tbuckley/cabot-search huggingface dataset:
Abstract 11507: Exposure to E-Cigarette Adversely Affects Blood Pressure and Heart Rate in Healthy Individuals: A Systematic Review and Meta-Analysis
Authors: Georgia Skotsimara, Alexios Antonopoulos, Evangelos Oikonomou, Nikolaos Ioakeimidis, Sotiris Tsalamandris, Christos Georgakopoulos, Georgia Vogiatzi, Leonidas Koliostasis, Gerasimos Siasos, Charalambos Vlachopoulos, Dimitris Tousoulis
Journal: Circulation (2018)

Introduction: Whilst tobacco smoking has well-established harmful effects, electronic cigarette (EC) products have been branded as a safe alternative to tobacco use. Nonetheless, accruing data deba...
Ivabradine in Catecholamine-Induced Tachycardia in a Patient with Paraganglioma
Authors: Gelinemae Malaza, Alessandra Brofferio, Frank Lin, Karel Pacak
Journal: New England Journal of Medicine (2019)

Ivabradine for Tachycardia in Paraganglioma The use of ivabradine, an If current inhibitor, to manage tachycardia and heart failure due to massive catecholamine release in a patient with a metastat...
Opioid–galanin receptor heteromers mediate the dopaminergic effects of opioids
Authors: Ning-Sheng Cai, César Quiroz, Jordi Bonaventura, Alessandro Bonifazi, Thomas O. Cole, Julia Purks, Amy S. Billing, Ebonie Massey, Michael Wagner, Eric D. Wish, Xavier Guitart, William Rea, Sherry Lam, Estefanía Moreno, Verònica Casadó-Anguera, Aaron D. Greenblatt, Arthur E. Jacobson, Kenner C. Rice, Vicent Casadó, Amy H. Newman, John W. Winkelman, Michael Michaelides, Eric Weintraub, Nora D. Volkow, Annabelle M. Belcher, Sergi Ferré
Journal: Journal of Clinical Investigation (2019)

Identifying nonaddictive opioid medications is a high priority in medical science, but μ-opioid receptors (MORs) mediate both the analgesic and addictive effects of opioids. We found a significant pharmacodynamic difference between morphine and methadone that is determined entirely by heteromerization of MORs with galanin Gal1 receptors (Gal1Rs), rendering a profound decrease in the potency of methadone. This finding was explained by the weaker proficiency of methadone in activating the dopaminergic system as compared with morphine and predicted a dissociation of the therapeutic and euphoric effects of methadone, which was corroborated by a significantly lower incidence of self-reports of feeling "high" in methadone-medicated patients. These results suggest that μ-opioid–Gal1R heteromers mediate the dopaminergic effects of opioids. The results further suggest a lower addictive liability of some opioids, such as methadone, due to their selective low potency for the μ-opioid–Gal1R heteromer.
QIM19-137: Effect of Socioeconomic Factors on Survival in Veterans With Acute Myeloid Leukemia
Authors: Falgun Mahendrakumar Modhia, Sarah E. Johnston, Daniel Zhao, Ankur Mody, Mohammad O. Khalil
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: There is limited information about socioeconomic factors effect on survival in veterans with acute myeloid leukemia (AML). Few studies published between the 1960s and 1980s suggested higher risks for leukemia mortality among veterans who were smokers. Few studies investigated socioeconomic factors like insurance status, care at private or academic center, marital status, and median household income effect on outcomes. Alcohol use and AML outcomes co-relation is not well studied in literature. Methods: Medical records of AML patients at the Oklahoma City VAHCS between 2010 and 2017 were reviewed. Information collected included home distance from treatment center (≤40 miles vs &gt;40 miles), marital status at diagnosis, tobacco use in the 3 months preceding diagnosis, history of alcohol abuse, level of college education (college education vs less than college education). Fisher-exact test was used for differences in survival rates. Kaplan-Meier analysis was used to estimate the survival and log-rank test to determine differences among groups. Results: Total number of veterans were 28. 15 patients (56%) had poor risk disease, 8 (30%) had intermediate risk disease, and 4 (15%) had good risk disease. Median survival for the whole group was 9.3 months. Patients with poor and intermediate risk cytogenetic/molecular status had median survival of 5.5 and 37.7 months, respectively ( P =.0066). There was an insufficient number of deaths in the good risk group at the time of this analysis. Median survival for veterans with history of alcohol use was 66 vs 7 months ( P =.15). Median survival for veterans who had some college education vs less than college education was 26.1 vs 6.9 ( P =.14). Median survival for veterans with history of tobacco use within 3 months of diagnosis vs others was 6.9 vs 26.1 ( P =.11). Median survival for veterans who were married at diagnosis vs non-married was 14 vs 7.89 ( P =.29). Median survival for veterans who lived &gt;40 miles from treatment center vs ≤40 miles was 7.43 vs 37.7 months ( P =.5). Conclusions: In our retrospective single institute study, poor risk cytogenetic/molecular risk group was associated with inferior survival. While there appeared to be a trend towards worse survival in association with lower education, smoking, non-married status, and longer distance from treatment center, none of these factors had a statistically significant effect. Larger studies are needed to confirm such observations.
Allergens in dog extracts: Implication for diagnosis and treatment
Authors: Anna Wintersand, Klara Asplund, Jonas Binnmyr, Erik Holmgren, Ola B. Nilsson, Guro Gafvelin, Hans Grönlund
Journal: Allergy (2019)

Five to ten percent of the population in affluent countries are allergic to dog. Diagnosis and treatment is based on allergen extracts from natural sources where composition and concentration are poorly defined.We aimed to quantify six dog allergens (Can f 1-6) in commercial skin prick test (SPT) solutions and to determine individual allergen profiles in dogs.The allergen content of SPT solutions from five vendors and allergen source material from three anatomical sites were analyzed. Fur and saliva samples were collected from a mixed population of 120 dogs. Can f 1-6 were quantified by inhibition ELISA using purified recombinant or natural allergens and polyclonal or monoclonal antibodies. Allergenicity was analyzed by basophil activation test.Extensive variation in allergen composition was observed in commercial SPT vials resulting in a patient-dependent ability to activate basophils. Extract heterogeneity depended on collection site and allergen composition in individual dogs and source materials. Can f 2 and Can f 6 exhibited low levels in fur and SPT solutions, whereas Can f 4, which was the dominating allergen in fur samples, did not display similar high proportions in SPT solutions. Can f 3 varied most among SPT solutions.There is a great variation of dog allergens in natural extracts raising questions of source, sampling, processing and ultimately of standardization and minimum allergen levels for accurate diagnosis and treatment.
A review of the influence of periodontal treatment in systemic diseases
Authors: Artur Falcao, Pedro Bullón
Journal: Periodontology 2000 (2019)

Abstract The effects and consequences of periodontal diseases might not be confined to the oral cavity. A great body of evidence has arisen supporting the claim demonstrating an association with several systemic conditions and diseases. With different levels of evidence, an association between periodontal disease and cardiovascular disease, diabetes, psoriasis, rheumatoid arthritis, pregnancy outcomes and respiratory diseases has been established. However, the true nature of this association, if it is causal, still remains elusive. For a better understanding of the complex relationships linking different conditions, interventional studies now begin to focus on the possible outcomes of periodontal treatment in relation to the events, symptoms and biomarkers of several systemic disorders, assessing if periodontal treatment has any impact on them, hopefully reducing their severity or prevalence. Therefore, we proceeded to review the recent literature on the subject, attempting to present a brief explanation of the systemic condition or disease, what proposed mechanisms might give biological plausibility to its association with periodontal disease, and finally and more importantly, what data are currently available pertaining to the effects periodontal treatment may have. Raising awareness and discussing the possible benefits of periodontal treatment on overall systemic health is important, in order to change the perception that periodontal diseases are only limited to the oral cavity, and ultimately providing better and comprehensive care to patients.
Fusidic acid cream for impetigo [3] (multiple letters)
Authors: Erwin M. Brown, Richard Wise, Olajumoke Sule, Nick Brown, Derek F.J. Brown, Nigel Burrows, Vivienne C. Weston, Timothy C.J. Boswell, Roger G. Finch, William Perkins, Bethan Stoddart, Timothy Collyns, Miles Denton, Paul Zadik, Nicola Young, Susannah E. Owen, John S. Cheesbrough, S. Koning, L. W.A. Van Suijlekom-Smit, J. L. Nouwen, C. M. Verduin, R. M.D. Bernsen, A. P. Oranje, S. Thomas, J. C. Van der Wouden
Journal: BMJ (2002)
LincK contributes to breast tumorigenesis by promoting proliferation and epithelial-to-mesenchymal transition
Authors: Jing Li, Yajing Hao, Wenzhe Mao, Xiaowei Xue, Pengchao Xu, Lihui Liu, Jiao Yuan, Dongdong Zhang, Na Li, Hua Chen, Lin Zhao, Zhao Sun, Jianjun Luo, Runsheng Chen, Robert Chunhua Zhao
Journal: Journal of Hematology & Oncology (2019)

Increasing evidence has demonstrated that mesenchymal stem cells (MSCs) play a role in the construction of tumor microenvironments. Co-culture between tumor cells and MSCs provides an easy and useful platform for mimicking tumor microenvironments and identifying the important members involved in tumor progress. The long non-coding RNAs (lncRNAs) have been shown to regulate different tumorigenic processes. In this study, we aimed to examine functional lncRNA deregulations associated with breast cancer malignancy instigated by MSC-MCF-7 co-culture. The microarrays were used to profile the expression changes of lncRNAs in MCF-7 cells during epithelial-mesenchymal transition (EMT) induced by co-culture with MSCs. We found that an intergenic lncRNA KB-1732A1.1 (termed LincK, partly overlapped with GASL1) was significantly elevated. To investigate the biological function of LincK, the expression of EMT markers, cell migration, invasion, proliferation, and colony formation were evaluated in vitro and xenograft assay in nude mice were performed in vivo. Furthermore, we detected LincK expression in clinical samples using RNAscope® technology and verified aberrant expression of LincK in breast cancer data sets from The Cancer Genome Atlas (TCGA) by bioinformatic analysis. The underlying mechanisms of LincK were investigated using mRNA microarray analyses, Western blot, RNA pull down, and RNA immunoprecipitation. LincK induced an EMT progress in breast cancer cells (BCC) MCF-7, MDA-MB-453, and MDA-MB-231. The depletion of LincK decreased the growth, migration, and invasion in BCC, whereas the overexpression of LincK exerted the opposite effects. Moreover, knockdown of LincK repressed tumorigenesis, and ectopic expression of LincK promoted tumor growth in MCF-7 xenograft model. LincK ablation in MDA-MB-231 cells dramatically impaired lung metastasis when incubated intravenously into nude mice. Further, LincK was frequently elevated in breast cancer compared with normal breast tissue in clinical samples. Mechanistically, LincK may share common miRNA response elements with PBK and ZEB1 and regulate the effects of miR-200 s. LincK plays a significant role in regulating EMT and tumor growth and could be a potential therapeutic target in breast cancer.
Rammya Mathew: Reframing the language around error
Authors: Rammya Mathew
Journal: BMJ (2019)

In medicine, we often equate being wrong with having made a mistake. But we should remember, as the 19th and 20th century physician William Osler observed, that “medicine is a science of uncertainty and an art of probability.” So, even when we have made the soundest of decisions, we may still get it wrong.

Our knee jerk response, which has been indoctrinated in us as part of the culture of appraisal, is that we should automatically change the way we practise whenever we make a wrong call. This is certainly appropriate when we’ve made a mistake. But it may …
Genomic Signatures Predict the Immunogenicity of BRCA-Deficient Breast Cancer
Authors: Adam A. Kraya, Kara N. Maxwell, Bradley Wubbenhorst, Brandon M. Wenz, John Pluta, Andrew J. Rech, Liza M. Dorfman, Nicole Lunceford, Amanda Barrett, Nandita Mitra, Jennifer J.D. Morrissette, Michael Feldman, Anupma Nayak, Susan M. Domchek, Robert H. Vonderheide, Katherine L. Nathanson
Journal: Clinical Cancer Research (2019)

Breast cancers with BRCA1/2 alterations have a relatively high mutational load, suggesting that immune checkpoint blockade may be a potential treatment option. However, the degree of immune cell infiltration varies widely, and molecular features contributing to this variability remain unknown.We hypothesized that genomic signatures might predict immunogenicity in BRCA1/2 breast cancers. Using The Cancer Genome Atlas (TCGA) genomic data, we compared breast cancers with (89) and without (770) either germline or somatic BRCA1/2 alterations. We also studied 35 breast cancers with germline BRCA1/2 mutations from Penn using WES and IHC.We found that homologous recombination deficiency (HRD) scores were negatively associated with expression-based immune indices [cytolytic index (P = 0.04), immune ESTIMATE (P = 0.002), type II IFN signaling (P = 0.002)] despite being associated with a higher mutational/neoantigen burden, in BRCA1/2 mutant breast cancers. Further, absence of allele-specific loss of heterozygosity (LOH negative; P = 0.01) or subclonality (P = 0.003) of germline and somatic BRCA1/2 mutations, respectively, predicted for heightened cytolytic activity. Gene set analysis found that multiple innate and adaptive immune pathways that converge on NF-κB may contribute to this heightened immunogenicity. IHC of Penn breast cancers demonstrated increased CD45+ (P = 0.039) and CD8+ infiltrates (P = 0.037) and increased PDL1 expression (P = 0.012) in HRD-low or LOH-negative cancers. Triple-negative cancers with low HRD had far greater CD8+ T cells (P = 0.0011) and Perforin 1 expression (P = 0.014) compared with hormone receptor-positive HRD-high cancers.HRD scores and hormone receptor subtype are predictive of immunogenicity in BRCA1/2 breast cancers and may inform the design of optimal immune therapeutic strategies.
Sex-Related Differences in Patients Undergoing Thoracic Aortic Surgery
Authors: Jennifer Chung, Louis-Mathieu Stevens, Maral Ouzounian, Ismail El-Hamamsy, Ismail Bouhout, Francois Dagenais, Andreanne Cartier, Mark D. Peterson, Munir Boodhwani, Ming Guo, John Bozinovski, Michael H. Yamashita, Carly Lodewyks, Rony Atoui, Bindu Bittira, Darrin Payne, Christopher Tarola, Michael W. A. Chu
Journal: Circulation (2019)

Contemporary outcomes after surgical management of thoracic aortic disease have improved; however, the impact of sex-related differences is poorly understood.A total of 1653 patients (498 [30.1%] female) underwent thoracic aortic surgery with hypothermic circulatory arrest between 2002 and 2017 in 10 institutions of the Canadian Thoracic Aortic Collaborative. Outcomes of interest were in-hospital death, stroke, and a modified Society of Thoracic Surgeons-defined composite for mortality or major morbidity (stroke, renal failure, deep sternal wound infection, reoperation, prolonged ventilation). Multivariable logistic regression was used to determine independent predictors of these outcomes.Women were older (mean±SD, 66±13 years versus 61±13 years; P<0.001), with more hypertension and renal failure, but had less coronary disease, less previous cardiac surgery, and higher ejection fraction than men. Rates of aortic dissection were similar between women and men. Rates of hemiarch, and total arch repair were similar between the sexes; however, women underwent less aortic root reconstruction including aortic root replacement, Ross, or valve-sparing root operations (29% versus 45%; P<0.001). Men experienced longer cross-clamp and cardiopulmonary bypass times, but similar durations of circulatory arrest, methods of cerebral perfusion, and nadir temperatures. Women experienced a higher rate of mortality (11% versus 7.4%; P=0.02), stroke (8.8% versus 5.5%; P=0.01), and Society of Thoracic Surgeons-defined composite end point for mortality or major morbidity (31% versus 27%; P=0.04). On multivariable analyses, female sex was an independent predictor of mortality (odds ratio, 1.81; P<0.001), stroke (odds ratio, 1.90; P<0.001), and Society of Thoracic Surgeons-defined composite end point for mortality or major morbidity (odds ratio, 1.40; P<0.001).Women experience worse outcomes after thoracic aortic surgery with hypothermic circulatory arrest. Further investigation is required to better delineate which measures may reduce sex-related outcome differences after complex aortic surgery.
Combination of Circulating Type I Collagen-Related Biomarkers Is Associated With Atrial Fibrillation
Authors: Susana Ravassa, Gabriel Ballesteros, Begoña López, Pablo Ramos, Jean Bragard, Arantxa González, María U. Moreno, Ramón Querejeta, Enrique Vives, Ignacio García-Bolao, Javier Díez
Journal: Journal of the American College of Cardiology (2019)
Considerations for the study of “incentive hope” and sign-tracking behaviors in humans
Authors: Eva R. Pool, David Sander
Journal: Behavioral and Brain Sciences (2019)

Abstract The amplification of reward-seeking behavior under uncertainty described by Anselme &amp; Güntürkün is based on the animal literature. However, this phenomenon could provide valuable information for the understanding of several dysfunctional human behaviors such as overeating and gambling. Therefore, we formulated some considerations on how the “incentive hope” hypothesis could be tested on a human population.
Combination of AZD4573, a Selective CDK9 Inhibitor, with Other Cell Death Inducing Agents Can Overcome De Novo Venetoclax Resistance in Preclinical Hematologic Tumor Models
Authors: Justin Cidado, Scott Boiko, Theresa Proia, Haley Woods, Omid Tavana, Maryann San Martin, Adriana E. Tron, Wenlin Shao, Lisa Drew
Journal: Blood (2018)
Does fluoxetine improve recovery after stroke?
Authors: Rob Cook, Vaughan Thomas, Rosie Martin
Journal: BMJ (2019)

The studyFOCUS Trial Collaboration. Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial. Lancet 2019;393:256-74.The study was funded by the UK Stroke Association and the NIHR Health Technology Assessment Programme project number 13/04/30.To read the full NIHR Signal, go to: https://discover.dc.nihr.ac.uk/content/signal-000729/a-commonly-used-antidepressant-doesnt-improve-recovery-after-stroke.
PIK3CA mutations frequently coexist with PTEN mutations in endometrial cancer and overexpression of ERBB2 and/or ERBB3 in breast cancer
Authors: Katsutoshi Oda, David Stokoe, Luika Timmerman, Takeshi Jimbo, Jennifer Okada, Yuji Taketani, Frank McCormick
Journal: Cancer Research (2006)

1463  The phosphatidylinositol 3’-kinase (PI3K) pathway is activated in many human cancers. In addition to inactivation of the PTEN tumor suppressor gene, mutations or amplifications of the catalytic subunit alpha of PI3K (PIK3CA) have been detected in various tumors. In breast cancer, overexpression of either ERBB2 or ERBB3 is involved in activating the PI3K pathway, as well as mutations in PIK3CA and loss of PTEN expression. However, it is not clear whether the pathway is fully activated by a single alteration, or whether multiple alterations further enhance activation. We screened 66 primary endometrial carcinomas for mutations in the helical and catalytic domains of PIK3CA and entire coding region of PTEN. Also, we analyzed 47 breast cancer cell lines for PIK3CA mutations and expression level of PTEN (by Western blotting), ERBB2 and ERBB3 (by Expression Array Hybridization). In endometrial carcinomas, we identified a total of 24 (36%) mutations in PIK3CA, 37(56%) mutations in PTEN, and coexistence of PIK3CA / PTEN mutations at high frequency (26%). PIK3CA mutations were more common in tumors with PTEN mutations (17/37=46%), compared to those without PTEN mutations (7/29=24%). Knocking down PTEN expression in HEC-1B endometrial cancer cell line, which possesses both K-Ras and PIK3CA mutations, further enhances phosphorylation of Akt (Ser 473), indicating that double mutation of PIK3CA and PTEN has an additive effect on PI3K activation. In breast cancer cell lines, PIK3CA mutation correlates with ERBB2 and/or ERBB3 overexpression (p=0.020 in Fisher’s exact test), but seems less common in cells with reduced PTEN protein expression. Also, ERBB2 and/or ERBB3 overexpression was less frequent in cell lines with reduced PTEN expression (1/11=9%), compared to those with normal PTEN expression (18/36=50%) (p=0.032 in Fisher’s exact test). Our data suggest that loss of PTEN expression alone might be sufficient to activate the PI3K pathway in breast cancer, but PIK3CA mutations frequently co-exist with ERBB2 and/or ERBB3 overexpression. In contrast, in endometrial cancer, coexistence of PIK3CA and PTEN mutation might have additive effects in activating the PI3K pathway.
Expanding and Underscoring the Hepato‐Encephalopathic Phenotype of QIL1/MIC13
Authors: Bianca E. Russell, Kaitlin G. Whaley, Kevin E. Bove, Anatalia Labilloy, Rachel C. Lombardo, Robert J. Hopkin, Nancy D. Leslie, Carlos Prada, Zahra Assouline, Giulia Barcia, Juliette Bouchereau, Maryline Chomton, Dominique Debray, Imen Dorboz, Philippe Durand, Pauline Gaignard, Dalila Habes, Claude Jardel, François Labarthe, Jonathan Lévy, Anne Lombès, Claire Mehler‐Jacob, Judith Melki, Laura Menvielle, Arnold Munnich, Charlotte Mussini, Samia Pichard, Marlène Rio, Agnès Rötig, Samira Sissaoui, Abdelhamid Slama, Alexander G Miethke, Manuel Schiff
Journal: Hepatology (2019)

Russell, Bianca E.; Whaley, Kaitlin G.; Bove, Kevin E.; Labilloy, Anatalia; Lombardo, Rachel C.; Hopkin, Robert J.; Leslie, Nancy D.; Prada, Carlos; Assouline, Zahra; Barcia, Giulia; Bouchereau, Juliette; Chomton, Maryline; Debray, Dominique; Dorboz, Imen; Durand, Philippe; Gaignard, Pauline; Habes, Dalila; Jardel, Claude; Labarthe, François; Lévy, Jonathan; Lombès, Anne; Mehler‐Jacob, Claire; Melki, Judith; Menvielle, Laura; Munnich, Arnold; Mussini, Charlotte; Pichard, Samia; Rio, Marlène; Rötig, Agnès; Sissaoui, Samira; Slama, Abdelhamid; Miethke, Alexander G; Schiff, Manuel Author Information