Discovering NDM-1 inhibitors using molecular substructure embeddings representations.

NDM-1 (New-Delhi-Metallo-ß-lactamase-1) is an enzyme developed by bacteria that is implicated in bacteria resistance to almost all known antibiotics. In this study, we deliver a new, curated NDM-1 bioactivities database, along with a set of unifying rules for managing different activity properties and inconsistencies. We define the activity classification problem in terms of Multiple Instance Learning, employing embeddings corresponding to molecular substructures and present an ensemble ranking and classification framework, relaying on a k-fold Cross Validation method employing a per fold hyper-parameter optimization procedure, showing promising generalization ability. The MIL paradigm displayed an improvement up to 45.7 %, in terms of Balanced Accuracy, in comparison to the classical Machine Learning paradigm. Moreover, we investigate different compact molecular representations, based on atomic or bi-atomic substructures. Finally, we scanned the Drugbank for strongly active compounds and we present the top-15 ranked compounds.

Learning to Classify Medical Discharge Summaries According to ICD-9.

CONTEXT: We present a post-hoc approach to improve the recall of ICD classification. METHOD: The proposed method can use any classifier as a backbone and aims to calibrate the number of codes returned per document. We test our approach on a new stratified split of the MIMIC-III dataset. RESULTS: When returning 18 codes on average per document we obtain a recall that is 20% better than a classic classification approach.

Patient Electronic Health Record as Temporal Graphs for Health Monitoring.

Machine learning methods are becoming increasingly popular to anticipate critical risks in patients under surveillance reducing the burden on caregivers. In this paper, we propose an original modeling that benefits of recent developments in Graph Convolutional Networks: a patient's journey is seen as a graph, where each node is an event and temporal proximities are represented by weighted directed edges. We evaluated this model to predict death at 24 hours on a real dataset and successfully compared our results with the state of the art.

EBBE-Text: Explaining Neural Networks by Exploring Text Classification Decision Boundaries.

While neural networks (NN) have been successfully applied to many NLP tasks, the way they function is often difficult to interpret. In this article, we focus on binary text classification via NNs and propose a new tool, which includes a visualization of the decision boundary and the distances of data elements to this boundary. This tool increases the interpretability of NN. Our approach uses two innovative views: (1) an overview of the text representation space and (2) a local view allowing data exploration around the decision boundary for various localities of this representation space. These views are integrated into a visual platform, EBBE-Text, which also contains state-of-the-art visualizations of NN representation spaces and several kinds of information obtained from the classification process. The various views are linked through numerous interactive functionalities that enable easy exploration of texts and classification results via the various complementary views. A user study shows the effectiveness of the visual encoding and a case study illustrates the benefits of using our tool for the analysis of the classifications obtained with several recent NNs and two datasets.

Acceptability and satisfaction with emma, a smartphone application dedicated to suicide ecological assessment and prevention.

Background: As mHealth may contribute to suicide prevention, we developed emma, an application using Ecological Momentary Assessment and Intervention (EMA/EMI). Objective: This study evaluated emma usage rate and acceptability during the first month and satisfaction after 1 and 6 months of use. Methods: Ninety-nine patients at high risk of suicide used emma for 6 months. The acceptability and usage rate of the EMA and EMI modules were monitored during the first month. Satisfaction was assessed by questions in the monthly EMA (Likert scale from 0 to 10) and the Mobile App Rating Scale (MARS; score: 0-5) completed at month 6. After inclusion, three follow-up visits (months 1, 3, and 6) took place. Results: Seventy-five patients completed at least one of the proposed EMAs. Completion rates were lower for the daily than weekly EMAs (60 and 82%, respectively). The daily completion rates varied according to the question position in the questionnaire (lower for the last questions, LRT = 604.26, df = 1, p-value < 0.0001). Completion rates for the daily EMA were higher in patients with suicidal ideation and/or depression than in those without. The most used EMI was the emergency call module (n = 12). Many users said that they would recommend this application (mean satisfaction score of 6.92 ± 2.78) and the MARS score at month 6 was relatively high (overall rating: 3.3 ± 0.87). Conclusion: Emma can target and involve patients at high risk of suicide. Given the promising users' satisfaction level, emma could rapidly evolve into a complementary tool for suicide prevention.

Hospital healthcare flows: A longitudinal clustering approach of acute coronary syndrome in women over 45 years.

Acute coronary syndrome (ACS) in women is a growing public health issue and a death leading cause. We explored whether the hospital healthcare trajectory was characterizable using a longitudinal clustering approach in women with ACS. From the 2009-2014 French nationwide hospital database, we extracted spatio-temporal patterns in ACS patient trajectories, by replacing the spatiality by their hospitalization cause. We used these patterns to characterize hospital healthcare flows in a visualization tool. We clustered these trajectories with kmlShape to identify time gap and tariff profiles. ACS hospital healthcare flows have three key categories: Angina pectoris, Myocardial Infarction or Ischemia. Elderly flows were more complex. Time gap profiles showed that readmissions were closer together as time goes by. Tariff profiles were different according to age and initial event. Our approach might be applied to monitoring other chronic diseases. Further work is needed to integrate these results into a medical decision-making tool.

Sequential Pattern Mining to Predict Medical In-Hospital Mortality from Administrative Data: Application to Acute Coronary Syndrome.

Prediction of a medical outcome based on a trajectory of care has generated a lot of interest in medical research. In sequence prediction modeling, models based on machine learning (ML) techniques have proven their efficiency compared to other models. In addition, reducing model complexity is a challenge. Solutions have been proposed by introducing pattern mining techniques. Based on these results, we developed a new method to extract sets of relevant event sequences for medical events' prediction, applied to predict the risk of in-hospital mortality in acute coronary syndrome (ACS). From the French Hospital Discharge Database, we mined sequential patterns. They were further integrated into several predictive models using a text string distance to measure the similarity between patients' patterns of care. We computed combinations of similarity measurements and ML models commonly used. A Support Vector Machine model coupled with edit-based distance appeared as the most effective model. We obtained good results in terms of discrimination with the receiver operating characteristic curve scores ranging from 0.71 to 0.99 with a good overall accuracy. We demonstrated the interest of sequential patterns for event prediction. This could be a first step to a decision-support tool for the prevention of in-hospital death by ACS.

Prediction of In-Hospital Mortality from Administrative Data: A Sequential Pattern Mining Approach.

Study of trajectory of care is attractive for predicting medical outcome. Models based on machine learning (ML) techniques have proven their efficiency for sequence prediction modeling compared to other models. Introducing pattern mining techniques contributed to reduce model complexity. In this respect, we explored methods for medical events' prediction based on the extraction of sets of relevant event sequences of a national hospital discharge database. It is illustrated to predict the risk of in-hospital mortality in acute coronary syndrome (ACS). We mined sequential patterns from the French Hospital Discharge Database. We compared several predictive models using a text string distance to measure the similarity between patients' patterns of care. We computed combinations of similarity measurements and ML models commonly used. A Support Vector Machine model coupled with edit-based distance appeared as the most effective model. Indeed discrimination ranged from 0.71 to 0.99, together with a good overall accuracy. Thus, sequential patterns mining appear motivating for event prediction in medical settings as described here for ACS.

A Digital Companion, the Emma App, for Ecological Momentary Assessment and Prevention of Suicide: Quantitative Case Series Study.

BACKGROUND: Many suicide risk factors have been identified, but traditional clinical methods do not allow for the accurate prediction of suicide behaviors. To face this challenge, emma, an app for ecological momentary assessment (EMA), ecological momentary intervention (EMI), and prediction of suicide risk in high-risk patients, was developed. OBJECTIVE: The aim of this case report study was to describe how subjects at high risk of suicide use the emma app in real-world conditions. METHODS: The Ecological Mental Momentary Assessment (EMMA) study is an ongoing, longitudinal, interventional, multicenter trial in which patients at high risk for suicide are recruited to test emma, an app designed to be used as a self-help tool for suicidal crisis management. Participants undergo clinical assessment at months 0, 1, 3, and 6 after inclusion, mainly to assess and characterize the presence of mental disorders and suicidal thoughts and behaviors. Patient recruitment is still ongoing. Some data from the first 14 participants who already completed the 6-month follow-up were selected for this case report study, which evaluated the following: (1) data collected by emma (ie, responses to EMAs), (2) metadata on emma use, (3) clinical data, and (4) qualitative assessment of the participants' experiences. RESULTS: EMA completion rates were extremely heterogeneous with a sharp decrease over time. The completion rates of the weekly EMAs (25%-87%) were higher than those of the daily EMAs (0%-53%). Most patients (10/14, 71%) answered the EMA questionnaires spontaneously. Similarly, the use of the Safety Plan Modules was very heterogeneous (2-75 times). Specifically, 11 patients out of 14 (79%) used the Call Module (1-29 times), which was designed by our team to help them get in touch with health care professionals and/or relatives during a crisis. The diversity of patient profiles and use of the EMA and EMI modules proposed by emma were highlighted by three case reports. CONCLUSIONS: These preliminary results indicate that patients have different clinical and digital profiles and needs that require a highly scalable, interactive, and customizable app. They also suggest that it is possible and acceptable to collect longitudinal, fine-grained, contextualized data (ie, EMA) and to offer personalized intervention (ie, EMI) in real time to people at high risk of suicide. To become a complementary tool for suicide prevention, emma should be integrated into existing emergency procedures. TRIAL REGISTRATION: ClinicalTrials.gov NCT03410381; https://clinicaltrials.gov/ct2/show/NCT03410381.

Mining social networks to improve suicide prevention: A scoping review.

Attention about the risks of online social networks (SNs) has been called upon reports describing their use to express emotional distress and suicidal ideation or plans. On the Internet, cyberbullying, suicide pacts, Internet addiction, and "extreme" communities seem to increase suicidal behavior (SB). In this study, the scientific literature about SBs and SNs was narratively reviewed. Some authors focus on detecting at-risk populations through data mining, identification of risks factors, and web activity patterns. Others describe prevention practices on the Internet, such as websites, screening, and applications. Targeted interventions through SNs are also contemplated when suicidal ideation is present. Multiple predictive models should be defined, implemented, tested, and combined in order to deal with the risk of SB through an effective decision support system. This endeavor might require a reorganization of care for SNs users presenting suicidal ideation.

Unveiling Online Suicide Behavior: What Can We Learn About Mental Health from Suicide Survivors of Reddit?

Suicide is a growing public health concern in online communities. In this paper, we analyze online communications on the topic of suicide in the social networking platform, Reddit. We combine lexical text characteristics with semantic information to identify comments with features of suicide attempts and methods. Then, we develop a set of machine learning methods to automatically extract suicide methods and classify the user comments. Our classification methods performance varied between suicide experiences, with F1-scores up to 0.92 for "drugs" and greater than 0.82 for "hanging" and "other methods". Our exploratory analysis reveals that the most frequent reported suicide methods are drug overdose, hanging, and wrist-cutting.

Hospital burden of coronary artery disease: Trends of myocardial infarction and/or percutaneous coronary interventions in France 2009-2014.

BACKGROUND: Currently, cardiovascular disease (CVD) is widely acknowledged to be the first leading cause of fatality in the world with 31% of all deaths worldwide and is predicted to remain as such in 2030. Furthermore, CVD is also a major cause of morbidity in adults worldwide. Among these diseases, the coronary artery disease (CAD) is the most common cause, accounting for over 40% of CVD deaths. Despite a decline in mortality rates, the consequences of more effective preventive and management programs, the burden of CAD remains significant. Indeed, the rise in the prevalence of modifiable risk factors due to changes in lifestyle and health behaviors has further increased the burden of this epidemic. Our objective was to evaluate the hospital burden of CAD via MI trends and Percutaneous Coronary Intervention (PCI) in the French Prospective Payment System (PPS). METHODS: MI/PCI were identified in the national PPS database from 2009 to 2014 for patients aged 20 to 99, living in metropolitan France. We examined hospitalisation, readmission and mortality trends using standardised rates. RESULTS: Over the six-year period, we identified 678,021 patients, representing 900,121 stays of which, 215,224 had a MI and a PCI. Admission trends increased by nearly 25%. Acute MI cases increased every year, with an alarming increase in women, and more specifically in young women. Men were 3 times more hospitalised than women, who were older. A North-South divide was noted. Twenty seven percent of patients experienced readmission within 1 month. Trajectories of care were significantly different by sex and age. Overall in-hospital death was 3.3%, decreasing by 15% during the period. The highest adjusted mortality rates were observed for inpatients aged <40 or >80. CONCLUSION: We outlined the public health burden of this condition and the importance of improving the trajectories of care as an aid for better care.

Expertise in French health forums.

More and more health websites hire medical experts (physicians, medical students, experienced volunteers, etc.) and indicate explicitly their medical role in order to notify that they provide high-quality answers. However, medical experts may participate in forum discussions even when their role is not officially indicated. Detecting posts written by medical experts facilitates the quick access to posts that have more chances of being correct and informative. The main objective of this work is to learn classification models that can be used to detect posts written by medical experts in any health forum discussions. Two French health forums have been used to discover the best features and methods for this text categorization task. The obtained results confirm that models learned on appropriate websites may be used efficiently on other websites (more than 98% of F1-measure has been obtained using a Random Forest classifier). A study of misclassified posts highlights the participation of medical experts in forum discussions even if their role is not explicitly indicated.

Reconciliation of patient/doctor vocabulary in a structured resource.

Today, social media is increasingly used by patients to openly discuss their health. Mining automatically such data is a challenging task because of the non-structured nature of the text and the use of many abbreviations and the slang terms. Our goal is to use Patient Authored Text to build a French Consumer Health Vocabulary on breast cancer field, by collecting various kinds of non-experts' expressions that are related to their diseases and then compare them to biomedical terms used by health care professionals. We combine several methods of the literature based on linguistic and statistical approaches to extract candidate terms used by non-experts and to link them to expert terms. We use messages extracted from the forum on ' cancerdusein.org ' and a vocabulary dedicated to breast cancer elaborated by the Institut National Du Cancer. We have built an efficient vocabulary composed of 192 validated relationships and formalized in Simple Knowledge Organization System ontology.

PaFloChar: An Innovating Approach to Characterise Patient Flows in Myocardial Infarction.

A better knowledge of patient flows would improve decision making in health planning. In this article, we propose a method to characterise patients flows and also to highlight profiles of care pathways considering times and costs. From medico-administrative data, we extracted spatio-temporal patterns. Then, we clustered time between hospitalisations and cost trajectories in order to identify profiles of change over time. This approach may support renewed management strategies.

Raising Awareness About Cervical Cancer Using Twitter: Content Analysis of the 2015 #SmearForSmear Campaign.

BACKGROUND: Cervical cancer is the second most common cancer among women under 45 years of age. To deal with the decrease of smear test coverage in the United Kingdom, a Twitter campaign called #SmearForSmear has been launched in 2015 for the European Cervical Cancer Prevention Week. Its aim was to encourage women to take a selfie showing their lipstick going over the edge and post it on Twitter with a raising awareness message promoting cervical cancer screening. The estimated audience was 500 million people. Other public health campaigns have been launched on social media such as Movember to encourage participation and self-engagement. Their result was unsatisfactory as their aim had been diluted to become mainly a social buzz. OBJECTIVE: The objectives of this study were to identify the tweets delivering a raising awareness message promoting cervical cancer screening (sensitizing tweets) and to understand the characteristics of Twitter users posting about this campaign. METHODS: We conducted a 3-step content analysis of the English tweets tagged #SmearForSmear posted on Twitter for the 2015 European Cervical Cancer Prevention Week. Data were collected using the Twitter application programming interface. Their extraction was based on an analysis grid generated by 2 independent researchers using a thematic analysis, validated by a strong Cohen kappa coefficient. A total of 7 themes were coded for sensitizing tweets and 14 for Twitter users' status. Verbatims were thematically and then statistically analyzed. RESULTS: A total of 3019 tweets were collected and 1881 were analyzed. Moreover, 69.96% of tweets had been posted by people living in the United Kingdom. A total of 57.36% of users were women, and sex was unknown in 35.99% of cases. In addition, 54.44% of the users had posted at least one selfie with smeared lipstick. Furthermore, 32.32% of tweets were sensitizing. Independent factors associated with posting sensitizing tweets were women who experienced an abnormal smear test (OR [odds ratio] 13.456, 95% CI 3.101-58.378, P<.001), female gender (OR 3.752, 95% CI 2.133-6.598, P<.001), and people who live in the United Kingdom (OR 2.097, 95% CI 1.447-3.038, P<.001). Nonsensitizing tweets were statistically more posted by a nonhealth or nonmedia company (OR 0.558, 95% CI 0.383-0.814, P<.001). CONCLUSIONS: This study demonstrates that the success of a public health campaign using a social media platform depends on its ability to get its targets involved. It also suggests the need to use social marketing to help its dissemination. The clinical impact of this Twitter campaign to increase cervical cancer screening is yet to be evaluated.

Patient healthcare trajectory. An essential monitoring tool: a systematic review.

BACKGROUND: Patient healthcare trajectory is a recent emergent topic in the literature, encompassing broad concepts. However, the rationale for studying patients' trajectories, and how this trajectory concept is defined remains a public health challenge. Our research was focused on patients' trajectories based on disease management and care, while also considering medico-economic aspects of the associated management. We illustrated this concept with an example: a myocardial infarction (MI) occurring in a patient's hospital trajectory of care. The patient follow-up was traced via the prospective payment system. We applied a semi-automatic text mining process to conduct a comprehensive review of patient healthcare trajectory studies. This review investigated how the concept of trajectory is defined, studied and what it achieves. METHODS: We performed a PubMed search to identify reports that had been published in peer-reviewed journals between January 1, 2000 and October 31, 2015. Fourteen search questions were formulated to guide our review. A semi-automatic text mining process based on a semantic approach was performed to conduct a comprehensive review of patient healthcare trajectory studies. Text mining techniques were used to explore the corpus in a semantic perspective in order to answer non-a priori questions. Complementary review methods on a selected subset were used to answer a priori questions. RESULTS: Among the 33,514 publications initially selected for analysis, only 70 relevant articles were semi-automatically extracted and thoroughly analysed. Oncology is particularly prevalent due to its already well-established processes of care. For the trajectory thema, 80% of articles were distributed in 11 clusters. These clusters contain distinct semantic information, for example health outcomes (29%), care process (26%) and administrative and financial aspects (16%). CONCLUSION: This literature review highlights the recent interest in the trajectory concept. The approach is also gradually being used to monitor trajectories of care for chronic diseases such as diabetes, organ failure or coronary artery and MI trajectory of care, to improve care and reduce costs. Patient trajectory is undoubtedly an essential approach to be further explored in order to improve healthcare monitoring.

E-Patient Reputation in Health Forums.

Online health forums are increasingly used by patients to get information and help related to their health. However, information reliability in these forums is unfortunately not always guaranteed. Obviously, consequences of self-diagnosis may be severe on the patient's health if measures are taken without consulting a doctor. Many works on trust issues related to social media have been proposed, but most of them mainly focus only on the structure part of the social network (number of posts, number of likes, etc.). In the case of online health forums, a lot of trust and distrust is expressed inside the posted messages and cannot be inferred by only considering the structure. In this study, we rather suggest inferring the user's trustworthiness from the replies he receives in the forum. The proposed method is divided into three main steps: First, the recipient(s) of each post must be identified. Next, the trust or distrust expressed in these posts is evaluated. Finally, the user's reputation is computed by aggregating all the posts he received. Conducted experiments using a manually annotated corpus are encouraging.

Genomics and Machine Learning for Taxonomy Consensus: The Mycobacterium tuberculosis Complex Paradigm.

Infra-species taxonomy is a prerequisite to compare features such as virulence in different pathogen lineages. Mycobacterium tuberculosis complex taxonomy has rapidly evolved in the last 20 years through intensive clinical isolation, advances in sequencing and in the description of fast-evolving loci (CRISPR and MIRU-VNTR). On-line tools to describe new isolates have been set up based on known diversity either on CRISPRs (also known as spoligotypes) or on MIRU-VNTR profiles. The underlying taxonomies are largely concordant but use different names and offer different depths. The objectives of this study were 1) to explicit the consensus that exists between the alternative taxonomies, and 2) to provide an on-line tool to ease classification of new isolates. Genotyping (24-VNTR, 43-spacers spoligotypes, IS6110-RFLP) was undertaken for 3,454 clinical isolates from the Netherlands (2004-2008). The resulting database was enlarged with African isolates to include most human tuberculosis diversity. Assignations were obtained using TB-Lineage, MIRU-VNTRPlus, SITVITWEB and an algorithm from Borile et al. By identifying the recurrent concordances between the alternative taxonomies, we proposed a consensus including 22 sublineages. Original and consensus assignations of the all isolates from the database were subsequently implemented into an ensemble learning approach based on Machine Learning tool Weka to derive a classification scheme. All assignations were reproduced with very good sensibilities and specificities. When applied to independent datasets, it was able to suggest new sublineages such as pseudo-Beijing. This Lineage Prediction tool, efficient on 15-MIRU, 24-VNTR and spoligotype data is available on the web interface "TBminer." Another section of this website helps summarizing key molecular epidemiological data, easing tuberculosis surveillance. Altogether, we successfully used Machine Learning on a large dataset to set up and make available the first consensual taxonomy for human Mycobacterium tuberculosis complex. Additional developments using SNPs will help stabilizing it.

Unraveling the molecular architecture of a G protein-coupled receptor/ß-arrestin/Erk module complex.

ß-arrestins serve as signaling scaffolds downstream of G protein-coupled receptors, and thus play a crucial role in a plethora of cellular processes. Although it is largely accepted that the ability of ß-arrestins to interact simultaneously with many protein partners is key in G protein-independent signaling of GPCRs, only the precise knowledge of these multimeric arrangements will allow a full understanding of the dynamics of these interactions and their functional consequences. However, current experimental procedures for the determination of the three-dimensional structures of protein-protein complexes are not well adapted to analyze these short-lived, multi-component assemblies. We propose a model of the receptor/ß-arrestin/Erk1 signaling module, which is consistent with most of the available experimental data. Moreover, for the ß-arrestin/Raf1 and the ß-arrestin/ERK interactions, we have used the model to design interfering peptides and shown that they compete with both partners, hereby demonstrating the validity of the predicted interaction regions.