tbuckley/cabot-search huggingface dataset:
Measurement of urinary kininogen (KNG) fragments as a noninvasive tool for early diagnosis of pancreatic cancer (PaCa).
Authors: Izumi Ohno, Shuichi Mitsunaga, Motoyasu Kan, Masafumi Ikeda, Hironobu Tsubouchi, Shigehisa Yanagi, Nobuhiro Matsumoto, Nobuaki Okumura, Toshifumi Takao, Masamitsu Nakazato
Journal: Journal of Clinical Oncology (2019)

209 Background: There is a clear need to identify a non-invasive biomarker for early diagnosis of PaCa, in order to improve the overall survival of PaCa patients. Secretion of large amounts of proteases is a hallmark of PaCa, which results in an abundance of protease-induced cleavage products being excreted in the urine. This has led to speculation that measurement of PaCa-specific fragments in the urine might be useful as a tool for discrimination between PaCa patients and healthy controls. Herein, we introduce urinary KNG fragments as a promising biomarker for early diagnosis of PaCa. Methods: Urine samples were collected from PaCa patients and healthy volunteers, with the written informed consent, from January 2014 to July 2016. Urinary protein tryptic fragments derived from protein C-termini were measured using isobaric tags (iTRAQ) for their relative quantitation, and the diagnostic ability of the urinary levels of these fragments was evaluated by receiver operating characteristic (ROC) curve analysis. The fragments which showed an area-under-the-curve (AUC) of over 0.8 were selected as candidate fragments for further validation by the multiple-reaction-monitoring technique (MRM) combined with high-speed liquid chromatography. The urinary level of each candidate fragment was quantified by MRM, and the diagnostic capability of each for discriminating PaCa patients from healthy controls was evaluated by ROC curve analysis. Results: Urine samples of 39 PaCa patients (7 resectable, 32 unresectable) and 42 healthy controls were examined by iTRAQ to find 12,783 fragments. ROC curve analysis was carried out to select two candidate fragments (fragments A, B), both of which turned out to be KNG cleavage products. The urinary levels of the two fragments were measured in 23 resectable PaCa, 118 unresectable PaCa patients, and 42 healthy volunteers using high-speed-LC-/MRM. The AUCs of serum CA19-9 and urinary levels of fragments A and B for discriminating patients of PaCa from healthy controls were 0.89, 0.81 and 0.70, respectively. Conclusions: Urinary KNG fragments showed favorable diagnostic capability and were considered as promising, noninvasively measurable biomarkers of PaCa.
Inhaled corticosteroids preventing pneumonia mortality: paradox or selection bias?
Authors: Samy Suissa
Journal: European Respiratory Journal (2019)

<b>The "paradoxical" effect of inhaled corticosteroids increasing pneumonia incidence but reducing post-pneumonia mortality in COPD is no paradox but due to selection bias: inhaled corticosteroids increase pneumonia incidence and pneumonia-related mortality</b>http://ow.ly/Yvfa30nb48V
Abstract 21287: Myocardial Oxygen Delivery is Progressively Impaired During Development of Pulmonary Hypertension
Authors: Richard W van Duin, Zongye Cai, Dirk J Duncker, Daphne Merkus
Journal: Circulation (2017)

Introduction: Pulmonary hypertension (PH) increases afterload of the right ventricle (RV), initially resulting in RV hypertrophy. Eventually the RV is unable to cope with the high afterload, resulting in RV failure and death. The transition of RV hypertrophy to failure is incompletely understood. Hypothesis: The increased workload together with the RV hypertrophy increases oxygen demand of the myocardium, which is insufficiently compensated by an increase in myocardial oxygen supply through the right coronary vasculature. This mismatch between oxygen supply and demand is exacerbated during physical activity when oxygen demand increases. Methods: PH was induced by banding of the confluent of the inferior pulmonary vein in juvenile swine (N=5), while 5 healthy swine served as controls. Swine were chronically instrumented to measure pressure in the RV, pulmonary artery, left atrium and aorta, and right coronary blood flow (CBF) rest and during graded treadmill exercise. Results: Pulmonary venous banding (PVB) resulted in PH as evidenced by an increase in pulmonary artery pressure (PVB: 29±1 mmHg (week 5) and 39±3 mmHg (week 12); CON 20±1 mmHg and 21±1 mmHg, both P&lt;0.05) that was accompanied by RV hypertrophy (RV/bodyweight 1.18±0.05 (CON), 1.70±0.15 (PVB), P=0.06). The relation between myocardial oxygen delivery (CBF*arterial oxygen content) and Myocardial work (heartrate*pulmonary artery pressure) was not different between CON and PVB at week 5 , but rotated downwards at week 12 weeks (Figure), indicative of a mismatch between oxygen supply and demand. Histology revealed an increase in cardiomyocyte size (717±35 vs 598±30 μm 2 , P&lt;0.05), whereas capillary density and interstitial fibrosis were not changed. Conclusions: Progression of PH leads to a mismatch between myocardial oxygen supply and demand, particularly during exercise. This mismatch between supply and demand may cause myocardial ischemia and contribute to the transition of RV hypertrophy to failure.
Abstract 11195: Differences in ST-T Changes Between Takotsubo Cardiomyopathy and Reperfused Non-Q-Wave Anterior Acute Myocardial Infarction
Authors: Masami Kosuge, Toshiaki Ebina, Kiyoshi Hibi, Noriaki Iwahashi, Nobuhiko Maejima, Yasushi Matsuzawa, Kazuo Kimura
Journal: Circulation (2016)

Introduction: In both takotsubo cardiomyopathy (TC) and reperfused non-Q-wave anterior acute myocardial infarction (AMI), giant negative T waves (Neg T) commonly appear after the resolution of ST-segment elevation (ST elevation) in precordial leads, reflecting viable but sympathetically denervated myocardium. Hypothesis: ST-T changes may differ between between TC and reperfused non-Q-wave anterior AMI, reflecting the differences in underlying electrophysiologic mechanisms between these 2 diseases. Methods: We studied 38 patients with TC and 253 with a first non-Q-wave anterior AMI who were admitted within 6 hours after symptom onset. All patients with anterior AMI underwent emergency coronary angiography, and the occlusion of the left anterior descending coronary artery was documanted and successful reperfusion (TIMI grade 3) was obtained. ECGs on admission and those with the greatest amplitude of subsequent Neg T (mean 2 days later) were studied. Results: As compared with patients with anterior AMI, those with TC were older (70 ± 11 vs 62 ± 11 years, p &lt; 0.01), more likely to be women (84% vs 20%, p&lt;0.01) and had a lower peak creatine kinase (461 ± 493 vs 1506 ± 934 mU/ml, p&lt;0.01) despite lower left ventricular ejection fraction on admission (40 ± 9 vs 51 ± 10%, p &lt; 0.01), respectively. TC was associated with a smaller maximal ST elevation on admission (4.6 ± 4.7 vs 5.9 ± 3.1 mm, p&lt;0.01), a greater maximal amplitude of Neg T (10.0 ± 4.1 vs 8.0 ± 4.8 mm, p &lt; 0.01), a greater number of leads with Neg T (9 ± 1 vs 6 ± 2, p &lt; 0.01) and a longer maximal QTc interval (643 ± 99 vs 586 ± 79 ms, p &lt; 0.01) in subacute phase, respectively. The prevalences of initial ST elevation and subsequent Neg T differed between TC and anterior AMI (Figure). Conclusions: ST-T changes in the acute and subacute phases clearly differed between TC and reperfused non-Q-wave anterior AMI. In TC, deeper NegT were more broadly distributed, suggesting that TC might be associated with more extensive viable but denervated myocardium.
Incidence of Post-Hematopoietic Stem Cell Transplantation (HSCT) Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome (VOD/SOS) without Hyperbilirubinemia at Diagnosis and Efficacy of Defibrotide in an Expanded-Access Program
Authors: Selim Corbacioglu, Nancy A. Kernan, Antonio Pagliuca, Robert Ryan, William Tappe, Paul Richardson
Journal: Blood (2018)
A Syndrome of IgA-Related Polycythemia
Authors: Camille Cohen, Severine Coulon, Kanit Bhukai, Michael Dussiot, Antoine Neuraz, Martin Flamant, Francois Vrstovsnik, Aurélie Hummel, Bertrand Knebelmann, Laurent Mesnard, Eric Rondeau, Marc Benhamou, Christophe Legendre, Olivier Hermine, Khalil El Karoui, Ivan C Moura
Journal: Blood (2017)
Treatment of Recurrent<i>Clostridium difficile</i>Infection—Reply
Authors: Sahil Khanna, Arjun Gupta, Adam S. Cifu
Journal: JAMA (2019)

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Patterns of Cause-Specific Mortality Among 2053 Survivors of Retinoblastoma, 1914–2016
Authors: Ruth A Kleinerman, Margaret A Tucker, Byron S Sigel, David H Abramson, Johanna M Seddon, Lindsay M Morton
Journal: JNCI Journal of the National Cancer Institute (2018)

Abstract Background Previous studies of hereditary retinoblastoma survivors have reported elevated mortality, particularly for sarcomas, compared with the general population. However, cause-specific mortality patterns for long-term hereditary and nonhereditary retinoblastoma survivors are poorly understood. Methods Among 2053 retinoblastoma patients diagnosed during 1914–2006 at two major US treatment centers and followed to 2016, we estimated cumulative mortality, standardized mortality ratios (SMRs), and absolute excess risks (AERs) compared with the US general population. Results Most deaths occurred in 1129 hereditary retinoblastoma patients (n = 518 deaths, cumulative mortality 70 years after retinoblastoma = 75.8%, 95% CI = 69.0% to 82.6%; SMR = 8.5, 95% CI = 7.7 to 9.2). Of these, 267 were due to subsequent cancers (SMR = 27.4, 95% CI = 24.2 to 30.9; AER = 72.3 deaths/10 000 person-years), for which SMRs were highest 15–29 years after diagnosis (n = 69, SMR = 89.9, 95% CI = 70.0 to 113.8) but remained statistically significantly elevated at 60 and more years (n = 14, SMR = 6.7, 95% CI = 3.6 to 11.2), whereas AERs increased with time (AER&lt;15years = 38.0; AER60+years = 327.5). Increased risk of death due to cancers of pancreas, large intestines, and kidney were noted for the first time. Overall risk of subsequent cancers was greater for those treated with radiotherapy and chemotherapy compared to radiotherapy alone, although patterns varied by organ site. For 924 patients with nonhereditary retinoblastoma, we noted a modestly increased risk of death for subsequent cancers (n = 27, SMR = 1.8, 95% CI = 1.2 to 2.6) possibly due to treatment or misclassification of hereditary status. Risks of noncancer causes of death were not elevated for hereditary or nonhereditary patients. Conclusion Hereditary retinoblastoma survivors died mainly from an excess risk of subsequent cancers up to six decades later, highlighting the need to develop long-term clinical management guidelines for hereditary retinoblastoma survivors treated in the past.
Blood and Marrow Transplantation (BMT) in Acute Leukemia Patients in Cuba: Current Results and Future Opportunities through International Collaboration
Authors: Calixto Hernandez Cruz, Jose Carnot Uria, Jorge Munio Perurena, Wilfredo Torres Yribar, Jesus Diego de la Campa, Yusaima Rodriguez Fraga, Julio Antonio Lopez Silva, Isbel Moya Perez, Carmen Rosa Rodriguez Rodriguez, Kali Cepero Llauger, Ibis Karina Pardo Ramirez, Karen Sweiss, Pritesh R. Patel, Damiano Rondelli
Journal: Blood (2016)
Abstract 14852: Clinical Performance of The HeartBuds, an Electronic Smartphone Listening Device, Compared to FDA Approved Class I and Class II Stethoscopes
Authors: Ritesh S Patel, Julio Schwarz, Valerie Danesh, Arnold M Einhorn, David Bello
Journal: Circulation (2015)

Background: Auscultation with stethoscopes is essential to the physical exam. However, the stethoscope has not appreciably changed since Leared and Cammann developed the first binaural stethoscopes in the mid 1800s. Technological advances make it possible to use smartphone technology to auscultate patients. The HeartBuds, a listening device that integrates with an iPhone app, achieves this purpose. The purpose of this study was to compare HeartBuds’ acoustic superiority over the FDA approved class I blue disposable stethoscopes, which are commonly used in practice to reduce hospital infection rates, and demonstrate equivalence to the gold standard FDA class I analog stethoscope, the Littmann Cardiology III, and the FDA class II digital stethoscope, the Littmann Electronic 3200. Methods: 50 adult patients were auscultated with each of the above-mentioned stethoscopes by two independent examiners. They rated their acoustic quality and completed surveys documenting body sounds heard. Results: The disposable stethoscope was significantly worse at identifying cardiac murmurs (p&lt;0.002), and performed poorly when auscultating for carotid bruits (p&lt;0.058). The HeartBuds stethoscope was equivalent to its more commonly used counterparts, the Littmann Cardiology III and the Littmann Electronic 3200. Examiners also found it to be of comparable acoustic quality to these models. Conclusion: HeartBuds is a smartphone compatible listening device that was superior in examining cardiovascular sounds to approved FDA Class I disposable stethoscopes, and equivalent to FDA approved class I and class II Littmann stethoscopes.
The antifibrotic potential of a sustained release formulation of a PDGFβ-receptor targeted rho kinase inhibitor
Authors: F. van Dijk, N. Teekamp, E. Post, D. Schuppan, Y.O. Kim, J. Zuidema, R. Steendam, Matthias H.M. Klose, Samuel M. Meier-Menches, A. Casini, P.L. Horvatovich, N.J. Sijbrandi, H.W. Frijlink, W.L.J. Hinrichs, K. Poelstra, L. Beljaars, P. Olinga
Journal: Journal of Controlled Release (2019)

Rho kinase activity in hepatic stellate cells (HSCs) is associated with activation, transformation and contraction of these cells, leading to extracellular matrix production and portal hypertension in liver cirrhosis. Inhibition of rho kinase activity can reduce these activities, but may also lead to side effects, for instance systemic hypotension. This can be circumvented by liver-specific delivery of a rho kinase inhibitor to effector cells. Therefore, we targeted the rho kinase inhibitor Y27632 to the key pathogenic cells in liver fibrosis, i.e. myofibroblasts including activated HSCs that highly express the PDGFβ-receptor, using the drug carrier pPB-MSA. This carrier consists of mouse serum albumin (MSA) covalently coupled to several PDGFβR-recognizing moieties (pPB). We aimed to create a prolonged release system of such a targeted construct, by encapsulating pPB-MSA-Y27632 in biodegradable polymeric microspheres, thereby reducing short-lasting peak concentrations and the need for frequent administrations. Firstly, we confirmed the vasodilating potency of PDGFβ-receptor targeted Y27632 in vitro in a contraction assay using HSCs seeded on a collagen gel. We subsequently demonstrated the in vivo antifibrotic efficacy of pPB-MSA-Y27632-loaded microspheres in the Mdr2-/- mouse model of progressive biliary liver fibrosis. A single subcutaneous microsphere administration followed by organ harvest one week later clearly attenuated liver fibrosis progression and significantly suppressed the expression of fibrosis related genes, such as several collagens, profibrotic cytokines and matrix metalloproteinases. In conclusion, we demonstrate that polymeric microspheres are suitable as drug delivery system for the sustained systemic delivery of targeted protein constructs with antifibrotic potential, such as pPB-MSA-Y27632. This formulation appears suitable for the sustained treatment of liver fibrosis and possibly other chronic diseases.
Mutational Signature Analysis Reveals NTHL1 Deficiency to Cause a Multi-tumor Phenotype
Authors: Judith E. Grolleman, Richarda M. de Voer, Fadwa A. Elsayed, Maartje Nielsen, Robbert D.A. Weren, Claire Palles, Marjolijn J.L. Ligtenberg, Janet R. Vos, Sanne W. ten Broeke, Noel F.C.C. de Miranda, Renske A. Kuiper, Eveline J. Kamping, Erik A.M. Jansen, M. Elisa Vink-Börger, Isabell Popp, Alois Lang, Isabel Spier, Robert Hüneburg, Paul A. James, Na Li, Marija Staninova, Helen Lindsay, David Cockburn, Olivera Spasic-Boskovic, Mark Clendenning, Kevin Sweet, Gabriel Capellá, Wenche Sjursen, Hildegunn Høberg-Vetti, Marjolijn C. Jongmans, Kornelia Neveling, Ad Geurts van Kessel, Hans Morreau, Frederik J. Hes, Rolf H. Sijmons, Hans K. Schackert, Clara Ruiz-Ponte, Dagmara Dymerska, Jan Lubinski, Barbara Rivera, William D. Foulkes, Ian P. Tomlinson, Laura Valle, Daniel. D. Buchanan, Sue Kenwrick, Julian Adlard, Aleksandar J. Dimovski, Ian G. Campbell, Stefan Aretz, Detlev Schindler, Tom van Wezel, Nicoline Hoogerbrugge, Roland P. Kuiper
Journal: Cancer Cell (2019)
Dynamic Renal Ptosis Demonstrated on 18F-FDG PET/CT
Authors: Justin Taylor, Kalpna Prasad, Rebecca Rohrer
Journal: Clinical Nuclear Medicine (2019)

Renal ptosis, otherwise known as nephroptosis or "floating kidney," is a condition of abnormal descent of the kidney, often asymptomatic with controversy over its clinical and therapeutic significance. The aberrant location of renal and renal collecting system activity associated with this condition may serve as a diagnostic pitfall in PET/CT interpretation. We report a case of dynamic renal ptosis demonstrated on F-FDG PET/CT, identified as right kidney migration from an ectopic location on attenuation correction CT images, obtained immediately after upright positioning, to the right renal fossa on subsequent PET images, obtained after approximately 10 min of supine positioning.
Reply to: “Comment on ‘Oral diabetes medications other than dipeptidyl peptidase-4 inhibitors are not associated with bullous pemphigoid: A Finnish nationwide case-control study’ and a case report of glucagon-like peptide-1 receptor agonist–induced bullous pemphigoid”
Authors: Outi Varpuluoma, Kaisa Tasanen, Laura Huilaja
Journal: Journal of the American Academy of Dermatology (2019)
Prevalence, Treatment, and Outcomes of Coexistent Pulmonary Hypertension and Interstitial Lung Disease in Systemic Sclerosis
Authors: Amber Young, Dharshan Vummidi, Scott Visovatti, Kate Homer, Holly Wilhalme, Eric S. White, Kevin Flaherty, Vallerie McLaughlin, Dinesh Khanna
Journal: Arthritis & Rheumatology (2019)

Systemic sclerosis (SSc) is associated with interstitial lung disease (ILD) and pulmonary hypertension (PH). This study was undertaken to determine the prevalence, characteristics, treatment, and outcomes of PH in a cohort of patients with SSc-associated ILD.
Assessment of Bidirectional Relationships Between Physical Activity and Depression Among Adults
Authors: Karmel W. Choi, Chia-Yen Chen, Murray B. Stein, Yann C. Klimentidis, Min-Jung Wang, Karestan C. Koenen, Jordan W. Smoller
Journal: JAMA Psychiatry (2019)

Increasing evidence shows that physical activity is associated with reduced risk for depression, pointing to a potential modifiable target for prevention. However, the causality and direction of this association are not clear; physical activity may protect against depression, and/or depression may result in decreased physical activity.
Abstract A06: LINC00261 acts as a tumor suppressor in lung adenocarcinoma
Authors: Jonathan Castillo, Shandy Shahabi, Vishaly Kumaran, Crystal Marconett
Journal: Clinical Cancer Research (2018)

Abstract Lung cancer is the leading cause of cancer-related mortality, with a 5-year mortality rate approaching 85%. My lab focuses on the major histologic subtype, lung adenocarcinoma (LUAD). Using a combination of bioinformatics and biologic analyses, we have uncovered a role for novel regulatory RNAs in the etiology of LUAD development. Our current research focuses primarily on a long noncoding RNA with effects on proliferation and metastasis of lung cancer cells. It is our hope to identity key regulators of cancer development and progression, so that targeted therapeutics can be developed to help improve the overall survival rate for this deadly disease. Citation Format: Jonathan Castillo, Shandy Shahabi, Vishaly Kumaran, Crystal Marconett. LINC00261 acts as a tumor suppressor in lung adenocarcinoma [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr A06.