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Tropical cyclones (TCs) produce strong winds and heavy rains accompanied by consecutive events such as landslides and storm surges, resulting in losses of lives and livelihoods, particularly in regions with high socioeconomic vulnerability. To proactively mitigate the impacts of TCs, humanitarian actors implement anticipatory action. In this work, we build upon such an existing anticipatory action for the Philippines, which uses an impact-based forecasting model for housing damage based on eXtreme Gradient Boosting (XGBoost) to release funding and trigger early action. We improve it in three ways. First, we perform a correlation and selection analysis to understand if Philippines-specific features can be left out or replaced with features from open global data sources. Secondly, we transform the target variable (percentage of completely damaged houses) and not yet grid-based global features to a 0.1∘ grid resolution by de-aggregation using Google Open Buildings data. Thirdly, we evaluate XGBoost regression models using different combinations of global and local features at grid and municipality spatial levels. We first introduce a two-stage model to predict if the damage is above 10 % and then use a regression model trained on all or only high-damage data. All experiments use data from 39 typhoons that impacted the Philippines between 2006–2020. Due to the scarcity and skewness of the training data, specific attention is paid to data stratification, sampling, and validation techniques. We demonstrate that employing only the global features does not significantly influence model performance. Despite excluding local data on physical vulnerability and storm surge susceptibility, the two-stage model improves upon the municipality-based model with local features. When applied to anticipatory action, our two-stage model would show a higher true-positive rate, a lower false-negative rate, and an improved false-positive rate, implying that fewer resources would be wasted in anticipatory action. We conclude that relying on globally available data sources and working at the grid level holds the potential to render a machine-learning-based impact model generalizable and transferable to locations outside of the Philippines impacted by TCs. Also, a grid-based model increases the resolution of the predictions, which may allow for a more targeted implementation of anticipatory action. However, it should be noted that an impact-based forecasting model can only be as good as the forecast skill of the TC forecast that goes into it. Future research will focus on replicating and testing the approach in other TC-prone countries. Ultimately, a transferable model will facilitate the scaling up of anticipatory action for TCs.

Background: Common bean (Phaseolus vulgaris) is one of the main nutritional resources in the world, and a low environmental impact source of protein. However, the majority of its cultivation areas are affected by drought and this scenario is only expected to worsen with climate change. Stomatal closure is one of the most important plant responses to drought and the MYB60 transcription factor is among the key elements regulating stomatal aperture. If targeting and mutating the MYB60 gene of common bean would be a valuable strategy to establish more drought-tolerant beans was therefore investigated., Results: The MYB60 gene of common bean, with orthology to the Arabidopsis AtMYB60 gene, was found to have conserved regions with MYB60 typical motifs and architecture. Stomata-specific expression of PvMYB60 was further confirmed by q-RT PCR on organs containing stomata, and stomata-enriched leaf fractions. Further, function of PvMYB60 in promoting stomata aperture was confirmed by complementing the defective phenotype of a previously described Arabidopsis myb60-1 mutant., Conclusions: Our study finally points PvMYB60 as a potential target for obtaining more drought-tolerant common beans in the present context of climate change which would further greatly contribute to food security particularly in drought-prone countries., (© 2024. The Author(s).)

This paper explores the potential of leveraging electronic health records (EHRs) for personalized health research through the application of artificial intelligence (AI) techniques, specifically Named Entity Recognition (NER). By extracting crucial patient information from clinical texts, including diagnoses, medications, symptoms, and lab tests, AI facilitates the rapid identification of relevant data, paving the way for future care paradigms. The study focuses on Non-small cell lung cancer (NSCLC) in Italian clinical notes, introducing a novel set of 29 clinical entities that include both presence or absence (negation) of relevant information associated with NSCLC. Using a state-of-the-art model pretrained on Italian biomedical texts, we achieve promising results (average F1-score of 80.8%), demonstrating the feasibility of employing AI for extracting biomedical information in the Italian language.

Two tomato genotypes were grown in open field by three cultivation systems (one conventional and two distinct organic for mulching) in three years, 2015, 2016 and 2017. Yields, sugars, organic acids, amino acids, ascorbic acid, biothiols, carotenoids and phenols were measured. Weather conditions largely differed among harvest years, with summer 2016 rainier and less warm, and an opposite summer 2017. Organic systems had lower yields than conventional one but also, interestingly, lower waste percentages. Furthermore, tilled and no-tilled organic systems provided comparable yields. With respect to 3-year average, sugars were higher in 2017, acids in 2016 and in organic fruits, and amino acids increased in 2015 and in conventional samples. A higher glutathione content was found in organic samples, and higher carotenoids in 2017. Phenols increased in 2016, with a higher chlorogenic acid content in organic tomatoes. Some differences between genotypes were observed, highlighting their different adaptability to growing systems., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The capsule robot (CR) is a promising endoscopic method in gastrointestinal diagnosis because of its low discomfort to users. Most CRs are used to acquire image information only and lack the ability to collect samples. Although some biopsy capsule robots (BCRs) have been developed, it remains challenging to acquire the intestinal tissue while avoiding tearing and adhesion due to the flexibility of colonic tissue. In this study, we develop a BCR with a novel sampling strategy in which soft tissue is scratched with sharp blades rotating at high speed to avoid tissue tearing. In the BCR design, a spiral spring with prestored energy is used to release high energy within a short period of time, which is difficult for a motor or magnet to perform within a small capacity installation space. The energy of the tightened spiral spring is transmitted to drive sharp blades to rotate quickly via a designed gear mechanism. To guarantee reliable sampling, a Bowden cable is used to transmit the user's manipulation to trigger the rotation of the blades, and the triggering force transmitted by the cable can be monitored in real time by a force sensor installed at the manipulating end. A prototype of the proposed BCR is designed and fabricated, and its performance is tested through in vitro experiments. The results show that the proposed BCR is effective and the size of its acquired samples satisfies clinical requirements., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2022 Zhibin Song et al.)

Background: Bronchiolitis is the most frequent cause of hospitalization in infants younger than 1 year of age. We sought to evaluate the correlation between lymphocyte count and clinical manifestation in infants hospitalized with bronchiolitis., Materials and Methods: We performed a retrospective cohort study evaluating 1297 children hospitalized for bronchiolitis from 2004 to 2019. A nasal washing was tested for 14 respiratory viruses by PCR. A clinical severity score, ranging 0-8, was assigned at hospital admission. History and clinical course were recorded for each infant. Patients were divided in 3 groups according to lymphocyte count tertiles. Parents of enrolled patients have been phoned annually over 5 years to evaluate respiratory sequelae., Results: A total of 433 children had 2914.2 ± 745.5/mm 3 lymphocytes (Group 1), 432 had 4897.6 ± 561.5/mm 3 lymphocytes (Group 2) and 432 had 7884 ± 1903.3/mm 3 lymphocytes (Group 3). Group 1 patients were more frequently infected by RSV and presented with fever, a worse clinical severity score. They more frequently needed oxygen supplementation, underwent a prolonged hospitalization needed to be admitted to pediatric intensive care unit. Finally, they had more frequently a family history of eczema, wheezing and asthma. We found no differences between lymphocytes count and respiratory sequelae (at least two episodes of wheezing per year)., Conclusions: Infants with low lymphocyte count are more likely to have a worse clinical course of bronchiolitis., (© 2022 Wiley Periodicals LLC.)

The development of effective tools for the sustainable supply of phyto-ingredients and natural substances with reduced environmental footprints can help mitigate the dramatic scenario of climate change. Plant cell cultures-based biorefineries can be a technological advancement to face this challenge and offer a potentially unlimited availability of natural substances, in a standardized composition and devoid of the seasonal variability of cultivated plants. Monounsaturated (MUFA) fatty acids are attracting considerable attention as supplements for biodegradable plastics, bio-additives for the cosmetic industry, and bio-lubricants. Cardoon ( Cynara cardunculus L. var. altilis ) callus cultures accumulate fatty acids and polyphenols and are therefore suitable for large-scale production of biochemicals and valuable compounds, as well as biofuel precursors. With the aim of boosting their potential uses, we designed a biotechnological approach to increase oleic acid content through Agrobacterium tumefaciens -mediated metabolic engineering. Bioinformatic data mining in the C. cardunculus transcriptome allowed the selection and molecular characterization of SAD (stearic acid desaturase) and FAD2.2 (fatty acid desaturase) genes, coding for key enzymes in oleic and linoleic acid formation, as targets for metabolic engineering. A total of 22 and 27 fast-growing independent CcSAD overexpressing (OE) and CcFAD2.2 RNAi knocked out (KO) transgenic lines were obtained. Further characterization of five independent transgenic lines for each construct demonstrated that, successfully, SAD overexpression increased linoleic acid content, e.g., to 42.5%, of the relative fatty acid content, in the CcSAD OE6 line compared with 30.4% in the wild type (WT), whereas FAD2.2 silencing reduced linoleic acid in favor of the accumulation of its precursor, oleic acid, e.g., to almost 57% of the relative fatty acid content in the CcFAD2.2 KO2 line with respect to 17.7% in the WT. Moreover, CcSAD OE6 and CcFAD2.2 KO2 were also characterized by a significant increase in total polyphenolic content up to about 4.7 and 4.1 mg/g DW as compared with 2.7 mg/g DW in the WT, mainly due to the accumulation of dicaffeoyl quinic and feruloyl quinic acids. These results pose the basis for the effective creation of an engineered cardoon cells-based biorefinery accumulating high levels of valuable compounds from primary and specialized metabolism to meet the industrial demand for renewable and sustainable sources of innovative bioproducts., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cappetta, De Palma, D’Alessandro, Aiello, Romano, Graziani, Ritieni, Paolo, Locatelli, Sparvoli, Docimo and Tucci.)

Introduction: Surgery for chronic anal fissure is challenging for every proctologist. Solving the pain by guaranteeing rapid and effective healing is the objective, but what is the price to pay today in functional terms? Though this result is nowadays partially achievable through interventions that include the execution of an internal sphincterotomy among the procedures, it is necessary to underline the high rate of patients who can present faecal incontinence. The aim of this study is to explore the effectiveness of scanner-assisted CO 2 laser fissurectomy. Methods: From April 2021 to September 2021, all consecutive patients who affected by chronic anal fissure suitable for surgery, meeting the inclusion and exclusion criteria, were evaluated. All planned data were recorded before surgery, then at 24 h, 1 week, and 1 month follow-up. A scanner-assisted CO 2 laser was used in this study to achieve a smooth and dried wound with a minimal tissue thermal damage, to ensure good postsurgical pain control, rapid and functional, elastic and stable healing, and to prevent potential relapses. Paracetamol 1 g every 8 h was prescribed for the first 24 h and then continued according to each patient's need. Ketorolac 15 mg was prescribed as rescue. Results: Mean pain intensity ≤3, considered as the principal endpoint, was recorded in 26 out of the 29 patients who enrolled in the study with a final success rate of 89.7% at 1-month follow-up. Pain and anal itching showed a statistically significant reduction while bleeding, burning, and maximum pain, and REALIS score showed a reduction too at the end of the follow-up period. Reepithelisation proved to be extremely fast and effective: 22 of 29 (75.9%) showed a complete healing and 5 showed a partial reepithelisation at 1-month follow-up. Discussion: Outcomes of this study showed that it is undoubtedly necessary to change the surgical approach in case of anal fissure. The internal sphincterotomy procedure must be most of all questioned, where the availability of cutting-edge technological tools must be avoided and offered only in selected cases. Scanner-assisted CO 2 laser showed great results in terms of pain control and wound healing, secondary to an extremely precise ablation, vaporisation, and debridement procedures with minimal lateral thermal damage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Iacopo, Tommaso, Chiara, Filippo, Paolo, Gianni, Cinzia, Giuseppina, Federico, Alessandra, Silvia, Antonella, Luca and Claudio.)

Cultivated cardoon ( Cynara cardunculus var. altilis L.) is a promising candidate species for the development of plant cell cultures suitable for large-scale biomass production and recovery of nutraceuticals. We set up a protocol for Agrobacterium tumefaciens -mediated transformation, which can be used for the improvement of cardoon cell cultures in a frame of biorefinery. As high lignin content determines lower saccharification yields for the biomass, we opted for a biotechnological approach, with the purpose of reducing lignin content; we generated transgenic lines overexpressing the Arabidopsis thaliana MYB4 transcription factor, a known repressor of lignin/flavonoid biosynthesis. Here, we report a comprehensive characterization, including metabolic and transcriptomic analyses of AtMYB4 overexpression cardoon lines, in comparison to wild type, underlining favorable traits for their use in biorefinery. Among these, the improved accessibility of the lignocellulosic biomass to degrading enzymes due to depletion of lignin content, the unexpected increased growth rates, and the valuable nutraceutical profiles, in particular for hydroxycinnamic/caffeoylquinic and fatty acids profiles.

CRISPR (clustered regularly interspaced short palindromic repeats) somatic genome editing, an important promissory technology, presents a case study of the movement of basic scientists into translational research. In this paper, we explore how scientists experience the pulls of CRISPR's power and the pushes of economic and societal pressures in adopting new translational roles. Given basic scientists' emerging contact with and influence upon individuals with genetic conditions, we also examine how scientists understand the perspectives of affected populations, both as potential subjects of early experiments and as the patients who could receive future treatments. Finally, we consider the ethical implications of our findings and call for innovative approaches to translational research that help scientists engage with people with genetic conditions in early translational research., (© 2021 by The Hastings Center. All rights reserved.)

Seed development is under the control of complex and coordinated molecular networks required for the formation of its different components. The seed coat development largely determines final seed size and shape, in addition to playing a crucial role in protecting the embryo and promoting germination. In this study, we investigated the role of three transcription factors known to be active during seed development in Arabidopsis thaliana : SEEDSTICK (STK) and GORDITA (GOA), two MADS-domain proteins, and AUXIN RESPONSE FACTOR 2 (ARF2), belonging to the ARF family. Through a reverse genetic approach, we characterized the seed phenotypes of all the single, double and triple loss-of-function mutants in relation to seed size/shape and the effects on metabolic pathways occurring in the seed coat. This approach revealed that dynamic networks involving these TFs are active throughout ovule and seed development, affecting the formation of the seed coat. Notably, while the genetic interaction among these genes results in synergies that control the promotion of cell expansion in the seed coat upon pollination and production of proanthocyanidins, functional antagonists arise in the control of cell proliferation and release of mucilage.

Plant specialized metabolites (SMs) play an important role in the interaction with the environment and are part of the plant defense response. These natural products are volatile, semi-volatile and non-volatile compounds produced from common building blocks deriving from primary metabolic pathways and rapidly evolved to allow a better adaptation of plants to environmental cues. Specialized metabolites include terpenes, flavonoids, alkaloids, glucosinolates, tannins, resins, etc. that can be used as phytochemicals, food additives, flavoring agents and pharmaceutical compounds. This review will be focused on Mediterranean crop plants as a source of SMs, with a special attention on the strategies that can be used to modulate their production, including abiotic stresses, interaction with beneficial soil microorganisms and novel genetic approaches.

Seed size is the result of complex molecular networks controlling the development of the seed coat (of maternal origin) and the two fertilization products, the embryo and the endosperm. In this study we characterized the role of Arabidopsis thaliana MADS-domain transcription factor SEEDSTICK (STK) in seed size control. STK is known to regulate the differentiation of the seed coat as well as the structural and mechanical properties of cell walls in developing seeds. In particular, we further characterized stk mutant seeds. Genetic evidence (reciprocal crosses) of the inheritance of the small-seed phenotype, together with the provided analysis of cell division activity (flow cytometry), demonstrate that STK acts in the earlier phases of seed development as a maternal activator of growth. Moreover, we describe a molecular mechanism underlying this activity by reporting how STK positively regulates cell cycle progression via directly activating the expression of E2Fa , a key regulator of the cell cycle. Altogether, our results unveil a new genetic network active in the maternal control of seed size in Arabidopsis .

Phytic acid (PA) represents the major storage form of seed phosphate (P). During seed maturation, it accumulates as phytate salts chelating various mineral cations, therefore reducing their bioavailability. During germination, phytase dephosphorylates PA releasing both P and cations which in turn can be used for the nutrition of the growing seedling. Animals do not possess phytase, thus monogastric animals assimilate only 10% of the phytate ingested with feed, whilst 90% is excreted and may contribute to cause P pollution of the environment. To overcome this double problem, nutritional and environmental, in the last four decades, many low phytic acid ( lpa ) mutants (most of which affect the PA-MRP transporters) have been isolated and characterized in all major crops, showing that the lpa trait can increase the nutritional quality of foods and feeds and improve P management in agriculture. Nevertheless, these mutations are frequently accompanied by negative pleiotropic effects leading to agronomic defects which may affect either seed viability and germination or plant development or in some cases even increase the resistance to cooking, thus limiting the interest of breeders. Therefore, although some significant results have been reached, the isolation of lpa mutants improved for their nutritional quality and with a good field performance remains a goal so far not fully achieved for many crops. Here, we will summarize the main pleiotropic effects that have been reported to date in lpa mutants affected in PA-MRP transporters in five productive agronomic species, as well as addressing some of the possible challenges to overcome these hurdles and improve the breeding efforts for lpa mutants., (Copyright © 2020 Colombo, Paolo, Cominelli, Sparvoli, Nielsen and Pilu.)

Seed phytic acid reduces mineral bioavailability by chelating minerals. Consumption of common bean seeds with the low phytic acid 1 (lpa1) mutation improved iron status in human trials but caused adverse gastrointestinal effects, presumably due to increased stability of lectin phytohemagglutinin L (PHA-L) compared to the wild type (wt). A hard-to-cook (HTC) defect observed in lpa1 seeds intensified this problem. We quantified the HTC phenotype of lpa1 common beans with three genetic backgrounds. The HTC phenotype in the lpa1 black bean line correlated with the redistribution of calcium particularly in the cell walls, providing support for the "phytase-phytate-pectin" theory of the HTC mechanism. Furthermore, the excess of free cations in the lpa1 mutation in combination with different PHA alleles affected the stability of PHA-L lectin., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The industrial transformation of tomato (Lycopersicon esculentum Mill.) produces processed foods, such as dried tomatoes. In this study two varieties (SaAb and PerBruzzo), grown in three cropping systems (one conventional and two organic ones), were processed by two types of small-scale drying (oven or sun drying), over two years of production. The dried samples were analyzed for their non-volatile and volatile composition, relating the results with sensory analysis. The multivariate analysis performed on collected data allowed a detailed comparison of the effects of processing, year-to year variation and cropping systems. Results indicated that drying methods mainly influenced the composition and flavor profile, also affected by the production year. The cropping system significantly influenced some quality indices, such as the acid and sugar amounts, and the aldehydes, respectively higher and lower in organic samples. The comprehensive PCA analysis allowed discrimination of drying methods and, to a lesser extent, cropping systems., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Unrealistic therapeutic beliefs are very common-the majority of patient-subjects (up to 94%) enrol in phase 1 trials seeking and expecting significant medical benefit, even though the likelihood of such benefit has historically proven very low. The high prevalence of therapeutic misestimation and unrealistic optimism in particular has stimulated debate about whether unrealistic therapeutic beliefs in early-phase clinical trials preclude adequate informed consent. We seek here to help resolve this controversy by showing that a crucial determination of when such therapeutic beliefs are ethically problematic turns on whether they are causally linked and instrumental to the motivation to participate in the trial. Thus, in practice, it is ethically incumbent on researchers to determine which understanding and beliefs lead to the participant's primary motivation for enrolling, not to simply assess understanding, beliefs and motivations independently. We further contend that assessing patient-subjects' appreciation as a component of informed consent-it is already an established component of decision-making capacity assessments-can help elucidate the link between understanding-beliefs and motivation; appreciation refers to an individual's understanding of the personal significance of both the medical facts and the experience of trial participation. Therefore, we recommend that: (1) in addition to the usual question, 'Why do you want to participate in this trial?', all potential participants should be asked the question: 'What are you giving up by participating in this trial?' and (2) researchers should consider the settings in which it may be possible and practical to obtain 'two-point consent'., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Fruits and seeds are the major food source on earth. Both derive from the gynoecium and, therefore, it is crucial to understand the mechanisms that guide the development of this organ of angiosperm species. In Arabidopsis, the gynoecium is composed of two congenitally fused carpels, where two domains: medial and lateral, can be distinguished. The medial domain includes the carpel margin meristem (CMM) that is key for the production of the internal tissues involved in fertilization, such as septum, ovules, and transmitting tract. Interestingly, the medial domain shows a high cytokinin signaling output, in contrast to the lateral domain, where it is hardly detected. While it is known that cytokinin provides meristematic properties, understanding on the mechanisms that underlie the cytokinin signaling pattern in the young gynoecium is lacking. Moreover, in other tissues, the cytokinin pathway is often connected to the auxin pathway, but we also lack knowledge about these connections in the young gynoecium. Our results reveal that cytokinin signaling, that can provide meristematic properties required for CMM activity and growth, is enabled by the transcription factor SPATULA (SPT) in the medial domain. Meanwhile, cytokinin signaling is confined to the medial domain by the cytokinin response repressor ARABIDOPSIS HISTIDINE PHOSPHOTRANSFERASE 6 (AHP6), and perhaps by ARR16 (a type-A ARR) as well, both present in the lateral domains (presumptive valves) of the developing gynoecia. Moreover, SPT and cytokinin, probably together, promote the expression of the auxin biosynthetic gene TRYPTOPHAN AMINOTRANSFERASE OF ARABIDOPSIS 1 (TAA1) and the gene encoding the auxin efflux transporter PIN-FORMED 3 (PIN3), likely creating auxin drainage important for gynoecium growth. This study provides novel insights in the spatiotemporal determination of the cytokinin signaling pattern and its connection to the auxin pathway in the young gynoecium.

Background: Sacral chordoma (SC) is a neoplasm arising from residual notochordal cells degeneration. SC is difficult to manage mainly because of anatomic location and tendency to extensive spread. Carbon ion radiotherapy (CIRT) is highly precise to selectively deliver high biological effective dose to the tumor target sparing the anatomical structure on its path even if when SC is contiguous to the intestine, and a surgical spacer might be an advantageous tool to create a distance around the target volume allowing radical curative dose delivery with a safe dose gradient to the surrounding organs. This paper describes a double approach-open and hand-assisted laparoscopic-for a silicon spacer placement in patients affected by sacral chordoma undergoing carbon ion radiotherapy., Methods: Six consecutive patients have been enrolled for surgical spacer placement-open (three) or hand-assisted (three)-prior carbon ion radiotherapy treatment in order to increase efficacy of carbon ion radiotherapy minimizing its side effects., Results: Results showed that silicon spacer placement for SC treatment is feasible both via laparoscopic and laparotomic approach., Conclusions: Its use might improve CIRT safety and thus efficacy for SC treatment.