An equity and environmental justice assessment of anti-science actions during the Trump administration.

In the United States, science shapes federal health and safety protections, but political officials can and do politicize federal science and science-based safeguards. Many presidential administrations have politicized science, but under the administration of President Trump, these attacks on science-such as buried research, censored scientists, halted data collection-increased in number to unprecedented levels. Underserved communities bore the brunt of the harms. Such attacks disproportionately harm Black, Indigenous, low-income communities, and communities of color, all of whom have long been burdened by pollution exposure and other stressors. We analyze the effects on underserved communities of the Trump administration's anti-science environmental and public health policy actions and offer policy recommendations for current and future administrations. Our goal is to strengthen scientific integrity, prioritize health disparity research, and meaningfully engage affected communities in federal rulemaking.

Perceived losses of scientific integrity under the Trump administration: A survey of federal scientists.

President Trump and his administration have been regarded by news outlets and scholars as one of the most hostile administrations towards scientists and their work. However, no study to-date has empirically measured how federal scientists perceive the Trump administration with respect to their scientific work. In 2018, we distributed a survey to over 63,000 federal scientists from 16 federal agencies to assess their perception of scientific integrity. Here we discuss the results of this survey for a subset of these agencies: Department of Interior (DOI) agencies (the US Fish and Wildlife Service (FWS), the US Geological Survey, and the National Park Service); the Centers for Disease Control and Prevention (CDC); the US Environmental Protection Agency (EPA); the Food and Drug Administration (FDA); and the National Oceanic and Atmospheric Administration (NOAA). We focus our analysis to 10 key questions fitting within three core categories that relate to perceptions of integrity in science. Additionally, we analyzed responses across agencies and compare responses in the 2018 survey to prior year surveys of federal scientists with similar survey questions. Our results indicate that federal scientists perceive losses of scientific integrity under the Trump Administration. Perceived loss of integrity in science was greater at the DOI and EPA where federal scientists ranked incompetent and untrustworthy leadership as top barriers to science-based decision-making, but this was not the case at the CDC, FDA, and NOAA where scientists positively associated leadership with scientific integrity. We also find that reports of political interference in scientific work and adverse work environments were higher at EPA and FWS in 2018 than in prior years. We did not find similar results at the CDC and FDA. These results suggest that leadership, positive work environments, and clear and comprehensive scientific integrity policies and infrastructure within agencies play important roles in how federal scientists perceive their agency's scientific integrity.

Public Perceptions on the Influence of Diet and Kidney Stone Formation.

Introduction: Public awareness regarding the influence of diet on kidney stones is unknown. We sought to evaluate such perceptions among an unselected community cohort. Materials and Methods: A survey was created to assess perception of beverages/foods on risk of kidney stone formation. Surveys were distributed to attendees of a State Fair. Participants were categorized to determine the effect of stone history on prevention knowledge (no prior stone vs prior stone). Results: Seven hundred fifty-three participants completed the survey, including 264 (35%) with a prior stone. Participants with prior stones were less likely to believe stones were preventable compared to those without (56% vs 65%, p = 0.01). Appropriate perceptions regarding influence of diet on stones were highest for water (>90% of participants) and cola/salt/red meat (>50%). Fewer than half of respondents correctly identified the influence of the remaining 14 substances. On multivariable analysis, stone formers were more likely to correctly identify the influence of lemonade (odds ratio [OR] 2.09; 95% confidence interval [CI] 1.32-3.31), nuts (OR 2.60; 95% CI 1.60-4.23), and spinach (OR 5.06; 95% CI 2.89-8.86), but less likely to identify the influence of coffee (OR 0.43; 95% CI 0.23-0.82) and red meat (OR 0.52; 95% CI 0.23-0.59). Conclusion: Patients with prior stones hold different attitudes regarding the influence of certain foods and drinks on stone formation relative to the public. Such attitudes are not always correct, and as a group they are less likely to believe in dietary stone prevention. Such findings may indicate confusion among stone formers and highlight an opportunity for improved dietary counseling.

Potential patient harms from misinterpretation of publically reported surgical outcomes.

OBJECTIVE: To determine how the general public interprets surgical complication rates presented from a publicly available online surgical-rating website. SUBJECTS AND METHODS: An in-person electronic survey was administered at the local State Fair to a convenience sample. Participants were presented with a representative output from an online surgeon-rating website and were asked to choose from three statistically equivalent surgeons for a hypothetical medical decision. We then suggested that their insurance company would only cover one surgeon and probed their willingness to pay to switch surgeons for a small chance of lowering the risk of a complication (0.7%, 95% confidence interval [CI] -8.1% to 9.5%, P = 0.9). We quantified the characteristics of those willing to switch, the degree of misinterpretation, and the subsequent potential patient harms. RESULTS: There were 343 completed responses. When presented with a hypothetical healthcare decision, most participants (n = 209, 61%) said they were willing to pay out-of-pocket expenses to switch to a statistically equivalent surgeon. Those who were willing to pay to switch surgeons were more likely to be older (odds ratio [OR] 1.02, 95% CI 1.01-1.03), poorer (OR 1.81, 95% CI 1.07-3.11), previously had cancer (OR 5.9, 95% CI 1.9-25), and misinterpreted the data (OR 3.03, 95% CI 1.87-4.96). Those who were willing to pay out-of-pocket expenses were more inaccurate in their estimation of surgeon complication rates (mean estimate 34.0% vs 8.9%, P < 0.001, correct rate = 3.6%), and on average were willing to pay $6 494 (95% CI 4 108-8 880). CONCLUSION: Understanding of a publicly reported surgical-complication website is often prone to misinterpretation by the general population and may lead to patient harm from a financial aspect.

3D microfluidic ex vivo culture of organotypic tumor spheroids to model immune checkpoint blockade.

Microfluidic culture has the potential to revolutionize cancer diagnosis and therapy. Indeed, several microdevices are being developed specifically for clinical use to test novel cancer therapeutics. To be effective, these platforms need to replicate the continuous interactions that exist between tumor cells and non-tumor cell elements of the tumor microenvironment through direct cell-cell or cell-matrix contact or by the secretion of signaling factors such as cytokines, chemokines and growth factors. Given the challenges of personalized or precision cancer therapy, especially with the advent of novel immunotherapies, a critical need exists for more sophisticated ex vivo diagnostic systems that recapitulate patient-specific tumor biology with the potential to predict response to immune-based therapies in real-time. Here, we present details of a method to screen for the response of patient tumors to immune checkpoint blockade therapy, first reported in Jenkins et al. Cancer Discovery, 2018, 8, 196-215, with updated evaluation of murine- and patient-derived organotypic tumor spheroids (MDOTS/PDOTS), including evaluation of the requirement for 3D microfluidic culture in MDOTS, demonstration of immune-checkpoint sensitivity of PDOTS, and expanded evaluation of tumor-immune interactions using RNA-sequencing to infer changes in the tumor-immune microenvironment. We also examine some potential improvements to current systems and discuss the challenges in translating such diagnostic assays to the clinic.

Molecular and Genomic Determinants of Response to Immune Checkpoint Inhibition in Cancer.

Molecularly targeted therapy and immunotherapy have dramatically changed the landscape of available treatment options for patients with advanced cancer. Improved understanding of the molecular and genomic features of cancers over the last decade has led to the development of successful targeted therapies and the field of precision cancer medicine. As a result of these advances, patients whose tumors harbor select molecular alterations are eligible for treatment with targeted therapies active against the unique molecular aberration. Concurrently, advances in tumor immunology have led to the development of immunomodulatory antibodies targeting T cell coinhibitory receptors CTLA-4 and PD-1 (programmed death-1) that have shown activity in several cancer histologies, reinvigorating antitumor immune responses in a subset of patients. These immunomodulatory antibodies offer the promise of durable disease control. However, discrete genomic determinants of response to cancer immunotherapy, unlike molecularly targeted therapies, have remained elusive, and robust biomarkers are lacking. Recent advances in tumor profiling have begun to identify novel genomic features that may influence response and resistance to cancer immunotherapy, including tumor mutational burden (e.g., microsatellite instability), copy-number alterations, and specific somatic alterations that influence immune recognition and response. Further investigation into the molecular and genomic features of response and resistance to cancer immunotherapy will be needed. We review the recent advances in understanding the molecular and genomic determinants of response to cancer immunotherapy, with an emphasis on immune checkpoint inhibitors.

Warmest extreme year in U.S. history alters thermal requirements for tree phenology.

The frequency of extreme warm years is increasing across the majority of the planet. Shifts in plant phenology in response to extreme years can influence plant survival, productivity, and synchrony with pollinators/herbivores. Despite extensive work on plant phenological responses to climate change, little is known about responses to extreme warm years, particularly at the intraspecific level. Here we investigate 43 populations of white ash trees (Fraxinus americana) from throughout the species range that were all grown in a common garden. We compared the timing of leaf emergence during the warmest year in U.S. history (2012) with relatively non-extreme years. We show that (a) leaf emergence among white ash populations was accelerated by 21 days on average during the extreme warm year of 2012 relative to non-extreme years; (b) rank order for the timing of leaf emergence was maintained among populations across extreme and non-extreme years, with southern populations emerging earlier than northern populations; (c) greater amounts of warming units accumulated prior to leaf emergence during the extreme warm year relative to non-extreme years, and this constrained the potential for even earlier leaf emergence by an average of 9 days among populations; and (d) the extreme warm year reduced the reliability of a relevant phenological model for white ash by producing a consistent bias toward earlier predicted leaf emergence relative to observations. These results demonstrate a critical need to better understand how extreme warm years will impact tree phenology, particularly at the intraspecific level.

BioCreative V BioC track overview: collaborative biocurator assistant task for BioGRID.

BioC is a simple XML format for text, annotations and relations, and was developed to achieve interoperability for biomedical text processing. Following the success of BioC in BioCreative IV, the BioCreative V BioC track addressed a collaborative task to build an assistant system for BioGRID curation. In this paper, we describe the framework of the collaborative BioC task and discuss our findings based on the user survey. This track consisted of eight subtasks including gene/protein/organism named entity recognition, protein-protein/genetic interaction passage identification and annotation visualization. Using BioC as their data-sharing and communication medium, nine teams, world-wide, participated and contributed either new methods or improvements of existing tools to address different subtasks of the BioC track. Results from different teams were shared in BioC and made available to other teams as they addressed different subtasks of the track. In the end, all submitted runs were merged using a machine learning classifier to produce an optimized output. The biocurator assistant system was evaluated by four BioGRID curators in terms of practical usability. The curators' feedback was overall positive and highlighted the user-friendly design and the convenient gene/protein curation tool based on text mining.Database URL: http://www.biocreative.org/tasks/biocreative-v/track-1-bioc/.

Argo: enabling the development of bespoke workflows and services for disease annotation.

Argo (http://argo.nactem.ac.uk) is a generic text mining workbench that can cater to a variety of use cases, including the semi-automatic annotation of literature. It enables its technical users to build their own customised text mining solutions by providing a wide array of interoperable and configurable elementary components that can be seamlessly integrated into processing workflows. With Argo's graphical annotation interface, domain experts can then make use of the workflows' automatically generated output to curate information of interest.With the continuously rising need to understand the aetiology of diseases as well as the demand for their informed diagnosis and personalised treatment, the curation of disease-relevant information from medical and clinical documents has become an indispensable scientific activity. In the Fifth BioCreative Challenge Evaluation Workshop (BioCreative V), there was substantial interest in the mining of literature for disease-relevant information. Apart from a panel discussion focussed on disease annotations, the chemical-disease relations (CDR) track was also organised to foster the sharing and advancement of disease annotation tools and resources.This article presents the application of Argo's capabilities to the literature-based annotation of diseases. As part of our participation in BioCreative V's User Interactive Track (IAT), we demonstrated and evaluated Argo's suitability to the semi-automatic curation of chronic obstructive pulmonary disease (COPD) phenotypes. Furthermore, the workbench facilitated the development of some of the CDR track's top-performing web services for normalising disease mentions against the Medical Subject Headings (MeSH) database. In this work, we highlight Argo's support for developing various types of bespoke workflows ranging from ones which enabled us to easily incorporate information from various databases, to those which train and apply machine learning-based concept recognition models, through to user-interactive ones which allow human curators to manually provide their corrections to automatically generated annotations. Our participation in the BioCreative V challenges shows Argo's potential as an enabling technology for curating disease and phenotypic information from literature.Database URL: http://argo.nactem.ac.uk.

Text Mining the History of Medicine.

Historical text archives constitute a rich and diverse source of information, which is becoming increasingly readily accessible, due to large-scale digitisation efforts. However, it can be difficult for researchers to explore and search such large volumes of data in an efficient manner. Text mining (TM) methods can help, through their ability to recognise various types of semantic information automatically, e.g., instances of concepts (places, medical conditions, drugs, etc.), synonyms/variant forms of concepts, and relationships holding between concepts (which drugs are used to treat which medical conditions, etc.). TM analysis allows search systems to incorporate functionality such as automatic suggestions of synonyms of user-entered query terms, exploration of different concepts mentioned within search results or isolation of documents in which concepts are related in specific ways. However, applying TM methods to historical text can be challenging, according to differences and evolutions in vocabulary, terminology, language structure and style, compared to more modern text. In this article, we present our efforts to overcome the various challenges faced in the semantic analysis of published historical medical text dating back to the mid 19th century. Firstly, we used evidence from diverse historical medical documents from different periods to develop new resources that provide accounts of the multiple, evolving ways in which concepts, their variants and relationships amongst them may be expressed. These resources were employed to support the development of a modular processing pipeline of TM tools for the robust detection of semantic information in historical medical documents with varying characteristics. We applied the pipeline to two large-scale medical document archives covering wide temporal ranges as the basis for the development of a publicly accessible semantically-oriented search system. The novel resources are available for research purposes, while the processing pipeline and its modules may be used and configured within the Argo TM platform.

Partial Nephrectomy for a Massive Sporadic Renal Angiomyolipoma: Case Report and Review of the Literature.

Introduction. Angiomyolipomas are the most common benign tumor of the kidney, associated with Tuberous Sclerosis in 20% of cases and arising sporadically in 80% of cases. Renal angiomyolipomas are neoplasms of mesenchymal origin with varying proportions of vasculature, smooth muscle spindle cells, and adipocytes, making management of such neoplasms a challenging endeavor. Possible management options include partial or radical nephrectomy and segmental renal artery embolization. Case Presentation. A 61-year-old woman admitted for a large retroperitoneal hemorrhage was discovered to have a giant, sporadic, 3818.3 g, 30.0 × 26.5 × 18.0 cm left perinephric angiomyolipoma. Given her hemodynamic instability upon presentation, she underwent segmental arterial embolization, followed by an open left partial nephrectomy. Ten-month follow-up revealed no noticeable loss of renal function. Discussion. Literature review revealed occasional renal angiomyolipomas of comparable size, with all angiomyolipomas larger than this requiring treatment with radical nephrectomy. Conclusion. We show that nephron-sparing surgery may be considered in the treatment of even the largest of renal angiomyolipomas.

Testing the evolutionary conservation of vocal motoneurons in vertebrates.

Medullary motoneurons drive vocalization in many vertebrate lineages including fish, amphibians, birds, and mammals. The developmental history of vocal motoneuron populations in each of these lineages remains largely unknown. The highly conserved transcription factor Paired-like Homeobox 2b (Phox2b) is presumed to be expressed in all vertebrate hindbrain branchial motoneurons, including laryngeal motoneurons essential for vocalization in humans. We used immunohistochemistry and in situ hybridization to examine Phox2b protein and mRNA expression in caudal hindbrain and rostral spinal cord motoneuron populations in seven species across five chordate classes. Phox2b was present in motoneurons dedicated to sound production in mice and frogs (bullfrog, African clawed frog), but not those in bird (zebra finch) or bony fish (midshipman, channel catfish). Overall, the pattern of caudal medullary motoneuron Phox2b expression was conserved across vertebrates and similar to expression in sea lamprey. These observations suggest that motoneurons dedicated to sound production in vertebrates are not derived from a single developmentally or evolutionarily conserved progenitor pool.

SciLite: a platform for displaying text-mined annotations as a means to link research articles with biological data.

The tremendous growth in biological data has resulted in an increase in the number of research papers being published. This presents a great challenge for scientists in searching and assimilating facts described in those papers. Particularly, biological databases depend on curators to add highly precise and useful information that are usually extracted by reading research articles. Therefore, there is an urgent need to find ways to improve linking literature to the underlying data, thereby minimising the effort in browsing content and identifying key biological concepts.   As part of the development of Europe PMC, we have developed a new platform, SciLite, which integrates text-mined annotations from different sources and overlays those outputs on research articles. The aim is to aid researchers and curators using Europe PMC in finding key concepts more easily and provide links to related resources or tools, bridging the gap between literature and biological data.

Text-mining-assisted biocuration workflows in Argo.

Biocuration activities have been broadly categorized into the selection of relevant documents, the annotation of biological concepts of interest and identification of interactions between the concepts. Text mining has been shown to have a potential to significantly reduce the effort of biocurators in all the three activities, and various semi-automatic methodologies have been integrated into curation pipelines to support them. We investigate the suitability of Argo, a workbench for building text-mining solutions with the use of a rich graphical user interface, for the process of biocuration. Central to Argo are customizable workflows that users compose by arranging available elementary analytics to form task-specific processing units. A built-in manual annotation editor is the single most used biocuration tool of the workbench, as it allows users to create annotations directly in text, as well as modify or delete annotations created by automatic processing components. Apart from syntactic and semantic analytics, the ever-growing library of components includes several data readers and consumers that support well-established as well as emerging data interchange formats such as XMI, RDF and BioC, which facilitate the interoperability of Argo with other platforms or resources. To validate the suitability of Argo for curation activities, we participated in the BioCreative IV challenge whose purpose was to evaluate Web-based systems addressing user-defined biocuration tasks. Argo proved to have the edge over other systems in terms of flexibility of defining biocuration tasks. As expected, the versatility of the workbench inevitably lengthened the time the curators spent on learning the system before taking on the task, which may have affected the usability of Argo. The participation in the challenge gave us an opportunity to gather valuable feedback and identify areas of improvement, some of which have already been introduced. Database URL: http://argo.nactem.ac.uk.

Processing biological literature with customizable Web services supporting interoperable formats.

Web services have become a popular means of interconnecting solutions for processing a body of scientific literature. This has fuelled research on high-level data exchange formats suitable for a given domain and ensuring the interoperability of Web services. In this article, we focus on the biological domain and consider four interoperability formats, BioC, BioNLP, XMI and RDF, that represent domain-specific and generic representations and include well-established as well as emerging specifications. We use the formats in the context of customizable Web services created in our Web-based, text-mining workbench Argo that features an ever-growing library of elementary analytics and capabilities to build and deploy Web services straight from a convenient graphical user interface. We demonstrate a 2-fold customization of Web services: by building task-specific processing pipelines from a repository of available analytics, and by configuring services to accept and produce a combination of input and output data interchange formats. We provide qualitative evaluation of the formats as well as quantitative evaluation of automatic analytics. The latter was carried out as part of our participation in the fourth edition of the BioCreative challenge. Our analytics built into Web services for recognizing biochemical concepts in BioC collections achieved the highest combined scores out of 10 participating teams. Database URL: http://argo.nactem.ac.uk.

Saccular ascending aortic aneurysm arising within localized chronic dissection.

An asymptomatic saccular ascending aortic aneurysm was diagnosed during workup for renal transplantation in a 39-year-old man. At operation, the aneurysm was noted to arise from within a localized and healed dissection, and was managed by ascending aortic replacement and sinotubular junction refashioning.

Iatrogenic tracheal rupture: bovine pericardial patch repair without flap reinforcement.

We describe a case of an extensive post-intubation membranous tracheal rupture in a 67-year old patient after emergency intubation. This was managed surgically by bovine pericardial patch repair. Other cases of autologous and bovine patch repair of tracheal lacerations exist in the literature, and we believe this is the first report of successful bovine patch repair without accessory autologous tissue reinforcement. This technique may be used in surgically managed cases of membranous tracheal rupture where primary repair is unsuitable, thereby reducing procedural complexity.