tbuckley/cabot-search huggingface dataset:
Predicting keratinocyte carcinoma in patients with actinic keratosis: development and internal validation of a multivariable risk‐prediction model
Authors: S. Tokez, M. Alblas, T. Nijsten, L.M. Pardo, M. Wakkee
Journal: British Journal of Dermatology (2019)

Patients with actinic keratosis (AK) are at increased risk for developing keratinocyte carcinoma (KC) but predictive factors and their risk rates are unknown.To develop and internally validate a prediction model to calculate the absolute risk of a first KC in patients with AK.The risk-prediction model was based on the prospective population-based Rotterdam Study cohort. We hereto analysed the data of participants with at least one AK lesion at cohort baseline using a multivariable Cox proportional hazards model and included 13 a priori defined candidate predictor variables considering phenotypic, genetic and lifestyle risk factors. KCs were identified by linkage of the data with the Dutch Pathology Registry.Of the 1169 AK participants at baseline, 176 (15·1%) developed a KC after a median follow-up of 1·8 years. The final model with significant predictors was obtained after backward stepwise selection and comprised the presence of four to nine AKs [hazard ratio (HR) 1·68, 95% confidence interval (CI) 1·17-2·42], 10 or more AKs (HR 2·44, 95% CI 1·65-3·61), AK localization on the upper extremities (HR 0·75, 95% CI 0·52-1·08) or elsewhere except the head (HR 1·40, 95% CI 0·98-2·01) and coffee consumption (HR 0·92, 95% CI 0·84-1·01). Evaluation of the discriminative ability of the model showed a bootstrap validated concordance index (c-index) of 0·60.We showed that the risk of KC in patients with AK can be calculated with the use of four easily assessable predictor variables. Given the c-index, extension of the model with additional, currently unknown predictor variables is desirable. Linked Comment: Kim et al. Br J Dermatol 2020; 183:415-416.
Assessment of Variability in End-of-Life Care Delivery in Intensive Care Units in the United States
Authors: Jacqueline M. Kruser, David A. Aaby, David G. Stevenson, Brenda T. Pun, Michele C. Balas, Mary Ann Barnes-Daly, Lori Harmon, E. Wesley Ely
Journal: JAMA Network Open (2019)

Overall, 1 of 5 decedents in the United States is admitted to an intensive care unit (ICU) before death.To describe structures, processes, and variability of end-of-life care delivered in ICUs in the United States.This nationwide cohort study used data on 16 945 adults who were cared for in ICUs that participated in the 68-unit ICU Liberation Collaborative quality improvement project from January 2015 through April 2017. Data were analyzed between August 2018 and June 2019.Published quality measures and end-of-life events, organized by key domains of end-of-life care in the ICU.Of 16 945 eligible patients in the collaborative, 1536 (9.1%) died during their initial ICU stay. Of decedents, 654 (42.6%) were women, 1037 (67.5%) were 60 years or older, and 1088 (70.8%) were identified as white individuals. Wide unit-level variation in end-of-life care delivery was found. For example, the median unit-stratified rate of cardiopulmonary resuscitation avoidance in the last hour of life was 89.5% (interquartile range, 83.3%-96.1%; range, 50.0%-100%). Median rates of patients who were pain free and delirium free in last 24 hours of life were 75.1% (interquartile range, 66.0%-85.7%; range, 0-100%) and 60.0% (interquartile range, 43.7%-85.2%; range, 9.1%-100%), respectively. Ascertainment of an advance directive was associated with lower odds of cardiopulmonary resuscitation in the last hour of life (odds ratio, 0.70; 95% CI, 0.49-0.99; P = .04), and a documented offer or delivery of spiritual support was associated with higher odds of family presence at the time of death (odds ratio, 1.95; 95% CI, 1.37-2.77; P < .001). Death in a unit with an open visitation policy was associated with higher odds of pain in the last 24 hours of life (odds ratio, 2.21; 95% CI, 1.15-4.27; P = .02). Unsupervised cluster analysis revealed 3 mutually exclusive unit-level patterns of end-of-life care delivery among 63 ICUs with complete data. Cluster 1 units (14 units [22.2%]) had the lowest rate of cardiopulmonary resuscitation avoidance but achieved the highest pain-free rate. Cluster 2 (25 units [39.7%]) had the lowest delirium-free rate but achieved high rates of all other end-of-life events. Cluster 3 (24 units [38.1%]) achieved high rates across all favorable end-of-life events.In this study, end-of-life care delivery varied substantially among ICUs in the United States, and the patterns of care observed suggest that units can be characterized as higher and lower performing. To achieve optimal care for patients who die in an ICU, future research should target unit-level variation and disseminate the successes of higher-performing units.
First Results of Phase I/II Studies Evaluating Viral Vector-Based Heterologous Prime/Boost Immunotherapy Against Predicted HLA Class I Neoantigens Demonstrate CD8 T Cell Responses In Patients with Advanced Cancers
Authors: M.L. Johnson, A. Spira, D.P. Carbone, C. Drake, B. Henick, M. Ingham, K. Caldwell, S. Chan, M. Hart, A. Malloy, E. Maloney, C. Palmer, A. Yang, M. Zhong, P. Basciano, E. Bournazou, A.R. Ferguson, D. Catenacci
Journal: Annals of Oncology (2019)
The neuropeptide VIP confers anticipatory mucosal immunity by regulating ILC3 activity
Authors: Cyril Seillet, Kylie Luong, Julie Tellier, Nicolas Jacquelot, Rui Dong Shen, Peter Hickey, Verena C. Wimmer, Lachlan Whitehead, Kelly Rogers, Gordon K. Smyth, Alexandra L. Garnham, Matthew E. Ritchie, Gabrielle T. Belz
Journal: Nature Immunology (2019)
malERA: An updated research agenda for basic science and enabling technologies in malaria elimination and eradication
Journal: PLoS Medicine (2017)

Basic science holds enormous power for revealing the biological mechanisms of disease and, in turn, paving the way toward new, effective interventions. Recognizing this power, the 2011 Research Agenda for Malaria Eradication included key priorities in fundamental research that, if attained, could help accelerate progress toward disease elimination and eradication. The Malaria Eradication Research Agenda (malERA) Consultative Panel on Basic Science and Enabling Technologies reviewed the progress, continuing challenges, and major opportunities for future research. The recommendations come from a literature of published and unpublished materials and the deliberations of the malERA Refresh Consultative Panel. These areas span multiple aspects of the Plasmodium life cycle in both the human host and the Anopheles vector and include critical, unanswered questions about parasite transmission, human infection in the liver, asexual-stage biology, and malaria persistence. We believe an integrated approach encompassing human immunology, parasitology, and entomology, and harnessing new and emerging biomedical technologies offers the best path toward addressing these questions and, ultimately, lowering the worldwide burden of malaria.
A Novel Expression Profile of Cell Cycle and DNA Repair Proteins in Nonfunctioning Pituitary Adenomas
Authors: Derya Metin-Armagan, Nil Comunoglu, Gulay Bulut, Pinar Kadioglu, Hiraku Kameda, Nurperi Gazioglu, Necmettin Tanriover, Melek Ozturk
Journal: Endocrine Pathology (2019)
Abstract C26: Oncogenic mechanism of soluble keratin 17 offers potential therapeutic vulnerability in pancreatic cancer
Authors: Ryan R. Kawalerski, Lucia Roa-Pena, Luke A. Torre-Healy, Taryn Boyle, Cindy V. Leiton, Natasha T. Snider, Kenneth R. Shroyer, Luisa F. Escobar-Hoyos
Journal: Cancer Research (2019)

Abstract Clinical Need and Objectives: Our previous reports suggest that keratin 17 (K17), an intermediate filament (IF), is an oncoprotein and biomarker of the most aggressive and treatment-resistant form of pancreatic ductal adenocarcinoma (PDAC). Importantly, K17 transitions from its “insoluble” IF form to a “soluble” form that can regulate cell cycle progression and gene expression, though the mechanisms that mediate K17 solubilization are yet unknown. Determining these mechanisms may uncover new keratin 17-specific PDAC therapeutic vulnerabilities. Methods and Results: We found that in human and murine PDAC models, the soluble fraction of K17 exists in the full-length form (flK17) and as a caspase-cleaved peptide (ccK17), each with potential roles as biomarkers and/or functional drivers of PDAC aggression. In a PDAC tumor mouse model and human samples, we show, independent of total K17 protein amount, that the percent of soluble and ccK17 in tumor cells is negatively prognostic. We sequenced both the soluble and cytoskeletal insoluble forms of K17 from primary PDACs using liquid chromatography mass spectrometry (LC-MS) and identified that K17 is phosphorylated on several N-terminal serine residues, some of which identify a semiconserved IF motif that may regulate caspase cleavage and solubilization. Serine phosphatase inhibition in vitro demonstrated that phosphorylation is necessary to trigger K17 solubilization followed by nuclear translocation. Mutagenesis of N-terminal serine sites demonstrated that phosphorylation of three serine residues is sufficient to solubilize K17 from its filamentous state, and that phosphorylation of K17 by a PKC-RSK signaling pathway is likely to induce solubilization. In vitro and in vivo experiments are ongoing to address the functional role of this mechanism in regulating PDAC pathogenesis. Conclusion: Phosphorylation is an important regulator of K17 dynamics in PDAC, promoting solubilization and, in some cases, caspase cleavage. Our results suggest that soluble K17 may have a functional role in promoting tumor aggression. Inhibiting RSK or PKC kinases that phosphorylate K17 could impact tumor growth by blocking K17 solubilization/cleavage, and this line of research could accelerate the development of more effective treatments, coupled to soluble K17 testing as a predictive biomarker for PDAC. Citation Format: Ryan R. Kawalerski, Lucia Roa-Pena, Luke A. Torre-Healy, Taryn Boyle, Cindy V. Leiton, Natasha T. Snider, Kenneth R. Shroyer, Luisa F. Escobar-Hoyos. Oncogenic mechanism of soluble keratin 17 offers potential therapeutic vulnerability in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr C26.
Nanomedicine in treatment of breast cancer – A challenge to conventional therapy
Authors: Muhammad Afzal, None Ameeduzzafar, Khalid Saad Alharbi, Nabil K Alruwaili, Fahad A. Al-Abassi, Abdulrahman Al Labeed Al-Malki, Imran Kazmi, Vikas Kumar, Mohammad Amjad Kamal, Muhammad Shahid Nadeem, Muhammad Aslam, Firoz Anwar
Journal: Seminars in Cancer Biology (2019)
Erythropoiesis defect observed in STAT3 GOF patients with severe anemia
Authors: Andrea A. Mauracher, Julia J.M. Eekels, Janine Woytschak, Audrey van Drogen, Alessandra Bosch, Seraina Prader, Matthias Felber, Maximillian Heeg, Lennart Opitz, Johannes Trück, Silke Schroeder, Eva Adank, Adam Klocperk, Eugenia Haralambieva, Dieter Zimmermann, Sofia Tantou, Kosmas Kotsonis, Aikaterini Stergiou, Maria G. Kanariou, Stephan Ehl, Onur Boyman, Anna Sediva, Raffaele Renella, Markus Schmugge, Stefano Vavassori, Jana Pachlopnik Schmid
Journal: Journal of Allergy and Clinical Immunology (2019)
B-cell clusters in the stroma at invasive tumour margin provide prognostic value in early-Stage oral-tongue cancer patients: The discovery and validation study
Authors: C. Phanthunane, R. Wijers, M. De Herdt, J. Hardillo, S. Sleijfer, S. Koljenovic, S. Desgupta, E. Balcioglu, R. Debets, R.J. Baatenburg de Jong
Journal: Annals of Oncology (2019)
Abstract 17901: Low Skeletal Muscle Mass Index is Associated With Cardiovascular Events in Patients After ST-Segment Elevation Myocardial Infarction
Authors: Ryosuke Satou, Yasushi Matsuzawa, Eiichi Akiyama, Chika Kawashima, Hiroyuki Suzuki, Masaaki Konishi, Nobuhiko Maejima, Noriaki Iwahashi, Kiyoshi Hibi, Masami Kosuge, Kazuo Kimura, Kouichi Tamura, Toshiaki Ebina
Journal: Circulation (2017)

Introduction: Although it has been implicated that the association between low skeletal muscle mass and cardiovascular diseases, the prognostic value of skeletal muscle mass in patients with ST-seg...
Increased Mortality and Bleeding in a Large Cohort of Patients on Heparin Anticoagulation Therapy with Discordant Anti-Factor Xa Activity and Activated Partial Thromboplastin Time (PTT); Implications for Clinical Management
Authors: Saurabh Gombar, Derek Boothroyd, Anandi Krishnan, Husham Sharifi, Joe Hsu, James Zehnder
Journal: Blood (2019)
Screening for Abdominal Aortic Aneurysm
Authors: Douglas K. Owens, Karina W. Davidson, Alex H. Krist, Michael J. Barry, Michael Cabana, Aaron B. Caughey, Chyke A. Doubeni, John W. Epling, Martha Kubik, C. Seth Landefeld, Carol M. Mangione, Lori Pbert, Michael Silverstein, Melissa A. Simon, Chien-Wen Tseng, John B. Wong
Journal: JAMA (2019)

<h3>Importance</h3> An abdominal aortic aneurysm (AAA) is typically defined as aortic enlargement with a diameter of 3.0 cm or larger. The prevalence of AAA has declined over the past 2 decades among screened men 65 years or older in various European countries. The current prevalence of AAA in the United States is unclear because of the low uptake of screening. Most AAAs are asymptomatic until they rupture. Although the risk for rupture varies greatly by aneurysm size, the associated risk for death with rupture is as high as 81%. <h3>Objective</h3> To update its 2014 recommendation, the USPSTF commissioned a review of the evidence on the effectiveness of 1-time and repeated screening for AAA, the associated harms of screening, and the benefits and harms of available treatments for small AAAs (3.0-5.4 cm in diameter) identified through screening. <h3>Population</h3> This recommendation applies to asymptomatic adults 50 years or older. However, the randomized trial evidence focuses almost entirely on men aged 65 to 75 years. <h3>Evidence Assessment</h3> Based on a review of the evidence, the USPSTF concludes with moderate certainty that screening for AAA in men aged 65 to 75 years who have ever smoked is of moderate net benefit. The USPSTF concludes with moderate certainty that screening for AAA in men aged 65 to 75 years who have never smoked is of small net benefit. The USPSTF concludes that the evidence is insufficient to determine the net benefit of screening for AAA in women aged 65 to 75 years who have ever smoked or have a family history of AAA. The USPSTF concludes with moderate certainty that the harms of screening for AAA in women aged 65 to 75 years who have never smoked and have no family history of AAA outweigh the benefits. <h3>Recommendations</h3> The USPSTF recommends 1-time screening for AAA with ultrasonography in men aged 65 to 75 years who have ever smoked. (B recommendation) The USPSTF recommends that clinicians selectively offer screening for AAA with ultrasonography in men aged 65 to 75 years who have never smoked rather than routinely screening all men in this group. (C recommendation) The USPSTF recommends against routine screening for AAA with ultrasonography in women who have never smoked and have no family history of AAA. (D recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for AAA with ultrasonography in women aged 65 to 75 years who have ever smoked or have a family history of AAA. (I statement)
The SSSPIN study—spin in studies of spin: meta-research analysis
Authors: Lisa Bero, Kellia Chiu, Quinn Grundy
Journal: BMJ (2019)

Abstract Objectives To identify and calculate the prevalence of spin in studies of spin. Design Meta-research analysis (research on research). Setting 35 studies of spin in the scientific literature. Main outcome measures Spin, categorised as: reporting practices that distort the presentation and interpretation of results, creating misleading conclusions; discordance between results and their interpretation, with presentation of favourable conclusions that are not supported by the data or results; attribution of causality when study design does not support it; and over-interpretation or inappropriate extrapolation of results. Results Five (14%) of 35 spin studies contained spin categorised as reporting practices that distort the presentation and interpretation of results (n=2) or categorised as over-interpretation or inappropriate extrapolation of results (n=3). Conclusion Spin occurs in research on spin. Although researchers on this topic should be sensitive to spinning their findings, our study does not undermine the need for rigorous interventions to reduce spin across various research fields. Conclusion with spin Our hypothesis that spin will be less prevalent in spin studies than in studies on other topics has been proven. Spin scholars are less likely to spin their conclusions than other researchers, and they should receive substantial resources to launch and test interventions to reduce spin and research waste in reporting.
Changes in Trends in Thyroid Cancer Incidence in the United States, 1992 to 2016
Authors: Ann E. Powers, Andrea R. Marcadis, Mark Lee, Luc G. T. Morris, Jennifer L. Marti
Journal: JAMA (2019)

Roy Xiao, MD, MS; Vinay K. Rathi, MD, MBA; Cary P. Gross, MD; Joseph S. Ross, MD, MHS; Rosh K. V. Sethi, MD, MPH
Trends in Intentional and Unintentional Opioid Overdose Deaths in the United States, 2000-2017
Authors: Mark Olfson, Lauren M. Rossen, Melanie M. Wall, Debra Houry, Carlos Blanco
Journal: JAMA (2019)

Taylor A. Ochalek, PhD; Kirk L. Cumpston, DO; Brandon K. Wills, DO; Tamas S. Gal, PhD; F. Gerard Moeller, MD
Type III interferons: Balancing tissue tolerance and resistance to pathogen invasion
Authors: Achille Broggi, Francesca Granucci, Ivan Zanoni
Journal: The Journal of Experimental Medicine (2019)

Type III IFNs, or IFN-λ, are the newest members of the IFN family and were long believed to play roles that were redundant with those of type I IFNs. However, IFN-λ displays unique traits that delineate them as primary protectors of barrier integrity at mucosal sites. This unique role stems both from the restricted expression of IFN-λ receptor, confined to epithelial cells and to a limited pool of immune cells, and from unique immunomodulatory properties of IFN-λ. Here, we discuss recent findings that establish the unique capacity of IFN-λ to act at the barriers of the host to balance tissue tolerance and immune resistance against viral and bacterial challenges.
Cardiometabolic disease costs associated with suboptimal diet in the United States: A cost analysis based on a microsimulation model
Authors: Thiago Veiga Jardim, Dariush Mozaffarian, Shafika Abrahams-Gessel, Stephen Sy, Yujin Lee, Junxiu Liu, Yue Huang, Colin Rehm, Parke Wilde, Renata Micha, Thomas A. Gaziano
Journal: PLoS Medicine (2019)

Background Poor diet is a leading risk factor for cardiometabolic disease (CMD) in the United States, but its economic costs are unknown. We sought to estimate the cost associated with suboptimal diet in the US. Methods and findings A validated microsimulation model (Cardiovascular Disease Policy Model for Risk, Events, Detection, Interventions, Costs, and Trends [CVD PREDICT]) was used to estimate annual cardiovascular disease (fatal and nonfatal myocardial infarction, angina, and stroke) and type 2 diabetes costs associated with suboptimal intake of 10 food groups (fruits, vegetables, nuts/seeds, whole grains, unprocessed red meats, processed meats, sugar-sweetened beverages, polyunsaturated fats, seafood omega-3 fats, sodium). A representative US population sample of individuals aged 35–85 years was created using weighted sampling from National Health And Nutrition Examination Surveys (NHANES) 2009–2012 cycles. Estimates were stratified by cost type (acute, chronic, drug), sex, age, race, education, BMI, and health insurance. Annual diet-related CMD costs were $301/person (95% CI $287–$316). This translates to $50.4 billion in CMD costs (18.2% of total) for the whole population, of which 84.3% are attributed to acute care ($42.6 billion). The largest annual per capita costs are attributed to low consumption of nuts/seeds ($81; 95% CI $74–$86) and seafood omega-3 fats ($76; 95% CI $70–$83), and the lowest are attributed to high consumption of red meat ($3; 95% CI $2.8–$3.5) and polyunsaturated fats ($20; 95% CI $19–$22). Individual costs are highest for men ($380), those aged ≥65 years ($408), blacks ($320), the less educated ($392), and those with Medicare ($481) or dual-eligible ($536) insurance coverage. A limitation of our study is that dietary intake data were assessed from 24-hour dietary recall, which may not fully capture a diet over a person's life span and is subject to measurement errors. Conclusions Suboptimal diet of 10 dietary factors accounts for 18.2% of all ischemic heart disease, stroke, and type 2 diabetes costs in the US, highlighting that timely implementation of diet policies could address these health and economic burdens.
Primary Preclinical and Clinical Evaluation of 68Ga-DOTA-TMVP1 as a Novel VEGFR-3 PET Imaging Radiotracer in Gynecological Cancer
Authors: Fei Li, Zhenzhong Zhang, Jiong Cai, Xi Chen, Ying Zhou, Xiangyi Ma, Qingjian Dong, Fang Li, Ling Xi
Journal: Clinical Cancer Research (2019)

Tumor periphery and lymph nodes of tumor-induced lymphangiogenesis often abundantly express VEGFR-3. In our previous study, we identified a 5-amino acid peptide named TMVP1, which binds specifically to VEGFR-3. The objective of this study was to develop a novel 68Ga-labeled TMVP1 for VEGFR-3 PET imaging and to investigate its safety, biodistribution, and tumor-localizing efficacy in xenograft tumor models and a small cohort of patients with recurrent ovarian and cervical cancer.The DOTA-conjugated TMVP1 peptide was labeled with radionuclide 68Ga. SPR and saturation binding assays were used for the receptor-binding studies. Gynecologic xenograft tumors were employed for small-animal PET imaging and biodistribution of 68Ga-DOTA-TMVP1 in vivo. In the clinical study, 5 healthy volunteers and 8 patients with gynecologic cancer underwent whole-body PET/CT after being injected with 68Ga-DOTA-TMVP1.DOTA-TMVP1 was successfully labeled with 68Ga. LECs showed higher binding capacity with 68Ga-DOTA-TMVP1 than LEC(shVEGFR-3) and human umbilical vein endothelial cells. In mice with subcutaneous C33-A and SKOV-3 xenografts, the tracer was rapidly eliminated through the kidney to the bladder, and the small-animal PET/CT helped to clearly visualize the tumors. In patients with recurrent ovarian cancer and cervical cancer, tracer accumulation well above the background level was demonstrated in most identified sites of disease; especially with recurrent endodermal sinus tumors, the diagnostic value of 68Ga-DOTA-TMVP1 was comparable with that of 18F-FDG PET/CT.68Ga-DOTA-TMVP1 is a potential PET tracer for imaging VEGFR-3 with favorable pharmacokinetics.
Vireo: Bayesian demultiplexing of pooled single-cell RNA-seq data without genotype reference
Authors: Yuanhua Huang, Davis J. McCarthy, Oliver Stegle
Journal: Genome biology (2019)

Multiplexed single-cell RNA-seq analysis of multiple samples using pooling is a promising experimental design, offering increased throughput while allowing to overcome batch variation. To reconstruct the sample identify of each cell, genetic variants that segregate between the samples in the pool have been proposed as natural barcode for cell demultiplexing. Existing demultiplexing strategies rely on availability of complete genotype data from the pooled samples, which limits the applicability of such methods, in particular when genetic variation is not the primary object of study. To address this, we here present Vireo, a computationally efficient Bayesian model to demultiplex single-cell data from pooled experimental designs. Uniquely, our model can be applied in settings when only partial or no genotype information is available. Using pools based on synthetic mixtures and results on real data, we demonstrate the robustness of Vireo and illustrate the utility of multiplexed experimental designs for common expression analyses.