tbuckley/cabot-search huggingface dataset:
Comparison of mineral oil and non-mineral oil placebo on coronary plaque progression by coronary computed tomography angiography
Authors: Suvasini Lakshmanan, Chandana Shekar, April Kinninger, Suraj Dahal, Afiachukwu Onuegbu, Andrew N Cai, Sajad Hamal, Divya Birudaraju, Sion K Roy, John R Nelson, Matthew J Budoff, Deepak L Bhatt
Journal: Cardiovascular Research (2019)

Light liquid paraffin (pharmaceutical grade mineral oil) has been used as a placebo in clinical trials of icosapent ethyl including MARINE, ANCHOR, and REDUCE-IT. Pharmaceutical grade mineral oil (distinct from technical/industrial or food grade mineral oils) was chosen as a suitable placebo to mimic the consistency, colour, and odourless properties of icosapent ethyl capsules. Since the results of REDUCE-IT, a few have raised questions regarding possible biological activity of mineral oil placebo due to small changes in some cardiac biomarkers including lipid levels and inflammatory markers in placebo arm patients, asking whether the mineral oil utilized in placebo capsules was physiologically inert or not.1 Mineral oil has been utilized in humans as a laxative for decades (typically in doses of 15–45 g/day), and the general safety has been inferred from clinical utilization. The ∼2 g twice per day of light liquid mineral oil taken by placebo group patients in clinical trials equates to less than a teaspoon per day.

EVAPORATE is an ongoing randomized, placebo-controlled trial that evaluates the effect of icosapent ethyl 4 g daily in statin-treated patients with elevated triglycerides on coronary plaque progression by coronary computed tomography angiography (coronary CTA) compared with mineral oil placebo to provide important imaging-derived mechanistic information that can add insight to clinical outcomes from REDUCE-IT.2 Coronary plaque volumes, including total plaque and total non-calcified plaque derived by coronary CTA, have been measured and are known to be associated with myocardial ischaemia and adverse cardiac outcomes.3–5 In the present observational study, we sought to compare differences in progression of total plaque and total non-calcified plaque volumes on coronary CTA in mineral oil placebo patients from EVAPORATE vs. the non-mineral oil placebo arm from another randomized clinical trial, Garlic 5.6 We hypothesized that progression of total plaque and total non-calcified plaque volumes on coronary CTA is independent of consumption of mineral oil placebo capsules.
Role of eHealth application Oncokompas in supporting self-management of symptoms and health-related quality of life in cancer survivors: a randomised, controlled trial
Authors: Anja van der Hout, Cornelia F van Uden-Kraan, Karen Holtmaat, Femke Jansen, Birgit I Lissenberg-Witte, Grard A P Nieuwenhuijzen, José A Hardillo, Robert J Baatenburg de Jong, Nicolette L Tiren-Verbeet, Dirkje W Sommeijer, Koen de Heer, Cees G Schaar, Robert-Jan E Sedee, Koop Bosscha, Michiel W M van den Brekel, Japke F Petersen, Matthijs Westerman, Jimmie Honings, Robert P Takes, Ilse Houtenbos, Wim T van den Broek, Remco de Bree, Patricia Jansen, Simone E J Eerenstein, C René Leemans, Josée M Zijlstra, Pim Cuijpers, Lonneke V van de Poll-Franse, Irma M Verdonck-de Leeuw
Journal: The Lancet Oncology (2019)
The fog is still not clearing!
Authors: Vipul Chaudhari, Meghraj Ingle, Vikas Pandey, Shamshersingh Chauhan, Akash Shukla
Journal: Endoscopy (2019)

See also:Clip-assisted endoscopic cyanoacrylate injection for gastric varices with a gastrorenal shunt: a multicenter studyEndoscopy 2019; 51(10): 936-940DOI: 10.1055/a-0977-3022See also:Reply to ChaudhariEndoscopy 2020; 52(01): 81-81DOI: 10.1055/a-1021-8805
Burden of Long-Term Morbidity Borne By Survivors of Acute Myeloid Leukemia (AML) Treated with Blood or Marrow Transplantation (BMT) - a Report from the BMT Survivor Study (BMTSS)
Authors: Saro H. Armenian, Yanjun Chen, Lindsey Hageman, Jessica Wu, Liton F. Francisco, Michelle Kung, Emily Ness, Mariel Parman, Wendy Landier, Alysia Bosworth, Lennie Wong, Daniel J. Weisdorf, Stephen J Forman, Mukta Arora, Smita Bhatia
Journal: Blood (2019)
PASTMUS: mapping functional elements at single amino acid resolution in human cells
Authors: Xinyi Zhang, Di Yue, Yinan Wang, Yuexin Zhou, Ying Liu, Yeting Qiu, Feng Tian, Ying Yu, Zhuo Zhou, Wensheng Wei
Journal: Genome biology (2019)

Identification of functional elements for a protein of interest is important for achieving a mechanistic understanding. However, it remains cumbersome to assess each and every amino acid of a given protein in relevance to its functional significance. Here, we report a strategy, PArsing fragmented DNA Sequences from CRISPR Tiling MUtagenesis Screening (PASTMUS), which provides a streamlined workflow and a bioinformatics pipeline to identify critical amino acids of proteins in their native biological contexts. Using this approach, we map six proteins-three bacterial toxin receptors and three cancer drug targets, and acquire their corresponding functional maps at amino acid resolution.
Liver diseases in the Asia-Pacific region: a Lancet Gastroenterology &amp; Hepatology Commission
Authors: Shiv K Sarin, Manoj Kumar, Mohammed Eslam, Jacob George, Mamun Al Mahtab, Sheikh M Fazle Akbar, Jidong Jia, Qiuju Tian, Rakesh Aggarwal, David H Muljono, Masao Omata, Yoshihiko Ooka, Kwang-Hyub Han, Hye Won Lee, Wasim Jafri, Amna S Butt, Chern H Chong, Seng G Lim, Raoh-Fang Pwu, Ding-Shinn Chen
Journal: The Lancet. Gastroenterology & hepatology (2019)
Predictive Value of the Platelet-to-Lymphocyte Ratio in Cancer Patients Undergoing Transcatheter Aortic Valve Replacement
Authors: Noriaki Tabata, Baravan Al-Kassou, Atsushi Sugiura, Jasmin Shamekhi, Hendrik Treede, Masanobu Ishii, Kenichi Tsujita, Nikos Werner, Eberhard Grube, Georg Nickenig, Jan-Malte Sinning
Journal: JACC CardioOncology (2019)

The purpose of this study is to investigate the predictive value of the platelet-to-lymphocyte ratio (PLR)in cancer patients undergoing transcatheter aortic valve replacement (TAVR).The PLR is a promising marker to predict clinical outcomes in various cancer types as well as in cardiovascular disease.Consecutive TAVR patients were enrolled in the study. We stratified patients into 2 groups: cancer and noncancer. Baseline complete blood counts with a differential hemogram were collected before TAVR. The primary outcome was all-cause death within a 3-year follow-up.In total, 240 of 1,204 patients (19.9%) had a cancer history. Cancer patients had a significantly higher baseline PLR than noncancer patients (median [interquartile range], 159.8 [109.6 to 244.6] vs. 150.3 [108.7 to 209.0]; p = 0.024). Kaplan-Meier analysis revealed that cancer patients had worse outcomes than noncancer patients (log-rank p < 0.001). Patients who died had a significantly higher baseline PLR than those who survived both in the cancer (p = 0.009) and noncancer (p = 0.027) groups. Multivariable analyses showed that the PLR (by 100 increase) was an independent predictor of adverse outcomes in both cancer (hazard ratio: 1.07; 95% confidence interval: 1.02 to 1.13; p = 0.006) and noncancer (hazard ratio: 1.20; 95% confidence interval: 1.06 to 1.36; p = 0.004). The highest mortality was observed for patients with cancer and increased PLR (above the median) (log-rank p < 0.001).Cancer patients undergoing TAVR had a significantly higher PLR than those without cancer. Higher PLR was associated with a worse outcome following TAVR.
Clearance of HPV Anal Premalignant Lesions and Modulation of Systemic Immune Responses to HPV Oncogenes with Low Dose Pomalidomide
Authors: M. Polizzotto, D. Van Bockel, C. Law, J. Roberts, G. Buckland, S. Just, S. Comben, R. Hillman, R. Gilson, S. Pett, M. Poynten, M. Law, A. Kelleher, S. Emery
Journal: Annals of Oncology (2019)
Association of Income With the Incidence Rates of First Psychiatric Hospital Admissions in Finland, 1996-2014
Authors: Kimmo Suokas, Anna-Maija Koivisto, Christian Hakulinen, Riittakerttu Kaltiala, Reijo Sund, Sonja Lumme, Olli Kampman, Sami Pirkola
Journal: JAMA Psychiatry (2019)

<h3>Importance</h3> The association between income and mental health has long been a question of interest. Nationwide register data provide means to examine trends and patterns of these associations. <h3>Objectives</h3> To compare income-specific trends in the incidence rates of first psychiatric hospital admissions and to evaluate whether an income gradient exists in the incidence rates at all levels of household income. <h3>Design, Setting, and Participants</h3> This population-based open cohort study used linked registry data from nationwide Finnish Hospital Discharge and Statistics Finland population registers to determine annual incidence rates of first psychiatric hospital admissions. All Finnish citizens (N = 6 258 033) living in the country at any time from January 1, 1996, through December 31, 2014, contributed to 96 184 614 person-years at risk of first inpatient treatment for mental disorders. The analyses were conducted from August 1, 2018, through September 30, 2019. <h3>Exposures</h3> Equivalized disposable income, sex, age group, reduction in income decile in the previous 3 years, urbanicity, educational level, and living alone status. <h3>Main Outcomes and Measures</h3> Annual percentage changes in the age-standardized incidence rates and incidence rate ratios (IRRs). <h3>Results</h3> Altogether, 186 082 first psychiatric inpatient treatment episodes occurred (93 431 [50.2%] men), with overall age-standardized incidence rates per 1000 person-years varying from 1.59 (95% CI, 1.56-1.63) in 2014 to 2.11 (95% CI, 2.07-2.15) in 2008. In the highest income deciles, a continuous mean decrease per year of 3.71% (95% CI, 2.82%-4.59%) in men and 0.91% (95% CI, 0.01%-1.80%) in women occurred throughout the study period, in contrast to the lowest deciles, where the trends first increased (1.31% [95% CI, 0.62%-2.01%] increase in men from 1996 to 2007 and 5.61% [95% CI, 2.36%-8.96%] increase in women from 1996 to 2001). In the adult population, an income gradient was observed at all levels of household income: the lower the income decile, the higher the adjusted IRRs compared with the highest decile. The IRRs in the lowest decile varied from 2.94 (95% CI, 2.78-3.11) to 4.46 (95% CI, 4.17-4.76). In other age groups, the gradient did not persist at the highest income deciles. Diagnosis-specific income gradient was steepest in schizophrenia and related psychotic disorders, with estimated IRRs of the lowest income decile of 5.89 (95% CI, 5.77-6.02). <h3>Conclusions and Relevance</h3> In this cohort study, clear negative income gradient in the incidence rates of first hospital-treated mental disorders was observed in the adult population of Finland. These findings suggest that reduction in the use of inpatient care has not taken place equally between different income groups.
Lack of the multidrug transporter MRP4/ABCC4 defines the PEL-negative blood group and impairs platelet aggregation
Authors: Slim Azouzi, Mahmoud Mikdar, Patricia Hermand, Emilie-Fleur Gautier, Virginie Salnot, Alexandra Willemetz, Gaël Nicolas, Cédric Vrignaud, Alexandre Raneri, Patrick Mayeux, Christine Bole-Feysot, Patrick Nitschké, Jean-Pierre Cartron, Yves Colin, Olivier Hermine, Gabriele Jedlitschky, Marc Cloutier, Jessica Constanzo-Yanez, Carole Ethier, Nancy Robitaille, Maryse St-Louis, Caroline Le Van Kim, Thierry Peyrard
Journal: Blood (2019)
TBCRC 032 IB/II Multicenter Study: Molecular Insights to AR Antagonist and PI3K Inhibitor Efficacy in Patients with AR+ Metastatic Triple-Negative Breast Cancer
Authors: Brian D. Lehmann, Vandana G. Abramson, Melinda E. Sanders, Erica L. Mayer, Tufia C. Haddad, Rita Nanda, Catherine Van Poznak, Anna Maria Storniolo, Julie R. Nangia, Paula I. Gonzalez-Ericsson, Violeta Sanchez, Kimberly N. Johnson, Richard G. Abramson, Sheau-Chiann Chen, Yu Shyr, Carlos L. Arteaga, Antonio C. Wolff, Jennifer A. Pietenpol
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Preclinical data demonstrating androgen receptor (AR)–positive (AR+) triple-negative breast cancer (TNBC) cells are sensitive to AR antagonists, and PI3K inhibition catalyzed an investigator-initiated, multi-institutional phase Ib/II study TBCRC032. The trial investigated the safety and efficacy of the AR-antagonist enzalutamide alone or in combination with the PI3K inhibitor taselisib in patients with metastatic AR+ (≥10%) breast cancer. Patients and Methods: Phase Ib patients [estrogen receptor positive (ER+) or TNBC] with AR+ breast cancer received 160 mg enzalutamide in combination with taselisib to determine dose-limiting toxicities and the maximum tolerated dose (MTD). Phase II TNBC patients were randomized to receive either enzalutamide alone or in combination with 4 mg taselisib until disease progression. Primary endpoint was clinical benefit rate (CBR) at 16 weeks. Results: The combination was tolerated, and the MTD was not reached. The adverse events were hyperglycemia and skin rash. Overall, CBR for evaluable patients receiving the combination was 35.7%, and median progression-free survival (PFS) was 3.4 months. Luminal AR (LAR) TNBC subtype patients trended toward better response compared with non-LAR (75.0% vs. 12.5%, P = 0.06), and increased PFS (4.6 vs. 2.0 months, P = 0.082). Genomic analyses revealed subtype-specific treatment response, and novel FGFR2 fusions and AR splice variants. Conclusions: The combination of enzalutamide and taselisib increased CBR in TNBC patients with AR+ tumors. Correlative analyses suggest AR protein expression alone is insufficient for identifying patients with AR-dependent tumors and knowledge of tumor LAR subtype and AR splice variants may identify patients more or less likely to benefit from AR antagonists.
Positron emission tomography as an adjuvant diagnostic test in the evaluation of checkpoint inhibitor-associated acute interstitial nephritis
Authors: David Qualls, Harish Seethapathy, Halla Bates, Shahein Tajmir, Pedram Heidari, Paul Endres, Kerry Reynolds, Donald Lawrence, Meghan Sise
Journal: Journal for ImmunoTherapy of Cancer (2019)

Acute interstitial nephritis is an immune-related adverse event that can occur in patients receiving immune checkpoint inhibitor therapy. Differentiating checkpoint inhibitor-associated acute interstitial nephritis from other causes of acute kidney injury in patients with cancer is challenging and can lead to diagnostic delays and/or unwarranted immunosuppression. In this case report, we assess the use of 18F-flourodeoxyglucose positron-emission tomography imaging as an alternative diagnostic modality in the evaluation of potential acute interstitial nephritis.A 55-year-old woman with metastatic vulvar melanoma underwent treatment with two cycles of ipilimumab plus nivolumab, followed by seven cycles of nivolumab combined with radiation therapy. During her treatment, she developed non-oliguric acute kidney injury to a creatinine of 4.5 mg/dL from a baseline of 0.5 mg/dL. A clinical diagnosis of acute interstitial nephritis was made, and steroids were initiated, with rapid improvement of her acute kidney injury. Retrospectively, four positron-emission tomography scans obtained for cancer staging purposes were reviewed. We found a markedly increased 18F-flourodeoxyglucose uptake in the renal cortex at the time acute interstitial nephritis was diagnosed compared to baseline. In three cases of acute kidney injury due to alternative causes there was no increase in 18F-flourodeoxyglucose uptake from baseline.To our knowledge, this is the first report describing increased 18F-flourodeoxyglucose uptake in the renal cortex in a patient with checkpoint inhibitor-associated acute interstitial nephritis. Our findings suggest that 18F-flourodeoxyglucose positron-emission tomography may be a valuable test for diagnosing immune-mediated nephritis, particularly in patients where timely kidney biopsy is not feasible.
Endoscopic closure of a colocutaneous fistula after placement of percutaneous endoscopic gastrostomy
Authors: Eduardo Rodrigues-Pinto, Ana L. Santos, Guilherme Macedo
Journal: Endoscopy (2019)

A 16-year-old boy with a history of neurofibromatosis type 1 and malignant peripheral nerve sheath tumor under chemotherapy underwent percutaneous endoscopic gastrostomy (PEG) placement for dysphagia, anorexia, and malnutrition. After PEG placement, the button was confirmed to be within the stomach. The feeding tube was replaced 5 months later, with the patient presenting with persistent diarrhea and weight loss. Contrast study revealed a colocutaneous fistula, with contrast infused through the PEG appearing in the colon ([Fig. 1]). The patient was referred to us for endoscopic closure ([Video 1]).
Transformation Mechanisms of the Nfia-ETO2 Fusion Gene Associated with Pediatric Pure Acute Erythroleukemia
Authors: Maria-Riera Piqué-Borràs, Frederik Otzen Bagger, Matheus Filgueira Bezerra, Amber Louwaige, Sabine Juge, Ioannis Nellas, Robert Ivanek, Alexandar Tzankov, Ute M Moll, Ramona Schulz-Heddergott, Thomas Mercher, Juerg Schwaller
Journal: Blood (2019)
Abstract I03: Immune contexture of human pancreatic cancer
Authors: Lisa M. Coussens
Journal: Cancer Research (2019)

Abstract The concept that leukocytes are critical components of solid tumors is now generally accepted; however, their role(s) in regulating aspects of neoplastic progression, and/or response to cytotoxic, targeted, and/or immune therapy is only beginning to be understood. Utilizing de novo mouse models of organ-specific solid tumor development (mammary, cutaneous, and pancreas carcinomas and mesothelioma), we now appreciate that adaptive leukocytes differentially regulate myeloid cell recruitment, activation, and effector function, and in turn, activated tumor-infiltrating myeloid cells engage tissue-based programs to foster malignancy and repress antitumor immunity by a diversity of mechanisms. Treatment of tumor-bearing mice with therapeutic agents that disrupt lymphocyte-myeloid cell interaction, myeloid cell activation, or myeloid cell functionality generally slow primary tumor growth kinetics when combined with cytotoxic therapy; however, their impact on metastases is variable. Similar to organ-specific regulatory programs co-opted to foster primary tumor growth, regulation of metastatic seeding and outgrowth is also regulated by tissue- and organ-specific mechanisms. Based on this, it stands to reason that therapeutic strategies may not be efficacious in both primary and metastatic locations. To be presented will be our recent insights into organ- and tissue-specific regulation of primary and metastatic cancer development by adaptive and innate immune cells, how systemic regulation of humoral immunity and complement-mediated pathways regulate pro- versus antitumor immune responses, and new studies evaluating how attenuating protumor properties of select lymphoid and myeloid cells can be exploited to enhance therapeutic responses to cytotoxic and immune-based therapy. (LMC acknowledges generous support from the NIH/NCI, the Department of Defense Breast Cancer Research Program, Susan G. Komen Foundation, the Breast Cancer Research Foundation, and the Brenden-Colson Center for Pancreatic Health.) Citation Format: Lisa M. Coussens. Immune contexture of human 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 I03.
Entrectinib in ROS1 fusion-positive non-small-cell lung cancer: integrated analysis of three phase 1–2 trials
Authors: Alexander Drilon, Salvatore Siena, Rafal Dziadziuszko, Fabrice Barlesi, Matthew G Krebs, Alice T Shaw, Filippo de Braud, Christian Rolfo, Myung-Ju Ahn, Jürgen Wolf, Takashi Seto, Byoung Chul Cho, Manish R Patel, Chao-Hua Chiu, Thomas John, Koichi Goto, Christos S Karapetis, Hendrick-Tobias Arkenau, Sang-We Kim, Yuichiro Ohe, Yu-Chung Li, Young K Chae, Christine H Chung, Gregory A Otterson, Haruyasu Murakami, Chia-Chi Lin, Daniel S W Tan, Hans Prenen, Todd Riehl, Edna Chow-Maneval, Brian Simmons, Na Cui, Ann Johnson, Susan Eng, Timothy R Wilson, Robert C Doebele
Journal: The Lancet Oncology (2019)
Association between systolic ejection time and outcomes in heart failure by ejection fraction
Authors: Priyesh A. Patel, Andrew P. Ambrosy, Matthew Phelan, Fawaz Alenezi, Karen Chiswell, Melissa K. Van Dyke, Jennifer Tomfohr, Narimon Honarpour, Eric J. Velazquez
Journal: European Journal of Heart Failure (2019)
NFATc1+CD31+CD45− circulating multipotent stem cells derived from human endocardium and their therapeutic potential
Authors: Han-Mo Yang, Ju-Young Kim, Hyun-Jai Cho, Joo-Eun Lee, Sooryeonhwa Jin, Jin Hur, Yoo-Wook Kwon, Moon-Woo Seong, Eue-Keun Choi, Hae-Young Lee, Hyun-Seob Lee, Mika Jeon, Joonoh Kim, Jaeseok Yang, Seil Oh, Kyung-Suk Suh, Sung-Soo Yoon, Ki-Bong Kim, Byung-Hee Oh, Young-Bae Park, Hyo-Soo Kim
Journal: Biomaterials (2019)
Abstract 19403: Deterioration of Cardiac Performance and Dysfunction of Sympathetic Activity Affects Respiratory Instability in Chronic Heart Failure: Non-invasive and Simple Quantitative Assessment of Respiratory Stability
Authors: Keitaro Domae, Shigeru Miyagawa, Satsuki Fukushima, Teruya Nakamura, Yasushi Yoshikawa, Shunsuke Saito, Daisuke Yoshioka, Yasushi Sakata, Kenji Yamada, Koichi Toda, Hidetsugu Asanoi, Yoshiki Sawa
Journal: Circulation (2015)

Background: Cardiac sympathetic activity, in general assessed by 123I-meta-iodobenzylguanidine cardiac scintigraphy (mIBG-s), has been shown to be a critical indicator to predict morbidity and mortality associated with chronic heart failure (HF). We herein hypothesized that nocturnal respiratory stability, which has been suggested to be impaired by autonomic dysfunction, may be correlated with sympathetic nerve activity in advanced HF. To test this hypothesis, we developed respiratory stability index (RSI), which is calculated by computer-based non-invasive measurements. Methods: Fifteen patients with chronic HF under intensive medical treatments including maximized beta-blocker therapy were enrolled. All patients echocardiographically displayed their ejection fraction (EF) less than 35%. Nocturnal respiratory signals were serially collected by the under-pillow sensor to evaluate the respiratory spectrum during asleep. RSI was calculated from average of the reciprocal of the standard deviation of respiratory spectral ranges (Figure). Results: RSI was successfully and reproducibly evaluated in all cohorts with an average value being 44±21. mIBG-s-based values to indicate sympathetic activity, such as heart-to-mediastinum ratio (HMR) or wash-out rate, showed abnormality in all cohorts. Of note, the RSI was strongly correlated with HMR (ρ=0.83, p&lt;0.01) or wash-out rate (ρ=-0.87, p&lt;0.01). In addition, RSI was significantly correlated with standard indicator of HF such as plasma brain natriuretic peptide level (ρ=-0.59, p&lt;0.05), EF (ρ=0.73, p&lt;0.05) or pulmonary capillary wedge pressure assessed by right heart catheter study (ρ=-0.70, p&lt;0.05). Conclusions: RSI showed a significant correlation with degree of autonomic dysfunction assessed by mIBG-s in advanced HF of chronic stage. This non-invasive method might enable serial evaluation to predict cardiac events even in patients on home healthcare, though further validation is required.