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Abstract Post marketing safety surveillance depends in part on the ability to detect concerning clinical events at scale. Spontaneous reporting might be an effective component of safety surveillance, but it requires awareness and understanding among healthcare professionals to achieve its potential. Reliance on readily available structured data such as diagnostic codes risks under-coding and imprecision. Clinical textual data might bridge these gaps, and natural language processing (NLP) has been shown to aid in scalable phenotyping across healthcare records in multiple clinical domains. In this study, we developed and validated a novel incident phenotyping approach using unstructured clinical textual data agnostic to Electronic Health Record (EHR) and note type. It’s based on a published, validated approach (PheRe) used to ascertain social determinants of health and suicidality across entire healthcare records. To demonstrate generalizability, we validated this approach on two separate phenotypes that share common challenges with respect to accurate ascertainment: (1) suicide attempt; (2) sleep-related behaviors. With samples of 89,428 records and 35,863 records for suicide attempt and sleep-related behaviors, respectively, we conducted silver standard (diagnostic coding) and gold standard (manual chart review) validation. We showed Area Under the Precision-Recall Curve of ~ 0.77 (95% CI 0.75–0.78) for suicide attempt and AUPR ~ 0.31 (95% CI 0.28–0.34) for sleep-related behaviors. We also evaluated performance by coded race and demonstrated differences in performance by race differed across phenotypes. Scalable phenotyping models, like most healthcare AI, require algorithmovigilance and debiasing prior to implementation.

Light and nitrogen availability are basic requirements for photosynthesis. Changing in light intensity and nitrogen concentration may require adaptive physiological and life process changes in phytoplankton cells. Our previous study demonstrated that two Thalassiosira species exhibited, respectively, distinctive physiological responses to light and nitrogen stresses. Transcriptomic analyses were employed to investigate the mechanisms behind the different physiological responses observed in two diatom species of the genus Thalassiosira. The results indicate that the congeneric species are different in their cellular responses to the same shifting light and nitrogen conditions. When conditions changed to high light with low nitrate (HLLN), the large-celled T. punctigera was photodamaged. Thus, the photosynthesis pathway and carbon fixation related genes were significantly down-regulated. In contrast, the small-celled T. pseudonana sacrificed cellular processes, especially amino acid metabolisms, to overcome the photodamage. When changing to high light with high nitrate (HLHN) conditions, the additional nitrogen appeared to compensate for the photodamage in the large-celled T. punctigera, with the tricarboxylic acid cycle (TCA cycle) and carbon fixation significantly boosted. Consequently, the growth rate of T. punctigera increased, which suggest that the larger-celled species is adapted for forming post-storm algal blooms. The impact of high light stress on the small-celled T. pseudonana was not mitigated by elevated nitrate levels, and photodamage persisted.

Fine-grained organic-rich sediments (FGORS) are accumulating in estuaries worldwide, with multi-faceted negative ecosystem impacts. A pilot experiment was carried out in a residential canal of the Indian River Lagoon estuary (IRL, Florida, USA) using an aeration treatment intended to mitigate the harmful ecological effects of organic-rich sediment pollution. Planktonic and benthic communities were monitored, and environmental data collected throughout the aeration process. Results were compared against control conditions to evaluate the efficacy of aeration in the mitigation of FGORS. During the aeration process, hurricane Irma impacted the study area, bringing heavy rainfall and spawning a brown tide event (Aureoumbra lagunensis). The overall thickness and volume of FGORS, and the organic content of surface sediments did not change during the aeration treatment. Dissolved oxygen was higher and ammonium concentrations were lower in aeration canal bottom water compared to the control canal. During treatment, aeration did facilitate benthic animal life when temperatures dropped below 25°C, likely due to water column mixing and the increased capacity of water to hold dissolved gasses. In general, aeration did not significantly change the planktonic community composition relative to the control canal, but, during the post-bloom period, aeration helped to weaken the brown tide and phytoplankton densities were 35–50% lower for A. lagunensis in aeration canal surface water compared to the control canal. Aeration has important management applications and may be useful for mitigating algal blooms in flow-restricted areas and promoting benthic communities in cooler environments.

The convergence of artificial intelligence (AI) and precision medicine promises to revolutionize health care. Precision medicine methods identify phenotypes of patients with less‐common responses to treatment or unique healthcare needs. AI leverages sophisticated computation and inference to generate insights, enables the system to reason and learn, and empowers clinician decision making through augmented intelligence. Recent literature suggests that translational research exploring this convergence will help solve the most difficult challenges facing precision medicine, especially those in which nongenomic and genomic determinants, combined with information from patient symptoms, clinical history, and lifestyles, will facilitate personalized diagnosis and prognostication.

To yield environmental benefits, fine sediments with ~10% organic matter, termed muck, were dredged from a tributary to the Indian River Lagoon. Key changes were documented by sampling amphipods, sediments, and the water column near the bottom before dredging, and approximately one month and one year after dredging. Overall, muck yielded the fewest taxa, muck or sediments in creeks that were dredged yielded a moderate number of taxa, and undisturbed sediments in the lagoon yielded the highest number of taxa. Amphipods did not appear in areas with muck until one month and one year after dredging. In contrast, amphipods in sediments that were not muck decreased after dredging. Increases in the occurrence of amphipods paralleled increases in concentrations of dissolved oxygen and decreases in the water, silt/clay, and organic content of sediments. Overall, results indicated that conditions for amphipods were improved by removing muck, and that dredging sandier sediment led to decreased taxonomic richness and numbers of amphipods, which resembled the effects of navigational dredging. Thus, this study suggested that managers should consider the type of sediment to be dredged when permitting projects.

Mesozooplankton, as abundant grazers of microalgae in coastal systems, have the potential to prevent or mitigate harmful algal blooms (HABs) and their effects. The Indian River Lagoon (IRL) is a subtropical estuary in eastern Florida (United States) where repeated blooms, dominated by the toxic dinoflagellate Pyrodinium bahamense, the brown tide species Aureoumbra lagunensis, pico/nano planktonic cyanobacteria and other nano-eukaryotes, have highlighted the need to better understand fluctuations in the grazing potential of mesozooplankton populations across bloom cycles. Mesozooplankton and abiotic environmental data were collected at five sites in the northern IRL system at 6-week intervals from November 2013 through June 2016. A total of 107 taxa from 14 phyla were detected. Communities varied across sites, dates and between bloom and non-bloom periods, with densities up to 338 individuals L–1. Eight taxa comprising 85–94% of the total population at each site were identified as primary potential grazers, including barnacle nauplii, cladocerans, adult copepods, gastropod veligers, larvaceans, and polychaete metatrochophores. Although abundant, the estimated grazing potential of the primary taxa, calculated from their measured densities and previously published grazing rates, suggest that mesozooplankton lack the capacity to suppress phytoplankton once they reach bloom levels. These findings illustrate the utility of monitoring data and underscore the importance of systematically evaluating algal bloom controls with a consideration for the dynamic conditions of each unique ecosystem.

Harmful algal blooms (HABs) are increasing in frequency and severity, underscoring the importance of understanding potential top-down controls of blooms. In the Indian River Lagoon (IRL), a shallow subtropical estuary, one harmful bloom was co-dominated by an unresolved prochlorophyte in the Family Prochlorothricaceae, which reached densities of > 106 cells ml–1 engendering the term “Superbloom.” Experiments were conducted to evaluate grazing rates and the potential for top-down control by an abundant herbivorous copepod, Parvocalanus crassirostris, on the prochlorophyte. Those grazing rates were lower than the rates on a palatable alternative algal food, Isochrysis galbana, when both algal species were presented in monocultures with identical densities. Grazing on the prochlorophyte decreased or ceased at densities over 4.8 × 105 cells ml–1. When the prochlorophyte and the palatable alternative each comprised half of the total density, both species were consumed, but grazing on I. galbana was reduced compared to the grazing rates in a monoculture of this species, especially at higher cell densities. Copepod mortality was observed in treatments with high concentrations of the prochlorophyte, and these treatments contained mucilage. Experiments simulating viscosities produced by prochlorophyte mucilage yielded results consistent with the original grazing experiments (i.e., copepods showed lower grazing rates and higher mortality rates in higher viscosity treatments). Results reveal potential limitations of top-down controls by this grazer on prochlorophyte blooms and HABs that produce mucilage.

Summary: The transplantation of human embryonic stem cell (hESC)-derived insulin-producing β cells for the treatment of diabetes is finally approaching the clinical stage. However, even with state-of-the-art differentiation protocols, a significant percentage of undefined non-endocrine cell types are still generated. Most importantly, there is the potential for carry-over of non-differentiated cell types that may produce teratomas. We sought to modify hESCs so that their differentiated progeny could be selectively devoid of tumorigenic cells and enriched for cells of the desired phenotype (in this case, β cells). Here we report the generation of a modified hESC line harboring two suicide gene cassettes, whose expression results in cell death in the presence of specific pro-drugs. We show the efficacy of this system at enriching for β cells and eliminating tumorigenic ones both in vitro and in vivo. Our approach is innovative inasmuch as it allows for the preservation of the desired cells while eliminating those with the potential to develop teratomas. : In this article, Domínguez-Bendala and colleagues present a strategy to modify pluripotent stem cells to allow for the selective destruction of tumorigenic escapees and/or fully developed teratomas, as well as for the specific selection of differentiated insulin-producing β-like cells. Cells engineered in this manner feature a double fail-safe mechanism designed to minimize the risks associated with their clinical transplantation. Keywords: human embryonic stem cells, beta cell differentiation, suicide genes, teratoma, transplantation

Harmful blooms of nanophytoplankton (2–20 μm) are increasingly common and sometimes severe, but requirements and controls of such blooms (e.g., water quality constraints, requirements for nutrients, and the presence of different guilds of grazers) are poorly understood. Laboratory grazing experiments were conducted to evaluate the potential for top-down control by the copepod Parvocalanus crassirostris on a small harmful algal species (an unidentified chlorophyte Picochlorum, 1–4 μm) and to test the effects of cell sizes on grazing rates. The Picochlorum sp. is a strain isolated from a long-lasting harmful algal bloom in the Indian River Lagoon that reached high densities (>1 × 106 cells ml–1). Experiments contrasted grazing on Picochlorum sp. with grazing on the palatable prymnesiophyte Isochrysis galbana (4–6 μm) in monocultures and mixed cultures. When presented in monocultures, grazing rates on Picochlorum sp. were lower than grazing rates on the palatable alternative. When Picochlorum sp. were presented alongside I. galbana, copepods essentially ceased feeding on the former. In additional experiments, P. crassirostris were fed plastic beads with diameters of 2.0–17.9 μm to control for differences in taste, toxicity, production of mucilage and shape of potential food. Paracalanus crassirostris fed most efficiently on beads with diameters of 7.0–7.9 μm. Results revealed that P. crassirostris can consume Picochlorum sp., but small size and the presence of palatable cells reduces the likelihood of top-down control of blooms of Picochlorum sp.