Hormonal networks involved in apical hook development in darkness and their response to light

In darkness, the dicot seedlings produce an apical hook as result of differential cell division and extension at opposite sides of the hypocotyl. This hook protects the apical meristem from mechanical damage during seedling emergence from the soil. In darkness, gibberellins act via the DELLA-PIF (PHYTOCHROME INTERACTING FACTORs) pathway, and ethylene acts via the EIN3/EIL1 (ETHYLENE INSENSITIE 3/EIN3 like 1)-HLS1 (HOOKLESS 1) pathway to control the asymmetric accumulation of auxin required for apical hook formation and maintenance. These core pathways form a network with multiple points of connection. Light perception by phytochromes and cryptochromes reduces the activity of PIFs and CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) --both required for hook formation in darkness--, lowers the levels of gibberellins, and triggers hook opening as a component of the switch between heterotrophic and photoautotrophic development. Apical hook opening is thus a suitable model to study the convergence of endogenous and exogenous signals on the control of cell division and cell growth.Fil: Mazzella, Maria Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; ArgentinaFil: Casal, Jorge Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; ArgentinaFil: Muschietti, Jorge Prometeo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental; ArgentinaFil: Fox, Ana Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentin

Design and conceptual development of a novel hybrid intelligent decision support system applied towards the prevention and early detection of forest fires

Forest fires have become a major problem that every year has devastating consequences at the environmental level, negatively impacting the social and economic spheres of the affected regions. Aiming to mitigate these terrible effects, intelligent prediction models focused on early fire detection are becoming common practice. Considering mainly a preventive approach, these models often use tools that indifferently apply statistical or symbolic inference techniques. However, exploring the potential for the hybrid use of both, as is already being done in other research areas, is a significant novelty with direct application to early fire detection. In this line, this work proposes the design, development, and proof of concept of a new intelligent hybrid system that aims to provide support to the decisions of the teams responsible for defining strategies for the prevention, detection, and extinction of forest fires. The system determines three risk levels: a general one called Objective Technical Fire Risk, based on machine learning algorithms, which determines the global danger of a fire in some area of the region under study, and two more specific others which indicate the risk over a limited area of the region. These last two risk levels, expressed in matrix form and called Technical Risk Matrix and Expert Risk Matrix, are calculated through a convolutional neural network and an expert system, respectively. After that, they are combined by means of another expert system to determine the Global Risk Matrix that quantifies the risk of fire in each of the study regions and generates a visual representation of these results through a color map of the region itself. The proof of concept of the system has been carried out on a set of historical data from fires that occurred in the Montesinho Natural Park (Portugal), demonstrating its potential utility as a tool for the prevention and early detection of forest fires. The intelligent hybrid system designed has demonstrated excellent predictive capabilities in such a complex environment as forest fires, which are conditioned by multiple factors. Future improvements associated with data integration and the formalization of knowledge bases will make it possible to obtain a standard tool that could be used and validated in real time in different forest areas

Integration of the Wang & Mendel algorithm into the application of Fuzzy expert systems to intelligent clinical decision support systems

The use of intelligent systems in clinical diagnostics has evolved, integrating statistical learning and knowledge-based representation models. Two recent works propose the identification of risk factors for the diagnosis of obstructive sleep apnea (OSA). The first uses statistical learning to identify indicators associated with different levels of the apnea-hypopnea index (AHI). The second paper combines statistical and symbolic inference approaches to obtain risk indicators (Statistical Risk and Symbolic Risk) for a given AHI level. Based on this, in this paper we propose a new intelligent system that considers different AHI levels and generates risk pairs for each level. A learning-based model generates Statistical Risks based on objective patient data, while a cascade of fuzzy expert systems determines a Symbolic Risk using symptom data from patient interviews. The aggregation of risk pairs at each level involves a fuzzy expert system with automatically generated fuzzy rules using the Wang-Mendel algorithm. This aggregation produces an Apnea Risk indicator for each AHI level, allowing discrimination between OSA and non-OSA cases, along with appropriate recommendations. This approach improves variability, usefulness, and interpretability, increasing the reliability of the system. Initial tests on data from 4400 patients yielded AUC values of 0.74–0.88, demonstrating the potential benefits of the proposed intelligent system architecture.Xunta de Galicia | Ref. ED481A-2020/03

Phytochrome b nuclear bodies respond to the low red to far-red ratio and to the reduced irradiance of canopy shade in Arabidopsis

The current consensus is that plant responses to canopy shade involve the perception of low red to far-red ratios (R:FRs) by phytochrome B (phyB), which leads to the direct activation of auxin synthesis genes by PHYTOCHROME INTERACTING FACTORs (PIFs). In addition to its effect on R:FRs, shade also reduces irradiance, but whether shade-induced drops in irradiance affect phyB activity has not been demonstrated. To address this issue, we investigated whether irradiance and R:FRs have similar effects on the nuclear distribution of phyB in petiole cells of light-grown plants. Under high-irradiance white light, phyB formed large nuclear bodies. Lowering irradiance without changing R:FRs or lowering R:FRs by adding far-red light led to the appearance of small nuclear bodies containing phyB. Large nuclear bodies remained but with some concomitant reduction in diameter. The appearance of small nuclear bodies was rapid, stable, and reversible upon the return to high irradiance and high R:FRs. High levels of red light but not of blue light were enough to restrain the formation of small phyB nuclear bodies. Irradiance was effective within the range found in natural canopies and even under relatively low R:FRs. The promotion of leaf hyponasty by lowering irradiance was impaired in phyB and pif mutants, as previously reported for the response to R:FRs. The expression of auxin-related genes showed a similar hierarchy of response to low R:FRs and low irradiance. We propose that phyB is able to perceive not only the low R:FRs, but also the low irradiance of shade.Fil: Trupkin, Santiago Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura; ArgentinaFil: Legris, Martina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Buchovsky, Ana Sabrina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura; ArgentinaFil: Tolava Rivero, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura; ArgentinaFil: Casal, Jorge Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura; Argentin

Proposal and definition of an intelligent clinical decision support system applied to the screening and early diagnosis of breast cancer

Breast cancer is the most frequently diagnosed tumor pathology on a global scale, being the leading cause of mortality in women. In light of this problem, screening programs have been implemented on the population at risk in the form of mammograms, starting in the 20th century. This has considerably reduced the associated deaths, as well as improved the prognosis of the patients who suffer from this disease. In spite of this, the evaluation of mammograms is not without certain variability and depends, to a large extent, on the experience and training of the medical team carrying out the assessment. With the aim of supporting the evaluation process of mammogram images and improving the diagnosis process, this work presents the design, development and proof of concept of a novel intelligent clinical decision support system, grounded on two predictive approaches that work concurrently. The first of them applies a series of expert systems based on fuzzy inferential engines, geared towards the treatment of the characteristics associated with the main findings present in mammograms. This allows the determination of a series of risk indicators, the Symbolic Risks, related to the risk of developing breast cancer according to the different findings. The second one implements a classification machine learning algorithm, which using data related to mammography findings as well as general patient information determines another metric, the Statistical Risk, also linked to the risk of developing breast cancer. These risk indicators are then combined, resulting in a new indicator, the Global Risk. This could then be corrected using a weighting factor according to the BI-RADS category, allocated to each patient by the medical team in charge. Thus, the Corrected Global Risk is obtained, which after interpretation can be used to establish the patient’s status as well as generate personalized recommendations. The proof of concept and software implementation of the system were carried out using a data set with 130 patients from a database from the School of Medicine and Public Health of the University of Wisconsin-Madison. The results obtained were encouraging, highlighting the potential use of the application, albeit pending intensive clinical validation in real environments. Moreover, its possible integration in hospital computer systems is expected to improve diagnostic processes as well as patient prognosis.Xunta de Galicia | Ref. ED481A-2020/03

Design and conceptual proposal of an intelligent clinical decision support system for the diagnosis of suspicious obstructive sleep apnea patients from health profile

Obstructive Sleep Apnea (OSA) is a chronic sleep-related pathology characterized by recurrent episodes of total or partial obstruction of the upper airways during sleep. It entails a high impact on the health and quality of life of patients, affecting more than one thousand million people worldwide, which has resulted in an important public health concern in recent years. The usual diagnosis involves performing a sleep test, cardiorespiratory polygraphy, or polysomnography, which allows characterizing the pathology and assessing its severity. However, this procedure cannot be used on a massive scale in general screening studies of the population because of its execution and implementation costs; therefore, causing an increase in waiting lists which would negatively affect the health of the affected patients. Additionally, the symptoms shown by these patients are often unspecific, as well as appealing to the general population (excessive somnolence, snoring, etc.), causing many potential cases to be referred for a sleep study when in reality are not suffering from OSA. This paper proposes a novel intelligent clinical decision support system to be applied to the diagnosis of OSA that can be used in early outpatient stages, quickly, easily, and safely, when a suspicious OSA patient attends the consultation. Starting from information related to the patient’s health profile (anthropometric data, habits, comorbidities, or medications taken), the system is capable of determining different alert levels of suffering from sleep apnea associated with different apnea-hypopnea index (AHI) levels to be studied. To that end, a series of automatic learning algorithms are deployed that, working concurrently, together with a corrective approach based on the use of an Adaptive Neuro-Based Fuzzy Inference System (ANFIS) and a specific heuristic algorithm, allow the calculation of a series of labels associated with the different levels of AHI previously indicated. For the initial software implementation, a data set with 4600 patients from the Álvaro Cunqueiro Hospital in Vigo was used. The results obtained after performing the proof tests determined ROC curves with AUC values in the range 0.8–0.9, and Matthews correlation coefficient values close to 0.6, with high success rates. This points to its potential use as a support tool for the diagnostic process, not only from the point of view of improving the quality of the services provided, but also from the best use of hospital resources and the consequent savings in terms of costs and time.Xunta de Galicia | Ref. ED481A-2020/03

Design of an intelligent decision support system applied to the diagnosis of obstructive sleep apnea

Obstructive sleep apnea (OSA), characterized by recurrent episodes of partial or total obstruction of the upper airway during sleep, is currently one of the respiratory pathologies with the highest incidence worldwide. This situation has led to an increase in the demand for medical appointments and specific diagnostic studies, resulting in long waiting lists, with all the health consequences that this entails for the affected patients. In this context, this paper proposes the design and development of a novel intelligent decision support system applied to the diagnosis of OSA, aiming to identify patients suspected of suffering from the pathology. For this purpose, two sets of heterogeneous information are considered. The first one includes objective data related to the patient’s health profile, with information usually available in electronic health records (anthropometric information, habits, diagnosed conditions and prescribed treatments). The second type includes subjective data related to the specific OSA symptomatology reported by the patient in a specific interview. For the processing of this information, a machine-learning classification algorithm and a set of fuzzy expert systems arranged in cascade are used, obtaining, as a result, two indicators related to the risk of suffering from the disease. Subsequently, by interpreting both risk indicators, it will be possible to determine the severity of the patients’ condition and to generate alerts. For the initial tests, a software artifact was built using a dataset with 4400 patients from the Álvaro Cunqueiro Hospital (Vigo, Galicia, Spain). The preliminary results obtained are promising and demonstrate the potential usefulness of this type of tool in the diagnosis of OSA.Xunta de Galicia | Ref. ED481A-2020/03

Inhaled Methoxyflurane Provides Greater Analgesia and Faster Onset of Action Versus Standard Analgesia in Patients With Trauma Pain: InMEDIATE: A Randomized Controlled Trial in Emergency Departments

Study objective: The objective of the InMEDIATE study was to evaluate the change in intensity of traumatic pain over the first 20 min in adult patients treated with methoxyflurane versus standard analgesic treatment in Spain. This the first randomized, active-controlled, multicenter trial of methoxyflurane in the emergency setting in Europe. Methods: This was a randomized, controlled study that enrolled adult patients with acute moderate to severe (score >= 4 on the 11-point Numeric Rating Scale) trauma-associated pain in 14 Spanish emergency departments. Patients were randomized 1:1 to methoxyflurane (up to 2x3 mL) or standard analgesic treatment. Coprimary endpoints were the change from baseline in Numeric Rating Scale pain intensity score during the first 20 minutes of treatment and time to first pain relief. Results: Three hundred five patients were randomized (methoxyflurane 156; standard analgesic treatment 149). Most patients in the standard analgesic treatment group (70%) received intravenous first-step analgesics and 9.4% of patients were treated with opioids. Mean decrease from baseline in Numeric Rating Scale pain intensity score was greater for methoxyflurane than standard analgesic treatment at all points, with a significant treatment difference overall up to 20 minutes (repeated-measures model 2.47 versus 1.39; treatment difference 1.00; 95% confidence interval 0.84 to 1.32). Median time to first pain relief was significantly shorter for methoxyflurane than standard analgesic treatment (3 versus 10 minutes). Methoxyflurane achieved better patient and clinician ratings for pain control and comfort of treatment than standard analgesic treatment and exceeded patient and clinician expectations of treatment in, respectively, 77% and 72% of cases compared with 38% and 19% for standard analgesic treatment. Conclusion: These results support consideration of methoxyflurane as a nonnarcotic, easy-to-administer, rapid-acting, first-line alternative to currently available analgesic treatments for trauma pain

Clustering COVID-19 ARDS patients through the first days of ICU admission. An analysis of the CIBERESUCICOVID Cohort

Background Acute respiratory distress syndrome (ARDS) can be classified into sub-phenotypes according to different inflammatory/clinical status. Prognostic enrichment was achieved by grouping patients into hypoinflammatory or hyperinflammatory sub-phenotypes, even though the time of analysis may change the classification according to treatment response or disease evolution. We aimed to evaluate when patients can be clustered in more than 1 group, and how they may change the clustering of patients using data of baseline or day 3, and the prognosis of patients according to their evolution by changing or not the cluster.Methods Multicenter, observational prospective, and retrospective study of patients admitted due to ARDS related to COVID-19 infection in Spain. Patients were grouped according to a clustering mixed-type data algorithm (k-prototypes) using continuous and categorical readily available variables at baseline and day 3.Results Of 6205 patients, 3743 (60%) were included in the study. According to silhouette analysis, patients were grouped in two clusters. At baseline, 1402 (37%) patients were included in cluster 1 and 2341(63%) in cluster 2. On day 3, 1557(42%) patients were included in cluster 1 and 2086 (57%) in cluster 2. The patients included in cluster 2 were older and more frequently hypertensive and had a higher prevalence of shock, organ dysfunction, inflammatory biomarkers, and worst respiratory indexes at both time points. The 90-day mortality was higher in cluster 2 at both clustering processes (43.8% [n = 1025] versus 27.3% [n = 383] at baseline, and 49% [n = 1023] versus 20.6% [n = 321] on day 3). Four hundred and fifty-eight (33%) patients clustered in the first group were clustered in the second group on day 3. In contrast, 638 (27%) patients clustered in the second group were clustered in the first group on day 3.Conclusions During the first days, patients can be clustered into two groups and the process of clustering patients may change as they continue to evolve. This means that despite a vast majority of patients remaining in the same cluster, a minority reaching 33% of patients analyzed may be re-categorized into different clusters based on their progress. Such changes can significantly impact their prognosis

ECMO for COVID-19 patients in Europe and Israel

Since March 15th, 2020, 177 centres from Europe and Israel have joined the study, routinely reporting on the ECMO support they provide to COVID-19 patients. The mean annual number of cases treated with ECMO in the participating centres before the pandemic (2019) was 55. The number of COVID-19 patients has increased rapidly each week reaching 1531 treated patients as of September 14th. The greatest number of cases has been reported from France (n = 385), UK (n = 193), Germany (n = 176), Spain (n = 166), and Italy (n = 136) .The mean age of treated patients was 52.6 years (range 16–80), 79% were male. The ECMO configuration used was VV in 91% of cases, VA in 5% and other in 4%. The mean PaO2 before ECMO implantation was 65 mmHg. The mean duration of ECMO support thus far has been 18 days and the mean ICU length of stay of these patients was 33 days. As of the 14th September, overall 841 patients have been weaned from ECMO support, 601 died during ECMO support, 71 died after withdrawal of ECMO, 79 are still receiving ECMO support and for 10 patients status n.a. . Our preliminary data suggest that patients placed on ECMO with severe refractory respiratory or cardiac failure secondary to COVID-19 have a reasonable (55%) chance of survival. Further extensive data analysis is expected to provide invaluable information on the demographics, severity of illness, indications and different ECMO management strategies in these patients