnings.

Environmental performance of rainbow trout (Oncorhynchus mykiss) production in Galicia-Spain: A Life Cycle Assessment approach.

Aquaculture is an increasingly important supplier of food worldwide. However, due to its high dependence on agricultural and fishing resources, its growth is constantly constrained by environmental impacts beyond aquaculture production systems. Within the European Union, Spain accounts for approximately 25 % of total aquaculture production, which implies that environmental impacts in rivers and marine ecosystems must be monitored to understand the role of aquaculture systems. While studies on the environmental performance of mussels or turbot production have been reported in the literature, Spanish rainbow trout (Oncorhynchus mykiss) has not received much attention despite its relative importance. In this sense, a Life Cycle Assessment (LCA) study of rainbow trout produced in a medium-sized plant in Galicia (NW Spain) was carried out in the present study. The study considered the production of round weight trout, as well as some commonly produced processed products, including filleting. The life cycle modelling included a high level of primary data in the foreground system. In addition to the widely considered environmental impact categories for this activity (e.g., global warming potential, terrestrial acidification and freshwater eutrophication), the recent proposed antibiotic resistance (ABR) enrichment impact category was included to explore the potential impact of antibiotic release in freshwater microbiota. The results highlighted the high contribution of aquafeed to most impact categories, due to upstream agricultural and fishing processes, whereas farm operation was responsible for the larger part of the impact in freshwater eutrophication, mainly due to direct emissions of nutrients from fish feeding. Amoxicillin release to recipient water bodies was the main driver to the ABR enrichment category. In contrast, the processing phase (i.e., gutting, freezing and packaging) showed low environmental burdens. In order to improve the environmental performance of the rainbow trout production system, decreasing the feed conversion ratio (FCR), shifting to renewable energy, using low environmental burden ingredients in aquafeed, and alternatives to control diseases without antibiotics could be considered.

Improving environmental sustainability of agriculture in Egypt through a life-cycle perspective.

Soil plays an essential role as a habitat, source of nutrients and support for vegetation. Promoting food security and environmental sustainability of agricultural systems requires an integrated approach to soil fertility management. Agricultural activities should be developed with preventive approaches aimed at avoiding or reducing negative impacts on the soil physicochemical and biological properties and the depletion of soil nutrient reserves. In this regard, Egypt has developed the Sustainable Agricultural Development Strategy to encourage environmentally friendly practices among farmers, such as crop rotation and water management, in addition to extending agriculture to desert areas, favoring the socio-economic development of the region. In order to evaluate the outcomes of the plan beyond quantitative data of production, yield, consumption and emissions, the environmental profile of agriculture in Egypt has been assessed under a life-cycle perspective in order to identify the associated environmental burdens and ultimately contribute to improving the sustainability policies of agricultural activity within the framework of a crop rotation system. In particular, a two-year crop rotation (Egyptian clover-maize-wheat) was analyzed in two distinct agricultural areas in Egypt: New Lands in desert regions and Old Lands along the Nile River, traditionally recognized as fertile areas due to the river alluvium and water availability. The New Lands had the worst environmental profile for all impact categories, except for Soil organic carbon deficit and Global potential species loss. Irrigation and on-field emissions associated with mineral fertilization were identified as the most critical hotspots of Egyptian agriculture. In addition, land occupation and land transformation were reported as the main drivers of biodiversity loss and soil degradation, respectively. Beyond these results, further research on biodiversity and soil quality indicators is needed to more accurately assess the environmental damage caused by the conversion of deserts into agricultural areas, given the species richness these regions hold.

Environmental and economic benefits of wheat and chickpea crop rotation in the Mediterranean region of Apulia (Italy).

Wheat plays an essential role in safeguarding global food security. However, its intensive agricultural production, aimed at maximizing crop yields and associated economic benefits, jeopardizes many ecosystem services and the economic stability of farmers. Rotations with leguminous are recognized as a promising strategy in favor of sustainable agriculture. However, not all crop rotations are suitable for promoting sustainability and their implications on agricultural soil and crop quality should be carefully analyzed. This research aims to demonstrate the environmental and economic benefits of introducing chickpea into a wheat-based system under Mediterranean pedo-climatic conditions. For this purpose, the crop rotation "wheat-chickpea" was evaluated and compared with the conventional regime (wheat monoculture) by means of life cycle assessment methodology. For this purpose, inventory data (e.g., agrochemical doses, machinery, energy consumption, production yield, among others) was compiled for each crop and cropping system, thus converted into environmental impacts based on two functional units: 1 ha per year and one € of gross margin. Eleven environmental indicators were analyzed, including soil quality and biodiversity loss. Results indicate that chickpea-wheat rotation system offers lower environmental impacts, regardless of the functional unit considered. Global warming (18 %) and freshwater ecotoxicity (20 %) were the categories with the largest reductions. Furthermore, a remarkable increase (96 %) in gross margin was observed with the rotation system, due to the low cost of chickpea cultivation and its higher market price. Nevertheless, proper fertilizer management remains essential to fully attain the environmental benefits of crop rotation with legumes.

Water-Energy-Food nexus index proposal as a sustainability criterion on dairy farms.

Cow milk is a fundamental nutrients source for the human diet at all stages of life. However, the decline in cow milk consumption over the years has been driven by increased consumer awareness of animal welfare and the environmental burdens associated. In this regard, different initiatives have emerged to mitigate the impacts of livestock farming, but many of them without addressing the multi-perspective view of environmental sustainability. Thus, the Water-Energy-Food (WEF) nexus emerges as a framework to consider the complex synergies among carbon emissions, water demand, energy requirements and food production. In this study, a novel and harmonised WEF nexus approach has been proposed and applied to evaluate a set of 100 dairy farms. For that, the assessment, normalisation, and weighting of three lifecycle indicators such as carbon, water and energy footprints, as well as the milk yield were carried out to obtain a single value, the WEF nexus index (WEFni), which varies from 0 to 100. Results show that the WEF nexus scores obtained vary from 31 to 90, demonstrating large differences among the farms assessed. A cluster ranking was performed to identify those farms with the worst WEF nexus indexes. For this group, consisting of 8 farms with an average WEFni of 39, three improvement actions focused on the feeding, digestive process and wellbeing of the cows were applied to determine the potential reduction in the two main hotspots identified: cow feeding and milk production level. The proposed methodology can establish a roadmap for promoting a more environmentally sustainable food industry, although further studies are still required in the pathway of a standardised WEFni.

Benchmarking machine learning approaches to predict radiation-induced toxicities in lung cancer patients.

Background and purpose: Radiation-induced toxicities are common adverse events in lung cancer (LC) patients undergoing radiotherapy (RT). An accurate prediction of these adverse events might facilitate an informed and shared decision-making process between patient and radiation oncologist with a clearer view of life-balance implications in treatment choices. This work provides a benchmark of machine learning (ML) approaches to predict radiation-induced toxicities in LC patients built upon a real-world health dataset based on a generalizable methodology for their implementation and external validation. Materials and Methods: Ten feature selection (FS) methods were combined with five ML-based classifiers to predict six RT-induced toxicities (acute esophagitis, acute cough, acute dyspnea, acute pneumonitis, chronic dyspnea, and chronic pneumonitis). A real-world health dataset (RWHD) built from 875 consecutive LC patients was used to train and validate the resulting 300 predictive models. Internal and external accuracy was calculated in terms of AUC per clinical endpoint, FS method, and ML-based classifier under analysis. Results: Best performing predictive models obtained per clinical endpoint achieved comparable performances to methods from state-of-the-art at internal validation (AUC ≥ 0.81 in all cases) and at external validation (AUC ≥ 0.73 in 5 out of 6 cases). Conclusion: A benchmark of 300 different ML-based approaches has been tested against a RWHD achieving satisfactory results following a generalizable methodology. The outcomes suggest potential relationships between underrecognized clinical factors and the onset of acute esophagitis or chronic dyspnea, thus demonstrating the potential that ML-based approaches have to generate novel data-driven hypotheses in the field.

Environmental assessment of the production of itaconic acid from wheat straw under a biorefinery approach.

This study performs the environmental assessment of itaconic acid (IA) production from wheat straw. The Life Cycle Assessment (LCA) methodology is used to determine the environmental hotspots, considering impact categories such as Global Warming (GW), Fossil Resource Scarcity (FRS), Water Consumption (WC), among others. A sensitivity analysis was performed considering an optimization of the steam explosion process and 100% renewable energy. Results report an impact of about 14.33 kg CO2 eq in GW, 4.15 kg of oil eq in FRS, for each kg of IA produced for the baseline scenario. Moreover, the pretreatment and fermentation stages constitute hotspots of the IA production. In addition, using a renewable energy source in production would reduce the impact by 82% in GW, 71% in PM and 82% in FRS categories. The optimization of the steam explosion process presents a better performance in GW and FRS but also lies in an increase in WC.

Offsetting the environmental impacts of single or multi-product biorefineries from wheat straw.

Moving toward a bioeconomy system is fundamental to climate change mitigation, nevertheless, the biotechnological routes should guarantee an environmental sustainability. Isobutene, a precursor in several industrial applications, is one of those chemicals that the environmental effects of its bio-based production have been scarcely explored. This study aims to assess the environmental performance of two biorefinery systems: the first one focuses only on the production of isobutene (I) and the second one on the co-production with lignin (I + L), both from the valorisation of wheat straw. The Life Cycle Assessment methodology is used to determine the environmental impacts considering mid-point and end-point categories. Biorefineries report 0.65 and 1.32 kg CO2-eq per kg of biomass processed for I and I + L system, respectively. The most affected endpoint damage category corresponds to Human Health, regardless of the scenarios. Moreover, the pre-treatment stage constitutes the main hotspot of both systems considering midpoint and endpoint perspectives.

Co-benefits of the EAT-Lancet diet for environmental protection in the framework of the Spanish dietary pattern.

The immediate need to build resilient food systems with lower greenhouse gas (GHG) emissions and protection of water resources is a global challenge. To address this, the EAT-Lancet Commission described the global reference diet with principles of nutritional quality and environmental sustainability. With this in mind, the carbon and water footprints of the current Spanish dietary pattern have been compared with the EAT-Lancet global dietary recommendations, taking into account deviations in food intake. To provide additional context, differences between the average Spanish dietary pattern and dietary guidelines applied in other countries in Europe (Italy, the Netherlands and the Mediterranean region) and America have also been analyzed and discussed from a sustainability approach. We found that the EAT-Lancet diet requires less water resources (3056 L·person-1·day-1) and lower level of GHG emissions (2.13 kgCO2eq·person-1·day-1) in comparison with the Spanish dietary pattern (3732 L·person-1·day-1 and 3.62 kgCO2eq·person-1·day-1, respectively). Starch-based products and oils and fats were identified as largest contributors to both environmental indicators in the EAT-Lancet diet. On the other hand, meat and dairy were the environmental hotspots in the Spanish dietary pattern. Comparison with other food-based dietary patterns also raises environmental concerns about the high meat consumption in Spain. Overall, this analysis suggests that reducing the consumption of beef meat and dairy to a level in line with the global environmental targets set by the EAT-Lancet Commission would ensure a shift in Spanish dietary habits towards more environmentally sustainable food consumption patterns.