tbuckley/cabot-search huggingface dataset:
Traditional Cardiovascular Risk Factors and Individual Prediction of Cardiovascular Events in Childhood Cancer Survivors
Authors: Yan Chen, Eric J Chow, Kevin C Oeffinger, William L Border, Wendy M Leisenring, Lillian R Meacham, Daniel A Mulrooney, Charles A Sklar, Marilyn Stovall, Leslie L Robison, Gregory T Armstrong, Yutaka Yasui
Journal: JNCI Journal of the National Cancer Institute (2019)

Abstract Background Childhood cancer survivors have an increased risk of heart failure, ischemic heart disease, and stroke. They may benefit from prediction models that account for cardiotoxic cancer treatment exposures combined with information on traditional cardiovascular risk factors such as hypertension, dyslipidemia, and diabetes. Methods Childhood Cancer Survivor Study participants (n = 22 643) were followed through age 50 years for incident heart failure, ischemic heart disease, and stroke. Siblings (n = 5056) served as a comparator. Participants were assessed longitudinally for hypertension, dyslipidemia, and diabetes based on self-reported prescription medication use. Half the cohort was used for discovery; the remainder for replication. Models for each outcome were created for survivors ages 20, 25, 30, and 35 years at the time of prediction (n = 12 models). Results For discovery, risk scores based on demographic, cancer treatment, hypertension, dyslipidemia, and diabetes information achieved areas under the receiver operating characteristic curve and concordance statistics 0.70 or greater in 9 and 10 of the 12 models, respectively. For replication, achieved areas under the receiver operating characteristic curve and concordance statistics 0.70 or greater were observed in 7 and 9 of the models, respectively. Across outcomes, the most influential exposures were anthracycline chemotherapy, radiotherapy, diabetes, and hypertension. Survivors were then assigned to statistically distinct risk groups corresponding to cumulative incidences at age 50 years of each target outcome of less than 3% (moderate-risk) or approximately 10% or greater (high-risk). Cumulative incidence of all outcomes was 1% or less among siblings. Conclusions Traditional cardiovascular risk factors remain important for predicting risk of cardiovascular disease among adult-age survivors of childhood cancer. These prediction models provide a framework on which to base future surveillance strategies and interventions.
Esthesioneuroblastoma on 68Ga DOTANOC PET/CT
Authors: Sarthak Tripathy, Rakesh Kumar, Aanchal Kakkar, Rajeev Kumar, Prateek Sharma, Shamim Ahmed Shamim
Journal: Clinical Nuclear Medicine (2019)

Abstract Esthesioneuroblastoma is a rare neoplasm arising from the neural crest cells of olfactory epithelium mostly in the nasal vault. We describe the 68 Ga DOTANOC PET/CT findings of a 44-year-old woman who was operated for right nasal mass diagnosed as paraganglioma in the past and then develop a mass in the right nasal cavity after 2 years which upon surgery diagnosed to be esthesioneuroblastoma on histopathology.
HIF1A Is a Critical Downstream Mediator for Hemophagocytic Lymphohistiocytosis
Authors: Yoshihiro Hayashi, Rui Huang, Xiaomei Yan, Jiachen Bu, Jieyu Wang, Yue Zhang, Yile Zhou, Yuting Tang, Lingyun Wu, Zefeng Xu, Xin Liu, Qianfei Wang, Jianfeng Zhou, Zhijian Xiao, James P Bridges, Rebecca A Marsh, Kejian Zhang, Michael B. Jordan, Yuhua Li, Gang Huang
Journal: Blood (2017)
Severe disseminated tuberculosis in HIV-negative refugees
Authors: Isabelle Suárez, Sarah Maria Fünger, Norma Jung, Clara Lehmann, Robert Peter Reimer, Dennis Mehrkens, Anne Bunte, Georg Plum, Natalie Jaspers, Matthias Schmidt, Gerd Fätkenheuer, Jan Rybniker
Journal: The Lancet Infectious Diseases (2019)
Environmental Electrophile-Mediated Toxicity in Mice Lacking Nrf2, CSE, or Both
Authors: Masahiro Akiyama, Takamitsu Unoki, Yasuhiro Shinkai, Isao Ishii, Tomoaki Ida, Takaaki Akaike, Masayuki Yamamoto, Yoshito Kumagai
Journal: Environmental Health Perspectives (2019)

Background: Transcription factor Nrf2 (nuclear factor-erythroid 2-related factor 2) plays a key role in detoxification of electrophiles via formation of glutathione (GSH) adducts and subsequent excretion into extracellular spaces. We found that reactive sulfur species (RSS), such as cysteine persulfides produced by cystathionine γ-lyase (CSE), capture environmental electrophiles through formation of sulfur adducts. However, contributions of Nrf2 and CSE to the blockage of environmental electrophile-mediated toxicity remain to be evaluated. Objectives: The aim of this study was to clarify roles that CSE and Nrf2 play in the protection against various environmental electrophiles. We also wished to clarify the molecular basis of the developmental window of toxicity through investigating expression levels of Nrf2, RSS-producing enzymes, and sulfur nucleophiles during developmental stages of mice. Methods: Wild-type (WT), CSE knockout (KO), Nrf2 KO, Nrf2/CSE double KO (DKO) mice, and their primary hepatocytes were analyzed in this study. Cadmium (Cd), methylmercury (MeHg), 1,4-naphthoquinone, crotonaldehyde, and acrylamide were used. We conducted Western blotting, real-time polymerase chain reaction (PCR), 3-(4,5-dimethylthiazol-2-yl)-2,5-triphenyl tetrazolium bromide (MTT) assays, liquid chromatography–electrospray ionization–tandem mass spectrometry (LC-ESI-MS/MS) analysis, alanine transaminase (ALT) activity, histopathological analysis, and rotarod test. Results: Primary hepatocytes from DKO mice were significantly more sensitive to the environmental electrophiles than each single KO counterpart. Both Nrf2 and CSE single KO mice were highly susceptible to Cd and MeHg, and such sensitivity was further exacerbated in the DKO mice. Lower-level expressions of CSE and sulfur nucleophiles than those in adult mice were observed in a window of developmental stage. Conclusions: Our mouse model provided new insights into the response to environmental electrophiles; while Nrf2 is recognized as a key transcription factor for detoxification of environmental electrophiles, CSE is crucial factor to repress their toxicity in a parallel mode. In addition, the sensitivity of fetuses to MeHg appears to be, at least in part, associated with the restricted production of RSS due to low-level expression of CSE. https://doi.org/10.1289/EHP4949
Hemostatic Efficacy of Pathogen-Inactivated Buffy Coat-Derived Platelet Concentrates in Hemato-Oncological Patients: Outcomes of the Prepares Trial
Authors: Pieter F. Van Der Meer, Paula F Ypma, Nan van Geloven, Rinie van Wordragen-Vlaswinkel, Anske van der Bom, Jean-Louis Kerkhoffs
Journal: Blood (2017)
Association of Habitual Daily Physical Activity With Glucose Tolerance and β-Cell Function in Adults With Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes From the Restoring Insulin Secretion (RISE) Study
Authors: Karla A. Temple, Ashley H. Tjaden, Karen M. Atkinson, Elena Barengolts, Tamara S. Hannon, Kieren J. Mather, Kristina M. Utzschneider, Sharon L. Edelstein, David A. Ehrmann, Babak Mokhlesi, Philip S. Zeitler, Jayne Williams, Melanie Cree-Green, Yesenia Garcia Reyes, Krista Vissat, David A. Ehrmann, Karla A. Temple, Abby Rue, Elena Barengolts, Babak Mokhlesi, Eve Van Cauter, Susan Sam, M. Annette Miller, Steven E. Kahn, Karen M. Atkinson, Jerry P. Palmer, Kristina M. Utzschneider, Tsige Gebremedhin, Abigail Kernan-Schloss, Alexandra Kozedub, Brenda K. Montgomery, Emily J. Morse, Kieren J. Mather, Tammy Garrett, Tamara S. Hannon, Amale Lteif, Aniket Patel, Robin Chisholm, Karen Moore, Vivian Pirics, Linda Pratt, Kristen J. Nadeau, Susan Gross, Peter J. Savage, Ellen W. Leschek, Silva A. Arslanian, Kathleen Brown, Nancy Guerra, Kristin Porter, Sonia Caprio, Mary Savoye, Bridget Pierpont, Thomas A. Buchanan, Anny H. Xiang, Enrique Trigo, Elizabeth Beale, Fadi N. Hendee, Namir Katkhouda, Krishan Nayak, Mayra Martinez, Cortney Montgomery, Xinhui Wang, Sharon L. Edelstein, John M. Lachin, Ashley H. Tjaden, Santica Marcovina, Jessica Harting, John Albers, Dave Hill
Journal: Diabetes Care (2019)

OBJECTIVE We examined the relationship between habitual daily physical activity and measures of glucose tolerance, insulin sensitivity, and β-cell responses in adults with impaired glucose tolerance (IGT) or drug-naive, recently diagnosed type 2 diabetes. RESEARCH DESIGN AND METHODS Participants included 230 adults (mean ± SD age 54.5 ± 8.5 years, BMI 35 ± 5.5 kg/m2; 42.6% women) who underwent a 3-h oral glucose tolerance test (OGTT) and hyperglycemic clamp. Wrist accelerometers worn for 7 consecutive days measured total physical activity counts (TAC) (daily mean 233,460 [∼50th percentile for age]). We evaluated whether TAC was associated with fasting plasma glucose, OGTT 2-h plasma glucose or glucose incremental area under the curve (G-iAUC), hyperglycemic clamp measures of insulin sensitivity (steady-state glucose infusion rate/insulin [M/I]) and β-cell responses (acute C-peptide response to glucose, steady-state C-peptide, and maximal β-cell response), and OGTT C-peptide index (ΔC-peptide0–30/Δglucose0–30). RESULTS After adjustments for confounders, there was no association of TAC with fasting plasma glucose, 2-h glucose, or G-iAUC. Higher TAC was associated with higher insulin sensitivity (M/I). After adjusting for M/I, higher TAC was not associated with measures of β-cell response. CONCLUSIONS In adults with IGT or drug-naive, recently diagnosed type 2 diabetes, higher levels of habitual physical activity are associated with higher insulin sensitivity. Further studies are needed to understand why higher levels of physical activity are not associated with better β-cell response.
Abstract 20658: Propensity Matched Analysis of Percutaneous Coronary Interventions vs Coronary Artery Bypass Grafting in Chronic Total Coronary Occlusions
Authors: Nirali Patel, Sopan Lahewala, Prashant Patel, Varun Kumar, Smit Patel, Mihir Dave, Byomesh Tripathi, Priti Malik, Vishwa Kundoor, Abhishek Mishra, Harshil Shah, Shilpkumar Arora, Sidakpal Panaich, Apurva Badheka
Journal: Circulation (2017)

Introduction: Chronic total coronary occlusions (CTO) are frequent and found in up to half of the patients with CAD referred for elective angiography. Despite technical advancements in CTO interven...
Type I Collagen–targeted Positron Emission Tomography Imaging in Idiopathic Pulmonary Fibrosis: First-in-Human Studies
Authors: Sydney B. Montesi, David Izquierdo-Garcia, Pauline Désogère, Eric Abston, Lloyd L. Liang, Subba Digumarthy, Ravi Seethamraju, Michael Lanuti, Peter Caravan, Ciprian Catana
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

mortality trends.Data from the Office of National Statistics suggest that the number of deaths assigned to the respiratory chapter as a whole decreased by 22% as a result of the introduction of ICD-10 codes, largely driven by the decrease in number of deaths assigned to pneumonia (10).It is possible that this may have resulted in further underestimating the actual number of IPF-CS-related deaths.These findings are consistent with our work demonstrating a progressive increase in IPF mortality in the United Kingdom (1, 2, 11).Increased case ascertainment could be a contributing factor to the trends seen, but it is also possible that the true incidence of IPF has continued to increase.If the marked increase in number of deaths is purely due to increased disease recognition, there is no evidence that ascertainment is complete, and continued upward trends in mortality are likely to be seen.In summary, IPF-CS now accounts for almost 7% of all respiratory deaths in the United Kingdom (4) and carries the same mortality burden as liver, bladder, and intracranial malignancies.Despite increasing research investment, it remains an important cause of respiratory mortality and a growing public health problem.
Abstract 13092: Clinical Results Indicating Effectiveness of PMZ-2010 (Centhaquin) as a Novel Resuscitative Agent for Hypovolemic Shock
Authors: Anil Gulati, Dinesh Jain, Nilesh R Agrawal, Soumen Das, Rajat Chowdhuri, Madhav Prabhu, Sameer Haveri, Rohit Agarwal, Manish S Lavhale
Journal: Circulation (2018)

Introduction: PMZ-2010 (centhaquin), was found to be a highly effective resuscitative agent in animal models of hemorrhagic shock and is currently in clinical development (CTRI/2017/03/008184). Met...
Abstract 12752: Optimal Myocardial Revascularization in the Era of Off-pump Coronary Surgery/Drug-eluting Stent: Insights from the CREDO-Kyoto Registry Cohort 2
Authors: Akira Marui, Takeshi Kimura, Michiya Hanyu, Tatsuhiko Komiya, Toru Kita, Ryuzo Sakata, CREDO-Kyoto Investigators
Journal: Circulation (2012)

Background: The current increase of percutaneous coronary intervention (PCI) with drug-eluting stent (DES) or off-pump CABG (OPCAB) may result in major changes in power relationship in myocardial r...
Abstract 18010: Temporal Kinetics of Remote Ischemic Preconditioning: Transfer of Protection With Plasma Dialysate From Healthy Volunteers to an Isolated Mouse Heart
Authors: Heike A Hildebrandt, Philipp Kahlert, Raimund Erbel, Gerd Heusch, Petra Kleinbongard
Journal: Circulation (2015)

Objective: We aimed to analyze the temporal kinetics of cardioprotection by humoral factor(s) in healthy volunteers undergoing remote ischemic preconditioning (RIPC), a maneuver known to protect against myocardial injury, using infarct size in an isolated mouse heart as read-out. Methods: Ten healthy volunteers underwent RIPC by 3 cycles of 5 min upper-limb blood pressure cuff inflation and 5 min deflation. Venous blood samples were obtained at baseline before RIPC and after 5 and 30 min, 1, 6 and 24 h and daily up to 7 days. Plasma was dialyzed against the 20-fold volume of Krebs-Henseleit buffer for 24 h (cut-off: 12-14 kDa). Isolated mouse hearts were mounted on a Langendorff apparatus and perfused with Krebs-Henseleit buffer at a pressure of 100 mmHg. Before undergoing 20 min global ischemia and 120 min reperfusion, hearts were perfused with dialysate for 15 min. Infarct size was assessed by TTC-staining. The cardioprotective potential of the plasma dialysate obtained 5 min after RIPC was further evaluated by decreasing its dilution (1:10) in those samples, which did not induce cardioprotection in a dilution of 1:20. Results: The cardioprotective effect of RIPC was present in all cases 30 min after RIPC, lasted for at least 6 days and vanished thereafter (see Figure). Plasma taken 5 min after RIPC induced cardioprotection in only 50 % of cases, when using a dialysate with a 1:20 dilution. Decreasing the dilution to 1:10 induced cardioprotection in all cases (Figure insert). Conclusion: A single RIPC-maneuver induces the release of (a) dialyzable, humoral factor(s), which reduce(s) infarct size no later than 5 min after RIPC and remain(s) operative for up to 6 days. These results imply that cardioprotection is at least in part effected by (a) factor(s) which is/are quickly released/activated, long-lasting and/or continuously produced for quite a while after RIPC.
Wnt-pathway Activating Mutations Are Associated with Resistance to First-line Abiraterone and Enzalutamide in Castration-resistant Prostate Cancer
Authors: Pedro Isaacsson Velho, Wei Fu, Hao Wang, Nooshin Mirkheshti, Fahad Qazi, Fabiola A.S. Lima, Farah Shaukat, Michael A. Carducci, Samuel R. Denmeade, Channing J. Paller, Mark C. Markowski, Catherine H. Marshall, Mario A. Eisenberger, Emmanuel S. Antonarakis
Journal: European Urology (2019)
A Novel Oxoglutarate Dehydrogenase-Like Mediated miR-214/TWIST1 Negative Feedback Loop Inhibits Pancreatic Cancer Growth and Metastasis
Authors: Yao Liu, Fanzheng Meng, Jiabei Wang, Mingyang Liu, Guangchao Yang, Ruipeng Song, Tongsen Zheng, Yingjian Liang, Shugeng Zhang, Dalong Yin, Jizhou Wang, Haiyan Yang, Shangha Pan, Bo Sun, Jihua Han, Jing Sun, Yaliang Lan, Yan Wang, Xirui Liu, Mingxi Zhu, Yifeng Cui, Bo Zhang, Dehai Wu, Shuhang Liang, Yufeng Liu, Xuan Song, Zhaoyang Lu, Jingxuan Yang, Min Li, Lianxin Liu
Journal: Clinical Cancer Research (2019)

As a main rate-limiting subunit of the 2-oxoglutarate dehydrogenase multienzyme complex, oxoglutarate dehydrogenase like (OGDHL) is involved in the tricarboxylic acid cycle, and frequently downregulated in human carcinoma and suppresses tumor growth. However, little is known about the role of OGDHL in human cancer, especially pancreatic cancer. Our goal is to study the underlying mechanism and define a novel signaling pathway controlled by OGDHL modulating pancreatic cancer progression.The expression and functional analysis of OGDHL, miR-214, and TWIST1 in human pancreatic cancer tissues, cell lines, and xenograft tumor model were investigated. The correlations between OGDHL and those markers were analyzed.OGDHL was downregulated in human pancreatic cancer and predicted poor prognosis. OGDHL overexpression inhibited migration and invasion of pancreatic cancer cells and suppressed pancreatic cancer tumor growth. OGDHL was shown to be negatively regulated by miR-214. TWIST1 upregulation induced miR-214 expression in pancreatic cancer. OGDHL suppressed TWIST1 expression through promoting ubiquitin-mediated proteasomal degradation of HIF1α and regulating AKT pathways. A combination of OGDHL downregulation and TWIST1 and miR-214 overexpression predicted worse prognosis in patients with pancreatic cancer.We demonstrated the prognostic value of OGDHL, miR-214, and TWIST1 in pancreatic cancer, and elucidated a novel pathway in OGDHL-regulated inhibition of pancreatic cancer tumorigenesis and metastasis. These findings may lead to new targeted therapy for pancreatic cancer through regulating OGDHL, miR-214, and TWIST1.
NHS will plug holes in public health services, pledges Stevens
Authors: Tom Moberly
Journal: BMJ (2019)

The NHS will step in to commission public health services in places where cuts to council spending are putting pressure on services, NHS England’s chief executive has told The BMJ .

Simon Stevens said that, if councils could not allocate enough of the funding they received from central government to public health, the NHS would quickly need to commission services itself. Stevens was speaking to The BMJ at the Health Foundation’s annual event on 23 May.

Responsibility for preventive public health services in England was transferred from the NHS to local councils in 2013 …
Venetoclax Combined with Either a Hypomethylating Agent or Low-Dose Cytarabine Shows Activity in Relapsed and Refractory Myeloid Malignancies
Authors: Aaron D Goldberg, Troy Z. Horvat, Meier Hsu, Sean M. Devlin, Bernadette M. Cuello, Ryan J. Daley, Amber C. King, Larry W Buie, Jacob L Glass, Michael J. Mauro, Eytan M. Stein, Ellin Berman, Virginia M. Klimek, Martin S. Tallman
Journal: Blood (2017)
Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer
Authors: Joseph A. Sparano, Robert J. Gray, Peter M. Ravdin, Della F. Makower, Kathleen I. Pritchard, Kathy S. Albain, Daniel F. Hayes, Charles E. Geyer, Elizabeth C. Dees, Matthew P. Goetz, John A. Olson, Tracy Lively, Sunil S. Badve, Thomas J. Saphner, Lynne I. Wagner, Timothy J. Whelan, Matthew J. Ellis, Soonmyung Paik, William C. Wood, Maccon M. Keane, Henry L. Gomez Moreno, Pavan S. Reddy, Timothy F. Goggins, Ingrid A. Mayer, Adam M. Brufsky, Deborah L. Toppmeyer, Virginia G. Kaklamani, Jeffrey L. Berenberg, Jeffrey Abrams, George W. Sledge
Journal: New England Journal of Medicine (2019)

The use of adjuvant chemotherapy in patients with breast cancer may be guided by clinicopathological factors and a score based on a 21-gene assay to determine the risk of recurrence. Whether the level of clinical risk of breast cancer recurrence adds prognostic information to the recurrence score is not known.
Abstract 26: Validity of Cardiovascular Data From Electronic Data Research Networks: The Multi-Ethnic Study of Atherosclerosis (MESA) and HealthLNK
Authors: Faraz S Ahmad, Cheeling Chan, Marc B Rosenman, Wendy S Post, Kiang J Liu, Abel N Kho, Norrina B Allen
Journal: Circulation (2017)

Background: Understanding the validity of data from electronic clinical data research networks compared to population-based CVD cohorts, the gold standard for epidemiological research, is essential for conducting epidemiological research across large, diverse populations more efficiently. Methods: We linked individual-level data from MESA with HealthLNK, a 2006-2012 database of electronic health records (EHRs) from 6 major Chicago hospitals. To evaluate for correlation and bias for blood pressure (BP) and BMI between HealthLNK and in-person MESA examinations, we used Pearson Correlation Coefficients and Bland-Altman plots. Median BMI and BP values between 2006-2008 in HealthLNK were compared to MESA exam 4 and between 2009-2012 were compared to MESA exam 5. Using diagnoses in MESA as the gold standard, we also calculated the performance of HealthLNK queries for hypertension (HTN) and obesity using ICD9 codes alone and with the addition of clinical data. Results: Of the 1164 MESA participants at the Chicago field center, 802 participants had data in HealthLNK. There was a high correlation between BMI in MESA and HealthLNK (0.94). HealthLNK only slightly underestimated BMI by 0.5 kg/m 2 (Figure). The correlation was lower for systolic BP and diastolic BP (0.3 and 0.4, respectively). Compared to MESA, HealthLNK significantly overestimated SBP and DBP by 6.5 and 3.6 mmHg, respectively. Using ICD9 codes alone, the sensitivity and specificity for HTN were 62.2% and 72.7% and for obesity were 28.1% and 97.4%. The addition of BP and medications to ICD9 codes increased sensitivity and decreased specificity for HTN to 73.2% and 53.2%. The addition of BMI increased sensitivity and decreased the specificity for obesity to 64.3% and 95.4%. Conclusion: Significant disagreement between risk factor status and BP exists between HealthLNK and MESA, while BMI is highly correlated. Identifying areas of concordance and discordance informs our understanding of the strengths and limitations of using EHR data for epidemiological research.
Transcatheter Aortic Valve Replacement in Patients With End-Stage Renal Disease
Authors: Molly Szerlip, Alan Zajarias, Sreekanth Vemalapalli, Matthew Brennan, Dadi Dai, Hersh Maniar, Brian R. Lindman, Ralph Brindis, John D. Carroll, Mohanad Hamandi, Fred H. Edwards, Fred Grover, Sean O’Brien, Eric Peterson, John S. Rumsfeld, Dave Shahian, E. Murat Tuzcu, David Holmes, Vinod H. Thourani, Michael Mack
Journal: Journal of the American College of Cardiology (2019)
Deep learning can predict microsatellite instability directly from histology in gastrointestinal cancer
Authors: Jakob Nikolas Kather, Alexander T. Pearson, Niels Halama, Dirk Jäger, Jeremias Krause, Sven H. Loosen, Alexander Marx, Peter Boor, Frank Tacke, Ulf Peter Neumann, Heike I. Grabsch, Takaki Yoshikawa, Hermann Brenner, Jenny Chang-Claude, Michael Hoffmeister, Christian Trautwein, Tom Luedde
Journal: Nature Medicine (2019)