tbuckley/cabot-search huggingface dataset:
Abstract 10036: An Investigation of Plant-Based, Mediterranean, Paleolithic and Dash Diets on Cardiovascular Disease Risk (VA Beach Diet Study)
Authors: Talreja Alex, Sophie Talreja, Deepak Talreja
Journal: Circulation (2021)

Introduction: Cardiovascular disease (CVD) is the leading cause of death in the United States for middle-aged men and women despite the fact that prevention and control of CVD is achievable by modifying risk factors through lifestyle changes and diet therapy. We examined the impact of four diet programs (plant-based (Vegan), Mediterranean, Paleolithic (Paleo) and DASH diets) on the CV risk factor profile of adults in the Hampton Roads area of Virginia. Hypothesis: Among the Diets studies, there will be a variable response with regards to impact on lipids. Methods: Nondiabetic adults (ages 35-85) with one or more risk factors for CVD were invited to participate in 1 of the 4 diet arms. Participants underwent a comprehensive nutrition education program prior to a 60-day diet intervention in which they kept a daily food log and met weekly with a multi-disciplinary study team. An initial health screen was performed to assess weight, blood pressure (BP), fasting glucose (FPG), A1C, lipids and lipoprotein particles, and repeated after 60 days on the diet and at 6-months follow-up. Results: 279 subjects completed the 60-day dietary intervention (58 Vegan, 80 Mediterranean, 76 Paleo, 65 DASH), and 199 returned for 6-month follow-up. Most subjects were female, Caucasian, mean age 56, mean BMI 33 kg/m2. At baseline, mean FPG, TG and HDL-C were within the normal range, whereas LDL-P and BP were elevated. After 60 days on the respective diets, subjects lost an average of 9 lbs (4.7% body weight, total 2,576 lbs), which was associated with improvements in BP across all groups. Subjects on the Vegan and Paleo diets lost the most weight (~6.5%) and showed the greatest improvement in lipid risk factors (11-14% decrease in LDL-P; 10-20% decrease in VLDL and TG). Conclusions: All four diets promoted weight loss and improved BP but had variable effects on lipid risk factors.
90 Unbiased proteomic profiling leads to the discovery of a novel non-invasive blood-based protein panel with significant positive predictive value in pancreatic and colorectal cancers
Authors: Kristina Beeler, Roland Bruderer, Marco Tognetti, Kamil Sklodowski, Sebastian Mueller, Dominique Kamber, Lukas Reiter
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Mass spectrometry-based discovery proteomics has recently emerged as a high-throughput method for the proteomic profiling in biofluid samples from large clinical and population screening cohorts. Despite this progress, a significant fraction of the plasma proteome is currently not covered by state-of-the-art discovery approaches and therefore not accessible for biomarker discovery. To close this analytical gap, we present a novel workflow combining automated plasma depletion and FAIMS-DIA-MS to bridge both sensitivity and scalability. We demonstrate the applicability of this workflow to support biomarker discovery and subject stratification in precision oncology in a case-control cohort. Methods The plasma samples were depleted in 96-well format using an automated MARS-14 depletion system. The depleted samples were processed to tryptic peptides and analyzed using a Thermo Scientific Orbitrap Exploris 480 equipped with a FAIMS Pro device. Data processing and analysis were performed using Biognosys’ SpectroMine and Spectronaut software. Results Using the unbiased discovery workflow, we investigated a cohort comprising of 180 plasma samples from healthy donors and subjects diagnosed with pancreatic, breast, prostate, colorectal and lung (NSCLC) cancer at either early or late stage of the disease. Overall, the optimized FAIMS-DIA-MS quantified 2,741 proteins across all samples and 1,849 proteins on average per sample measurement. Based on estimated plasma protein concentrations (Human Protein Atlas), quantified proteins span across 8 orders of magnitude, down to single digit pg/mL. Within this dynamic range, we could interrogate the tissue leakage proteome, interleukins and signaling proteins. Using classification algorithms, we were able to select candidates to build protein panels which provide significant positive predictive values associated with different disease stages, especially in the sub-cohorts for pancreatic and colorectal cancer. Conclusions We demonstrate the capabilities of a novel discovery workflow for deep, quantitative profiling of plasma samples at large scale, providing a rich proteomic resource for precision oncology.
68 Rapid detection of somatic variants in human leukocyte antigen class 1 genes from solid tumor samples
Authors: Ramit Bharanikumar, Karl Beutner, Aly Khan, Jason Perera
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Human Leukocyte Antigens (HLA) class 1 proteins are important for recognizing tumor specific mutations (neoantigens) and presenting them to CD8+ T-cells. Somatic mutations in HLA genes can potentially reduce the set of neoantigens available for presentation to T-cells, providing a possible immune escape mechanism for tumors. The presence of mutations in HLA genes may thus affect an individual’s response to Immune Checkpoint Blockade therapy but calling somatic variants in HLA genes is challenging given high degrees of polymorphism and the presence of pseudogenes in HLA loci. Here, we present a rapid, modular algorithm to detect somatic variants in HLA class 1 genes from next-generation sequencing data. Methods Our method takes as input matched tumor and normal sequencing (BAM) files and a patient‘s HLA type. Our first step involves mapping and aligning reads to the full-length HLA class 1 genes of an individual patient. Next, we filter reads to minimize sequencing errors and process them to account for potential cross-mapping between genes in the broader HLA locus. Our algorithm uses the final set of processed reads from matched tumor and normal sequencing files to call somatic variants. The final set of variants are then provided with a genetic variant annotation that summarizes their functional effect. Results We validated the efficacy of our approach using TCGA samples that were previously known to contain somatic HLA mutations. Out of a total of 46 mutations previously characterized from 41 samples, our algorithm detected 43 mutations with the correct functional annotation and did so with a computational run-time that is an order of magnitude faster than the current gold-standard approach. Eight of these mutations were previously validated using PacBio long-read sequencing, and all of these validated mutations were detected by our method. Additionally, we analyzed transcriptomic data in samples containing nonsense mutations and detected a transcriptomic signature in RNA-seq data that corresponded to the Nonsense Mediated Decay pathway. Conclusions Our findings show that our algorithm can reliably and rapidly detect somatic mutations in HLA class 1 classical genes. We leveraged multi-modal TCGA data and modules developed at Tempus to link samples with nonsense mutations to the nonsense mediated decay pathway. This allowed us to posit a possible biological mechanism that could result in increased resistance to immunotherapy because of somatic HLA mutations. Finally, we emphasize that our approach is modular and can be extended to call somatic variants in other non-classical and class 2 HLA genes.
Correction: Comparison of artemether-lumefantrine and chloroquine with and without primaquine for the treatment of Plasmodium vivax infection in Ethiopia: A randomized controlled trial
Authors: Tesfay Abreha, Jimee Hwang, Kamala Thriemer, Yehualashet Tadesse, Samuel Girma, Zenebe Melaku, Ashenafi Assef, Moges Kassa, Mark D. Chatfield, Keren Z. Landman, Stella M. Chenet, Naomi W. Lucchi, Venkatachalam Udhayakumar, Zhiyong Zhou, Ya Ping Shi, S. Patrick Kachur, Daddi Jima, Amha Kebede, Hiwot Solomon, Addis Mekasha, Bereket Hailegiorgis Alemayehu, Joseph L. Malone, Gunewardena Dissanayake, Hiwot Teka, Sarah Auburn, Lorenz von Seidlein, Ric N. Price
Journal: PLoS Medicine (2018)

The numbers in the second paragraph in the section entitled, "Partial primaquine dose and unsupervised primaquine treatment" are incorrect owing to a transcription error in the final preparation of the paper.The paragraph should read: "For all subsequent recurrences, only the first dose of the antimalarial drugs was supervised.The risk of recurrence after 6 mo of follow-up between the primary and secondary treatments did not differ significantly for patients in either the CQ arm (HR = 1.2 [95% CI 0.8-1.84],p = 0.5) or the AL arm (HR = 0.8 [95% CI 0.5-1.3],p = 0.4).However, patients were at significantly greater risk of recurrent P. vivax after the unsupervised PQ retreatment than after the partially supervised initial PQ treatment: 36.8% (95%CI 16.6%-68.3%)versus 14.7% (95% CI 8.6%-24.6%) in patients in the CQ+PQ arm (HR = 3.9 [95% CI 1.3-11.4],p = 0.014) and 48.1% (95%CI 26.5%-75.6%)versus 17.5% (95%CI 10.7%-27.8%) in patients in the AL+PQ arm (HR = 3.5 [95% CI 1.4-8.9],p = 0.008) (S2 Fig)."
Regulation of CNS Lymphoma Progression By the Myeloid Microenvironment
Authors: Hua-Xin Gao, Eleanor Fraser, Mario Merlini, Huimin Geng, Lingjing Chen, Ming Lu, Yasmin Moshfegh, Joseph Cleveland, Jae Ryu, Jigyasa Sharma, David A. Solomon, Katerina Akassoglou, Clifford Lowell, James L. Rubenstein
Journal: Blood (2021)
Outcomes of Patients with AML Treated with CPX-351 Based on the 2017 ELN Risk Stratification
Authors: Akriti G Jain, Somedeb Ball, David A. Sallman, Rami S. Komrokji, Andrew T. Kuykendall, Eric Padron, Onyee Chan, Jeffrey E. Lancet, Kendra Sweet
Journal: Blood (2021)
<i>Notes from the Field:</i>Acute Nonviral Hepatitis Linked to a Brand of Alkaline Bottled Water — Clark County, Nevada and California, 2020
Authors: Jeanne C. Ruff, Ying Zhang, David P. Bui, Colin Therriault, Daniel Nogee, Stephen L. Guthery, Johnni Daniel
Journal: MMWR Morbidity and Mortality Weekly Report (2021)
Abstract 9531: Septin4 Deletion Prevents Hypertrophy to Heart Failure Transition After Transverse Aortic Constriction
Authors: Dogacan Yucel, Preethy Parthiban, An Xie, Jop H Van Berlo
Journal: Circulation (2021)

Introduction: In response to cardiac injury or increased workload, the mammalian heart undergoes ventricular remodeling to maintain cardiac function. Initially, these changes are compensatory, although ultimately, they lead to cardiomyocyte death and progression to heart failure. As one of the aspects of ventricular remodeling, cardiac fibrosis significantly reduces cardiac function. To identify potential new therapeutic targets, it is essential to understand the underlying mechanisms that regulate cardiac fibrosis. Previous research highlighted a possible interplay between TGF-β and Sept4. However, it is unknown if Sept4 is involved in TGF-β mediated cardiac fibrosis. Hypothesis: We hypothesized that Sept4 deletion prevents cardiac fibrosis and heart failure after transverse aortic constriction (TAC). Methods: 10-week old Sept4 knockout (S4KO) and wild type (WT) mice were subjected to TAC or Sham surgery. Cardiac function was assessed 1- and 4-week post-injury. At both timepoints, hearts were harvested and used for transcriptomic and proteomic analyses. For cell culture experiments, primary cells were isolated from healthy 10-week old S4KO and WT mice and treated with TGF-β (10 ng/ml) or vehicle. Results: S4KO mice demonstrated improved cardiac function compared to WT mice at 1- and 4-weeks after TAC. Importantly, both groups displayed comparable levels of cardiomyocyte contractility ex vivo , highlighting that the beneficial effects of Sept4 deletion is through the non-cardiomyocyte population. Moreover, S4KO hearts demonstrated decreased levels of fibrosis compared to WTs at baseline and after injury. Lastly, by using primary cardiac fibroblasts, we discovered that Sept4 deletion prevents fibroblast activation and collagen secretion primarily by inhibiting Smad2 phosphorylation. Conclusions: Our results identify Sept4 as a potent mediator of cardiac fibrosis through regulation of Smad2 activity.
Step-in Dosing in the Bosutinib Dose Optimization Study (BODO) Failed to Reduce Gastrointestinal (GI) Toxicity in Patients Failing Second Generation TKI (2G-TKI) in Chronic Phase Chronic Myeloid Leukemia (CML) but Suggests Promising Molecular Response
Authors: Susanne Isfort, Dominik Wolf, Lino L. Teichmann, Martina Crysandt, Andreas Burchert, Andreas Hochhaus, Susanne Saussele, Alexander Kiani, Joachim R. Göthert, Thomas Illmer, Philippe Schafhausen, Mareille Warnken-Uhlich, Uta Wolber, Denise Kohn, Kirsi Manz, Markus Pfirrmann, Tim H Brümmendorf
Journal: Blood (2021)
CHOP Plus Sequential Mogamulizumab As First-Line Therapy for Untreated Adult T-Cell Leukemia-Lymphoma
Authors: Kazuki Tanimoto, Koji Kato, Takatoshi Aoki, Goichi Yoshimoto, Ilseung Choi, Masanori Kadowaki, Yasuhiro Sugio, Takuro Kuriyama, Noriaki Kawano, Ritsuro Suzuki, Kohta Miyawaki, Hideho Henzan, Noriyuki Saito, Takanori Ohta, Toshihiro Miyamoto, Koichi Akashi
Journal: Blood (2021)
N-末端プロ-B型ナトリウム利尿ペプチドは正常心電図,心エコーおよび心酵素の不安定狭心症患者において顕著な冠動脈病変を予測する
Authors: Hong Seo Na, Yoon Nam Sik, Ahn Youngkeun, Lim Sang Yub, Kim Yong Sook, Yun Kyung Ho, Kang Dong Koo, Lee Sang Hyun, Lee Yeon Sang, Kim Kye Hun, Son Il Seok, Hong Young Joon, Park Hyung Wook, Kim Ju Han, Jeong Myung Ho, Cho Jeong Gwan, Park Jong Chun, Kang Jung Chaee
Journal: Circulation (2005)
Abstract 9316: Role of Bile Acids in Calcific Aortic Valve Stenosis
Authors: Negar Atefi, Arun Surendran, Michael Raabe, Davinder S Jassal, Ashish H Shah, Amir Ravandi
Journal: Circulation (2021)

Introduction: Calcific aortic valve stenosis (CAVS) is the most common valvular pathology seen in the Western world. Patients with symptomatic CAVS have a poor prognosis with the only therapy being valvular intervention. There is currently no known mechanism and therefore medical therapy for controlling the progression of CAVS. Our recent metabolomics analysis of human aortic valve tissue identified bile acid biosynthesis as a potential mitigator of valvular stenosis. In this study, utilizing a targeted metabolomics approach, we investigated the role of valvular and plasma bile acids in the degree of severity and the rate of progression of CAVS. Methods: Human aortic valves from 102 patients who underwent AVR surgery were collected. Bile acid profiling (80 bile acids) of valvular tissues along with 19 plasma samples was carried out by a targeted mass spectrometry approach. The explanted aortic valves were graded from mild, moderate, and severe categories based on mean pressure gradient (MPG) and valvular calcification score by transthoracic echocardiography. CAVS progression was determined in a subset of our cohort (N=49), categorizing patients as “fast” and “slow” progressors based on echocardiography measures of the peak jet velocity. Results: Bile acids nordeoxycholic acid, norcholic acid, and glycodeoxycholic acid were significantly altered (p&lt;0.05) across CAVS severity stages based on MPG. Similarly, six bile acids namely nordeoxycholic acid, norcholic acid, 3β,7α-diOH-5-cholestenoic acid, 3β-OH-5-cholestenoic acid, glycolithocholic acid, and glycoallocholic acid were significantly altered (p&lt;0.05) based on valvular calcification scores. Taurodeoxycholic acid showed a significant difference (p&lt;0.05) between the slow and fast progressors. Additionally, valvular tissue levels of these bile acids correlate with plasma levels. Conclusions: In this report, we present a potential novel mechanistic pathway correlating bile acids with the pathogenesis of CAVS. Our goal is to validate these findings in a large cohort of patients with CAVS. Given that bile acid modulating therapies are already used in clinical practice, this represents a potential novel therapeutic target to prevent or delay the progression of CAVS.
Optimization of Autologous Hematopoietic Progenitor Stem Cell Apheresis Collection from Plerixafor-Mobilized Patients with Sickle Cell Disease
Authors: Yan Zheng, Akshay Sharma, Alexis Leonard, Kamille West, Naoya Uchida, Shuyu E, Lilora Kearney, Cortina Williams, Kirsten Hartwell, Regina Bosnick, Sandhya R. Panch, David F. Stroncek, Leigh Poston, Salem M. Akel, Neha Gupta, Jane S Hankins, Courtney D. Fitzhugh, Matthew Hsieh, John F. Tisdale, Mitchell J. Weiss
Journal: Blood (2021)
48 Immune environment correlates with NSCLC and CRC patient survival
Authors: Dannah Miller, Huong Nguyen, Kate Hieber, Charles Caldwell, Roberto Gianani
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Immune cells within the tumor microenvironment (TME) play a vital role in regulating tumor progression. Therefore, immunotherapies that stimulate anti-tumor responses are of great interest for the treatment of various cancers. PD-L1 expression on immune cells is positively correlated with increased patient survival. Our hypothesis is that non-small cell lung carcinoma (NSCLC) and colorectal cancer (CRC) patients with high immune infiltration and greater amounts of anti-tumor immune cells within the tumor compartment have an increased time of survival compared to cancers with immune excluded or immune desert environments. Methods One NSCLC and one CRC tumor microarray (TMA) containing primary tumors, metastases, and normal tissue were stained via multiplex immunofluorescence (mIF) for 6 different immune markers: CD3, CD8, CD56, CD68, CD163, and PD-L1. This multiplex panel was designed to evaluate the immune cell population as well as tumor and immune cell PD-L1 status to aid in research for immunotherapies, specifically anti-PD-L1 therapies. The stained TMAs were analyzed utilizing Flagship Biosciences’ proprietary image analysis platform. Machine learning algorithms stratified cells as belonging to the tumoral or stromal space based on their cellular features. Core level expression data was pulled and represented on a whole-cohort basis. All staining and image analysis outputs were reviewed by a board-certified, MD pathologist. Kaplan-meier curves were generated based on survival data in relation to the levels of immune cells present within the tumor cores as well as the percentage of immune cells infiltrating into the tumor. Results There is a clear correlation between patient survival and the presence or absence of various types of immune cells, including helper T cells, cytotoxic T cells, M1 macrophages, M2, macrophages, NK cells, as well as PDL1 expression on tumor and immune cells. Specifically, the increased presence of anti-tumor immune cells as well as increased expression of PD-L1 on immune cells within the tumor compartment correlates with an increase in patient survival. Conclusions Data generated through Flagship Biosciences’ image analysis platform showed a strong relationship between immune cell presence and localization and NSCLC and CRC patient survival. Altering the immune cells within the tumor to an anti-tumor immune environment could increase patient survival times. Combining immune checkpoint inhibitors with current FDA approved therapies for NSCLC and CRC are of interest to further extend patient survival. Further, utilizing Flagship Biosciences’ image analysis software to understand cancer immune microenvironments should be further utilized to aid in diagnosis and treatment decisions.
Sars-Cov-2 Vaccination in Patients with Pre-Existing Immune Thrombocytopenia
Authors: Eun-Ju Lee, Marina Beltrami Moreira, Hanny Al-Samkari, Adam Cuker, Jennifer MacWhirter - DiRaimo, Terry B. Gernsheimer, Alexandra Kruse, Craig M. Kessler, Caroline Kruse, Andrew D Leavitt, Alfred Ian Lee, Howard A. Liebman, Adrian C. Newland, Ashley E. Ray, Michael D Tarantino, Jecko Thachil, David J. Kuter, Douglas B. Cines, James B Bussel
Journal: Blood (2021)
Interim Results from the First Clinical Study of CC-95251, an Anti-Signal Regulatory Protein-Alpha (SIRPα) Antibody, in Combination with Rituximab in Patients with Relapsed and/or Refractory Non-Hodgkin Lymphoma (R/R NHL)
Authors: Paolo Strati, Eliza Hawkes, Nilanjan Ghosh, Joseph M. Tuscano, Quincy Chu, Mary Ann Anderson, Amar Patel, Michael R. Burgess, Kristen Hege, Sapna Chhagan, Sarandeep Boyanapalli, Tracey Day, Frank Shen, Amitkumar Mehta
Journal: Blood (2021)
PATH-22. GENETIC VARIATION BETWEEN IDH MUTANT AND IDH WILD-TYPE GLIOMA
Authors: shaoqun Li, Mingyao Lai, Jiangfen Zhou, junjie Zhen, Linbo Cai
Journal: Neuro-Oncology (2021)

Abstract OBJECTIVE The prognosis of IDH mutant glioma was significantly different from that of IDH wild-type glioma. In order to explore the differences between them at the genetic level, we analyzed the genetic results of IDH mutant and IDH wild-type glioma. METHODS This study analyzed the clinical data and genetic results of 45 glioma patients from Jan. 2017 to Dec. 2019, exploring relevant prognostic indicators and the difference in genetic profile between IDH mutant glioma and IDH wild-type glioma. RESULTS 45 patients were included in this study, including 15 IDH mutant glioma patients and 30 IDH wild-type glioma patients. Genetic analysis showed that there was no difference in tumor mutation burden (TMB) and microsatellite instability (MSI) between IDH mutant glioma and IDH wild-type glioma. But somatic mutation between IDH mutant and IDH wild-type glioma was different. The expressions of IDH1, CIC, SYNE1 and TP53 were different in the two groups, among which IDH1 and CIC were more significantly different. Copy number variations (CNV) was also different between IDH mutant glioma and IDH wild-type glioma. STIL occured more frequently in IDH wild-type gliomas. Genetic analysis also showed the difference in variant allel frequence (VAF). IDH mutant gliomas were more likely to be combined with ATRX and TP53 mutations, while IDH wild-type gliomas, in addition to the combination of TP53 mutations, often also combined with the mutations of NF1, BRAF and PTEN. In survival analysis, glioma with IDH mutation has a good prognosis, and IDH wild-type patients have a poor prognosis. In IDH wild-type patients, patients with PTEN mutation have a worse prognosis. CONCLUSION There is an obvious genetic difference between IDH mutation and IDH wild-type glioma, and PTEN mutation is a poor prognostic factor for IDH wild-type patients.