Immunologic predictors of vaccine responsiveness in patients with lymphoma and CLL.

Patients with B-cell lymphomas have altered cellular components of vaccine responses due to malignancy and therapy, and the optimal timing of vaccination relative to therapy remains unknown. SARS-CoV-2 vaccines created an opportunity for new insights in vaccine timing because patients were challenged with a novel antigen across multiple phases of treatment. We studied serologic mRNA vaccine response in retrospective and prospective cohorts with lymphoma and CLL, paired with clinical and research immune parameters. Reduced serologic response was observed more frequently during active therapies, but non-response was also common within observation and post-treatment groups. Total IgA and IgM correlated with successful vaccine response. In individuals treated with CART-19, non-response was associated with reduced B and T follicular helper cells. Predictors of vaccine response varied by disease and therapeutic group, and therefore further studies of immune health during and after cancer therapies are needed to allow individualized vaccine timing.

Improving the Quality and Utility of Electronic Health Record Data through Ontologies.

The translational research community, in general, and the Clinical and Translational Science Awards (CTSA) community, in particular, share the vision of repurposing EHRs for research that will improve the quality of clinical practice. Many members of these communities are also aware that electronic health records (EHRs) suffer limitations of data becoming poorly structured, biased, and unusable out of original context. This creates obstacles to the continuity of care, utility, quality improvement, and translational research. Analogous limitations to sharing objective data in other areas of the natural sciences have been successfully overcome by developing and using common ontologies. This White Paper presents the authors' rationale for the use of ontologies with computable semantics for the improvement of clinical data quality and EHR usability formulated for researchers with a stake in clinical and translational science and who are advocates for the use of information technology in medicine but at the same time are concerned by current major shortfalls. This White Paper outlines pitfalls, opportunities, and solutions and recommends increased investment in research and development of ontologies with computable semantics for a new generation of EHRs.

Online Public Health Nurse-Delivered Group Cognitive Behavioral Therapy for Postpartum Depression: A Randomized Controlled Trial During the COVID-19 Pandemic.

Objective: Rates of postpartum depression (PPD) increased during the COVID-19 pandemic, further highlighting the need for effective, accessible treatments for PPD. While public health nurses (PHNs) can be trained to help treat PPD, it is not known if they can effectively deliver evidence-based psychotherapies online to those with PPD.Methods: Mothers (n = 159) living in Ontario, Canada, with an Edinburgh Postnatal Depression Scale (EPDS) score ≥ 10 and an infant < 12 months of age were randomized to receive a 9-week group cognitive behavioral therapy (CBT) intervention delivered by PHNs over Zoom, between October 2020 and November 2021. Experimental group participants received CBT plus treatment as usual (TAU), and control participants received TAU alone. Participants were assessed at baseline (T1), 9 weeks later (T2), and 6 months after T2 (T3). Primary outcomes were changes in EPDS score and current major depressive disorder (MDD) as measured by the Mini International Neuropsychiatric Interview. Secondary outcomes included worry, social support, the mother-infant relationship, and infant temperament.Results: At T2, experimental group participants showed clinically and statistically significant reductions on the EPDS (d = 0.65) and decreases in postpartum worry (d = 0.38) and rejection and pathological anger toward their infant (d = 0.44). They were also less likely to meet diagnostic criteria for current MDD compared to control participants (OR = 5.09; 95% CI, 1.18-21.98; number needed to treat [NNT: 3.7]). These improvements remained stable 6 months later (T3).Conclusions: PHNs can be trained to deliver effective online group CBT for PPD to reduce depression and worry and improve aspects of the mother-infant relationship, and they represent an important way to increase access to effective treatment for PPD.Trial Registration: ClinicalTrials.gov identifier: NCT04928742.

Longitudinal changes in term and preterm infant night wakings: The role of caregiver anxious-depression.

Changes in infant night waking during the first year of life are associated with individual (e.g., prematurity) and family (e.g., caregiver psychopathology) factors. This study examined the association between infant night waking and caregiver anxious-depressive symptoms during the first year of life in preterm and term infants. We considered between-person differences and within-person changes in caregiver anxious-depressive symptoms in relation to changes in infant night waking from 2- to 9-months. Racially (30.0% Black, 60.4% White, 9.5% multiracial/other) and socioeconomically (40.0% below median household income) diverse caregivers (N = 445) of full term (n = 258) and preterm (n = 187) infants were recruited from hospitals and clinics in two midwestern states. Caregivers completed measures of anxious-depression and their infant's night waking at four sampling periods (2-, 4-, 6-, and 9-months). Infant night wakings declined from 2- to 9-months. Between-person differences were observed, such that caregivers with higher average anxious-depressive symptoms or infants born full term reported more night wakings. Within-person effects of caregiver anxious-depressive symptoms were not significant. Caregiver anxious-depression is closely associated with infant night wakings. By considering a caregiver's average severity of anxious-depression, healthcare providers can more effectively plan infant sleep interventions. If caregiver anxious-depressive symptoms are ameliorated, night wakings may also decrease.

Los cambios en el despertar nocturno del infante durante el primer año de vida se asocian con factores individuales (v.g. nacimiento prematuro) y familiares (v.g. sicopatología de quien presta el cuidado). Este estudio examinó la asociación entre el despertar nocturno del infante y los síntomas de depresión por ansiedad de quien presta el cuidado durante el primer año de vida de infantes nacidos prematuramente y de ciclo completo. Tomamos en cuenta las diferencias entre las personas y los cambios dentro de las personas en los síntomas de depresión por ansiedad de quien presta el cuidado con relación a los cambios en el despertar nocturno del infante de los 2 a los 9 meses. Se reclutaron en hospitales y clínicas de dos estados del medio oeste cuidadores (N = 445) racial (30.0% de raza negra, 60.4% blancos, 9.5% multirraciales o de otra raza) y socioeconómicamente (40.0% por debajo del promedio de ingresos caseros) diversos, de infantes de ciclo completo (n = 258) y prematuros (n = 187). Los cuidadores completaron medidas de depresión por ansiedad y el despertar nocturno de sus infantes en cuatro períodos muestra (a los 2, 4, 6 y 9 meses). El despertar nocturno del infante declinó de los 2 a los 9 meses. Se observaron las diferencias entre personas, de tal manera que los cuidadores con un promedio mayor de síntomas de depresión por ansiedad o infantes nacidos en el ciclo completo reportaron más despertar nocturno. Los efectos de dentro de las personas de los síntomas de depresión por ansiedad del cuidador no fueron significativos. La depresión por ansiedad del cuidador se asocia cercanamente con el despertar nocturno del infante. Por medio de considerar el promedio de la severidad de la depresión por ansiedad del cuidador, quienes ofrecen el cuidado de salud pueden planear más eficazmente las intervenciones en cuanto al sueño del infante. Si se mejoran los síntomas de depresión por ansiedad de quien presta el cuidado, el despertar nocturno también podría disminuir.

Les changements dans le réveil nocturne du bébé pendant la première année sont liés à des facteurs individuels (par exemple la prématurité) et familiaux (par exemple la psychopathologie de la personne prenant soin de l'enfant). Cette étude a examiné le lien entre le réveil nocturne du bébé et les symptômes anxieux-dépressifs de la personne prenant soin de l'enfant durant la première année de vie de bébés prématurés et à terme. Nous avons considéré les différences entre les personnes et les changements au sein de la personne dans les symptômes anxieux-dépressifs de la personne prenant soin de l'enfant, en lien aux changements dans le réveil nocturne du bébé de 2 à 9 mois. Des personnes (N = 445) prenant soin d'un bébé à plein terme (n = 258) et prématuré (n = 187), divers du point de vue de leur race (30,0% noirs, 60,4% blancs, 9,5% multiracial/autre) et de leur statut socioéconomique (40,0% en dessous du revenu moyen d'une famille) ont été recrutés dans des hôpitaux et des cliniques des états au centre nord des Etats-Unis. Les personnes prenant soin du bébé ont rempli des mesures de dépression anxiété et de la nuit de leur bébé à quatre périodes de prélèvement des renseignements (2-, 4-, 6-, et 9- mois). Les réveils nocturnes du bébé ont décliné de 2- à 9- mois. Des différences entre les personnes ont été observées, au point que les personnes prenant soin du bébé avec la moyenne de symptômes anxieux-dépressifs la plus élevée ou des bébé nés à terme ont fait état de plus de réveils nocturnes. Les effets au sein de la personne des personnes prenant soin du bébé avec des symptômes anxieux-dépressifs n'étaient pas importants. La personne prenant du bébé avec une dépression anxieuse est fortement liée aux réveils nocturnes du bébé. En considérant la sévérité moyenne de la dépression anxieuse de la personne prenant soin du bébé, les prestataires de santé peuvent planifier les interventions concernant le sommeil du bébé de manière plus efficace. Si les symptômes anxieux-dépressifs de la personne prenant soin du bébé sont améliorer, alors les réveils nocturnes pourraient aussi diminuer.

Efficient recall of Omicron-reactive B cell memory after a third dose of SARS-CoV-2 mRNA vaccine.

We examined antibody and memory B cell responses longitudinally for ∼9-10 months after primary 2-dose SARS-CoV-2 mRNA vaccination and 3 months after a 3rd dose. Antibody decay stabilized between 6 and 9 months, and antibody quality continued to improve for at least 9 months after 2-dose vaccination. Spike- and RBD-specific memory B cells remained durable over time, and 40%-50% of RBD-specific memory B cells simultaneously bound the Alpha, Beta, Delta, and Omicron variants. Omicron-binding memory B cells were efficiently reactivated by a 3rd dose of wild-type vaccine and correlated with the corresponding increase in neutralizing antibody titers. In contrast, pre-3rd dose antibody titers inversely correlated with the fold-change of antibody boosting, suggesting that high levels of circulating antibodies may limit the added protection afforded by repeat short interval boosting. These data provide insight into the quantity and quality of mRNA-vaccine-induced immunity over time through 3 or more antigen exposures.

Efficient recall of Omicron-reactive B cell memory after a third dose of SARS-CoV-2 mRNA vaccine.

Despite a clear role in protective immunity, the durability and quality of antibody and memory B cell responses induced by mRNA vaccination, particularly by a 3 rd dose of vaccine, remains unclear. Here, we examined antibody and memory B cell responses in a cohort of individuals sampled longitudinally for ∼9-10 months after the primary 2-dose mRNA vaccine series, as well as for ∼3 months after a 3 rd mRNA vaccine dose. Notably, antibody decay slowed significantly between 6- and 9-months post-primary vaccination, essentially stabilizing at the time of the 3 rd dose. Antibody quality also continued to improve for at least 9 months after primary 2-dose vaccination. Spike- and RBD-specific memory B cells were stable through 9 months post-vaccination with no evidence of decline over time, and ∼40-50% of RBD-specific memory B cells were capable of simultaneously recognizing the Alpha, Beta, Delta, and Omicron variants. Omicron-binding memory B cells induced by the first 2 doses of mRNA vaccine were boosted significantly by a 3rd dose and the magnitude of this boosting was similar to memory B cells specific for other variants. Pre-3 rd dose memory B cell frequencies correlated with the increase in neutralizing antibody titers after the 3 rd dose. In contrast, pre-3 rd dose antibody titers inversely correlated with the fold-change of antibody boosting, suggesting that high levels of circulating antibodies may limit reactivation of immunological memory and constrain further antibody boosting by mRNA vaccines. These data provide a deeper understanding of how the quantity and quality of antibody and memory B cell responses change over time and number of antigen exposures. These data also provide insight into potential immune dynamics following recall responses to additional vaccine doses or post-vaccination infections.

mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern.

The durability of immune memory after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccination remains unclear. In this study, we longitudinally profiled vaccine responses in SARS-CoV-2­naïve and ­recovered individuals for 6 months after vaccination. Antibodies declined from peak levels but remained detectable in most subjects at 6 months. By contrast, mRNA vaccines generated functional memory B cells that increased from 3 to 6 months postvaccination, with the majority of these cells cross-binding the Alpha, Beta, and Delta variants. mRNA vaccination further induced antigen-specific CD4+ and CD8+ T cells, and early CD4+ T cell responses correlated with long-term humoral immunity. Recall responses to vaccination in individuals with preexisting immunity primarily increased antibody levels without substantially altering antibody decay rates. Together, these findings demonstrate robust cellular immune memory to SARS-CoV-2 and its variants for at least 6 months after mRNA vaccination.

Rapid induction of antigen-specific CD4+ T cells is associated with coordinated humoral and cellular immunity to SARS-CoV-2 mRNA vaccination.

SARS-CoV-2 mRNA vaccines have shown remarkable clinical efficacy, but questions remain about the nature and kinetics of T cell priming. We performed longitudinal antigen-specific T cell analyses on healthy SARS-CoV-2-naive and recovered individuals prior to and following mRNA prime and boost vaccination. Vaccination induced rapid antigen-specific CD4+ T cell responses in naive subjects after the first dose, whereas CD8+ T cell responses developed gradually and were variable in magnitude. Vaccine-induced Th1 and Tfh cell responses following the first dose correlated with post-boost CD8+ T cells and neutralizing antibodies, respectively. Integrated analysis revealed coordinated immune responses with distinct trajectories in SARS-CoV-2-naive and recovered individuals. Last, whereas booster vaccination improved T cell responses in SARS-CoV-2-naive subjects, the second dose had little effect in SARS-CoV-2-recovered individuals. These findings highlight the role of rapidly primed CD4+ T cells in coordinating responses to the second vaccine dose in SARS-CoV-2-naive individuals.

mRNA Vaccination Induces Durable Immune Memory to SARS-CoV-2 with Continued Evolution to Variants of Concern.

SARS-CoV-2 mRNA vaccines have shown remarkable efficacy, especially in preventing severe illness and hospitalization. However, the emergence of several variants of concern and reports of declining antibody levels have raised uncertainty about the durability of immune memory following vaccination. In this study, we longitudinally profiled both antibody and cellular immune responses in SARS-CoV-2 naïve and recovered individuals from pre-vaccine baseline to 6 months post-mRNA vaccination. Antibody and neutralizing titers decayed from peak levels but remained detectable in all subjects at 6 months post-vaccination. Functional memory B cell responses, including those specific for the receptor binding domain (RBD) of the Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2) variants, were also efficiently generated by mRNA vaccination and continued to increase in frequency between 3 and 6 months post-vaccination. Notably, most memory B cells induced by mRNA vaccines were capable of cross-binding variants of concern, and B cell receptor sequencing revealed significantly more hypermutation in these RBD variant-binding clones compared to clones that exclusively bound wild-type RBD. Moreover, the percent of variant cross-binding memory B cells was higher in vaccinees than individuals who recovered from mild COVID-19. mRNA vaccination also generated antigen-specific CD8+ T cells and durable memory CD4+ T cells in most individuals, with early CD4+ T cell responses correlating with humoral immunity at later timepoints. These findings demonstrate robust, multi-component humoral and cellular immune memory to SARS-CoV-2 and current variants of concern for at least 6 months after mRNA vaccination. Finally, we observed that boosting of pre-existing immunity with mRNA vaccination in SARS-CoV-2 recovered individuals primarily increased antibody responses in the short-term without significantly altering antibody decay rates or long-term B and T cell memory. Together, this study provides insights into the generation and evolution of vaccine-induced immunity to SARS-CoV-2, including variants of concern, and has implications for future booster strategies.

Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination.

Novel mRNA vaccines for SARS-CoV-2 have been authorized for emergency use. Despite their efficacy in clinical trials, data on mRNA vaccine-induced immune responses are mostly limited to serological analyses. Here, we interrogated antibody and antigen-specific memory B cells over time in 33 SARS-CoV-2 naïve and 11 SARS-CoV-2 recovered subjects. SARS-CoV-2 naïve individuals required both vaccine doses for optimal increases in antibodies, particularly for neutralizing titers against the B.1.351 variant. Memory B cells specific for full-length spike protein and the spike receptor binding domain (RBD) were also efficiently primed by mRNA vaccination and detectable in all SARS-CoV-2 naive subjects after the second vaccine dose, though the memory B cell response declined slightly with age. In SARS-CoV-2 recovered individuals, antibody and memory B cell responses were significantly boosted after the first vaccine dose; however, there was no increase in circulating antibodies, neutralizing titers, or antigen-specific memory B cells after the second dose. This robust boosting after the first vaccine dose strongly correlated with levels of pre-existing memory B cells in recovered individuals, identifying a key role for memory B cells in mounting recall responses to SARS-CoV-2 antigens. Together, our data demonstrated robust serological and cellular priming by mRNA vaccines and revealed distinct responses based on prior SARS-CoV-2 exposure, whereby COVID-19 recovered subjects may only require a single vaccine dose to achieve peak antibody and memory B cell responses. These findings also highlight the utility of defining cellular responses in addition to serologies and may inform SARS-CoV-2 vaccine distribution in a resource-limited setting.

Longitudinal Analysis Reveals Distinct Antibody and Memory B Cell Responses in SARS-CoV2 Naïve and Recovered Individuals Following mRNA Vaccination.

Novel mRNA vaccines for SARS-CoV2 have been authorized for emergency use and are currently being administered to millions of individuals worldwide. Despite their efficacy in clinical trials, there is limited data on vaccine-induced immune responses in individuals with a prior SARS-CoV2 infection compared to SARS-CoV2 naïve subjects. Moreover, how mRNA vaccines impact the development of antibodies as well as memory B cells in COVID-19 experienced versus COVID-19 naïve subjects remains poorly understood. In this study, we evaluated antibody responses and antigen-specific memory B cell responses over time in 33 SARS-CoV2 naïve and 11 SARS-CoV2 recovered subjects. mRNA vaccination induced significant antibody and memory B cell responses against full-length SARS-CoV2 spike protein and the spike receptor binding domain (RBD). SARS-CoV2 naïve individuals benefitted from both doses of mRNA vaccine with additional increases in antibodies and memory B cells following booster immunization. In contrast, SARS-CoV2 recovered individuals had a significant immune response after the first dose with no increase in circulating antibodies or antigen-specific memory B cells after the second dose. Moreover, the magnitude of the memory B cell response induced by vaccination was lower in older individuals, revealing an age-dependence to mRNA vaccine-induced B cell memory. Side effects also tended to associate with post-boost antibody levels, but not with post-boost memory B cells, suggesting that side effect severity may be a surrogate of short-term antibody responses. The frequency of pre-vaccine antigen-specific memory B cells in SARS-CoV2 recovered individuals strongly correlated with post-vaccine antibody levels, supporting a key role for memory B cells in humoral recall responses to SARS-CoV2. This observation may have relevance for future booster vaccines and for responses to viral variants that partially escape pre-existing antibodies and require new humoral responses to be generated from memory B cells. Finally, post-boost antibody levels were not correlated with post-boost memory responses in SARS-CoV2 naïve individuals, indicating that short-term antibody levels and memory B cells are complementary immunological endpoints that should be examined in tandem when evaluating vaccine response. Together, our data provide evidence of both serological response and immunological memory following mRNA vaccination that is distinct based on prior SARS-CoV2 exposure. These findings may inform vaccine distribution in a resource-limited setting.

A realism-based approach to an ontological representation of symbiotic interactions.

BACKGROUND: The symbiotic interactions that occur between humans and organisms in our environment have a tremendous impact on our health. Recently, there has been a surge in interest in understanding the complex relationships between the microbiome and human health and host immunity against microbial pathogens, among other things. To collect and manage data about these interactions and their complexity, scientists will need ontologies that represent symbiotic interactions as they occur in reality. METHODS: We began with two papers that reviewed the usage of 'symbiosis' and related terms in the biology and ecology literature and prominent textbooks. We then analyzed several prominent standard terminologies and ontologies that contain representations of symbiotic interactions, to determine if they appropriately defined 'symbiosis' and related terms according to current scientific usage as identified by the review papers. In the process, we identified several subtypes of symbiotic interactions, as well as the characteristics that differentiate them, which we used to propose textual and axiomatic definitions for each subtype of interaction. To both illustrate how to use the ontological representations and definitions we created and provide additional quality assurance on key definitions, we carried out a referent tracking analysis and representation of three scenarios involving symbiotic interactions among organisms. RESULTS: We found one definition of 'symbiosis' in an existing ontology that was consistent with the vast preponderance of scientific usage in biology and ecology. However, that ontology changed its definition during the course of our work, and discussions are ongoing. We present a new definition that we have proposed. We also define 34 subtypes of symbiosis. Our referent tracking analysis showed that it is necessary to define symbiotic interactions at the level of the individual, rather than at the species level, due to the complex nature in which organisms can go from participating in one type of symbiosis with one organism to participating in another type of symbiosis with a different organism. CONCLUSION: As a result of our efforts here, we have developed a robust representation of symbiotic interactions using a realism-based approach, which fills a gap in existing biomedical ontologies.

Parent Perceptions of Pediatric Primary Care Providers' Mental Health-Related Communication and Practices.

INTRODUCTION: The pediatric primary care office is an ideal setting to address children's socioemotional-behavioral health. However, research is limited regarding parents' experiences and satisfaction in sharing mental-health concerns about their children during well-child visits. METHOD: One thousand seven hundred sixty-three parents and caregivers with children aged 3-17 years completed an online survey that addressed mental-health-related communication. RESULTS: Findings supported the key role that primary care providers play in communicating about mental-health issues; 75% of parents who had such a concern about their child raised it during the visit, although the majority desired more time devoted to discussing mental health. Parents' comfort discussing mental-health concerns was inversely related to providers' dismissing those concerns. DISCUSSION: Despite satisfaction with how providers addressed mental-health issues, results suggested that nonjudgmental, knowledgeable staff and discussion of child and parent strengths could facilitate both parental comfort and communication between parents and pediatricians.

Web-based LGBT cultural competency training intervention for oncologists: Pilot study results.

BACKGROUND: Lesbian, gay, bisexual, and transgender (LGBT) cancer patients experience substantial health disparities, including poorer overall health and lower satisfaction with their cancer care than their heterosexual and cisgender counterparts, which may be due in part to a lack of culturally competent providers. To address these disparities, a web-based LGBT cultural competency training tailored to oncologists was developed by an interdisciplinary team of scientists, LGBT cancer survivors, cultural competency experts, oncologists, a web designer, and an instructional designer. METHODS: Oncologists (n = 44) were recruited from 3 academic cancer centers in Florida. Participants were administered the LGBT cultural competency training Curriculum for Oncologists on LGBT populations to Optimize Relevance and Skills (COLORS) and completed pre- and posttraining measures regarding LGBT-related knowledge, attitudes (including general negative attitudes and health care-related attitudes), and clinical practices. After the training, participants completed training acceptability measures. RESULTS: Of the 44 participants, 33 (75%) completed the COLORS training. Participants were 55% non-Hispanic white, 63% male, and had a mean age of 47 years. Participants demonstrated significant improvements in LGBT-related knowledge (t = -4.9, P < .001), attitudes (Z = -3.0, P = .002; t = -2.5, P = .019), and clinical practices (Z = -3.5, P < .001) after completing the COLORS training (Wilcoxon signed rank tests were used for nonnormally distributed variables). Moreover, training acceptability was high, with 82% of participants rating the training as high quality, and 97% being willing to recommend the training to a colleague. CONCLUSION: The COLORS training is both feasible to administer and acceptable for use with oncologists, and may improve oncologists' LGBT-related knowledge, attitudes, and clinical practices. Larger trials are needed to examine the training's effectiveness in reducing LGBT cancer disparities, as well as its applicability to other types of care providers.

Developing a web-based LGBT cultural competency training for oncologists: The COLORS training.

OBJECTIVE: Despite substantial LGBT cancer health disparities, there are no LGBT cultural competency trainings tailored for oncologists. Here we describe the systematic development of a web-based, oncology-focused LGBT cultural competency training. METHODS: A literature review regarding LGBT cancer outcomes and competency training was conducted to identify potential training content. An expert panel meeting, including LGBT cancer survivors, cultural competency experts, oncologists, a web designer, and an instructional designer, was held to solidify the training content focus. Following the panel, the training was developed in collaboration with an instructional designer, a web designer, and LGBT community members. RESULTS: The training modules include: 1) LGBT Basics; 2) Inclusive Environments; 3) Initiating Oncology Care with LGBT Patients; and 4) Issues in Cancer Survivorship among LGBT Patients. Module content is interactive, and models effective communication. CONCLUSION: The process of collaboration with a diverse group of stakeholders and three cancer centers in Florida has resulted in a practical and efficient web-based resource for LGBT cultural competency training for oncologists. PRACTICE IMPLICATIONS: Feedback from stakeholders indicates that training in this area is needed and will be well-received by oncologists. We are currently conducting an evaluation of this training among oncologists and LGBT community members.

Therapeutic indications and other use-case-driven updates in the drug ontology: anti-malarials, anti-hypertensives, opioid analgesics, and a large term request.

BACKGROUND: The Drug Ontology (DrOn) is an OWL2-based representation of drug products and their ingredients, mechanisms of action, strengths, and dose forms. We originally created DrOn for use cases in comparative effectiveness research, primarily to identify historically complete sets of United States National Drug Codes (NDCs) that represent packaged drug products, by the ingredient(s), mechanism(s) of action, and so on contained in those products. Although we had designed DrOn from the outset to carefully distinguish those entities that have a therapeutic indication from those entities that have a molecular mechanism of action, we had not previously represented in DrOn any particular therapeutic indication. RESULTS: In this work, we add therapeutic indications for three research use cases: resistant hypertension, malaria, and opioid abuse research. We also added mechanisms of action for opioid analgesics and added 108 classes representing drug products in response to a large term request from the Program for Resistance, Immunology, Surveillance and Modeling of Malaria in Uganda (PRISM) project. The net result is a new version of DrOn, current to May 2016, that represents three major therapeutic classes of drugs and six new mechanisms of action. CONCLUSIONS: A therapeutic indication of a drug product is represented as a therapeutic function in DrOn. Adverse effects of drug products, as well as other therapeutic uses for which the drug product was not designed are dispositions. Our work provides a framework for representing additional therapeutic indications, adverse effects, and uses of drug products beyond their design. Our work also validated our past modeling decisions for specific types of mechanisms of action, namely effects mediated via receptor and/or enzyme binding. DrOn is available at: http://purl.obolibrary.org/obo/dron.owl . A smaller version without NDCs is available at: http://purl.obolibrary.org/obo/dron/dron-lite.owl.

Development of a Pediatric Adverse Events Terminology.

In 2009, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) established the Pediatric Terminology Harmonization Initiative to establish a core library of terms to facilitate the acquisition and sharing of knowledge between pediatric clinical research, practice, and safety reporting. A coalition of partners established a Pediatric Terminology Adverse Event Working Group in 2013 to develop a specific terminology relevant to international pediatric adverse event (AE) reporting. Pediatric specialists with backgrounds in clinical care, research, safety reporting, or informatics, supported by biomedical terminology experts from the National Cancer Institute's Enterprise Vocabulary Services participated. The multinational group developed a working definition of AEs and reviewed concepts (terms, synonyms, and definitions) from 16 pediatric clinical domains. The resulting AE terminology contains >1000 pediatric diseases, disorders, or clinical findings. The terms were tested for proof of concept use in 2 different settings: hospital readmissions and the NICU. The advantages of the AE terminology include ease of adoption due to integration with well-established and internationally accepted biomedical terminologies, a uniquely temporal focus on pediatric health and disease from conception through adolescence, and terms that could be used in both well- and underresourced environments. The AE terminology is available for use without restriction through the National Cancer Institute's Enterprise Vocabulary Services and is fully compatible with, and represented in, the Medical Dictionary for Regulatory Activities. The terminology is intended to mature with use, user feedback, and optimization.

OC-2-KB: A software pipeline to build an evidence-based obesity and cancer knowledge base.

Obesity has been linked to several types of cancer. Access to adequate health information activates people's participation in managing their own health, which ultimately improves their health outcomes. Nevertheless, the existing online information about the relationship between obesity and cancer is heterogeneous and poorly organized. A formal knowledge representation can help better organize and deliver quality health information. Currently, there are several efforts in the biomedical domain to convert unstructured data to structured data and store them in Semantic Web knowledge bases (KB). In this demo paper, we present, OC-2-KB (Obesity and Cancer to Knowledge Base), a system that is tailored to guide the automatic KB construction for managing obesity and cancer knowledge from free-text scientific literature (i.e., PubMed abstracts) in a systematic way. OC-2-KB has two important modules which perform the acquisition of entities and the extraction then classification of relationships among these entities. We tested the OC-2-KB system on a data set with 23 manually annotated obesity and cancer PubMed abstracts and created a preliminary KB with 765 triples. We conducted a preliminary evaluation on this sample of triples and reported our evaluation results.