tbuckley/cabot-search huggingface dataset:
Abstract 17713: Fetal Brain Volume as a Predictor of Postnatal Brain Injury in Neonates With Critical Congenital Heart Disease
Authors: Shabnam Peyvandi, Joanne Lau, Theodore Kingdom, Duan Xu, Anita Moon-Grady, Mike Seed, Steven Miller, Hosung Kim, Patrick McQuillen
Journal: Circulation (2016)

Objective: Pre-operative brain injury is reported in 30% of neonates with critical congenital heart disease (CHD), appearing in the form of white matter injury (WMI) or stroke. Compared to controls...
The β-Adrenergic Agonist Albuterol Improves Pulmonary Vascular Reserve in Heart Failure With Preserved Ejection Fraction
Authors: Yogesh N.V. Reddy, Masaru Obokata, Katlyn E. Koepp, Alexander C. Egbe, Brandon Wiley, Barry A. Borlaug
Journal: Circulation Research (2019)

Pulmonary vascular resistance fails to decrease appropriately during exercise in patients with heart failure with preserved ejection fraction (HFpEF). Interventions that enhance pulmonary vasodilation might be beneficial in this cohort but could also worsen left atrial hypertension, exacerbating lung congestion. Intravenous β-agonists reduce pulmonary vascular resistance but are not suitable for chronic use.We hypothesized that the inhaled β-adrenergic agonist albuterol would improve pulmonary vasodilation during exercise in patients with HFpEF, without increasing left heart filling pressures.We performed a randomized, double-blind, placebo-controlled trial testing the effects of inhaled albuterol on resting and exercise hemodynamics in subjects with HFpEF using high-fidelity micromanometer catheters and expired gas analysis. The primary end point was pulmonary vascular resistance during exercise. Subjects with HFpEF (n=30) underwent resting and exercise hemodynamic assessment and were then randomized 1:1 to inhaled, nebulized albuterol or placebo. Rest and exercise hemodynamic testing was then repeated. Albuterol improved the primary end point of exercise pulmonary vascular resistance as compared with placebo (-0.6±0.5 versus +0.1±0.7 WU; P=0.003). Albuterol enhanced cardiac output reserve and right ventricular pulmonary artery coupling, reduced right atrial and pulmonary artery pressures, improved pulmonary artery compliance, and enhanced left ventricular transmural distending pressure (all P <0.01), with no increase in pulmonary capillary hydrostatic pressures.Albuterol improves pulmonary vascular reserve in patients with HFpEF without worsening left heart congestion. Further study is warranted to evaluate the chronic efficacy of β-agonists in HFpEF and other forms of pulmonary hypertension.URL: http://www.clinicaltrials.gov . Unique identifier: NCT02885636.
Alpha‐1 Antitrypsin Deficiency Liver Disease, Mutational Homogeneity Modulated by Epigenetic Heterogeneity With Links to Obesity
Authors: Liguo Wang, George W. Marek, Ryan A. Hlady, Ryan T. Wagner, Xia Zhao, Virginia C. Clark, Alex Xiucheng Fan, Chen Liu, Mark Brantly, Keith D. Robertson
Journal: Hepatology (2019)

Alpha‐1 antitrypsin deficiency (AATD) liver disease is characterized by marked heterogeneity in presentation and progression, despite a common underlying gene mutation, strongly suggesting the involvement of other genetic and/or epigenetic modifiers. Variation in clinical phenotype has added to the challenge of detection, diagnosis, and testing of new therapies in patients with AATD. We examined the contribution of DNA methylation (5‐methylcytosine [5mC]) to AATD liver disease heterogeneity because 5mC responds to environmental and genetic cues and its deregulation is a major driver of liver disease. Using liver biopsies from adults with early‐stage AATD and the ZZ genotype, genome‐wide 5mC patterns were interrogated. We compared DNA methylation among patients with early AATD, and among patients with normal liver, cirrhosis, and hepatocellular carcinoma derived from multiple etiologic exposures, and linked patient clinical/demographic features. Global analysis revealed significant genomic hypomethylation in AATD liver–impacting genes related to liver cancer, cell cycle, and fibrosis, as well as key regulatory molecules influencing growth, migration, and immune function. Further analysis indicated that 5mC changes are localized, with hypermethylation occurring within a background of genome‐wide 5mC loss and with patients with AATD manifesting distinct epigenetic landscapes despite their mutational homogeneity. By integrating clinical data with 5mC landscapes, we observed that CpGs differentially methylated among patients with AATD disease are linked to hallmark clinical features of AATD (e.g., hepatocyte degeneration and polymer accumulation) and further reveal links to well‐known sex‐specific effects of liver disease progression. Conclusion: Our data reveal molecular epigenetic signatures within this mutationally homogeneous group that point to ways to stratify patients for liver disease risk.
Outcomes of Pediatric Patients with Acute Leukemia Following Adult Unrelated Donor Transplant: The Impact of Donor KIR Gene Content and KIR Ligand Matching
Authors: Michael R Verneris, Tao Wang, Stephen R. Spellman, Jennifer A. Sees, Michael D. Haagenson, Sarah Cooley, Katharine C. Hsu, Katharina Fleischhauer, Katharina Fleischhauer, Dean Anthony Lee, Sophie Paczesny, Hemalatha G. Rangarajan, Jeffrey S. Miller, Stephanie J. Lee
Journal: Blood (2018)
Long-Term Outcomes After Aortic Valve Surgery in Patients With Asymptomatic Chronic Aortic Regurgitation and Preserved LVEF
Authors: Alaa Alashi, Tamanna Khullar, Amgad Mentias, A Marc Gillinov, Eric E Roselli, Lars G Svensson, Zoran B Popovic, Brian P Griffin, Milind Y Desai
Journal: JACC. Cardiovascular imaging (2019)
Inter‐rater reliability of phenotypes and exploratory genotype–phenotype analysis in inherited hidradenitis suppurativa
Authors: J.W. Frew, J.E. Hawkes, M. Sullivan‐Whalen, P. Gilleaudeau, J.G. Krueger
Journal: British Journal of Dermatology (2019)

Genotype–phenotype correlation measures the correlation between the presence of a physical trait with a group of similar mutations but is dependent on reliable phenotyping. It can provide information on disease pathogenesis, future disease progression, severity or activity. Such indicators would be valuable in hidradenitis suppurativa (HS). To assess inter‐rater reliability (IRR) of HS clinical phenotypes and perform exploratory genotype–phenotype correlation in cases of HS with identified sequence variants. Linkage disequilibrium between variants was assessed. Genotype–phenotype correlations were explored using Spearman correlation coefficients. IRR was calculated using Cohen's κ. Correlation between phenotype classifications was assessed using the χ2 statistic. Forty‐three sequence variants with clinical information were identified. Clinical phenotypes were classified as LC2 (n = 29; 67%), scarring folliculitis (n = 18; 42%), atypical (n = 38; 88%) and nodular (n = 26; 60%). LC1 phenotype was associated with regular (χ2 = 41·289, P < 0·001) and typical (χ2 = 29·013, P < 0·001) phenotypes. Cohen's κ was highest for van der Zee and Jemec (0·815), followed by Martorell‐Calatayud et al. (0·813), Naasan and Affleck (0·774) and Canoui‐Poitrine et al. (0·435) classifications. High linkage disequilibrium was seen between variants of Han Chinese pedigrees. No significant genotype–phenotype correlations were identified. These findings may be influenced by selection, publication bias and the assumption that HS is a monogenic disorder. The poor IRR of existing phenotype measures suggests limited utility of existing measures. Further investigations into the correlation of clinical phenotypes with inflammatory biomarkers may aid in prognostic efforts for this disease. What's already known about this topic? Genotype–phenotype correlation can provide information regarding disease pathogenesis and predictions for future disease progression, severity or activity. The identification of such indicators in hidradenitis suppurativa (HS) would be valuable for patients and clinicians alike, given the lack of biomarkers or clinical predictors of disease. What does this study add? Sixty‐five sequence variants across 20 separate genes were identified. There was no significant correlation between phenotype classification in four separate classification schema and gene, mutation type or impact on Notch signalling. Utility of current phenotype measurements are limited. The lack of genotype–phenotype correlation in HS is suggestive that the underlying assumption of inherited HS as a monogenic disorder may need revision.
Gastric adenocarcinoma prognosis in a multiracial population.
Authors: Jared David Acoba
Journal: Journal of Clinical Oncology (2019)

158 Background: Gastric adenocarcinoma is a major health issue, with a high prevalence among Asian and Pacific Islander populations. We analyzed a hospital tumor registry and demonstrated that in a multiracial population, patients who were uninsured and Filipinos with resectable disease had worse outcomes. To further investigate these findings, we performed a comprehensive analysis of the National Cancer Database. Methods: We analyzed data from 183,204 patients with gastric or gastroesophageal adenocarcinoma diagnosed between 2004 and 2015. Multivariable Cox proportional hazards regression models for survival were built adjusting for race, age at diagnosis, sex, insurance status, comorbidities, treatment facility type, histologic grade, stage, and treatment. Results: We included 86,663 patients in our analysis. Pacific Islanders presented at a younger age and higher stage. Asians had fewer comorbidities and were diagnosed at earlier stages. Older age (HR 1.97, 95% CI 1.92-2.03), lower income (HR 1.13, 1.11-1.16), more comorbidities (HR 1.59, 1.51-1.67), treatment at a community center (HR 1.22, 1.20-1.24), higher tumor grade (HR 2.00, 1.92-2.08), and advanced stage (HR 5.71, 5.57-5.85) were poor prognostic factors. Compared to whites, Asians had a more favorable prognosis (HR 0.74, 0.71-0.76). However, Filipino race was adversely associated with survival compared to other Asian races (HR 1.48, 1.29-1.69), even after adjusting for other prognostic factors. Conclusions: Asian race is an independent favorable prognostic factor. Among Asians, Filipinos did not fare as well even after adjusting for income, insurance status, comorbidities, stage and other prognostic factors. Further study in this area should be pursued. Given the differences in survival within the Asian race, studies exploring the relationship between race and cancer should consider analysis by subgroup.
Impact of Insulin and Metformin Versus Metformin Alone on β-Cell Function in Youth With Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes
Authors: Kristen J. Nadeau, Tamara S. Hannon, Sharon L. Edelstein, Silva A. Arslanian, Sonia Caprio, Ellen W. Leschek, Philip S. Zeitler, Thomas A. Buchanan, David A. Ehrmann, Kieren J. Mather, Steven E. Kahn, Susan Gross, Jayne Williams, Melanie Cree-Green, Yesenia Garcia Reyes, Krista Vissat, Kathleen Brown, Nancy Guerra, Kristin Porter, Mary Savoye, Bridget Pierpont, Tammy Garrett, Amale Lteif, Aniket Patel, Robin Chisholm, Karen Moore, Vivian Pirics, Linda Pratt, Karla A. Temple, Abby Rue, Elena Barengolts, Babak Mokhlesi, Eve Van Cauter, Susan Sam, M. Annette Miller, Karen M. Atkinson, Jerry P. Palmer, Kristina M. Utzschneider, Tsige Gebremedhin, Abigail Kernan-Schloss, Alexandra Kozedub, Brenda K. Montgomery, Emily J. Morse, Anny H. Xiang, Enrique Trigo, Elizabeth Beale, Fadi N. Hendee, Namir Katkhouda, Krishan Nayak, Mayra Martinez, Cortney Montgomery, Xinhui Wang, John M. Lachin, Ashley N. Hogan, Santica Marcovina, Jessica Harting, John Albers, Dave Hill, Peter J. Savage
Journal: Diabetes Care (2018)

OBJECTIVE Pediatric type 2 diabetes prevalence is increasing, with β-cell dysfunction key in its pathogenesis. The RISE Pediatric Medication Study compared two approaches—glargine followed by metformin and metformin alone—in preserving or improving β-cell function in youth with impaired glucose tolerance (IGT) or recently diagnosed type 2 diabetes during and after therapy withdrawal. RESEARCH DESIGN AND METHODS Ninety-one pubertal, overweight/obese 10–19-year-old youth with IGT (60%) or type 2 diabetes of &amp;lt;6 months duration (40%) were randomized to either 3 months of insulin glargine with a target glucose of 4.4–5.0 mmol/L followed by 9 months of metformin or to 12 months of metformin alone. β-Cell function (insulin sensitivity paired with β-cell responses) was assessed by hyperglycemic clamp at baseline, 12 months (on treatment), and 15 months (3 months off treatment). RESULTS No significant differences were observed between treatment groups at baseline, 12 months, or 15 months in β-cell function, BMI percentile, HbA1c, fasting glucose, or oral glucose tolerance test 2-h glucose results. In both treatment groups, clamp-measured β-cell function was significantly lower at 12 and 15 months versus baseline. HbA1c fell transiently at 6 months within both groups. BMI was higher in the glargine followed by metformin versus metformin alone group between 3 and 9 months. Only 5% of participants discontinued the interventions, and both treatments were well tolerated. CONCLUSIONS In youth with IGT or recently diagnosed type 2 diabetes, neither 3 months of glargine followed by 9 months of metformin nor 12 months of metformin alone halted the progressive deterioration of β-cell function. Alternate approaches to preserve β-cell function in youth are needed.
LPCD framework: Analytical tool or psychological model?
Authors: David Danks
Journal: Behavioral and Brain Sciences (2018)

Abstract The target article uses a mathematical framework derived from Bayesian decision making to demonstrate suboptimal decision making but then attributes psychological reality to the framework components. Rahnev &amp; Denison's (R&amp;D) positive proposal thus risks ignoring plausible psychological theories that could implement complex perceptual decision making. We must be careful not to slide from success with an analytical tool to the reality of the tool components.
Deep brain stimulation: current challenges and future directions
Authors: Andres M. Lozano, Nir Lipsman, Hagai Bergman, Peter Brown, Stephan Chabardes, Jin Woo Chang, Keith Matthews, Cameron C. McIntyre, Thomas E. Schlaepfer, Michael Schulder, Yasin Temel, Jens Volkmann, Joachim K. Krauss
Journal: Nature Reviews Neurology (2019)
Omalizumab Gets Tolerance In Patients With Severe Food Allergy: A Real-Life Study
Authors: Stefania Arasi, Maria C. Artesani, Carla Riccardi, Maurizio Mennini, Valentina Pecora, Vincenzo Fierro, Veronica Calandrelli, Lamia Dahdah, Rocco Valluzzi, Alessandro G. Fiocchi
Journal: Journal of Allergy and Clinical Immunology (2019)
Surgery versus surgery with adjuvant radiotherapy for T4 colon cancer.
Authors: Nikhil Sebastian, Eric David Miller, Dayssy Alexandra Diaz Pardo
Journal: Journal of Clinical Oncology (2019)

673 Background: There is no randomized prospective evidence to clarify the role of adjuvant radiotherapy in localized colon cancer. Despite this, national consensus guidelines recommend that adjuvant radiotherapy be considered for patients with T4 disease. Given the lack of prospective data, the aim of this study was to evaluate the role of adjuvant radiation therapy (RT) in colon cancer using two large national databases to help to guide treatment decisions. Methods: We evaluated the association of receipt of adjuvant RT with overall survival (OS), using the National Cancer Database (NCDB) and Surveillance, Epidemiology, and End Results Program (SEER), as well as with disease-specific survival (DSS) using SEER. We analyzed cohorts of patients with histologically confirmed locally advanced T4 adenocarcinoma of the colon, who underwent oncologic surgery with or without adjuvant radiation and had at least 5 years of follow up. For the NCDB cohort, we restricted RT patients to those who received a dose of 45-60 Gy and those who received treatment within 3 months after surgery. We used nearest-neighbor propensity score matching on the basis of age, race, sex, year of diagnosis, grade, N-stage, receipt of chemotherapy, anatomical subsite, margin status, and comorbidity score. To validate our findings, using SEER, we used propensity matching using the same covariates (except comorbidity). Results: After matching of the NCDB cohort, cox regression showed no statistically significant association of adjuvant radiotherapy with OS (HR=1.08; 95% CI 0.89 - 1.30; p=0.448). Using SEER, cox regression showed no statistically significant association of adjuvant radiotherapy with OS (HR=0.9; 95% CI 0.50 - 1.63; p=0.731) or DSS (HR=0.84; 0.54 – 1.33; p=0.46). Conclusions: In summary, after comprehensively adjusting for covariates using two independent national databases, we found no statistically significant association of adjuvant RT with overall- or disease-specific survival for T4 colon cancer. These findings are limited by the retrospective nature of the data and should be tested in a prospective fashion.
Adult Patients With Marfan Syndrome and Ascending Aortic Surgery
Authors: Milind Y. Desai, Vidyasagar Kalahasti, Erica Hutt Centeno, Kevin Chen, Alaa Alashi, Carlos Godoy Rivas, Eric E. Roselli, Douglas R. Johnston, Brian P. Griffin, Lars G. Svensson
Journal: Journal of the American College of Cardiology (2019)
Abstract 17845: Nucleostemin Maintains Cardiac Progenitor Cell “Stemness” and Cardiac Youth
Authors: Nirmala Hariharan, Pearl Quijada, Anya Joyo, Kaitlen Samse, Megan Monsanto, Andrea De La Torre, Mark Sussman
Journal: Circulation (2014)

Background: Functional decline in stem cell-mediated regeneration contributes to aging associated with cellular senescence in c-kit+ cardiac progenitor cells (CPCs). Clinical implementation of CPC-based therapy with elderly patients would benefit tremendously from understanding molecular characteristics of senescence to antagonize aging. Nucleostemin (NS) is a nucleolar protein regulating stem cell proliferation and pluripotency. This study demonstrates that NS preserves characteristics associated with “stemness” and antagonizes senescence in CPCs. Methods & Results: Human adult failing heart CPCs (AhCPCs) exhibit decreased NS expression (-56%) relative to fetal human heart CPCs (FhCPC) correlating with lowered proliferation potential and shortened telomere length (p<0.01) AhCPC characteristics resemble CPCs isolated from old mice (OCPCs) with flat, senescent, multinucleated cell phenotype. OCPC phenotype is induced by NS silencing resulting in cell flattening, senescence, multinucleated cells, decreased ...
Abstract B026: Axl may support dormancy of disseminated tumor cells by inducing cell clustering and decreasing proliferation of metastatic prostate cancer cells
Authors: Haley D. Axelrod, Kenneth C. Valkenburg, Jessica L. Hicks, Angelo M. DeMarzo, Kenneth J. Pienta
Journal: Cancer Research (2018)

Abstract While the majority of prostate cancer (PCa) patients are cured by radical prostatectomy and/or radiation, 10-15% of these men eventually develop recurrent disease in the form of lethal metastases. The most common site for PCa metastasis is the bone marrow. The time from primary tumor removal to recurrence can range from 1-2 years to decades, and constitutes a period of minimal residual disease in which cancer cells remain in the body but are clinically undetectable. It is thought that these disseminated tumor cells (DTCs) are able to maintain a state of cellular dormancy in the bone marrow in which they are not proliferating or dying, and may be the seeds for lethal metastases. By understanding the mechanism(s) that regulate dormancy, we may be able to prevent metastasis altogether. Our group has previously found that the secreted bone marrow factor Gas6 and the expression of its receptor Axl are associated with dormant DTCs in xenograft mouse models. Thus, we hypothesize that Gas6 signaling through Axl mediates dormancy. In this study, we sought to functionally support this hypothesis both in vitro and in human PCa tissue. Overexpression of Axl in the C42B PCa cell line decreased proliferation in vitro, and this was independent of Gas6 when Axl was highly overexpressed. Axl overexpression also led to aggregation of C42B cells, suggestive of a possible role in circulating tumor cell (CTC) clustering to survive the circulation and inhabit the bone marrow. Furthermore, immunohistochemical staining of a PCa tissue microarray showed almost no Axl positivity in cancer cells, regardless of Gleason score and other clinical outcomes. Negative staining was also observed in sections from liver, lymph node, and tibial metastases. Consistent with this, Axl expression correlates with decreased incidence of biochemical recurrence and increased overall survival in the GRID and TCGA databases, respectively. These results indicate an antiproliferative role for Axl in PCa, and suggest its temporal expression during the natural history of PCa. Ongoing work includes assessing the expression of Axl on patient CTCs and DTCs, and using xenograft mouse models of metastasis to analyze the effects of Axl overexpression and knockout in PCa cell lines. Citation Format: Haley D. Axelrod, Kenneth C. Valkenburg, Jessica L. Hicks, Angelo M. DeMarzo, Kenneth J. Pienta. Axl may support dormancy of disseminated tumor cells by inducing cell clustering and decreasing proliferation of metastatic prostate cancer cells [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B026.
Siglec‐7 on peripheral blood eosinophils: Surface expression and function
Authors: Fanny Legrand, Nadine Landolina, Ilan Zaffran, Robert O. Emeh, Elizabeth Chen, Amy D. Klion, Francesca Levi‐Schaffer
Journal: Allergy (2019)

Abstract Background Siglec‐7 is an inhibitory receptor ( IR ) expressed on human blood eosinophils. Whereas activation of other IR s, including Siglec‐8 and CD 300a, has been shown to downregulate eosinophil function, little is known about the role of Siglec‐7 on human eosinophils. Objective To examine Siglec‐7 expression and function in eosinophils from normal ( ND ) and eosinophilic ( EO ) donors. Methods Eosinophil expression of Siglec‐7 was quantified by flow cytometry and quantitative PCR . Soluble Siglec‐7 (sSiglec‐7) levels were measured by ELISA in serum. The effect of Siglec‐7 on eosinophil viability and degranulation was assessed in vitro by AnnexinV‐ FITC /7‐ AAD staining and by measuring GM ‐ CSF ‐induced mediator release in culture supernatants. Signal transduction was studied by Western blot. Results Siglec‐7 was expressed ex vivo on blood eosinophils from all eosinophilic and normal individuals studied. Siglec‐7 surface, but not SIGLEC ‐7 mRNA expression, was correlated with absolute eosinophil count ( AEC ). Siglec‐7 was upregulated on purified eosinophils after in vitro stimulation with GM ‐ CSF or IL ‐5. Serum sSiglec‐7 was detectable in 133/144 subjects tested and correlated with AEC . Siglec‐7 cross‐linking inhibited GM ‐ CSF ‐induced release of eosinophil peroxidase, TNF ‐α, and IL ‐8 (n = 7–8) but did not promote eosinophil apoptosis (n = 5). Finally, Siglec‐7 cross‐linking on GM ‐ CSF ‐activated eosinophils induced phosphorylation of SHP ‐1 and de‐phosphorylation of ERK 1/2 and p38. Conclusions Siglec‐7 is constitutively expressed on human eosinophils and downmodulates eosinophil activation. Targeting of Siglec‐7 on eosinophils might enhance treatment efficacy in eosinophil‐driven disorders. Conversely, therapeutic interventions that inhibit Siglec‐7 could have unanticipated consequences and promote eosinophilic inflammation.