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Background and purpose: To review available data on toxicity during and/or after treatment of abdominal-pelvic lymph node oligometastases (A-P LN) with stereotactic body radiation therapy (SBRT) and to provide an overview of adverse events and its relation to dose or fractionation. Material and methods: For this systematic review, we searched MEDLINE, Embase, Web of Science Core Collection, and CINAH for studies published between the database inception and October 3rd, 2023. Inclusion criteria were (1) patients with 1–5 A-P LN oligometastases, (2) treatment with SBRT to a median prescribed dose of ≥55 Gy BED10, and (3) description of acute and/or late toxicity. There were no language or date restrictions. Results: A total of 35 studies, including 1,512 patients, were selected. Late grade 3 and 4 adverse events occurred in 0.6% and 0.1% of the patients treated for A-P LN oligometastases. All late adverse events grade ≥ 3 occurred after treatment of the tumor with a minimum BED10 of 72 Gy. Of the 11 patients with severe late toxicity, five patients were re-irradiated. Late grade 2 and 1 toxicity was reported in 3.4% and 8.3% of the patients. Acute toxicity grades 4, 3, 2, and 1 occurred in 0.1%, 0.2%, 4.4%, and 19.8% of the patients, respectively. Interpretation: SBRT for A-P LN oligometastases show low toxicity rates. Nearly 50% of late adverse events ≥ grade 3 were associated with re-irradiation.

Google Earth Engine has deeply changed the way in which Earth observation data are processed, allowing the analysis of wide areas in a faster and more efficient way than ever before. Since its inception, many functions have been implemented by a rapidly expanding community, but none so far has focused on the computation of phenological metrics in mountain areas with high-resolution data. This work aimed to fill this gap by developing an open-source Google Earth Engine algorithm to map phenological metrics (PMs) such as the Start of Season, End of Season, and Length of Season and detect the Peak of Season in mountain areas worldwide using high-resolution free satellite data from the Landsat collection and Sentinel-2. The script was tested considering the entire Alpine chain. The validation was performed by the cross-computation of PMs using the R package greenbrown, which permits land surface phenology and trend analysis, and the Moderate-Resolution Imaging Spectroradiometer (MODIS) in homogeneous quote and land cover alpine landscapes. MAE and RMSE were computed. Therefore, this algorithm permits one to compute with a certain robustness PMs retrieved from higher-resolution free EO data from GEE in mountain areas worldwide.

It remains critical to identify colorectal cancers (CRC) that will disseminate as early as possible. Here, the authors identify CRC tumours that are aggressive and prone to early dissemination, characterised by epithelial TGFβ and growth-factor signalling - which could be targeted with MEK/EGFR inhibitors.

Cellular plasticity defines the capacity of cells to adopt distinct identities during development, tissue homeostasis and regeneration. Dynamic fluctuations between different states, within or across lineages, are regulated by changes in chromatin accessibility and in gene expression. When deregulated, cellular plasticity can contribute to cancer initiation and progression. Cancer cells are remarkably plastic which contributes to phenotypic and functional heterogeneity within tumours as well as resistance to targeted therapies. It is for these reasons that the scientific community has become increasingly interested in understanding the molecular mechanisms governing cancer cell plasticity. The purpose of this mini-review is to discuss different examples of cellular plasticity associated with metaplasia and epithelial-mesenchymal transition with a focus on therapy resistance.

Abstract Smith-Magenis syndrome (SMS) is a neurodevelopmental disorder characterized by cognitive and behavioral symptoms, obesity, and sleep disturbance, and no therapy has been developed to alleviate its symptoms or delay disease onset. SMS occurs due to haploinsufficiency of the retinoic acid-induced-1 (RAI1) gene caused by either chromosomal deletion (SMS-del) or RAI1 missense/nonsense mutation. The molecular mechanisms underlying SMS are unknown. Here, we generated and characterized primary cells derived from four SMS patients (two with SMS-del and two carrying RAI1 point mutations) and four control subjects to investigate the pathogenetic processes underlying SMS. By combining transcriptomic and lipidomic analyses, we found altered expression of lipid and lysosomal genes, deregulation of lipid metabolism, accumulation of lipid droplets, and blocked autophagic flux. We also found that SMS cells exhibited increased cell death associated with the mitochondrial pathology and the production of reactive oxygen species. Treatment with N-acetylcysteine reduced cell death and lipid accumulation, which suggests a causative link between metabolic dyshomeostasis and cell viability. Our results highlight the pathological processes in human SMS cells involving lipid metabolism, autophagy defects and mitochondrial dysfunction and suggest new potential therapeutic targets for patient treatment.

We examined the feasibility of using the neofunctional deep breathing (NDB) technique to reduce the allostatic load following the Trier Social Stress Test (TSST). Forty‐four healthy subjects were randomised into experimental and control groups. Following the TSST procedure, participants underwent either a single session of NDB or an attention control intervention. The Procomp Infinity Biofeedback system measured breath per minute (BPM), respiratory amplitude, HRV linear domains, skin conductance, and trapezius muscle electromyographic activity. Cortisol and cytokine salivary concentrations, perceived stress, and anxiety levels were also assessed. These parameters were combined into an allostatic load index (ALI) to measure the intervention's effect. This pilot RCT demonstrated the feasibility of the study design and practicality of the intervention. The NDB group showed reduced ALI, increased respiratory abdominal amplitude, decreased BPM, increased HRV indicating parasympathetic activation, and decreased cortisol and inflammatory cytokines. This study highlighted the feasibility of testing the NDB technique in reducing allostatic load through a neurobiological and anti‐inflammatory response after exposure to psychosocial stress. This protocol can represent a non‐invasive therapeutic adjutant in disorders related to a dysregulation of the HPA axis or to an inflammatory state. Trial Registration: NCT04102813 [ABSTRACT FROM AUTHOR]

The influence of mRNA splicing on colon cancer development and progression is unclear. In this study, the authors demonstrate that the SRSF1 splicing factor is essential to sustain the stem cell phenotype of WNT-activated colorectal cancers.

Abstract RAC1B is a tumour-related alternative splice isoform of the small GTPase RAC1, found overexpressed in a large number of tumour types. Building evidence suggests it promotes tumour progression but compelling in vivo evidence, demonstrating a role in driving tumour invasion, is currently lacking. In the present study, we have overexpressed RAC1B in a colorectal cancer mouse model with potential invasive properties. Interestingly, RAC1B overexpression did not trigger tumour invasion, rather it led to an acceleration of tumour initiation and reduced mouse survival. By modelling early stages of adenoma initiation we observed a reduced apoptotic rate in RAC1B overexpressing tumours, suggesting protection from apoptosis as a mediator of this phenotype. RAC1B overexpressing tumours displayed attenuated TGFβ signalling and functional analysis in ex vivo organoid cultures demonstrated that RAC1B negatively modulates TGFβ signalling and confers resistance to TGFβ-driven cell death. This work defines a novel mechanism by which early adenoma cells can overcome the cytostatic and cytotoxic effects of TGFβ signalling and characterises a new oncogenic function of RAC1B in vivo.

RAC1 is a downstream target of the Wnt signaling that promotes intestinal stem cell expansion and tumorigenesis. Here, the authors identify the specific splice variant RAC1B as an important mediator of colorectal tumourigenesis and a potential target for enhancing the efficacy of EGFR inhibitor treatment.

Earth observation data have assumed a key role in environmental monitoring, as well as in risk assessment. Rising temperatures and consequently heat waves due to ongoing climate change represent an important risk considering the population, as well as animals, exposed. This study was focused on the Aosta Valley Region in NW Italy. To assess population exposure to these patterns, the following datasets have been considered: (1) HDX Meta population dataset refined and updated in order to map population distribution and its features; (2) Landsat collection (missions 4 to 9) from 1984 to 2022 obtained and calibrated in Google Earth Engine to model LST trends. A pixel-based analysis was performed considering Aosta Valley settlements and relative population distribution according to the Meta population dataset. From Landsat data, LST trends were modelled. The LST gains computed were used to produce risk exposure maps considering the population distribution and structure (such as ages, gender, etc.). To check the consistency and quality of the HDX population dataset, MAE was computed considering the ISTAT population dataset at the municipality level. Exposure-risk maps were finally realized adopting two different approaches. The first one considers only LST gain maximum by performing an ISODATA unsupervised classification clustering in which the separability of each class obtained and was checked by computing the Jeffries–Matusita (J-M) distances. The second one was to map the rising temperature exposure by developing and performing a risk geo-analysis. In this last case the input parameters considered were defined after performing a multivariate regression in which LST maximum was correlated and tested considering (a) Fractional Vegetation Cover (FVC), (b) Quote, (c) Slope, (d) Aspect, (e) Potential Incoming Solar Radiation (mean sunlight duration in the meteorological summer season), and (f) LST gain mean. Results show a steeper increase in LST maximum trend, especially in the bottom valley municipalities, and especially in new built-up areas, where more than 60% of the Aosta Valley population and domestic animals live and where a high exposure has been detected and mapped with both approaches performed. Maps produced may help the local planners and the civil protection services to face global warming from a One Health perspective.

European long shelf-life (LSL) tomato landraces can be classified into two main groups: the Italian group, including ‘Piennolo’ landraces, and the Spanish group, including the ‘Penjar’ and ‘Ramellet’ landraces. In this study, a partially common set of ‘Piennolo’ and ‘Penjar-Ramellet’ varieties was grown in Italy and Spain to evaluate the effect of different agro-environmental and storage conditions on fruit quality and shelf-life. Overall, both Italian and Spanish LSL genotypes lost their peculiar phenotype in terms of physicochemical properties and shelf-life behavior when not grown in their original agro-environment. To better understand the sensory attributes that drive consumers’ preferences, all varieties were characterized using descriptive sensory analysis combined with hedonic tests. The evaluations were conducted postharvest on raw and processed products according to the country’s culinary tradition (baked in Italy; spread on bread in Spain). Sensory description by trained panels conducted on raw and processed products highlighted different sensory profiles between the two LSL tomato groups. In the ‘Piennolo’ group, a reduction in sensory diversity among the genotypes was observed in the baked products compared to the raw ones, while this trend was not observed for the ‘Penjar-Ramellet’ group. None of the varieties fully met the consumers’ preferences.

Earth Observation services guarantee continuous land cover mapping and are becoming of great interest worldwide. The Google Earth Engine Dynamic World represents a planetary example. This work aims to develop a land cover mapping service in geomorphological complex areas in the Aosta Valley in NW Italy, according to the newest European EAGLE legend starting in the year 2020. Sentinel-2 data were processed in the Google Earth Engine, particularly the summer yearly median composite for each band and their standard deviation with multispectral indexes, which were used to perform a k-nearest neighbor classification. To better map some classes, a minimum distance classification involving NDVI and NDRE yearly filtered and regularized stacks were computed to map the agronomical classes. Furthermore, SAR Sentinel-1 SLC data were processed in the SNAP to map urban and water surfaces to improve optical classification. Additionally, deep learning and GIS updated datasets involving urban components were adopted beginning with an aerial orthophoto. GNSS ground truth data were used to define the training and the validation sets. In order to test the effectiveness of the implemented service and its methodology, the overall accuracy was compared to other approaches. A mixed hierarchical approach represented the best solution to effectively map geomorphological complex areas to overcome the remote sensing limitations. In conclusion, this service may help in the implementation of European and local policies concerning land cover surveys both at high spatial and temporal resolutions, empowering the technological transfer in alpine realities.

Kras is often mutated in colorectal cancer but how this oncogenic mutation alters signalling pathways globally is undetermined. Here, the authors analyse how this mutation affects protein interaction networks and signal flow showing an extensive re‐wiring of signalling in response to KRas mutation

Anthocyanins are a large group of water-soluble flavonoid pigments. These specialized metabolites are ubiquitous in the plant kingdom and play an essential role not only in plant reproduction and dispersal but also in responses to biotic and abiotic stresses. Anthocyanins are recognized as important health-promoting and chronic-disease-preventing components in the human diet. Therefore, interest in developing food crops with improved levels and compositions of these important nutraceuticals is growing. This review focuses on work conducted to elucidate the genetic control of the anthocyanin pathway and modulate anthocyanin content in eggplant (Solanum melongena L.) and tomato (Solanum lycopersicum L.), two solanaceous fruit vegetables of worldwide relevance. While anthocyanin levels in eggplant fruit have always been an important quality trait, anthocyanin-based, purple-fruited tomato cultivars are currently a novelty. As detailed in this review, this difference in the anthocyanin content of the cultivated germplasm has largely influenced genetic studies as well as breeding and transgenic approaches to improve the anthocyanin content/profile of these two important solanaceous crops. The information provided should be of help to researchers and breeders in devising strategies to address the increasing consumer demand for nutraceutical foods. [ABSTRACT FROM AUTHOR]

Wnt ligands are essential for intestinal homoeostasis and stem cell maintenance. Here, the authors show that reduction in Wnt secretion reduces the number of intestinal stem cells; this results in rapid fixation of mutated stem cells and accelerated adenoma formation due to lack of cell competition.

Consumer dissatisfaction with the flavor quality of many modern fresh market tomato varieties has fostered breeders’ interest in sensory quality improvement, and the demand for traditional varieties, which are generally associated with better flavor. To achieve further knowledge on the factors influencing the sensory quality and consumers’ preferences and perception, European traditional and modern fresh market tomato varieties were grown and evaluated in France, Italy, and Spain. Different growing conditions were tested in France (soilless vs. soil) and in Spain (open field vs. greenhouse), while in Italy fruits were evaluated at two ripening stages. Fruit quality was assessed by integrating physicochemical analyses, sensory profiles, and consumer tests. In all three countries, overall modern varieties were perceived as having more intense “tomato flavor” and “overall flavor” than traditional ones. In France and Spain, consumers’ preferences were more oriented towards modern varieties than traditional ones. Significant growing condition effects were found on sensory and physicochemical traits, while the effect on consumers’ overall liking was not significant, largely depending on the genotype. A fair agreement between product configurations from descriptive analysis by trained assessors and Check-All-That-Apply (CATA) questions by consumers was observed. Penalty-lift analysis based on CATA allowed identifying positive and negative drivers of liking.

Background and purpose: To review available data on toxicity during and/or after treatment of abdominal-pelvic lymph node oligometastases (A-P LN) with stereotactic body radiation therapy (SBRT) and to provide an overview of adverse events and its relation to dose or fractionation. Material and methods: For this systematic review, we searched MEDLINE, Embase, Web of Science Core Collection, and CINAH for studies published between the database inception and October 3rd, 2023. Inclusion criteria were (1) patients with 1-5 A-P LN oligometastases, (2) treatment with SBRT to a median prescribed dose of =55 Gy BED10, and (3) description of acute and/or late toxicity. There were no language or date restrictions. Results: A total of 35 studies, including 1,512 patients, were selected. Late grade 3 and 4 adverse events occurred in 0.6% and 0.1% of the patients treated for A-P LN oligometastases. All late adverse events grade = 3 occurred after treatment of the tumor with a minimum BED10 of 72 Gy. Of the 11 patients with severe late toxicity, five patients were re-irradiated. Late grade 2 and 1 toxicity was reported in 3.4% and 8.3% of the patients. Acute toxicity grades 4, 3, 2, and 1 occurred in 0.1%, 0.2%, 4.4%, and 19.8% of the patients, respectively. Interpretation: SBRT for A-P LN oligometastases show low toxicity rates. Nearly 50% of late adverse events = grade 3 were associated with re-irradiation. [ABSTRACT FROM AUTHOR]

Abstract Cancer genome sequencing projects have identified hundreds of genetic alterations, often at low frequencies, raising questions as to their functional relevance. One exemplar gene is HUWE1, which has been found to be mutated in numerous studies. However, due to the large size of this gene and a lack of functional analysis of identified mutations, their significance to carcinogenesis is unclear. To determine the importance of HUWE1, we chose to examine its function in colorectal cancer, where it is mutated in up to 15 per cent of tumours. Modelling of identified mutations showed that they inactivate the E3 ubiquitin ligase activity of HUWE1. Genetic deletion of Huwe1 rapidly accelerated tumourigenic in mice carrying loss of the intestinal tumour suppressor gene Apc, with a dramatic increase in tumour initiation. Mechanistically, this phenotype was driven by increased MYC and rapid DNA damage accumulation leading to loss of the second copy of Apc. The increased levels of DNA damage sensitised Huwe1‐deficient tumours to DNA‐damaging agents and to deletion of the anti‐apoptotic protein MCL1. Taken together, these data identify HUWE1 as a bona fide tumour suppressor gene in the intestinal epithelium and suggest a potential vulnerability of HUWE1‐mutated tumours to DNA‐damaging agents and inhibitors of anti‐apoptotic proteins.