Text Mining Methods for Analyzing Online Health Information and Communication

The Internet provides an alternative way to share health information. Specifically, social network systems such as Twitter, Facebook, Reddit, and disease specific online support forums are increasingly being used to share information on health related topics. This could be in the form of personal health information disclosure to seek suggestions or answering other patients\u27 questions based on their history. This social media uptake gives a new angle to improve the current health communication landscape with consumer generated content from social platforms. With these online modes of communication, health providers can offer more immediate support to the people seeking advice. Non-profit organizations and federal agencies can also diffuse preventative information in such networks for better outcomes. Researchers in health communication can mine user generated content on social networks to understand themes and derive insights into patient experiences that may be impractical to glean through traditional surveys. The main difficulty in mining social health data is in separating the signal from the noise. Social data is characterized by informal nature of content, typos, emoticons, tonal variations (e.g. sarcasm), and ambiguities arising from polysemous words, all of which make it difficult in building automated systems for deriving insights from such sources. In this dissertation, we present four efforts to mine health related insights from user generated social data. In the first effort, we build a model to identify marketing tweets on electronic cigarettes (e-cigs) and assess different topics in marketing and non-marketing messages on e-cigs on Twitter. In our next effort, we build ensemble models to classify messages on a mental health forum for triaging posts whose authors need immediate attention from trained moderators to prevent self-harm. The third effort deals with models from our participation in a shared task on identifying tweets that discuss adverse drug reactions and those that mention medication intake. In the final task, we build a classifier that identifies whether a particular tweet about the popular Juul e-cig indicates the tweeter actually using the product. Our methods range from linear classifiers (e.g., logistic regression), classical nonlinear models (e.g., nearest neighbors), recent deep neural networks (e.g., convolutional neural networks), and ensembles of all these models in using different supervised training regimens (e.g., co-training). The focus is more on task specific system building than on building specific individual models. Overall, we demonstrate that it is possible to glean insights from social data on health related topics through natural language processing and machine learning with use-cases from substance use and mental health

On Assessing the Sentiment of General Tweets

Abstract. With the explosion of publicly accessible social data, sentiment analysis has emerged as an important task with applications in e-commerce, politics, and social sciences. Hence, so far, researchers have largely focused on sentiment analysis of texts involving entities such as products, persons, institutions, and events. However, a significant amount of chatter on microblogging websites may not be directed at a particular entity. On Twitter, users share information on their general state of mind, details about how their day went, their plans for the next day, or just conversational chatter with other users. In this paper, we look into the problem of assessing the sentiment of publicly available general stream of tweets. Assessing the sentiment of such tweets helps us assess the overall sentiment being expressed in a geographic location or by a set of users (scoped through some means), which has applications in social sciences, psychology, and health sciences. The only prior effor

Data and systems for medication-related text classification and concept normalization from Twitter: insights from the Social Media Mining for Health (SMM4H)-2017 shared task

Objective: We executed the Social Media Mining for Health (SMM4H) 2017 shared tasks to enable the community-driven development and large-scale evaluation of automatic text processing methods for the classification and normalization of health-related text from social media. An additional objective was to publicly release manually annotated data.Materials and Methods: We organized 3 independent subtasks: automatic classification of self-reports of 1) adverse drug reactions (ADRs) and 2) medication consumption, from medication-mentioning tweets, and 3) normalization of ADR expressions. Training data consisted of 15 717 annotated tweets for (1), 10 260 for (2), and 6650 ADR phrases and identifiers for (3); and exhibited typical properties of social-media-based health-related texts. Systems were evaluated using 9961, 7513, and 2500 instances for the 3 subtasks, respectively. We evaluated performances of classes of methods and ensembles of system combinations following the shared tasks.Results: Among 55 system runs, the best system scores for the 3 subtasks were 0.435 (ADR class F1-score) for subtask-1, 0.693 (micro-averaged F1-score over two classes) for subtask-2, and 88.5% (accuracy) for subtask-3. Ensembles of system combinations obtained best scores of 0.476, 0.702, and 88.7%, outperforming individual systems.Discussion: Among individual systems, support vector machines and convolutional neural networks showed high performance. Performance gains achieved by ensembles of system combinations suggest that such strategies may be suitable for operational systems relying on difficult text classification tasks (eg, subtask-1).Conclusions: Data imbalance and lack of context remain challenges for natural language processing of social media text. Annotated data from the shared task have been made available as reference standards for future studies (http://dx.doi.org/10.17632/rxwfb3tysd.1).</div

Triglyceride-mimetic approaches for targeted drug delivery to the lymphatic system: a mechanistic study

The lymphatic system plays a number of roles in key physiological and pathological events, including propagation of the immune response, lipid transport and tumour metastases. Enhanced delivery of drugs to the lymphatic system therefore has the potential to benefit the treatment of diseases such as autoimmune disorders, immune diseases, metabolic syndrome, lymphoma and tumour metastases. Inspired by the realisation that dietary triglycerides (TG) are digested, absorbed, resynthesised and efficiently transported into and through the intestinal lymphatic system, this thesis examines TG-mimetic prodrugs as a potential conduit for drug delivery to the lymphatics. The studies reported herein investigate 1) the mechanisms underlying integration of lymph-directing prodrug strategies into lipid digestion-absorption-resynthesis-lipoprotein assembly pathways; 2) the factors that promote and that limit lymphotropic affinity and 3) potential strategies to combat such limitations. Mycophenolic acid (MPA, an immunosuppresant that acts by inhibiting lymphocyte proliferation) was chosen as a model drug for these studies as it has little intrinsic affinity for the lymph, but would benefit from targeted delivery to the lymphatic system where lymphocytes are resident at high concentrations. In the first set of studies, two classes of prodrugs of MPA (alkyl chain derivatives and TG mimetics) were examined with regard to their ability to promote lymphatic transport in rats. Three alkyl chain derivatives with varied chain lengths and linkers were examined, however, poor enzyme stability and low absorption appeared to limit lymphatic transport. In contrast, the TG mimetic, 1,3-dipalmitoyl-2-mycophenoloyl glycerol (2-MPA-TG), which was designed to promote biochemical integration into TG metabolism pathways, was significantly more effective in enhancing lymphatic transport. 2-MPA-TG resulted in increases in lymphatic transport of ~80-fold when compared to underivatised MPA. Subsequent mechanistic studies confirmed that lymphatic access of 2-MPA-TG resulted from a series of site-specific metabolic processes, including a) lipolysis in the intestinal lumen (facilitated by pancreatic lipases), b) re-esterification in enterocytes (enabled via glyceride acyltransferases), and 3) integration into intestinal LP (promoted by co-administered lipids). Each step was identified as being critical since inhibition of any of these processes resulted in significant attenuation of lymphatic transport. Importantly, following access of the re-esterification products of 2-MPA-TG into the lymphatics, conversion from pharmacologically inactive 2-MPA-TG derivatives to active free MPA was apparent and MPA concentrations in mesenteric lymph nodes were significantly higher than that obtained after administration of equimolar doses of MPA. Subsequent studies focused on the potential for structural change to the TG mimetic prodrugs to alter lymphatic transport and MPA release. The data revealed significant specificity with regards to the point of conjugation and the nature of the conjugation chemistry. MPA conjugation at the 2-position of the glycerol backbone and via an ester bond appeared to be critical requirements for optimal lymphatic transport. In addition, the insertion of straight chain alkyl linkers between MPA and the TG backbone appeared to potentiate parent drug release, although the overall extent of lymphatic transport of prodrug derivatives was not improved. Finally, methyl substitution of the alkyl chain,  and β to the ester bond between the alkyl chain and the glyceryl backbone, was attempted to promote the stability of the digested monoglyceride derivative of the prodrug in the intestine. This was effective in enhancing lymphatic transport relative to the non-methylated equivalent but lymphatic transport remained below that for the directly linked 2-MPA-TG. Finally, the utility of the prodrug strategy was confirmed by studies conducted in conscious greyhound dogs where GI physiology is expected to be more representative of that in humans. Following oral administration of 2-MPA-TG to fed dogs, lymphatic transport of MPA related materials was markedly enhanced (288 fold, when compared to that after MPA dosing) and conversion to the pharmacologically active form, MPA, was evident in lymphocytes. The data demonstrate that triglyceride mimetic prodrugs provide a mechanism to increase lymphatic drug transport, and may thus ultimately provide opportunities in the treatment of lymph-resident disease

Triglyceride-mimetic approaches for targeted drug delivery to the lymphatic system: a mechanistic study

The lymphatic system plays a number of roles in key physiological and pathological events, including propagation of the immune response, lipid transport and tumour metastases. Enhanced delivery of drugs to the lymphatic system therefore has the potential to benefit the treatment of diseases such as autoimmune disorders, immune diseases, metabolic syndrome, lymphoma and tumour metastases. Inspired by the realisation that dietary triglycerides (TG) are digested, absorbed, resynthesised and efficiently transported into and through the intestinal lymphatic system, this thesis examines TG-mimetic prodrugs as a potential conduit for drug delivery to the lymphatics. The studies reported herein investigate 1) the mechanisms underlying integration of lymph-directing prodrug strategies into lipid digestion-absorption-resynthesis-lipoprotein assembly pathways; 2) the factors that promote and that limit lymphotropic affinity and 3) potential strategies to combat such limitations. Mycophenolic acid (MPA, an immunosuppresant that acts by inhibiting lymphocyte proliferation) was chosen as a model drug for these studies as it has little intrinsic affinity for the lymph, but would benefit from targeted delivery to the lymphatic system where lymphocytes are resident at high concentrations. In the first set of studies, two classes of prodrugs of MPA (alkyl chain derivatives and TG mimetics) were examined with regard to their ability to promote lymphatic transport in rats. Three alkyl chain derivatives with varied chain lengths and linkers were examined, however, poor enzyme stability and low absorption appeared to limit lymphatic transport. In contrast, the TG mimetic, 1,3-dipalmitoyl-2-mycophenoloyl glycerol (2-MPA-TG), which was designed to promote biochemical integration into TG metabolism pathways, was significantly more effective in enhancing lymphatic transport. 2-MPA-TG resulted in increases in lymphatic transport of ~80-fold when compared to underivatised MPA. Subsequent mechanistic studies confirmed that lymphatic access of 2-MPA-TG resulted from a series of site-specific metabolic processes, including a) lipolysis in the intestinal lumen (facilitated by pancreatic lipases), b) re-esterification in enterocytes (enabled via glyceride acyltransferases), and 3) integration into intestinal LP (promoted by co-administered lipids). Each step was identified as being critical since inhibition of any of these processes resulted in significant attenuation of lymphatic transport. Importantly, following access of the re-esterification products of 2-MPA-TG into the lymphatics, conversion from pharmacologically inactive 2-MPA-TG derivatives to active free MPA was apparent and MPA concentrations in mesenteric lymph nodes were significantly higher than that obtained after administration of equimolar doses of MPA. Subsequent studies focused on the potential for structural change to the TG mimetic prodrugs to alter lymphatic transport and MPA release. The data revealed significant specificity with regards to the point of conjugation and the nature of the conjugation chemistry. MPA conjugation at the 2-position of the glycerol backbone and via an ester bond appeared to be critical requirements for optimal lymphatic transport. In addition, the insertion of straight chain alkyl linkers between MPA and the TG backbone appeared to potentiate parent drug release, although the overall extent of lymphatic transport of prodrug derivatives was not improved. Finally, methyl substitution of the alkyl chain,  and β to the ester bond between the alkyl chain and the glyceryl backbone, was attempted to promote the stability of the digested monoglyceride derivative of the prodrug in the intestine. This was effective in enhancing lymphatic transport relative to the non-methylated equivalent but lymphatic transport remained below that for the directly linked 2-MPA-TG. Finally, the utility of the prodrug strategy was confirmed by studies conducted in conscious greyhound dogs where GI physiology is expected to be more representative of that in humans. Following oral administration of 2-MPA-TG to fed dogs, lymphatic transport of MPA related materials was markedly enhanced (288 fold, when compared to that after MPA dosing) and conversion to the pharmacologically active form, MPA, was evident in lymphocytes. The data demonstrate that triglyceride mimetic prodrugs provide a mechanism to increase lymphatic drug transport, and may thus ultimately provide opportunities in the treatment of lymph-resident disease