tbuckley/cabot-search huggingface dataset:
Vitamin B6 catabolism and lung cancer risk: results from the Lung Cancer Cohort Consortium (LC3)
Authors: H. Zuo, P.M. Ueland, Ø Midttun, G.S. Tell, A. Fanidi, W. Zheng, X. Shu, Y. Xiang, J. Wu, R. Prentice, M. Pettinger, C.A. Thomson, G.G. Giles, A. Hodge, Q. Cai, W.J. Blot, M. Johansson, J. Hultdin, K. Grankvist, V.L. Stevens, M.L. McCullough, S.J. Weinstein, D. Albanes, R.G. Ziegler, N.D. Freedman, N.E. Caporaso, A. Langhammer, K. Hveem, M. Næss, J.E. Buring, I. Lee, J.M. Gaziano, G. Severi, X. Zhang, M.J. Stampfer, J. Han, A. Zeleniuch-Jacquotte, L.L. Marchand, J. Yuan, R. Wang, W. Koh, Y. Gao, U. Ericson, K. Visvanathan, M.R. Jones, C. Relton, P. Brennan, M. Johansson, A. Ulvik
Journal: Annals of Oncology (2019)

BackgroundIncreased vitamin B6 catabolism related to inflammation, as measured by the PAr index (the ratio of 4-pyridoxic acid over the sum of pyridoxal and pyridoxal-5'-phosphate), has been positively associated with lung cancer risk in two prospective European studies. However, the extent to which this association translates to more diverse populations is not known.Materials and methodsFor this study, we included 5323 incident lung cancer cases and 5323 controls individually matched by age, sex, and smoking status within each of 20 prospective cohorts from the Lung Cancer Cohort Consortium. Cohort-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between PAr and lung cancer risk were calculated using conditional logistic regression and pooled using random-effects models.ResultsPAr was positively associated with lung cancer risk in a dose-response fashion. Comparing the fourth versus first quartiles of PAr resulted in an OR of 1.38 (95% CI: 1.19–1.59) for overall lung cancer risk. The association between PAr and lung cancer risk was most prominent in former smokers (OR: 1.69, 95% CI: 1.36–2.10), men (OR: 1.60, 95% CI: 1.28–2.00), and for cancers diagnosed within 3 years of blood draw (OR: 1.73, 95% CI: 1.34–2.23).ConclusionBased on pre-diagnostic data from 20 cohorts across 4 continents, this study confirms that increased vitamin B6 catabolism related to inflammation and immune activation is associated with a higher risk of developing lung cancer. Moreover, PAr may be a pre-diagnostic marker of lung cancer rather than a causal factor.
Abstract 18692: Evolution of Diastolic Parameters and Their Relationship to Heart Rate in the 7-15 Week Human Fetus
Authors: Claudine M Bohun, Lisa Howley, Jesus Serrano Lomelin, Winnie Savard, Lindsay Mills, Angela McBrien, Dora Gyenes, Tarek Motan, Venu Jain, Lisa K Hornberger
Journal: Circulation (2015)

Objectives: Fetal echo offers a unique opportunity to investigate cardiac function in humans from the 1st trimester. We sought to explore the evolution left ventricular (LV) diastolic parameters and their relationship to fetal heart rate (HR) from 7-15 weeks gestational age (GA). Methods: We prospectively performed fetal echo in 137 healthy pregnancies recruited from 7+0 to 15+0 (mean 11.5±2.1) weeks GA. From Doppler studies we measured LV isovolumic relaxation time (IRT), mitral valve (MV) inflow patterns,and duration, diastolic time (IRT+inflow duration), LV ejection time (ET) and systolic time interval (isovolumic contraction time+ET). All variables were compared to GA and HR and were assessed as a proportion of the cardiac cycle length (R-R). Data were analyzed by regression and correlation analyses. Results: Results: From 7+0-15+0 weeks, HR and GA showed a non-linear relationship (R2=0.55, p&lt;0.001) with low HRs at 7-8 weeks, peaking between 8-9 weeks, then falling thereafter. Diastolic time linearly increased with GA (R2=0.65, p&lt;0.001) and inversely correlated with HR (r=0.77, p&lt;0.001). IRT showed a nonlinear inverse relationship with GA (R2= 0.70, p&lt;0.001), but did not correlate with HR, and IRT/RR increased linearly with GA (R2=0.71, p&lt;0.001). Both inflow duration and inflow duration/R-R linearly increased with GA (R2=0.81,p&lt;0.001). Inflow duration inversely correlated with HR (r=-0.70) and with IRT (r=-0.71) and IRT/R-R (r=-0.83, p&lt;0.001 for all 3). A uniphasic MV atrial systolic inflow signal was present in 20/21 fetuses at 7+1-9+0 weeks, whereas, biphasic MV inflow was seen in 45% at 9+1-10+0 , 76% at 10+1-11+0 , 95% at 11+1-13+0 and 100% after 13+1 weeks GA. Inflow duration was significantly longer (146.9±25.4 vs 85.2±12.6ms, p&lt;0.001) and HR was lower (160±9 vs 170±10 bpm, p&lt;0.001) in fetuses with a biphasic flow pattern. ET demonstrated a weak relationship with GA (R2=0.41) and no relationship with HR, IVRT,or IVRT/R-R, and the systolic time showed a nonlinear trend of decreasing with GA (R2=0.46). Conclusions: In the 7-15 week fetus, improvements in relaxation suggested by decreasing IRT, decreasing HR, and, to a lesser extent, decreasing systolic time likely contribute to increasing inflow duration and to early ventricular filling.
Vasculitis as a major morbidity factor in patients with hypomorphic RAG mutations
Authors: Christoph B. Geier, Jocelyn R. Farmer, Zsofia Foldvari, Boglarka Ujhazi, Martha M. Eibl, Hermann M. Wolf, John W. Sleasman, Suhag Parikh, Meredith A. Dilley, Sung-Yun Pai, Lauren Henderson, Melissa Hazen, Benedicte Neven, Svetlana O. Sharapova, Snezhina Mihailova, Kevin Byram, Jim M. Fernandez, Leonard Calabrese, Jolan E. Walter
Journal: Journal of Allergy and Clinical Immunology (2019)
Abstract P3-03-29: Evaluation of a direct reverse transcription loop-mediated isothermal amplification method without RNA extraction (direct RT-LAMP) for the detection of lymph node metastasis in early breast cancer
Authors: IH Lee, J Jung, S Lee, J Lee, RK Lee, H Park, J Jung, J Kang, Y Chae
Journal: Cancer Research (2019)

Abstract Backgroud: The detection of lymph node metastasis by reverse transcription loop-mediated isothermal amplification method (RT-LAMP) had been studied previously. Even though, RT-LAMP method provides improved performance compared to intraoperative histology sentinel lymph node (SLN) evaluation, direct RT-LAMP method without RNA extraction can be more efficient and easily accessible process. Therefore, we evaluated the performance and efficacy of a direct reverse transcription loop-mediated isothermal amplification (direct RT-LAMP) assay for visual detection of CK19, CK20, and CEA mRNAs to identify lymph node metastasis in patients with early breast cancer. Methods: A total of 92 lymph nodes dissected from 40 patients with breast cancer were collected at the breast cancer center of Kyungpook National University Chilgok Hospital between November 2015 and February 2016. All of the samples were analyzed by direct RT-LAMP assay and routine histopathology examination. Cutoff values to distinguish metastasis and nonmetasis were determined by measuring cytokerain 19 (CK19) mRNA in histopathologically positive and negative lymph node using direct RT-LAMP. Results: We set the cutoff value of direct RT-LAMP assay for CK 19 mRNA at 1ng to distinguish status of LN metastasis. The sensitivity and specificity of the RT-LAMP assay were 85.7% and 100%, respectively. The positive predictive value and negative predictive value were 100% and 94.4%. Conclusion: Direct RT-LAMP assay can allow detection of SLN metastasis in breast cancer patients intraoperatively with a good sensitivity through cost-effective and time–saving manner. Citation Format: Lee IH, Jung J, Lee S, Lee J, Lee RK, Park H, Jung J, Kang J, Chae Y. Evaluation of a direct reverse transcription loop-mediated isothermal amplification method without RNA extraction (direct RT-LAMP) for the detection of lymph node metastasis in early breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-29.
Eliminating visceral leishmaniasis in South Asia: the road ahead
Authors: Suman Rijal, Shyam Sundar, Dinesh Mondal, Pradeep Das, Jorge Alvar, Marleen Boelaert
Journal: BMJ (2019)

Suman Rijal and colleagues highlight lessons from a regional collaboration to eliminate visceral leishmaniasis and identify priorities for the post-elimination plan
CMS-PDX: A 20-gene genomic panel to predict consensus molecular subtypes in patient-derived xenografts (PDX) of colorectal cancer.
Authors: Steven Allen Buechler, Yesim Gokmen-Polar, Sunil S. Badve
Journal: Journal of Clinical Oncology (2019)

598 Background: The consensus molecular subtypes (CMS1-4) partition colorectal cancer (CRC) into subgroups with varying prognoses and treatment responses. We previously reported the ColotypeR-CMS genomic scores (4 scores defined with 5 genes each) that accurately define the CMS subtypes of primary CRC tumors. There is also a critical need to develop an epithelial cell based algorithm for CMS subtyping of PDX models. Methods: To define scores predicting CMS subtypes for PDX models, genes that both predict CMS subtypes in primary CRC tissue and that have linearly correlated expression in primary tumor and tissue-matched PDX models, were identified in GSE35144 (N = 64, Affymetrix microarray). Using the identified genes, a 20-gene CMS-PDX score was developed using multistate gene methodology. ROC curve (AUC) analysis was used to measure the ability of CMS-PDX scores to predict subtypes obtained with CMScaller (473 genes), a preclinical CMS classifier. The ability of CMS subtypes to determine cetuximab response in PDX cohorts was analyzed in GSE78806 (N = 121, Affymetrix microarray) and GSE76402 (N = 529, Illumina beadarray). Results: In GSE78806 (N = 121), CMS1-4 subtypes obtained with CMScaller were predicted by CMS-PDX scores with AUC 0.88, 0.94, 0.81, 0.86, respectively; in GSE78806 CMScaller failed to classify 32% of samples. In CRC-derived PDX models, higher values of the CMS-PDX CMS2 score were predictive of reduced tumor volume following cetuximab treatment (p = 1.7 x 10 -5 in GSE78806, p &lt; 2.2 x 10 -16 in GSE76402, by linear regression.) In contrast, higher values of the CMS1 score were predictive of increased tumor volume (p = 3.8 x 10 -5 in GSE78806, p = 2.9 x 10 -10 in GSE76402.) Change in tumor volume was independent of the CMS-PDX CMS4 score in both PDX cohorts. Conclusions: We showed that the 20-genes CMS-PDX scores are predictive of CMS subtypes obtained with CMScaller. Moreover, CMS2, by CMS-PDX scores, was highly predictive of sensitivity to cetuximab treatment in CRC PDX models.
A multicenter, open-label, phase I study of nivolumab alone or in combination with gemcitabine plus cisplatin in patients with unresectable or recurrent biliary tract cancer.
Authors: Masafumi Ikeda, Makoto Ueno, Chigusa Morizane, Satoshi Kobayashi, Izumi Ohno, Shunsuke Kondo, Naohiro Okano, Keisuke Kimura, Suguru Asada, Yoshinobu Namba, Takuji Okusaka, Junji Furuse
Journal: Journal of Clinical Oncology (2019)

306 Background: This phase 1 study evaluated the safety and efficacy of the immune checkpoint inhibitor nivolumab (monotherapy or combined with chemotherapy) in Japanese patients with biliary tract cancer (BTC). Methods: In the monotherapy cohort (N = 30), patients with unresectable/recurrent BTC refractory or intolerant to gemcitabine-based treatment regimens received nivolumab monotherapy (240 mg, 2-week intervals). In the combined therapy cohort (N = 30), chemonaïve patients with unresectable/recurrent BTC received nivolumab (240 mg, 2-week intervals) plus cisplatin-gemcitabine chemotherapy. The primary objective was tolerability and safety. Secondary efficacy endpoints included overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) (central assessment). Results: The most frequently reported nivolumab-related adverse events were decreased appetite (5/30, 17%), malaise (4/30, 13%), and pruritus (4/30, 13%) in the monotherapy cohort, and malaise (8/30, 27%) and decreased appetite (7/30, 23%) in the combined therapy cohort. Median duration of follow-up for efficacy (Table) was 5.1 months (mo; monotherapy cohort) and 8.2 mo (combined therapy cohort). In the monotherapy cohort, median OS and median PFS were longer in patients with programmed death-ligand 1 (PD-L1) ≥ 1% (including the patient who responded) than in those with PD-L1 &lt; 1% (Table). In the combined therapy cohort, the ORR was higher, but median OS and median PFS were lower, in patients with PD-L1 ≥ 1% than in those with PD-L1 &lt; 1% (Table). Conclusions: Nivolumab was well tolerated, with a manageable safety profile and signs of clinical activity, in this phase 1 study in patients with unresectable/recurrent BTC. PD-L1 expression status may predict clinical activity of nivolumab in advanced BTC. Clinical trial information: JapicCTI-153098. [Table: see text]
The Orphan Drug Act Revisited
Authors: Shailin Thomas, Arthur Caplan
Journal: JAMA (2019)

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Molecular Quantification of Tissue Mast Cell Burden in Systemic Mastocytosis: A New Approach for Diagnostics and Prognostication
Authors: Greiner Georg, Michael Gurbisz, Franz Ratzinger, Nadine Witzeneder, Svenja-Verena Class, Ingrid Simonitsch-Klupp, Harald Esterbauer, Matthias Mayerhofer, Wolfgang R. Sperr, Leonhard Muellauer, Peter Valent, Gregor Hoermann
Journal: Blood (2018)
Abstract 19366: NG2 Ablation Aggravates Obesity and Hyperlipidemia but Reduces Atherogenesis
Authors: Zhi-Gang She, Yunchao Chang, Jeffrey W Smith, Erkki Ruoslahti, William B Stallcup
Journal: Circulation (2012)

Background &amp; Hypothesis: Ablation of chondroitin sulfate proteoglycan 4 (NG2) impairs brown fat development and function, leading to increased levels of serum lipids, increased lipid storage, and increased white fat mass. Since obesity and hyperlipidemia are two key risk factors for atherosclerosis, we wondered how NG2 ablation would affect atherogenesis. In addition to its expression by white and brown adipocytes, NG2 is also highly expressed by mesenchymal stromal cells (MSCs) in both human and mouse atherosclerotic plaques. NG2 could therefore could affect atherogenesis in the context of MSC function, as well as in the context of adipocyte function. Methods &amp; Results: We compared atherosclerotic plaque formation between ApoE null/NG2 wild type and ApoE null/NG2 null mice fed with a Western diet. Body weight, serum cholesterol, and triglyceride levels are similar in the two lines of mice in the early (10 weeks) and middle (16 weeks) stages of atherogenesis. However, all three parameters are significantly increased in the double null mice after 26 weeks of high fat diet induction. Aortic plaque areas are also similar in the two mouse lines at 10 and 16 weeks, but are reduced by 30% in double null male mice after 26 weeks of induction. Lipid content, collagen content, and the abundance of macrophages, smooth muscle cells, and MSCs are all reduced in plaques by 20-30% in double null males at 26 weeks. Like other chondroitin sulfate proteoglycans, purified NG2 exhibits strong LDL binding in ELISA tests. At the cellular level, cultured NG2 null MSCs bind less LDL than wild type MSCs. In vivo, LDL retention in NG2/ApoE double knock-out plaques is about 30% less than that seen in ApoE null/NG2 wild type plaques. Summary &amp; Significance: In spite of the obese and hyperlipidemic phenotype of ApoE null/NG2 null mice during later stages of atherogenesis, the absence of NG2 nevertheless results in less retention of LDL in the mouse aorta, thus restricting plaque expansion. Inhibition of NG2 may be a promising therapeutic strategy for atherosclerosis and related diseases.
Abstract 14609: Serum Protein Fingerprinting: A New Approach to the Clinical Screening of Coronary Artery Disease
Authors: Katharine G Wigginton, Luis J Dlouhy, Ronald D Macfarlane
Journal: Circulation (2015)

Introduction: A major goal of the 21st century is to mitigate disease and healthcare costs. Coronary artery disease (CAD) kills 370,000 Americans and costs the United States $109 billion each year. More accurate screening tools are needed to ameliorate CAD related morbidity and mortality. A new approach to the direct analysis of blood serum led to the development of a prospective clinical screening tool for CAD involving sodium dodecyl sulfate (SDS) capillary gel electrophoresis (CGE). Hypothesis: The novel method generates serum protein profiles which can be used to screen individuals for heart disease by distinguishing profile features of macromolecules involved in CAD. Methods: Serum profiles were generated by SDS-CGE for each study participant (n=48), 30 with CAD and 18 ‘NonCAD’ as identified by histories of CAD or unremarkable coronary angiographies. Univariate and multivariate analyses of the profile features were conducted to identify biomarkers and statistically classify participants as CAD or NonCAD. To compare the accuracy of the method with that of an established clinical tool, participants’ 10 Year Framingham Risk Scores (FRS) were calculated. Individuals with FRS scores less than 10% (low) risk were classified as NonCAD and those with greater than 10% (moderate to severe) risk were classified as CAD. Results: A “serum protein fingerprint” profile is shown. Relative standard deviations of 2% for MW and 20% for absorbance indicate method repeatability. In the classification of participants as CAD or NonCAD, the respective accuracies of the multivariate canonical and linear discriminant analyses were 90% (p-value of 7E-5) and 94%. The classification accuracy of FRS was less than 42%. Two features of the serum profiles (#’s 3 and 7 (with Prob&gt;F values of 0.01 and 4E-5 respectively)) are potentially novel markers for CAD. Conclusions: The proposed serum protein analysis method correlated proteins with CAD and was more accurate than the FRS method in this study.
Results of Inter-B-NHL Ritux 2010 - Phase II Study of DA-EPOCH-R for Children and Adolescents with Primary Mediastinal Large B-Cell Lymphoma (PMLBL) on Behalf of European Intergroup for Childhood Non Hodgkin's Lymphoma (EICNHL) and Children's Oncology Group (COG)
Authors: G A Amos Burke, Thomas G. Gross, Marta Pillon, Veronique Minard-colin, Raphael F Delgado, József Zsíros, Anne Uyttebroeck, Jean Michon, Catherine M. Bollard, Monika Csoka, Donald A Barkauskas, Keith Wheatley, Anne Aupérin, Catherine Patte
Journal: Blood (2017)
Characterization and treatment of congenital thrombotic thrombocytopenic purpura
Authors: Ferras Alwan, Chiara Vendramin, Ri Liesner, Amanda Clark, William Lester, Tina Dutt, William Thomas, Richard Gooding, Tina Biss, H. G. Watson, Nichola Cooper, Rachel Rayment, Tanya Cranfield, Joost J. van Veen, Quentin A. Hill, Sarah Davis, Jayashree Motwani, Neha Bhatnagar, Nicole Priddee, Marianna David, Maeve P. Crowley, Jayanthi Alamelu, Hamish Lyall, John-Paul Westwood, Mari Thomas, Marie Scully
Journal: Blood (2019)
Mettl3 Mediated m6A Modification Is Essential in Fetal Hematopoiesis
Authors: Yimeng Gao, Radovan Vasic, Toma Tebaldi, Yuanbin Song, Rhea Teng, Poorval Joshi, Gabriella Viero, Andrew Xiao, Pedro Batista, Huabing Li, Richard Flavell, Stephanie Halene
Journal: Blood (2018)
Isolation of CD34− and CD34+ Leukemia Stem Cells from Acute Myeloid Leukemia Blasts Using CD200
Authors: Jenny M. Ho, Stephanie M. Dobson, Jessica McLeod, Veronique Voisin, Alex Murison, James Kennedy, Sasan Zandi, Kolja Eppert, Mark D. Minden, Mathieu Lupien, John E. Dick, Jean C.Y. Wang
Journal: Blood (2018)
Abstract 20246: Temporal Variability of Native T1 and T2 Mapping in Healthy Volunteers
Authors: Mustafa A Altaha, Mark T Nolan, Kim A Connelly, Maria Michalowska, Bernd J Wintersperger, Paaladinesh Thavendiranathan
Journal: Circulation (2017)

Objectives: Cardiac MRI (CMR) measured myocardial T2 and T1 values provide assessment of myocardial tissue abnormalities. There has been a growing interest in using these values to detect myocardia...
Measuring liver radioembolization dose with positron emission tomography.
Authors: Vladimir Avkshtol, Iavor Veltchev, Jian Qin Yu, Mohan Doss, Gary S Cohen, Joseph N Panaro, Crystal S. Denlinger, Jordan Anaokar, Elizabeth A. Handorf, Adam Anderson, Graeme Williams, Eugene Fourkal, Joshua E. Meyer
Journal: Journal of Clinical Oncology (2019)

290 Background: There is no established way to measure radiation dose deposition during liver radioembolization to help quantify the shortcomings of prescription calculations, which do not consider size, shape, and location of tumors. We aimed to establish a standardized method of radioembolization dose measurement though a novel technique using Positron Emission Tomography and Computed Tomography (PET-CT). Methods: Patients who were recommended for liver radioembolization treatment were enrolled in a prospective single-arm registry study. Index lesions were contoured on the patients’ CT simulation scans. Immediate post-treatment PET/CTs were used to measure the deposited radiation dose by capturing the positron emission from the Yttrium-90’s daughter nuclei. The CT simulation scans were fused to the post-treatment PET/CT scans using rigid registration around the index lesions. The primary dosimetric outcomes were mean dose and dose to 70% of the tumor volume (D70). The optimal mean dose and D70 were &gt; 100 Gy and &gt; 70 Gy, respectively. Results: From November 2014 to November 2015, fifteen consecutive patients with either hepatocellular carcinoma (n = 4) or liver metastases (n = 11) were enrolled in the study. A total of 43 index lesions were contoured with a mean and median size of 18.2 cc and 5.4 cc, respectively. The average mean dose to the index lesions was 99.9 Gy (mean dose range: 2 – 298 Gy; Table). The mean and median D70 were 66.9 Gy and 71 Gy, respectively (range: 1.4 – 211 Gy; standard deviation [SD]: 40.3 Gy). The mean and median D90s were 43 Gy and 41 Gy, respectively. A total of 20 (46.5%) lesions received optimal mean dose and 23 (53.5%) lesions received optimal D70 dose. Conclusions: We established a successful standardized procedure utilizing PET/CT scans to measure the radiation dose delivered during liver radioembolization. The range of the doses received by the tumors underlines the need to collect dosimetric data for future treatment optimization. Dosimetric parameters. Clinical trial information: NCT02088775. [Table: see text]
Consumer Responses to Price Disclosure in Direct-to-Consumer Pharmaceutical Advertising
Authors: Jace B. Garrett, William B. Tayler, Ge Bai, Mariana P. Socal, Antonio J. Trujillo, Gerard F. Anderson
Journal: JAMA Internal Medicine (2019)

Michael J. DiStefano, PhD; Jenny M. Markell, BA; Caroline C. Doherty, MHS; G. Caleb Alexander, MD; Gerard F. Anderson, PhD