tbuckley/cabot-search huggingface dataset:
The Cancer Care Treatment Outcomes Ontology (CCTO): A computable ontology for profiling treatment outcomes of patients with solid tumors.
Authors: Frank Po-Yen Lin, Tudor Groza, Simon Kocbek, Erick Antezana, Richard J Epstein
Journal: Journal of Clinical Oncology (2017)

e18137 Background: Systematic enhancement of knowledge about outcomes of cancer therapy is a central goal for oncology research, practice and audit. However, there is no resource standardizing the disparate vocabulary used to describe treatment outcomes, which prevents translating the data acquired into value-adding information for better cancer care. Methods: To build an application ontology that organizes high-level concepts describing treatment outcomes in solid tumors, provisionally named Cancer Care Treatment Outcomes (CCTO), we extracted all trial endpoints listed in ClinicalTrials.gov, queried it using the keyword ‘cancer’, followed by an expert appraisal. Term definitions and synonyms were automatically imported from the National Cancer Institute thesaurus, and extra terms were imported from Common Toxicity Criteria for Adverse Events. Logical relationships between concepts were represented by forward chaining rules, aiding conversion between concepts. The coverage of CCTO was tested against MEDLINE abstracts, and the applicability of 1825 rules was tested in a case of metastatic colon cancer (index case). Results: After removing duplicated terms from 54705 trial entries, an ontology (CCTO), holding 1145 terms and organized into 13 concept groups (including but not limited to efficacy, safety, and quality of life), was built. CCTO not only captures a comprehensive taxonomic hierarchy (through is_a relationships) but also an evaluative hierarchy ( is_assessed_by) to aid the acquisition of treatment outcome data. At least one CCTO term was mentioned in 29493 of 29951 (98%) MEDLINE abstracts on phase 1-3 cancer trials; concepts about efficacy were mentioned in 7208 (79%) phase 1, 15051 (92%) phase 2, and 3884 (86%) phase 3 trials. We show that, by applying the relationship rules in an expert system shell, the event sequence of the index case can be readily converted into a comprehensive profile that incorporates survival measures, treatment responses, and adverse events. Conclusions: CCTO efficiently captures and categorizes high-level concepts of treatment endpoints in oncologic practice and enables rapid profiling of clinical outcomes for cancer patients.
Abstract 308: Differential Regulation of Alpha1a-adrenergic Receptor and its Genetic Variant Signaling by Novel Spinophilin-RGS2 Signalosome in Human Cells
Authors: Ekaterina Babaeva, Irina Gradinaru, Debra A Schwinn, Anush Oganesian
Journal: Circulation Research (2016)

α 1- adrenergic receptors (α 1a , α 1b , α 1d ), members of G protein-coupled receptor (GPCR) family, regulate stress-facilitated changes in the cardiovascular (CV) system and human blood pressure (BP) via smooth muscle cell (SMC) proliferation and vasoconstriction. The α 1a AR is the predominant subtype in human heart and resistance vessels. The α 1a AR G247R (247R) genetic variant was discovered in a patient with severe hypertension and in a cohort of patients enriched for CV disorders. We reported a unique coupling of this genetic variant to βarrestin/MMP/EGFR transactivation pathway in rat fibroblasts, cardiomyoblasts and vascular SMCs leading to hyperproliferation and hypertrophy. Here we present that differential interaction of 247R or α 1a AR (WT) with scaffolding/regulatory proteins mediate unique signaling of 247R. Physiological levels of 247R but not WT upregulate endogenous levels of scaffolding protein spinophilin (SPL) in rat SMCs and cardiomyoblasts. SPL knockdown or overexpression of RGS2 (negative R egulators of G -protein S ignaling) inhibits 247R-mediated hyperproliferation. Overexpression of SPL with RGS2 restores hyperproliferation suggesting that SPL binds RGS2 and prevents 247R-RGS2 interaction. To determine if 247R hyperproliferation is in effect in human cells, we generated human iPSCs from primary fibroblasts and differentiated them to SMCs with characteristic morphology and expression of SMC markers (RT-PCR at various passages). Consistent with our findings in rat cells, expression of 247R but not WT in hiPSC-derived SMCs triggered ~70% increased proliferation. Agonist treatment resulted in increased hypertrophy in 247R cells compared with WT. Co-immunoprecipitation from HEK293 cells expressing HA-α 1 ARs and full length Myc-SPL or Flag-RGS2 revealed that SPL exhibits ~2-fold stronger interaction with WT than with 247R. Consequently, SPL recruits RGS2 and inhibits receptor signaling. In contrast, weaker SPL-247R interaction results in diminished RGS2 inhibitory effect allowing hyperproliferation of 247R cells. Thus, we identify novel SPL/RGS2 signalosome responsible for α 1a AR signaling in human cells and identify SPL as a potential novel target for treatment of α 1 AR-mediated human CV disorders.
Measurable residual disease in chronic lymphocytic leukemia: expert review and consensus recommendations
Authors: William G. Wierda, Andrew Rawstron, Florence Cymbalista, Xavier Badoux, Davide Rossi, Jennifer R. Brown, Alexander Egle, Virginia Abello, Eduardo Cervera Ceballos, Yair Herishanu, Stephen P. Mulligan, Carsten U. Niemann, Colin P. Diong, Teoman Soysal, Ritsuro Suzuki, Hoa T. T. Tran, Shang-Ju Wu, Carolyn Owen, Stephan Stilgenbauer, Paolo Ghia, Peter Hillmen
Journal: Leukemia (2021)

Abstract Assessment of measurable residual disease (often referred to as “minimal residual disease”) has emerged as a highly sensitive indicator of disease burden during and at the end of treatment and has been correlated with time-to-event outcomes in chronic lymphocytic leukemia. Undetectable-measurable residual disease status at the end of treatment demonstrated independent prognostic significance in chronic lymphocytic leukemia, correlating with favorable progression-free and overall survival with chemoimmunotherapy. Given its utility in evaluating depth of response, determining measurable residual disease status is now a focus of outcomes in chronic lymphocytic leukemia clinical trials. Increased adoption of measurable residual disease assessment calls for standards for nomenclature and outcomes data reporting. In addition, many basic questions have not been systematically addressed. Here, we present the work of an international, multidisciplinary, 174-member panel convened to identify critical questions on key issues pertaining to measurable residual disease in chronic lymphocytic leukemia, review evaluable data, develop unified answers in conjunction with local expert input, and provide recommendations for future studies. Recommendations are presented regarding methodology for measurable residual disease determination, assay requirements and in which tissue to assess measurable residual disease, timing and frequency of assessment, use of measurable residual disease in clinical practice versus clinical trials, and the future usefulness of measurable residual disease assessment. Nomenclature is also proposed. Adoption of these recommendations will work toward standardizing data acquisition and interpretation in future studies with new treatments with the ultimate objective of improving outcomes and curing chronic lymphocytic leukemia.
Covalent linkage of sulfated hyaluronan to the collagen scaffold Mucograft® enhances scaffold stability and reduces proinflammatory macrophage activation in vivo
Authors: Sarah Al-Maawi, Sandra Rother, Norbert Halfter, Karen M. Fiebig, Juliane Moritz, Stephanie Moeller, Matthias Schnabelrauch, Charles James Kirkpatrick, Robert Sader, Hans-Peter Wiesmann, Dieter Scharnweber, Vera Hintze, Shahram Ghanaati
Journal: Bioactive Materials (2021)

Sulfated glycosaminoglycans (sGAG) show interaction with biological mediator proteins. Although collagen-based biomaterials are widely used in clinics, their combination with high-sulfated hyaluronan (sHA3) is unexplored. This study aims to functionalize a collagen-based scaffold (Mucograft®) with sHA3 via electrostatic (sHA3/PBS) or covalent binding to collagen fibrils (sHA3+EDC/NHS). Crosslinking without sHA3 was used as a control (EDC/NHS Ctrl). The properties of the sHA3-functionalized materials were characterized. In vitro growth factor and cytokine release after culturing with liquid platelet-rich fibrin was performed by means of ELISA. The cellular reaction to the biomaterials was analyzed in a subcutaneous rat model. The study revealed that covalent linking of sHA3 to collagen allowed only a marginal release of sHA3 over 28 days in contrast to electrostatically bound sHA3. sHA3+EDC/NHS scaffolds showed reduced vascular endothelial growth factor (VEGF), transforming growth factor beta 1 (TGF-β1) and enhanced interleukin-8 (IL-8) and epithelial growth factor (EGF) release in vitro compared to the other scaffolds. Both sHA3/PBS and EDC/NHS Ctrl scaffolds showed a high proinflammatory reaction (M1: CD-68+/CCR7+) and induced multinucleated giant cell (MNGC) formation in vivo. Only sHA3+EDC/NHS scaffolds reduced the proinflammatory macrophage M1 response and did not induce MNGC formation during the 30 days. SHA3+EDC/NHS scaffolds had a stable structure in vivo and showed sufficient integration into the implantation region after 30 days, whereas EDC/NHS Ctrl scaffolds underwent marked disintegration and lost their initial structure. In summary, functionalized collagen (sHA3+EDC/NHS) modulates the inflammatory response and is a promising biomaterial as a stable scaffold for full-thickness skin regeneration in the future.
Dose Dependent Effect of Strong Lipophilic Statin on Cardiac Structure and Function in Patients with Coronary Artery Disease
Authors: Miwa Hirotaka, Kawasaki Masanori, Tanaka Ryuhei, Ono Koji, Watanabe Takatomo, Yoshizane Takashi, Yagasaki Hiroto, Tokoro Fumitaka, Matsuoka Reiko, Abe Shintaro, Goto Yoshiaki, Warita Shunichiro, Kojima Tai, Kawade Masafumi, Iwama Makoto, Hirose Takeshi, Tanihata Shintaro, Arai Masazumi, Noda Toshiyuki, Watanabe Sachiro, Minatoguchi Shinya
Journal: Circulation (2014)
Outcomes of Implantable Cardioverter-Defibrillator Use in Patients With Comorbidities
Authors: Benjamin A Steinberg, Sana M Al-Khatib, Rex Edwards, JooYoon Han, Gust H Bardy, J Thomas Bigger, Alfred E Buxton, Arthur J Moss, Kerry L Lee, Richard Steinman, Paul Dorian, Alfred Hallstrom, Riccardo Cappato, Alan H Kadish, Peter J Kudenchuk, Daniel B Mark, Lurdes Y T Inoue, Gillian D Sanders
Journal: JACC Heart Failure (2014)
T-cell engager antibodies enable T cells to control HBV infection and to target HBsAg-positive hepatoma in mice
Authors: Oliver Quitt, Shanshan Luo, Marten Meyer, Zhe Xie, Forough Golsaz-Shirazi, Eva Loffredo-Verde, Julia Festag, Jan Hendrik Bockmann, Lili Zhao, Daniela Stadler, Wen-Min Chou, Raindy Tedjokusumo, Jochen Martin Wettengel, Chunkyu Ko, Elfriede Noeßner, Nadja Bulbuc, Fazel Shokri, Sandra Lüttgau, Mathias Heikenwälder, Felix Bohne, Gerhard Moldenhauer, Frank Momburg, Ulrike Protzer
Journal: Journal of Hepatology (2021)
American Board of Medical Specialties Board Examination Lactation Accommodation Policies
Authors: Kevin T. Nead, Candice L. Hinkston, Eleni Linos, Sharon H. Giordano, Mackenzie R. Wehner
Journal: JAMA Internal Medicine (2021)

estimator tools required personal health plan information to access price or cost-sharing information; discounted cash prices could be viewed without plan information since they are not insurer-specific.Of the 100 highest-revenue hospitals, 75 (75%; 95% CI, 65%-83%) were noncompliant with at least 1 requirement (Figure).Only 35 reported payer-specific negotiated rates, and 40 reported discounted cash prices in a machinereadable file.A total of 86 offered a price estimator tool, of which 34 (39.5%) posted payer-specific negotiated rates in a machine-readable file.Discussion | As of March 2021, a small proportion of US hospitals were compliant with the major requirements of the new federal rule requiring disclosure of negotiated prices.Hospitals exhibited selectively higher compliance with the requirement of a price estimator for patients to view personalized out-of-pocket costs for shoppable services; a smaller proportion made their data fully accessible to the public by posting a machine-readable file with payer-specific negotiated rates.Selective compliance was especially pronounced for the 100 highest-revenue hospitals, a low proportion of which fully disclosed their negotiated rates despite high compliance with the price estimator tool requirement.Because patientoriented price estimator tools make prices visible only for a given patient and insurance plan and not to payers or the public, selective compliance may fail to expose abuses of market power, affect price negotiations, or support broad analysis of price variation to the extent intended by the transparency initiative.Policy makers could consider several strategies to improve compliance, including stiffer penalties, technical assistance, and public reporting of noncompliance.A limitation of this study is that the low overall compliance must be interpreted in context.We examined websites 65 to 70 days after the rule's implementation, and the rule took effect during the COVID-19 pandemic.The rule was finalized well before the pandemic, however, and the effective date was set in November 2019.
Эффективность применения Велоза в лечении пациентов с гастроэзофагеальной рефлюксной болезнью
Authors: Yu.M. Stepanov, I.Ya. Budzak
Journal: GASTROENTEROLOGY (2013)

В статье дан обзор клинических исследований, посвященных оценке эффективности рабепразола у больных с гастроэзофагеальной рефлюксной болезнью. Также приведены результаты собственных исследований эффективности генерического рабепразола — Велоза у пациентов с данной патологией. Результаты клинической оценки и данные рН-мониторинга показали эффективность Велоза.
Estimating the incidence of cocaine use and mortality with music lyrics about cocaine
Authors: Yulin Hswen, Amanda Zhang, John S. Brownstein
Journal: npj Digital Medicine (2021)

Abstract In the United States, cocaine use and mortality have surged in the past 5 years. Considering cocaine’s reputation as a fashionable social drug, the rise of cocaine mentions in popular music may provide a signal of epidemiological trends of cocaine use. We characterized the relationship between mentions of cocaine in song lyrics and incidence of cocaine use and mortality in the US. Incidence of cocaine use from 2002 to 2017 was obtained from the National Survey on Drug Use and Health and cocaine overdose mortality rate from 2000 to 2017 was obtained from the Centers for Disease Control. Distributed lag models were fit using ordinary least squares on the first difference to identify associations between changes in cocaine lyric mentions and changes in incidence of cocaine use and mortality. A total of 5955 song lyrics with cocaine mentions were obtained from Lyrics.com. Cocaine mentions in song lyrics were stable from 2000 to 2010 then increased by 190% from 2010 to 2017. The first-order distributed lag model estimated that a 0.01 increase in mentions of cocaine in song lyrics is associated with an 11% increase in incidence of cocaine use within the same year and a 14% increase in cocaine mortality with a 2-year lag. Lag-times were confirmed with cross-correlation analyses and the association remained after accounting for street pricing of cocaine. Mentions of cocaine in song lyrics are associated with the rise of incidence of cocaine use and cocaine overdose mortality. Popular music trends are a potentially valuable tool for understanding cocaine epidemiology trends.
Germline ATG2B/GSKIP-containing 14q32 duplication predisposes to early clonal hematopoiesis leading to myeloid neoplasms
Authors: Jean Pegliasco, Pierre Hirsch, Christophe Marzac, Françoise Isnard, Jean-Côme Meniane, Caroline Deswarte, Philippe Pellet, Céline Lemaitre, Gwendoline Leroy, Graciela Rabadan Moraes, Hélène Guermouche, Barbara Schmaltz-Panneau, Florence Pasquier, Chrystelle Colas, Patrick R. Benusiglio, Odile Bera, Jean-Henri Bourhis, Eolia Brissot, Olivier Caron, Samy Chraibi, Pascale Cony-Makhoul, Christine Delaunay-Darivon, Simona Lapusan, Flore Sicre de Fontbrune, Pascal Fuseau, Albert Najman, William Vainchenker, François Delhommeau, Jean-Baptiste Micol, Isabelle Plo, Christine Bellanné-Chantelot
Journal: Leukemia (2021)
Impact of COVID-19 on Diabetes Health Care and Service Provision in Australian Diabetes Centers
Authors: Matthew Quigley, Arul Earnest, Naomi Szwarcbard, Natalie Wischer, Sophia Zoungas
Journal: Diabetes Care (2021)

Coronavirus disease 2019 (COVID-19) has mandated substantive changes in health care provision to minimize the risk of transmission within health care facilities. Introduction of physical distancing, a heightened focus on hand hygiene and workplace cleanliness, and widespread moves to telehealth provision have been observed (1,2). However, little is known about the impact of the pandemic on provision of diabetes care in countries like Australia with universal health care coverage.

Because of mandated changes in clinical environments, we were unable to administer the scheduled Australian National Diabetes Audit (ANDA), a national annual benchmarking audit of diabetes center performance. In lieu of ANDA, we developed and administered the ANDA–COVID-19 service survey in consultation with the National Association of Diabetes Centres. The survey examined seven areas of service delivery: preparedness and ability to adapt to a crisis such as COVID-19; changes made to the health service space; challenges in delivery; changes in access to services from other health professionals and shortages of medications; and the impact on staffing as a result of COVID-19, workload in key clinical areas, and different modes of health care delivery. A health professional from each participating site was invited to complete the survey. Monash Health Human and Research Ethics Committee approved the study as an amendment to ANDA (LNR/17/MonH/123, amendment number AM/35106/MonH-2020-212691). …
Obesity Is Associated with Younger Age at Presentation and More Severe Cytopenias in Myelodysplastic Syndromes
Authors: Santiago Thibaud, Diego Adrianzen Herrera, Rosebella Snyder, Justin D. Kaner, Ioannis Mantzaris, Swati Goel, Amit Verma, Aditi Shastri
Journal: Blood (2017)
Incidence of immune checkpoint inhibitor–mediated diarrhea and colitis (imDC) in patients with cancer and preexisting inflammatory bowel disease: a propensity score–matched retrospective study
Authors: Joseph Sleiman, Wei Wei, Ravi Shah, Muhammad Salman Faisal, Jessica Philpott, Pauline Funchain
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background and aims The risk of use of immune-mediated diarrhea and colitis (imDC) in patients with preexisting inflammatory bowel disease (IBD) is not fully understood. We report the incidence of imDC in these patients, and compare with a matched cohort of patients with cancer and without IBD. Methods Patients with IBD from a tertiary center cancer registry who underwent immune checkpoint inhibitor (ICI) therapy from 2011 to 2019 were identified. A 1:5 matched cohort of patients with and without a history of IBD was created, based on age, ICI therapy, and cancer type. Demographic data, clinical history of IBD, cancer, ICI agent, imDC events after ICI therapy, and overall survival were analyzed. Overall survival and time-to-imDC (TTimDC) were estimated by Kaplan-Meier and multivariate Cox proportional-hazards models. Results From a retrospective cohort of 3900 patients who received ICI therapy, 30 patients with IBD were matched with 150 patients without a history of IBD. Most patients received PD-1/PD-L1 inhibitor monotherapy (154/180, 85.6%). Individuals with preexisting IBD showed significantly shorter TTimDC than those in the non-IBD group (1-year imDC-free rate 67% vs 93%; HR 7.59, 95% CI 3.00 to 19.15, p&lt;0.0001). Eleven (36%) from the IBD cohort experienced imDC events; none led to life-threatening conditions needing surgical interventions or death. Corticosteroids or biologics were needed in 8/11 (73%) patients, and discontinuation of therapy improved imDC in the remaining three. Half of patients required hospitalization. In contrast, no significant difference in overall survival was observed between IBD and non-IBD cohorts (HR 0.89, 95% CI 0.54 to 1.48). Both groups had overall comparable rates of other non-imDC immune-related adverse events. Conclusion Patients with preexisting IBD had worse time-to-imDC than non-IBD matched controls, yet did not exhibit worse overall survival. While close monitoring of patients with preexisting IBD is warranted while on immunotherapy, this comorbidity should not preclude ICI therapy if clinically required.
Using high-throughput multiple optical phenotyping to decipher the genetic architecture of maize drought tolerance
Authors: Xi Wu, Hui Feng, Di Wu, Shijuan Yan, Pei Zhang, Wenbin Wang, Jun Zhang, Junli Ye, Guoxin Dai, Yuan Fan, Weikun Li, Baoxing Song, Zedong Geng, Wanli Yang, Guoxin Chen, Feng Qin, William Terzaghi, Michelle Stitzer, Lin Li, Lizhong Xiong, Jianbing Yan, Edward Buckler, Wanneng Yang, Mingqiu Dai
Journal: Genome biology (2021)

Abstract Background Drought threatens the food supply of the world population. Dissecting the dynamic responses of plants to drought will be beneficial for breeding drought-tolerant crops, as the genetic controls of these responses remain largely unknown. Results Here we develop a high-throughput multiple optical phenotyping system to noninvasively phenotype 368 maize genotypes with or without drought stress over a course of 98 days, and collected multiple optical images, including color camera scanning, hyperspectral imaging, and X-ray computed tomography images. We develop high-throughput analysis pipelines to extract image-based traits (i-traits). Of these i-traits, 10,080 were effective and heritable indicators of maize external and internal drought responses. An i-trait-based genome-wide association study reveals 4322 significant locus-trait associations, representing 1529 quantitative trait loci (QTLs) and 2318 candidate genes, many that co-localize with previously reported maize drought responsive QTLs. Expression QTL (eQTL) analysis uncovers many local and distant regulatory variants that control the expression of the candidate genes. We use genetic mutation analysis to validate two new genes, ZmcPGM2 and ZmFAB1A , which regulate i-traits and drought tolerance. Moreover, the value of the candidate genes as drought-tolerant genetic markers is revealed by genome selection analysis, and 15 i-traits are identified as potential markers for maize drought tolerance breeding. Conclusion Our study demonstrates that combining high-throughput multiple optical phenotyping and GWAS is a novel and effective approach to dissect the genetic architecture of complex traits and clone drought-tolerance associated genes.
Clinical Outcomes for Patients With Anosmia 1 Year After COVID-19 Diagnosis
Authors: Marion Renaud, Claire Thibault, Floriane Le Normand, Emily G. Mcdonald, Benoît Gallix, Christian Debry, Aina Venkatasamy
Journal: JAMA Network Open (2021)

Underwent subjective and objective assessment 2 Included at 12-mo follow-up: reported partial recovery 46 Underwent subjective assessment only 49 Cumulative patients with total subjective recovery at 12 mo 32 Cumulative patients with total subjective recovery at 12 mo 29 Not evaluated at 4-mo follow-up From the initial cohort of 97 patients with polymerase chain reaction (PCR)-proven COVID-19 with acute olfactory disorders lasting for more than 7 days, 51 patients were followed up for a year, with subjective and objective olfactory assessment every 4 months, until normalization of objective olfactory test results.ENT indicates ear, nose, and throat.