Low-dose acetylsalicylic acid for cancer prevention considering risk factors: a retrospective cohort study.

PURPOSE: Aspirin (acetylsalicylic acid) has been reported to protect against certain cancers. However, patient-related risk factors may moderate protective effects, including excess weight, smoking, risky alcohol use, and diabetes. We explore the cancer-risk relationship between aspirin intake and those four factors. METHODS: Retrospective cohort study of cancers, aspirin intake, and four risk factors in persons aged ≥50 years. Participants received medication during 2007-2016, and cancers were diagnosed in 2012-2016. Adjusted hazard ratios (aHR) for 95% confidence intervals (95%CI) were calculated for aspirin intake and risk factors using Cox proportional hazard modeling. RESULTS: Of 118,548 participants, 15,793 consumed aspirin, and 4003 had cancer. Results indicated a significant protective effect of aspirin against colorectal (aHR: 0.7; 95%CI: 0.6-0.8), pancreatic (aHR: 0.5; 95%CI: 0.2-0.9), prostate (aHR: 0.6; 95%CI: 0.5-0.7) cancers and lymphomas (aHR: 0.5; 95%CI: 0.2-0.9), and also, although not significantly, against esophageal (aHR: 0.5; 95%CI: 0.2-1.8), stomach (aHR: 0.7; 95%CI: 0.4-1.3), liver (aHR: 0.7; 95%CI: 0.3-1.5), breast (aHR: 0.8; 95%CI: 0.6-1.0), and lung and bronchial (aHR: 0.9; 95%CI: 0.7-1.2) cancers. Aspirin intake was not significantly protective against leukemia (aHR: 1.0; 95%CI: 0.7-1.4) or bladder cancer (aHR: 1.0; 95%CI: 0.8-1.3). CONCLUSIONS: Our results suggest that aspirin intake is associated with a reduced incidence of colorectal, pancreatic, and prostate cancers and lymphomas.

Exploring Cancer Incidence, Risk Factors, and Mortality in the Lleida Region: Interactive, Open-source R Shiny Application for Cancer Data Analysis.

BACKGROUND: The cancer incidence rate is essential to public health surveillance. The analysis of this information allows authorities to know the cancer situation in their regions, especially to determine cancer patterns, monitor cancer trends, and help prioritize the allocation of health resource. OBJECTIVE: This study aimed to present the design and implementation of an R Shiny application to assist cancer registries conduct rapid descriptive and predictive analytics in a user-friendly, intuitive, portable, and scalable way. Moreover, we wanted to describe the design and implementation road map to inspire other population registries to exploit their data sets and develop similar tools and models. METHODS: The first step was to consolidate the data into the population registry cancer database. These data were cross validated by ASEDAT software, checked later, and reviewed by experts. Next, we developed an online tool to visualize the data and generate reports to assist decision-making under the R Shiny framework. Currently, the application can generate descriptive analytics using population variables, such as age, sex, and cancer type; cancer incidence in region-level geographical heat maps; line plots to visualize temporal trends; and typical risk factor plots. The application also showed descriptive plots about cancer mortality in the Lleida region. This web platform was built as a microservices cloud platform. The web back end consists of an application programming interface and a database, which NodeJS and MongoDB have implemented. All these parts were encapsulated and deployed by Docker and Docker Compose. RESULTS: The results provide a successful case study in which the tool was applied to the cancer registry of the Lleida region. The study illustrates how researchers and cancer registries can use the application to analyze cancer databases. Furthermore, the results highlight the analytics related to risk factors, second tumors, and cancer mortality. The application shows the incidence and evolution of each cancer during a specific period for gender, age groups, and cancer location, among other functionalities. The risk factors view permitted us to detect that approximately 60% of cancer patients were diagnosed with excess weight at diagnosis. Regarding mortality, the application showed that lung cancer registered the highest number of deaths for both genders. Breast cancer was the lethal cancer in women. Finally, a customization guide was included as a result of this implementation to deploy the architecture presented. CONCLUSIONS: This paper aimed to document a successful methodology for exploiting the data in population cancer registries and propose guidelines for other similar records to develop similar tools. We intend to inspire other entities to build an application that can help decision-making and make data more accessible and transparent for the community of users.

Acetylsalicylic Acid Effect in Colorectal Cancer Taking into Account the Role of Tobacco, Alcohol and Excess Weight.

Excess weight, smoking and risky drinking are preventable risk factors for colorectal cancer (CRC). However, several studies have reported a protective association between aspirin and the risk of CRC. This article looks deeper into the relationships between risk factors and aspirin use with the risk of developing CRC. We performed a retrospective cohort study of CRC risk factors and aspirin use in persons aged >50 years in Lleida province. The participants were inhabitants with some medication prescribed between 2007 and 2016 that were linked to the Population-Based Cancer Registry to detect CRC diagnosed between 2012 and 2016. Risk factors and aspirin use were studied using the adjusted HR (aHR) with 95% confidence intervals (CI) using a Cox proportional hazard model. We included 154,715 inhabitants of Lleida (Spain) aged >50 years. Of patients with CRC, 62% were male (HR = 1.8; 95% CI: 1.6-2.2), 39.5% were overweight (HR = 2.8; 95% CI: 2.3-3.4) and 47.3% were obese (HR = 3.0; 95% CI: 2.6-3.6). Cox regression showed an association between aspirin and CRC (aHR = 0.7; 95% CI: 0.6-0.8), confirming a protective effect against CRC and an association between the risk of CRC and excess weight (aHR = 1.4; 95% CI: 1.2-1.7), smoking (aHR = 1.4; 95% CI: 1.3-1.7) and risky drinking (aHR = 1.6; 95% CI: 1.2-2.0). Our results show that aspirin use decreased the risk of CRC and corroborate the relationship between overweight, smoking and risky drinking and the risk of CRC.

Voiceprint and machine learning models for early detection of bulbar dysfunction in ALS.

BACKGROUND AND OBJECTIVE: Bulbar dysfunction is a term used in amyotrophic lateral sclerosis (ALS). It refers to motor neuron disability in the corticobulbar area of the brainstem which leads to a dysfunction of speech and swallowing. One of the earliest symptoms of bulbar dysfunction is voice deterioration characterized by grossly defective articulation, extremely slow laborious speech, marked hypernasality and severe harshness. Recently, research efforts have focused on voice analysis to capture this dysfunction. The main aim of this paper is to provide a new methodology to diagnose this dysfunction automatically at early stages of the disease, earlier than clinicians can do. METHODS: The study focused on the creation of a voiceprint consisting of a pattern generated from the quasi-periodic components of a steady portion of the five Spanish vowels and the computation of the five principal and independent components of this pattern. Then, a set of statistically significant features was obtained using multivariate analysis of variance and the outcomes of the most common supervised classification models were obtained. RESULTS: The best model (random forest) obtained an accuracy, sensitivity and specificity of 88.3%, 85.0% and 95.0% respectively when classifying bulbar vs. control participants but the results worsened when classifying bulbar vs. no-bulbar patients (accuracy, sensitivity and specificity of 78.7%, 80.0% and 77.5% respectively for support vector machines). Due to the great uncertainty found in the annotated corpus of the ALS patients without bulbar involvement, we used a safe semi-supervised support vector machine to relabel the ALS participants diagnosed without bulbar involvement as bulbar and no-bulbar. The performance of the results obtained increased, especially when classifying bulbar and no-bulbar patients obtaining an accuracy, sensitivity and specificity of 91.0%, 83.3% and 100.0% respectively for support vector machines. This demonstrates that our model can improve the diagnosis of bulbar dysfunction compared not only with clinicians, but also the methods published to date. CONCLUSIONS: The results obtained demonstrate the efficiency and applicability of the methodology presented in this paper. It may lead to the development of a cheap and easy-to-use tool to identify this dysfunction in early stages of the disease and monitor progress.

A Free App for Diagnosing Burnout (BurnOut App): Development Study.

BACKGROUND: Health specialists take care of us, but who takes care of them? These professionals are the most vulnerable to the increasingly common syndrome known as burnout. Burnout is a syndrome conceptualized as a result of chronic workplace stress that has not been successfully managed. OBJECTIVE: This study aims to develop a useful app providing burnout self-diagnosis and tracking of burnout through a simple, intuitive, and user-friendly interface. METHODS: We present the BurnOut app, an Android app developed using the Xamarin and MVVMCross platforms, which allows users to detect critical cases of psychological discomfort by implementing the Goldberg and Copenhagen Burnout Inventory tests. RESULTS: The BurnOut app is robust, user-friendly, and efficient. The good performance of the app was demonstrated by comparing its features with those of similar apps in the literature. CONCLUSIONS: The BurnOut app is very useful for health specialists or users, in general, to detect burnout early and track its evolution.

Use of Multiple Correspondence Analysis and K-means to Explore Associations Between Risk Factors and Likelihood of Colorectal Cancer: Cross-sectional Study.

BACKGROUND: Previous works have shown that risk factors are associated with an increased likelihood of colorectal cancer. OBJECTIVE: The purpose of this study was to detect these associations in the region of Lleida (Catalonia) by using multiple correspondence analysis (MCA) and k-means. METHODS: This cross-sectional study was made up of 1083 colorectal cancer episodes between 2012 and 2015, extracted from the population-based cancer registry for the province of Lleida (Spain), the Primary Care Centers database, and the Catalan Health Service Register. The data set included risk factors such as smoking and BMI as well as sociodemographic information and tumor details. The relations between the risk factors and patient characteristics were identified using MCA and k-means. RESULTS: The combination of these techniques helps to detect clusters of patients with similar risk factors. Risk of death is associated with being elderly and obesity or being overweight. Stage III cancer is associated with people aged ≥65 years and rural/semiurban populations, while younger people were associated with stage 0. CONCLUSIONS: MCA and k-means were significantly useful for detecting associations between risk factors and patient characteristics. These techniques have proven to be effective tools for analyzing the incidence of some factors in colorectal cancer. The outcomes obtained help corroborate suspected trends and stimulate the use of these techniques for finding the association of risk factors with the incidence of other cancers.

A Machine-Learning Model for Lung Age Forecasting by Analyzing Exhalations.

Spirometers are important devices for following up patients with respiratory diseases. These are mainly located only at hospitals, with all the disadvantages that this can entail. This limits their use and consequently, the supervision of patients. Research efforts focus on providing digital alternatives to spirometers. Although less accurate, the authors claim they are cheaper and usable by many more people worldwide at any given time and place. In order to further popularize the use of spirometers even more, we are interested in also providing user-friendly lung-capacity metrics instead of the traditional-spirometry ones. The main objective, which is also the main contribution of this research, is to obtain a person's lung age by analyzing the properties of their exhalation by means of a machine-learning method. To perform this study, 188 samples of blowing sounds were used. These were taken from 91 males (48.4%) and 97 females (51.6%) aged between 17 and 67. A total of 42 spirometer and frequency-like features, including gender, were used. Traditional machine-learning algorithms used in voice recognition applied to the most significant features were used. We found that the best classification algorithm was the Quadratic Linear Discriminant algorithm when no distinction was made between gender. By splitting the corpus into age groups of 5 consecutive years, accuracy, sensitivity and specificity of, respectively, 94.69%, 94.45% and 99.45% were found. Features in the audio of users' expiration that allowed them to be classified by their corresponding lung age group of 5 years were successfully detected. Our methodology can become a reliable tool for use with mobile devices to detect lung abnormalities or diseases.

Detecting Bulbar Involvement in Patients with Amyotrophic Lateral Sclerosis Based on Phonatory and Time-Frequency Features.

The term "bulbar involvement" is employed in ALS to refer to deterioration of motor neurons within the corticobulbar area of the brainstem, which results in speech and swallowing dysfunctions. One of the primary symptoms is a deterioration of the voice. Early detection is crucial for improving the quality of life and lifespan of ALS patients suffering from bulbar involvement. The main objective, and the principal contribution, of this research, was to design a new methodology, based on the phonatory-subsystem and time-frequency characteristics for detecting bulbar involvement automatically. This study focused on providing a set of 50 phonatory-subsystem and time-frequency features to detect this deficiency in males and females through the utterance of the five Spanish vowels. Multivariant Analysis of Variance was then used to select the statistically significant features, and the most common supervised classifications models were analyzed. A set of statistically significant features was obtained for males and females to capture this dysfunction. To date, the accuracy obtained (98.01% for females and 96.10% for males employing a random forest) outperformed the models in the literature. Adding time-frequency features to more classical phonatory-subsystem features increases the prediction capabilities of the machine-learning models for detecting bulbar involvement. Studying men and women separately gives greater success. The proposed method can be deployed in any kind of recording device (i.e., smartphone).

Automated detection of COVID-19 cough.

Easy detection of COVID-19 is a challenge. Quick biological tests do not give enough accuracy. Success in the fight against new outbreaks depends not only on the efficiency of the tests used, but also on the cost, time elapsed and the number of tests that can be done massively. Our proposal provides a solution to this challenge. The main objective is to design a freely available, quick and efficient methodology for the automatic detection of COVID-19 in raw audio files. Our proposal is based on automated extraction of time-frequency cough features and selection of the more significant ones to be used to diagnose COVID-19 using a supervised machine-learning algorithm. Random Forest has performed better than the other models analysed in this study. An accuracy close to 90% was obtained. This study demonstrates the feasibility of the automatic diagnose of COVID-19 from coughs, and its applicability to detecting new outbreaks.

The Use of Multiple Correspondence Analysis to Explore Associations Between Categories of Qualitative Variables and Cancer Incidence.

BACKGROUND: Previous works have shown that risk factors for some kinds of cancer depend on people's lifestyle (e.g. rural or urban residence). This article looks into this, seeking relationships between cancer, age group, gender and population in the region of Lleida (Catalonia, Spain) using Multiple Correspondence Analysis (MCA). METHODS: The dataset analysed was made up of 3408 cancer episodes between 2012 and 2014, extracted from the Population-based Cancer Registry (PCR) for Lleida province. The cancers studied were colon and rectal (1059 cases), lung (551 cases), urinary bladder (446 cases), prostate (609 cases) and breast (743 cases). The MCA technique was applied and used to search relationships among the main qualitative features. The basic statistics were the percentage explaining (variance), the inertia and the contribution of each qualitative variable. RESULTS: General outcomes showed a low and moderate contribution of living in rural areas to colorectal and male prostate cancer. Males in urban areas were slightly and heavily affected by lung and urinary bladder cancer respectively. The analysis of each cancer provided additional information. Colorectal cancer greatly affected males aged <60, urban residents aged 70-79, and rural females aged ≥ 80. The impact of lung cancer was high among urban females <60, moderate among males aged 70-79 and high among rural females aged ≥ 80. The results for urinary bladder cancer results were similar to those for lung cancer. Prostate cancer affected both the <60 and ≥ 80 age groups significantly in rural areas. Breast cancer hit the 70-79 group significantly and, somewhat less so, rural females aged ≥ 80. CONCLUSIONS: MCA was a significant help for detecting the contributions of qualitative variables and the associations between them. MCA has proven to be an effective technique for analyzing the incidence of cancer. The outcomes obtained help to corroborate suspected trends, as well as detecting and stimulating new hypotheses about the risk factors associated with a specific area and cancer. These findings will be helpful for encouraging new studies and prevention campaigns to highlight observed singularities.

Detection of Bulbar Involvement in Patients With Amyotrophic Lateral Sclerosis by Machine Learning Voice Analysis: Diagnostic Decision Support Development Study.

BACKGROUND: Bulbar involvement is a term used in amyotrophic lateral sclerosis (ALS) that refers to motor neuron impairment in the corticobulbar area of the brainstem, which produces a dysfunction of speech and swallowing. One of the earliest symptoms of bulbar involvement is voice deterioration characterized by grossly defective articulation; extremely slow, laborious speech; marked hypernasality; and severe harshness. Bulbar involvement requires well-timed and carefully coordinated interventions. Therefore, early detection is crucial to improving the quality of life and lengthening the life expectancy of patients with ALS who present with this dysfunction. Recent research efforts have focused on voice analysis to capture bulbar involvement. OBJECTIVE: The main objective of this paper was (1) to design a methodology for diagnosing bulbar involvement efficiently through the acoustic parameters of uttered vowels in Spanish, and (2) to demonstrate that the performance of the automated diagnosis of bulbar involvement is superior to human diagnosis. METHODS: The study focused on the extraction of features from the phonatory subsystem-jitter, shimmer, harmonics-to-noise ratio, and pitch-from the utterance of the five Spanish vowels. Then, we used various supervised classification algorithms, preceded by principal component analysis of the features obtained. RESULTS: To date, support vector machines have performed better (accuracy 95.8%) than the models analyzed in the related work. We also show how the model can improve human diagnosis, which can often misdiagnose bulbar involvement. CONCLUSIONS: The results obtained are very encouraging and demonstrate the efficiency and applicability of the automated model presented in this paper. It may be an appropriate tool to help in the diagnosis of ALS by multidisciplinary clinical teams, in particular to improve the diagnosis of bulbar involvement.

EasyModel: user-friendly tool for building and analysis of simple mathematical models in systems biology.

SUMMARY: EasyModel is a new user-friendly web application that contains ready-for-simulation versions of the BioModels Database, and allows for the intuitive creation of new models. Its main target audience is the experimental biologist and students of bioinformatics or systems biology without programming skills. Expert users can also benefit from it by implementing basic models quickly and downloading the code for further tailoring. AVAILABILITY AND IMPLEMENTATION: Freely available on the web at https://easymodel.udl.cat. Implementation is described in its own section.

Automatic Methods for Carotid Contrast-Enhanced Ultrasound Imaging Quantification of Adventitial Vasa Vasorum.

Adventitial vasa vasorum are physiologic microvessels that nourish artery walls. In the presence of cardiovascular risk factors, these microvessels proliferate abnormally. Studies have reported that they are the first stage of atheromatous disease. Contrast-enhanced ultrasound (CEUS) of the carotid allows direct, quantitative and non-invasive visualization of the adventitial vasa vasorum. Hence, the development of computer-assisted methods that speed image analysis and eliminate user subjectivity is important. We developed methods for automatic analyses and quantification of vasa vasorum neovascularization in CEUS and tested these methods in a cohort of 186 individuals, 63 of whom were healthy volunteers. We implemented alternative automatic strategies for using the images to stratify patients according to their risk group and compare the strategies with respect to diagnostic performance. An automatic single-parameter strategy performs less effectively than the corresponding Arcidiacono method based on manual interpretation of the images (68 < area under the receiver operating characteristic curve [AUROC] for the manual Arcidiacono method < 82; 60 < AUROC for the automatic single-parameter strategy < 63). However, by use of additional image parameters, an automatic multiparameter strategy has significantly improved performance with respect to the manual Arcidiacono method (78 < AUROC < 90). The automatic multiparameter strategy is a valuable alternative to the manual Arcidiacono method, improving both diagnostic speed and diagnostic accuracy.

MetReS, an Efficient Database for Genomic Applications.

MetReS (Metabolic Reconstruction Server) is a genomic database that is shared between two software applications that address important biological problems. Biblio-MetReS is a data-mining tool that enables the reconstruction of molecular networks based on automated text-mining analysis of published scientific literature. Homol-MetReS allows functional (re)annotation of proteomes, to properly identify both the individual proteins involved in the processes of interest and their function. The main goal of this work was to identify the areas where the performance of the MetReS database performance could be improved and to test whether this improvement would scale to larger datasets and more complex types of analysis. The study was started with a relational database, MySQL, which is the current database server used by the applications. We also tested the performance of an alternative data-handling framework, Apache Hadoop. Hadoop is currently used for large-scale data processing. We found that this data handling framework is likely to greatly improve the efficiency of the MetReS applications as the dataset and the processing needs increase by several orders of magnitude, as expected to happen in the near future.

Characterization of the CPAP-treated patient population in Catalonia.

There are different phenotypes of obstructive sleep apnoea (OSA), many of which have not been characterised. Identification of these different phenotypes is important in defining prognosis and guiding the therapeutic strategy. The aim of this study was to characterise the entire population of continuous positive airway pressure (CPAP)-treated patients in Catalonia and identify specific patient profiles using cluster analysis. A total of 72,217 CPAP-treated patients who contacted the Catalan Health System (CatSalut) during the years 2012 and 2013 were included. Six clusters were identified, classified as "Neoplastic patients" (Cluster 1, 10.4%), "Metabolic syndrome patients" (Cluster 2, 27.7%), "Asthmatic patients" (Cluster 3, 5.8%), "Musculoskeletal and joint disorder patients" (Cluster 4, 10.3%), "Patients with few comorbidities" (Cluster 5, 35.6%) and "Oldest and cardiac disease patients" (Cluster 6, 10.2%). Healthcare facility use and mortality were highest in patients from Cluster 1 and 6. Conversely, patients in Clusters 2 and 4 had low morbidity, mortality and healthcare resource use. Our findings highlight the heterogeneity of CPAP-treated patients, and suggest that OSA is associated with a different prognosis in the clusters identified. These results suggest the need for a comprehensive and individualised approach to CPAP treatment of OSA.

TControl: A mobile app to follow up tobacco-quitting patients.

BACKGROUND AND OBJECTIVE: Tobacco smoking is a major risk factor for a wide range of respiratory and circulatory diseases in active and passive smokers. Well-designed campaigns are raising awareness to the problem and an increasing number of smokers seeks medical assistance to quit their habit. In this context, there is the need to develop mHealth Apps that assist and manage large smoke quitting programs in efficient and economic ways. OBJECTIVES: Our main objective is to develop an efficient and free mHealth app that facilitates the management of, and assistance to, people who want to quit smoking. As secondary objectives, our research also aims at estimating the economic effect of deploying that App in the public health system. METHODS: Using JAVA and XML we develop and deploy a new free mHealth App for Android, called TControl (Tobacco-quitting Control). We deploy the App at the Tobacco Unit of the Santa Maria Hospital in Lleida and determine its stability by following the crashes of the App. We also use a survey to test usability of the app and differences in aptitude for using the App in a sample of 31 patients. Finally, we use mathematical models to estimate the economic effect of deploying TControl in the Catalan public health system. RESULTS: TControl keeps track of the smoke-quitting users, tracking their status, interpreting it, and offering advice and psychological support messages. The App also provides a bidirectional communication channel between patients and clinicians via mobile text messages. Additionally, registered patients have the option to interchange experiences with each other by chat. The App was found to be stable and to have high performances during startup and message sending. Our results suggest that age and gender have no statistically significant effect on patient aptitude for using TControl. Finally, we estimate that TControl could reduce costs for the Catalan public health system (CPHS) by up to € 400M in 10 years. CONCLUSIONS: TControl is a stable and well behaved App, typically operating near optimal performance. It can be used independent of age and gender, and its wide implementation could decrease costs for the public health system.

BPcontrol. A Mobile App to Monitor Hypertensive Patients.

BACKGROUND: Hypertension or high blood pressure is on the rise. Not only does it affect the elderly but is also increasingly spreading to younger sectors of the population. Treating this condition involves exhaustive monitoring of patients. The current mobile health services can be improved to perform this task more effectively. OBJECTIVE: To develop a useful, user-friendly, robust and efficient app, to monitor hypertensive patients and adapted to the particular requirements of hypertension. METHODS: This work presents BPcontrol, an Android and iOS app that allows hypertensive patients to communicate with their health-care centers, thus facilitating monitoring and diagnosis. Usability, robustness and efficiency factors for BPcontrol were evaluated for different devices and operating systems (Android, iOS and system-aware). Furthermore, its features were compared with other similar apps in the literature. RESULTS: BPcontrol is robust and user-friendly. The respective start-up efficiency of the Android and iOS versions of BPcontrol were 2.4 and 8.8 times faster than a system-aware app. Similar values were obtained for the communication efficiency (7.25 and 11.75 times faster for the Android and iOS respectively). When comparing plotting performance, BPcontrol was on average 2.25 times faster in the Android case. Most of the apps in the literature have no communication with a server, thus making it impossible to compare their performance with BPcontrol. CONCLUSIONS: Its optimal design and the good behavior of its facilities make BPcontrol a very promising mobile app for monitoring hypertensive patients.

Computer-assisted initial diagnosis of rare diseases.

Introduction. Most documented rare diseases have genetic origin. Because of their low individual frequency, an initial diagnosis based on phenotypic symptoms is not always easy, as practitioners might never have been exposed to patients suffering from the relevant disease. It is thus important to develop tools that facilitate symptom-based initial diagnosis of rare diseases by clinicians. In this work we aimed at developing a computational approach to aid in that initial diagnosis. We also aimed at implementing this approach in a user friendly web prototype. We call this tool Rare Disease Discovery. Finally, we also aimed at testing the performance of the prototype. Methods. Rare Disease Discovery uses the publicly available ORPHANET data set of association between rare diseases and their symptoms to automatically predict the most likely rare diseases based on a patient's symptoms. We apply the method to retrospectively diagnose a cohort of 187 rare disease patients with confirmed diagnosis. Subsequently we test the precision, sensitivity, and global performance of the system under different scenarios by running large scale Monte Carlo simulations. All settings account for situations where absent and/or unrelated symptoms are considered in the diagnosis. Results. We find that this expert system has high diagnostic precision (≥80%) and sensitivity (≥99%), and is robust to both absent and unrelated symptoms. Discussion. The Rare Disease Discovery prediction engine appears to provide a fast and robust method for initial assisted differential diagnosis of rare diseases. We coupled this engine with a user-friendly web interface and it can be freely accessed at http://disease-discovery.udl.cat/. The code and most current database for the whole project can be downloaded from https://github.com/Wrrzag/DiseaseDiscovery/tree/no_classifiers.

A production planning model considering uncertain demand using two-stage stochastic programming in a fresh vegetable supply chain context.

Production planning models are achieving more interest for being used in the primary sector of the economy. The proposed model relies on the formulation of a location model representing a set of farms susceptible of being selected by a grocery shop brand to supply local fresh products under seasonal contracts. The main aim is to minimize overall procurement costs and meet future demand. This kind of problem is rather common in fresh vegetable supply chains where producers are located in proximity either to processing plants or retailers. The proposed two-stage stochastic model determines which suppliers should be selected for production contracts to ensure high quality products and minimal time from farm-to-table. Moreover, Lagrangian relaxation and parallel computing algorithms are proposed to solve these instances efficiently in a reasonable computational time. The results obtained show computational gains from our algorithmic proposals in front of the usage of plain CPLEX solver. Furthermore, the results ensure the competitive advantages of using the proposed model by purchase managers in the fresh vegetables industry.

Identification of line-specific strategies for improving carotenoid production in synthetic maize through data-driven mathematical modeling.

Plant synthetic biology is still in its infancy. However, synthetic biology approaches have been used to manipulate and improve the nutritional and health value of staple food crops such as rice, potato and maize. With current technologies, production yields of the synthetic nutrients are a result of trial and error, and systematic rational strategies to optimize those yields are still lacking. Here, we present a workflow that combines gene expression and quantitative metabolomics with mathematical modeling to identify strategies for increasing production yields of nutritionally important carotenoids in the seed endosperm synthesized through alternative biosynthetic pathways in synthetic lines of white maize, which is normally devoid of carotenoids. Quantitative metabolomics and gene expression data are used to create and fit parameters of mathematical models that are specific to four independent maize lines. Sensitivity analysis and simulation of each model is used to predict which gene activities should be further engineered in order to increase production yields for carotenoid accumulation in each line. Some of these predictions (e.g. increasing Zmlycb/Gllycb will increase accumulated ß-carotenes) are valid across the four maize lines and consistent with experimental observations in other systems. Other predictions are line specific. The workflow is adaptable to any other biological system for which appropriate quantitative information is available. Furthermore, we validate some of the predictions using experimental data from additional synthetic maize lines for which no models were developed.