tbuckley/cabot-search huggingface dataset:
Abstract 14107: Early Right Ventricular Reverse Remodeling Predicts Long-term Survival After Isolated Tricuspid Valve Surgery
Authors: Sri Harsha Patlolla, Hartzell V Schaff, Joseph A Dearani, Kevin L Greason, Alberto Pochettino, Richard C Daly, Robert L Frye, Rick A Nishimura
Journal: Circulation (2020)

Introduction: There are limited data on the impact of isolated tricuspid valve (TV) surgery on recovery of right ventricular (RV) function and RV reverse remodeling. Methods: Among 223 patients who had isolated TV procedures between 2001 and 2017, 60 (27%) underwent TV repair and 163 (73%) received TV replacement. RV reverse remodeling was assessed by echocardiography at a median of 11.3 months (IQR 5.9-13.5) post dismissal. Kaplan-Meier analysis and the log-rank test were used to estimate and create survival curves. Cox proportional hazards analysis was performed to study the association of clinical and echocardiographic parameters with mortality. Results: Mean age was 67.3 ± 13.7 years, and 57% were female. Indication for surgery was functional TR in 64% (n=143) patients. Overall 30-day mortality was 2.7%. After a median follow-up period of 9.5 years (IQR 3.6-12.9) there were a total of 122 (54.7%) deaths. Adjusted Cox regression analysis revealed comparable survival for TV repair and replacement and identified older age, and presence of RV dysfunction (HR 1.84, 95% CI 1.14-2.98; P=0.01) as independent predictors of poor survival. Impact of early RV reverse remodeling on survival after TV surgery was evaluated in 90 patients; In 39 RV function and/or RV size recovered, but in 51 RV dysfunction and/or RV enlargement persisted or worsened. Patients who exhibited RV reverse remodeling had significantly improved survival compared to those who did not (Log-Rank P=0.005) and reverse remodeling was independently associated with improved survival (HR 0.42, 95% CI 0.24-0.74; P=0.003). In a multivariable analysis lower preoperative right atrial pressure (OR 0.83, 95% CI 0.73-0.94; P=0.004) was an independent predictor of early right heart reverse remodeling. Conclusions: Isolated TV surgery can be performed with acceptable outcomes, and overall survival is best in patients who receive the operation before developing severe RV systolic dysfunction. Adjusted survival was similar for patients undergoing TV repair or replacement. Reverse remodeling of RV during the first 18 months after surgery appears to provide survival benefit. Preoperative RA pressure is an independent determinant of postoperative RV remodeling.
Abstract PO-078: Single-cell transcriptomic analysis of highly-multiplexed IHC images via antigen mapping
Authors: Kiya W. Govek, Emma C. Troisi, Zhen Miao, Steven Woodhouse, Pablo G. Camara
Journal: Cancer Research (2020)

Abstract Recently developed technologies for digital imaging and highly multiplexed immunohistochemistry (mIHC) are enabling complex quantitative descriptions of tissue architecture. Imaging mass cytometry, multiplexed ion beam imaging, and co-detection by indexing can be used to profile the expression of dozens of proteins in a tissue section with single-cell resolution. Despite this progress, the amount of cell types and states that can be simultaneously identified by mIHC in a tissue section is still limited. Standard methods for identifying cell populations cluster cells according to expression similarities of the profiled antigens. These clusters are then manually annotated using previous knowledge of cell population markers. However, this is generally a partial, subjective, and biased process. Clusters often differ little in their antigenic profile and the interpretation of those differences is unclear. Moreover, the design of comprehensive antibody panels that include specific markers for every cell type and state present in the tissue is usually unfeasible. To overcome these limitations and increase the level of annotation of mIHC data, we propose an approach for enriching mIHC slides with single-cell RNA-seq data. Currently available single-cell RNA-seq technologies profile the expression of thousands of genes in each cell, allowing researchers to finely classify cells based on their gene expression profile. Some of the most recent approaches, like CITE-seq, REAP-seq, and Ab-seq, allow augmenting single-cell transcriptomes with concurrent protein measurements by staining dissociated cells with oligo-tagged antibodies. These approaches can be therefore used to determine the quantitative relation between gene and antigen expression levels. Here, we build upon CITE-seq and computational methods for the integration of single-cell omics data to identify and annotate cell populations in mIHC images in an automated way based on single-cell gene expression data from the same tissue. Our method, Spatially-resolved Transcriptomics via Epitope Anchoring (STvEA), performs transcriptome-guided annotation of mIHC datasets. It increases the phenotypic resolution of histological analyses by enabling annotation of subtle cell populations, spatial patterns of transcription, and interactions between cell types. We use the murine spleen as a test system to benchmark the stability and performance of STvEA and demonstrate its utility by using it to annotate published CODEX and CyTOF datasets of this organ. Citation Format: Kiya W. Govek, Emma C. Troisi, Zhen Miao, Steven Woodhouse, Pablo G. Camara. Single-cell transcriptomic analysis of highly-multiplexed IHC images via antigen mapping [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-078.
Reply to Amit Bansal, Ruchir Maheshwari, and Anant Kumar’s Letter to the Editor re: Beatriz Goulao, Sonya Carnell, Jing Shen, et al. Surgical Treatment for Recurrent Bulbar Urethral Stricture: A Randomised Open-label Superiority Trial of Open Urethroplasty Versus Endoscopic Urethrotomy (the OPEN Trial). Eur Urol 2020;78:572–80
Authors: Luke Vale, Beatriz Goulao, Graeme MacLennan, Nick Watkin
Journal: European Urology (2020)
Emergency seed funding for COVID-19 research: lessons from Johns Hopkins University
Authors: Julie Messersmith, Chasmine Stoddart-Osumah, Marc Lennon, Denis Wirtz
Journal: Journal of Clinical Investigation (2020)

Seed grant programs are an efficient mechanism for universities to invest in high-risk ideas, encourage collaborative research, support early-career faculty, and direct faculty toward a specific goal.When deployed effectively, they can
Review of the American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Treatment of Left-Sided Colonic Diverticulitis
Authors: David B. Stewart
Journal: JAMA Surgery (2020)

This article summarizes the newest version of the American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Treatment of Left-Sided Colonic Diverticulitis, which was released in June 2020.
Abstract 354: Teaching Effective Cardiopulmonary Resuscitation to 4 <sup>Th</sup> <sub>and</sub> 5 <sup>Th</sup> Grade Elementary Students
Authors: Cyle Rogotzke, Sherrie Bencik, Joseph Billian, Maureen Ford, Nathan Elg, Cambrie Bencik, Joshua Mastenbrook
Journal: Circulation (2020)

Background: Cardiac arrests are a leading cause of mortality in the US. Many states have CPR training requirements for high school graduation. There is a paucity of research on CPR education and assessment in elementary students. We hypothesized that 4 th and 5 th graders could attain the knowledge of, and be physically equipped to provide, hands-only CPR. Methods: Forth and fifth grade students from one school district were taught basic resuscitation physiology and hands-only CPR using videos and inflatable CPR manikins. Knowledge gain was assessed by a 13-question pre-test and a 2-week follow-up post-test, at which time students also performed 1 minute of hands-only CPR on an adult high-fidelity manikin. CPR skills were assessed by an 11-step checklist. Manikin software analyzed the compression effectiveness. A secondary analysis evaluated for association between compression effectiveness and age, gender, and BMI. Results: Three hundred fifty-five students completed the high-fidelity portion of the study. On average, students answered 1.1 more questions correctly on the post-test than the pre-test (P&lt;0.0001). The proportion of students self-reporting adequate CPR knowledge increased from 45% (155/345) to 98% (339/345) (p&lt;0.0001) pre-test to post-test. The proportion of students willing to perform CPR increased from 92% (320/349) to 96% (335/349) (p=0.0018). At least 8/11 resuscitation steps were completed by 72% (256/355) (95% CI, 68-77%) of students. The most frequently missed step was “get the attention of an adult,” which was only demonstrated by 5.9% (21/355) of students. Seventy-six percent (271/355) (95% CI, 72-81%) were able to deliver at least half of their compressions effectively. Age, BMI, and gender were not significantly associated with compression effectiveness. Conclusions: The education intervention resulted in a significant increase in the number of questions answered correctly from the pre-test to the post-test. Most students were able to learn hands-only CPR, apply the knowledge in a simulated cardiac arrest, and deliver effective chest compressions. Following the intervention, the students felt more prepared and were more willing to do CPR. It would be reasonable for older elementary students to be taught hands-only CPR.
What’s Missing in Secular Bioethics? The False Dichotomy between “the Secular” and “the Theological”
Authors: Isabel Roldán Gómez
Journal: The American Journal of Bioethics (2020)

This article is referred to by:Response to Open Peer Commentaries for “There’s No Harm in Talking: Reestablishing the Relationship Between Theological and Secular Bioethics”
Abstract 13423: Impact of Anemia on Growth Differentiation Factor 15 and Mortality in Patients With Stable Coronary Artery Disease: The ANOX Study
Authors: Moritake Iguchi, masahiro suzuki, Morihiro Matsuda, Yoichi Ajiro, Tsuyoshi Shinozaki, Satoru Sakagami, Kazuya Yonezawa, masatoshi shimizu, JUNICHI FUNADA, Takashi Takenaka, Yukiko Morita, Toshihiro Nakamura, Kazuteru Fujimoto, Hiromi Matsubara, Toru Kato, Takashi Unoki, Daisuke Takagi, Kyohma Wada, Miyaka Wada, Nobutoyo Masunaga, MITSURU ISHII, Kazuhiko Kotani, Mitsuru Abe, Masaharu Akao, Koji Hasegawa, Hiromichi Wada
Journal: Circulation (2020)

Background: Growth differentiation factor 15 (GDF-15) is a stress responsive cytokine of the transforming growth factor superfamily. Circulating levels of GDF-15 are elevated in various conditions including anemia and stable coronary artery disease (CAD), and associated with the risk of mortality in patients with stable CAD. However, whether anemia modifies the relationship between GDF-15 and mortality in patients with stable CAD is unknown. Methods: Using data from a multicenter, prospective cohort of 1460 patients with stable CAD, we assessed the association between anemic status and GDF-15 and the impact of anemia on the association between GDF-15 levels and the risk of all-cause death. GDF-15 was measured in 564 anemic and 896 non-anemic patients enrolled in the ANOX Study. Results: The mean age (standard deviation [SD]) of the patients was 71.7 (9.4) years; 74.4% were men. Patients with anemia exhibited significantly higher levels of GDF-15 compared to those without anemia (median [interquartile range], 1953 [1302-3110] vs. 1175 [838-1579] pg/mL, respectively; P &lt;0.001). Stepwise multiple linear regression analysis revealed that the log-transformed (Ln-) GDF-15 level was independently associated with higher age, diabetes, current smoking, lower estimated glomerular filtration rate, anemia, no use of aspirin, Ln-N-terminal pro-natriuretic peptide, and Ln-high-sensitivity C-reactive protein ( P &lt;0.005 for all). In the entire patient cohort, the GDF-15 level was significantly associated with all-cause death after adjusting for potential clinical confounders (hazard ratio per 1-SD increase [HR], 1.51; 95% confidence interval [CI], 1.33-1.71). This association was still significant in patients with anemia (HR, 1.71; 95% CI, 1.44-2.05) and in those without anemia (HR, 1.44; 95% CI, 1.21-1.71). However, GDF-15 provided incremental prognostic information to the model with potential clinical confounders and the established cardiovascular biomarkers in the entire cohort and in patients with anemia, but not in those without anemia. Conclusions: Higher levels of GDF-15 were independently associated with anemia in patients with stable CAD. The prognostic value of GDF-15 on mortality was pronounced in patients with anemia.
Abstract 14701: Prognostic Role of Cardiac Magnetic Resonance Imaging for Quantification of Functional Mitral Regurgitation in Patients With Non-ischemic Cardiomyopathy
Authors: Tom Kai Ming Wang, Duygu Kocyigit, Harry Choi, Jennifer Bullen, Alex Milinovich, Jin Jian, Zoran B Popovic, Brian P Griffin, Scott D Flamm, Wai Hong W Tang, Deborah H Kwon
Journal: Circulation (2020)

Background: Functional mitral regurgitation (MR) is associated with poor outcomes and the prognostic role of cardiac magnetic resonance imaging (CMR) quantification of secondary MR has rarely been studied. We evaluated the associations between CMR-derived MR-fraction and adverse outcomes in non-ischemic cardiomyopathy (NICM) patients. Methods: We retrospectively studied 840 consecutive NICM patients undergoing CMR during 2001/4/1-2019/3/31. Multivariable Cox proportional hazards regression was performed for MR-fraction and two composite endpoints: primary (time to death, heart transplant and/or left ventricular assist device) and secondary (primary endpoint plus heart failure hospitalizations). Results: The cohort had mean age of 53.0±15.9 years, 319 (38.0) were female, and mean MR-fraction of 14±13% by CMR. There were 141 (16.8%) primary and 223 (26.5%) secondary endpoints over a mean follow-up of 3.6±3.0 years. Multivariable analyses results are shown in the Table. MR-fraction was independently associated with the primary and secondary endpoints with hazards ratios of 1.13 (95%CI 1.07-1.20) and 1.13 (95%CI 1.07-1.19) respectively per 5% increase in MR-fraction. MR-fraction provided stronger prognostic power compared to late gadolinium enhancement (LGE) in both models. Older age and diabetes were independently associated with both composite endpoints, while lower LVEF was independently associated with the secondary endpoint only. Conclusion: CMR quantification of functional MR is a powerful predictor of adverse outcomes and demonstrated stronger associations with poor prognosis compared to LGE and left ventricular remodeling in a large cohort of patients with NICM.
Deep sequencing reveals a DAP1 regulatory haplotype that potentiates autoimmunity in systemic lupus erythematosus
Authors: Prithvi Raj, Ran Song, Honglin Zhu, Linley Riediger, Dong-Jae Jun, Chaoying Liang, Carlos Arana, Bo Zhang, Yajing Gao, Benjamin E. Wakeland, Igor Dozmorov, Jinchun Zhou, Jennifer A. Kelly, Bernard R. Lauwerys, Joel M. Guthridge, Nancy J. Olsen, Swapan K. Nath, Chandrashekhar Pasare, Nicolai van Oers, Gary Gilkeson, Betty P. Tsao, Patrick M. Gaffney, Peter K. Gregersen, Judith A. James, Xiaoxia Zuo, David R. Karp, Quan-Zhen Li, Edward K. Wakeland
Journal: Genome biology (2020)

Abstract Background Systemic lupus erythematosus (SLE) is a clinically heterogeneous autoimmune disease characterized by the development of anti-nuclear antibodies. Susceptibility to SLE is multifactorial, with a combination of genetic and environmental risk factors contributing to disease development. Like other polygenic diseases, a significant proportion of estimated SLE heritability is not accounted for by common disease alleles analyzed by SNP array-based GWASs. Death-associated protein 1 (DAP1) was implicated as a candidate gene in a previous familial linkage study of SLE and rheumatoid arthritis, but the association has not been explored further. Results We perform deep sequencing across the DAP1 genomic segment in 2032 SLE patients, and healthy controls, and discover a low-frequency functional haplotype strongly associated with SLE risk in multiple ethnicities. We find multiple cis-eQTLs embedded in a risk haplotype that progressively downregulates DAP1 transcription in immune cells. Decreased DAP1 transcription results in reduced DAP1 protein in peripheral blood mononuclear cells, monocytes, and lymphoblastoid cell lines, leading to enhanced autophagic flux in immune cells expressing the DAP1 risk haplotype. Patients with DAP1 risk allele exhibit significantly higher autoantibody titers and altered expression of the immune system, autophagy, and apoptosis pathway transcripts, indicating that the DAP1 risk allele mediates enhanced autophagy, leading to the survival of autoreactive lymphocytes and increased autoantibody. Conclusions We demonstrate how targeted sequencing captures low-frequency functional risk alleles that are missed by SNP array-based studies. SLE patients with the DAP1 genotype have distinct autoantibody and transcription profiles, supporting the dissection of SLE heterogeneity by genetic analysis.
Accelerating precision medicine in metastatic prostate cancer
Authors: Joaquin Mateo, Rana McKay, Wassim Abida, Rahul Aggarwal, Joshi Alumkal, Ajjai Alva, Felix Feng, Xin Gao, Julie Graff, Maha Hussain, Fatima Karzai, Bruce Montgomery, William Oh, Vaibhav Patel, Dana Rathkopf, Matthew Rettig, Nikolaus Schultz, Matthew Smith, David Solit, Cora Sternberg, Eliezer Van Allen, David VanderWeele, Jake Vinson, Howard R. Soule, Arul Chinnaiyan, Eric Small, Jonathan W. Simons, William Dahut, Andrea K. Miyahira, Himisha Beltran
Journal: Nature Cancer (2020)
Association of Tyrosine Kinase Inhibitors with Vascular Adverse Events: A Cohort Study Using Pooled Electronic Health Record
Authors: Olivia Copelan, Aaron T. Gerds, Hetty E. Carraway, Anjali S. Advani, Aziz Nazha, Navneet S. Majhail, Mikkael A. Sekeres, Matt Kalaycio, Sudipto Mukherjee
Journal: Blood (2017)
Body mass index (BMI) and outcome of metastatic melanoma patients receiving targeted therapy and immunotherapy: a multicenter international retrospective study
Authors: Piotr Rutkowski, Alice Indini, Matilde De Luca, Barbara Merelli, Anna Mariuk-Jarema, Pawel Teterycz, Pawel Rogala, Iwona Lugowska, Bożena Cybulska-Stopa, Alice Labianca, Lorenza Di Guardo, Michele Del Vecchio, Jacopo Pigozzo, Giovanni Randon, Francesca Corti, Carlo Alberto Tondini, Eliana Rulli, Mario Mandala
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Obesity is a risk factor for malignancy; however, its prognostic role in patients with metastatic melanoma is controversial. We aim to investigate the prognostic role of body mass index (BMI) in patients with metastatic melanoma receiving mitogen-activated pathway kinase inhibitors (MAPKi), immune checkpoint inhibitors (ICIs) alone or their sequence. Methods Data on patients with metastatic melanoma receiving ≥1 line of systemic treatment were retrieved from prospectively collected databases. Progression-free survival (PFS) and overall survival (OS) were analyzed by means of multivariable stratified Cox regression models; disease control rate (DCR) was analyzed by multivariable stratified logistic regression models. Subgroup analyzes according to the type of treatments received, and in BRAF -mutated patients were pre-planned. All multivariable models included BMI, age, gender, American Joint Committee on Cancer stage, performance status, lactate dehydrogenase and treatment sequencing strategy as covariates. Results Between November 2010 and November 2018, 688 patients from three Italian and two Polish centers were enrolled. 379 (57%) patients had M1c/d disease, 273 (41%) were female and the mean BMI was 27.1 (SD=4.9). Considering first-line treatment, 446 patients (66.8%) received ICIs and 222 MAPKi. No impact of BMI on OS was detected either considering the first line of ICIs, or ICIs sequencing (HR=1.02, 95% CI: 0.99 to 1.05, p=0.202, and HR=1.02, 95% CI: 0.99 to 1.04, p=0.237, respectively). A late effect of BMI on OS was found in patients treated with MAPKi: for five units increment, a 51% of risk reduction at 18 months and a 76% of risk reduction at 30 months were observed. No significant effect of BMI on PFS and DCR was found in any of the subgroup analyzes. Conclusion In patients with metastatic melanoma receiving ICIs, there is no impact of BMI on DCR, PFS and OS. The late prognostic effect of BMI in patients treated with MAPKi should be considered hypothesis generating and needs to be further investigated.
Safety and immunogenicity of a two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in adults in Europe (EBOVAC2): a randomised, observer-blind, participant-blind, placebo-controlled, phase 2 trial
Authors: Andrew J Pollard, Odile Launay, Jean-Daniel Lelievre, Christine Lacabaratz, Sophie Grande, Neil Goldstein, Cynthia Robinson, Auguste Gaddah, Viki Bockstal, Aurelie Wiedemann, Maarten Leyssen, Kerstin Luhn, Laura Richert, Christine Bétard, Malick M Gibani, Elizabeth A Clutterbuck, Matthew D Snape, Yves Levy, Macaya Douoguih, Rodolphe Thiebaut, Christopher McShane, Benoit Callendret, Stephanie Dincq, Camille Ferrault, Siew Pin Chai, Maire Paule Gyselen, Marleen van Looveren, Sylvia van Ballert, Tinne de Cnodder, Len Roza, Chiara Forcheh, Kate Stevens, Carmela Mastrandrea, Sanne de Ridder, Rachana Gundluru, Nathalie Swales, Vanessa Errijegers, Wouter Willems, Veronika Roorda, Nicola Orzabal, Magdalena Assenberg, Karine Vialatte, Frédéric Remblier, Elodie Porcar, Anton Ottavi, Eugénie Destandau, Christine Schwimmer, Laetitia Moinot, Cédrick Wallet, Florence Allais, Hélène Savel, Naouel Nedjaai, Anaïs Maugard, Nehza Lenzi, Pierre Loulergue, Mathilde Bahuaud, Fabrice Lainé, Bruno Laviolle, Nolwenn Boissel, Elise Thébault, David Vallée, Jean-François Nicolas, Sophie Gilbert, Karima Dahel, Karen Sagorny, Frédéric Lucht, Stéphane Paul, Alice Haccourt Chanavat, Florent Charra, Catherine Mutter, Monique Lambour, Caroline Muller, Anne Hutt-Clauss, Olivia Aranda, Louis Bernard, Valérie Gissot, Marie-Charlotte Hallouin-Bernard, Alain Goudeau, Steve Suzzoni, Eva Auostin, Lysiane Brick, Jose-Luis Lopez-Zaragoza, Giovanna Melic, Murial Carvalho, Chrystel Chesnel, Hakim Hocini, Aurélie Wiedemann, Laurent Hanot, Véronique Rieux, Adeep Puri, Temitope Adeloye, Malcolm Boyce, Jeremy Dennison, Inge Loewenstein, Omar Sahgal, Frans van den Berg, Wendy Calvert, Mary Faldon, Bruce McClain, Marie-Lousie Newell, Geert Molenberghs
Journal: The Lancet Infectious Diseases (2020)