tbuckley/cabot-search huggingface dataset:
FP12.04 Obesity is Associated With Greater Overall Survival in Patients With Metastatic NSCLC Receiving First-Line Pembrolizumab
Authors: F. Thomson, C. Stratton, I. Phillips, M. Mackean, C. Barrie, S. Campbell, A. Tufail, K. Maclennan, T. Evans, M. Stares
Journal: Journal of Thoracic Oncology (2021)
Abstract MP081: Short-long-short Sequence of RR Intervals is Associated With Increased Risk of Sudden Cardiac Death: the Atherosclerosis Risk in Community Study
Authors: Muammar Kabir, Jason Thomas, Golriz Sedaghat, Jonathan Waks, Srini V Mukundan, Charles Henrikson, Wendy Post, Nona Sotoodehnia, Scott Solomon, Elsayed Soliman, David Siscovick, Alfred Buxton, Mark Josephson, Larisa G Tereshchenko
Journal: Circulation (2017)

Introduction: A Short-long-short sequence of RR’ intervals frequently precedes ventricular tachyarrhythmia. However, an association of RR’ alternans with sudden cardiac death (SCD) in the general population has not been previously studied. Hypothesis: We hypothesized that RR’ alternans is associated with SCD. Methods: We analyzed baseline visit 10-second ECG in 14,250 participants of the Atherosclerosis Risk in Communities (ARIC) cohort (mean age 54.1±5.87y; 45% men; 74% white). Only normal sinus beats were included in the semi-automated analysis. Digital 12-lead ECG was transformed into orthogonal ECG, from which respiratory signal was derived. Joint symbolic analysis was used to assess increase or decrease in successive RR’ intervals and R-instant respiratory phases calculated using the Hilbert transform. Short-long-short or long-short-long RR’ sequence was defined as RR’ alternans. RR’ alternans occurring during respiratory phase transitions were not considered. SCD, non-SCD, and non-cardiac death served as competing outcomes. Three competing risks models were constructed. Model 1 was adjusted for age, sex, race, and study center. Model 2 was in addition adjusted for prevalent CVD. Model 3 was further adjusted for subclinical CVD, its risk factors, including traditional ECG predictors, and medications affecting SA or AV nodes. Results: Over median follow-up of 24.4 years, there were 497 SCDs (incidence 1.66 [95%CI 1.52-1.82], 742 non-sudden cardiac deaths (incidence 2.48 [95%CI 2.31-2.67], and 3,753 non-cardiac deaths (incidence 12.6 [95%CI 12.1-13.0]) per 1,000 person-years. RR alternans was present in 1,679(11.8%) participants. In competing risks analysis (Table) the presence of RR’ alternans, excluding those occurring due to respiratory phase changes, was independently associated with increased risk of SCD. Conclusion: In competing risks analysis the presence of RR’ alternans that are not due to respiratory phase transition is associated with SCD. Further study of RR’ alternans is warranted.
P07.02 Real World data of Advanced Non-Small Cell Lung Cancer Patients EGFR Mutated from a Peruvian Cohort
Authors: M. Galvez-Nino, R. Ruiz, S. Lozano, K. Roque, O. Coanqui, N. Valdivieso, M. Olivera, L. Mas
Journal: Journal of Thoracic Oncology (2021)
OA10.01 Perceptions of Biomarker Testing for Underserved Patients With Lung Cancer: A Mixed-Methods Survey of Us-Based Oncology Clinicians
Authors: L. Boehmer, U. Roy, J. Schrag, N. Martin, G. Salinas, B. Coleman, A. Howson, L. Shivakumar
Journal: Journal of Thoracic Oncology (2021)
FP06.01 Unexpected Aggressive Histological Component in Subsolid Lung Adenocarcinoma: Priority for Resection Without Delay
Authors: M. Yotsukura, K. Nakagawa, Y. Yoshida, H. Watanabe, M. Kusumoto, Y. Yatabe, S. Watanabe
Journal: Journal of Thoracic Oncology (2021)
Prognostic Value of Computed Tomography-Derived Fractional Flow Reserve Comparison With Myocardial Perfusion Imaging
Authors: Ahmed Ibrahim Ahmed, Yushui Han, Mahmoud Al Rifai, Talal Alnabelsi, Faisal Nabi, Su Min Chang, Myra Cocker, Chris Schwemmer, Juan C. Ramirez-Giraldo, Neal S. Kleiman, William A. Zoghbi, John J. Mahmarian, Mouaz H. Al-Mallah
Journal: JACC. Cardiovascular imaging (2021)
CD300a blockade enhances efferocytosis by infiltrating myeloid cells and ameliorates neuronal deficit after ischemic stroke
Authors: Chigusa Nakahashi-Oda, Satoshi Fujiyama, Yuta Nakazawa, Kazumasa Kanemaru, Yaqiu Wang, Wenxin Lyu, Takashi Shichita, Jiro Kitaura, Fumie Abe, Akira Shibuya
Journal: Science Immunology (2021)

Immune responses contribute to tissue injury and repair during and after ischemic stroke. However, the spatiotemporal and initiating molecular events remain incompletely understood. Here, we show that mice deficient in the phosphatidylserine receptor CD300a, which is highly expressed on brain myeloid cells including Ly6Chi monocytes, exhibited ameliorated neurological deficit after middle cerebral artery occlusion (MCAO). CD300a inhibited signaling through the CD300b-DNAX-activation protein 12 (DAP12) signaling pathway to prevent efferocytosis of apoptotic cells. Deficiency of CD300a enhanced efferocytosis by myeloid cells infiltrating the brain as early as 1 hour after MCAO and reduced release of damage-associated molecular patterns from dead cells, resulting in milder inflammation in the penumbral region. Treatment with an anti-CD300a neutralizing antibody ameliorated the neurological deficit after MCAO. These findings reveal an important role of efferocytosis in the super-acute phase of ischemic stroke pathology and identified CD300a as a target for immunotherapy in treating ischemic stroke.
Controls for Phylogeny and Robust Analysis in Pareto Task Inference
Authors: Miri Adler, Avichai Tendler, Jean Hausser, Yael Korem, Pablo Szekely, Noa Bossel, Yuval Hart, Omer Karin, Avi Mayo, Uri Alon
Journal: Molecular Biology and Evolution (2021)

Understanding the tradeoffs faced by organisms is a major goal of evolutionary biology. One of the main approaches for identifying these tradeoffs is Pareto task inference (ParTI). Two recent papers claim that results obtained in ParTI studies are spurious due to phylogenetic dependence (Mikami T, Iwasaki W. 2021. The flipping t-ratio test: phylogenetically informed assessment of the Pareto theory for phenotypic evolution. Methods Ecol Evol. 12(4):696-706) or hypothetical p-hacking and population-structure concerns (Sun M, Zhang J. 2021. Rampant false detection of adaptive phenotypic optimization by ParTI-based Pareto front inference. Mol Biol Evol. 38(4):1653-1664). Here, we show that these claims are baseless. We present a new method to control for phylogenetic dependence, called SibSwap, and show that published ParTI inference is robust to phylogenetic dependence. We show how researchers avoided p-hacking by testing for the robustness of preprocessing choices. We also provide new methods to control for population structure and detail the experimental tests of ParTI in systems ranging from ammonites to cancer gene expression. The methods presented here may help to improve future ParTI studies.
MA08.03 Adjuvant Chemotherapy for Patients with High-Risk Stage I Lung Adenocarcinoma Stratified by Epidermal Growth Factor Receptor Mutation Status
Authors: Y. Tsutani, M. Ito, T. Mimae, Y. Miyata, Y. Shimada, H. Ito, N. Ikeda, H. Nakayama, M. Okada
Journal: Journal of Thoracic Oncology (2021)
Widespread Erythematous Plaques With Prominent Telangiectases
Authors: Ayan Kusari, Philip E. LeBoit, Anna Haemel
Journal: JAMA Dermatology (2021)

A woman in her 50s with a history of nasal-type natural killer/T-cell lymphoma and chronic pulmonary coccidiomycosis was admitted for fever, hypotension, and asymptomatic widespread rash. What is your diagnosis?
A novel linear and broadly neutralizing peptide in the SARS-CoV-2 S2 protein for universal vaccine development
Authors: Tuofan Li, Qiuqi Kan, Jinying Ge, Zhimin Wan, Mengqi Yuan, Yao Huang, Quan Xie, Yi Yang, Hongxia Shao, Xiangdong Li, Lilin Ye, Aijian Qin, Zhigao Bu, Pinghuang Liu, Jianqiang Ye
Journal: Cellular and Molecular Immunology (2021)
APOL1 risk variants in individuals of African genetic ancestry drive endothelial cell defects that exacerbate sepsis
Authors: Junnan Wu, Ziyuan Ma, Archana Raman, Pazit Beckerman, Poonam Dhillon, Dhanunjay Mukhi, Matthew Palmer, Hua Chang Chen, Cassiane Robinson Cohen, Thomas Dunn, John P. Reilly, Nuala J. Meyer, Michael G.S. Shashaty, Zoltan Arany, György Haskó, Krzysztof Laudanski, Adriana Hung, Katalin Susztak
Journal: Immunity (2021)
Facial rash and ocular pain
Authors: D Fernandez-Nieto, T Salva-Palomeque
Journal: BMJ (2021)

A previously healthy man in his 60s presented to the emergency department with ocular pain, red eye, and mild bilateral visual deterioration for one week. Pruritic facial lesions appeared two days before the ocular symptoms. Scattered erythematous blisters and crusts were seen across his face and anterior neck, without dermatomal distribution or oral involvement (fig 1). Ophthalmological examination showed a normal pupillary reaction, mild ciliary hyperaemia, and multiple diffuse dendritic epithelial ulcers throughout the cornea in both eyes (fig 2) (a dendritic ulcer is a linear, branched lesion with terminal bulbs and raised epithelial edges, affecting beyond the basement membrane). The patient had no …
Development of an etoposide prodrug that is selectively activated by rabbit carboxylesterase, for combination with irinotecan, in enzyme-prodrug activation approaches to therapy
Authors: K. Jin Yoon, Joanna S. Remack, Jianjun Qi, Richard E. Lee, Philip M. Potter, Mary K. Danks
Journal: Cancer Research (2005)

1410  In principle, therapeutic approaches such as antibody- or viral-directed enzyme prodrug therapy (ADEPT or VDEPT) have the potential to achieve tumor cell-selective activation of prodrugs and to produce tumor-specific cytotoxicity. We demonstrated previously that rabbit liver carboxylesterase (rCE) efficiently activates the DNA topoisomerase I inhibitor irinotecan (CPT-11), and we are investigating the potential use of rCE/CPT-11 for VDEPT approaches to the treatment of neuroblastoma and other pediatric solid tumors. However, ADEPT and VDEPT approaches developed thus far are comprised of a single enzyme and a single prodrug; therefore, even if tumor cell-selectivity is achieved, these approaches comprise single agent therapy. One of the goals of our laboratories is to develop prodrugs of other mechanistic classes that are activated by rCE and that might be combined with CPT-11 to achieve tumor-selective combination therapy. Toward accomplishing this goal, we synthesized a series of etoposide prodrugs, and evaluated the activation of these prodrugs by purified CEs and by determining the IC50s of these compounds in SK-N-AS neuroblastoma cell lines transfected to express rCE or one of the two human CEs, hCE1 or hiCE (hCE2). A novel dipiperidine derivative of etoposide (dp-VP-16) was preferentially activated by rCE > hiCE > hCE1 in vitro. In transfected neuroblastoma cells, expression of rCE (581 units), hiCE (200 units), or hCE1 (394 units) decreased the IC50 of dp-VP-16 by 8.3-, 3.4-, and 0.9-fold, respectively. SK-N-ASpIRESrCE cells exposed sequentially to CPT-11 (10-9 - 10-4 M) for 4 hours followed by continuous exposure to the IC50 of dp-VP-16 decreased the IC50 of CPT-11 to 420 nM. This compared to an IC50 for CPT-11 alone of 21 microM for control-transfected SK-N-ASpIRESneo cells. Our data suggest that design of enzyme/prodrug systems with multiple prodrugs having complementary mechanisms of cytotoxicity merits further investigation.
NATIVE LIVER SURVIVAL IN PATIENTS WITH FIC1 DEFICIENCY : IMPACT OF GENOTYPE, SERUM BILE ACID CONCENTRATIONS AND SURGICAL BILIARY DIVERSION.
Authors: NAt Course Prognosis Pfic Effect, Daan van Wessel, Richard J. Thompson, Emmanuel M. Gonzales, Irena Jankowska, Benjamin L. Shneider, Etienne Sokal, Tassos Grammatikopoulos, Agustina Kadaristiana, Emmanuel Jacquemin, Anne Spraul, Patryk Lipinski, Piotr Czubkowski, Nathalie Rock, Mohammad Shagrani, Dieter Broering, Talal Algoufi, Nejat Mazhar, Emanuele Nicastro, Deirdre Kelly, Gabriela Nebbia, Henrik Arnell, Bjorn Fischler, Jan Hulscher, Daniele Serranti, Cigdem Arikan, Esra Polat, Dominique Debray, Florence Lacaille, Cristina Goncalves, Loreto Hierro, Gema Munoz Bartolo, Yael Mozer-Glassberg, Amer Azaz, Jernej Brecelj, Antal Dezsofi, Pier Luigi Calvo, Enke Grabhorn, Steffen Hartleif, Wendy Van der Woerd, Jian-She Wang, Liting Li, Ozlem Durmaz, Nanda Kerkar, Marianne Horby Jorgensen, Ryan T. Fischer, Carolina Jimenez-Rivera, Seema Alam, Mara Cananzi, Noemie Laverdure, Henkjan J. Verkade
Journal: Hepatology (2020)
Recommended reporting items for epidemic forecasting and prediction research: The EPIFORGE 2020 guidelines
Authors: Simon Pollett, Michael A. Johansson, Nicholas G. Reich, David Brett-Major, Sara Y. Del Valle, Srinivasan Venkatramanan, Rachel Lowe, Travis Porco, Irina Maljkovic Berry, Alina Deshpande, Moritz U. G. Kraemer, David L. Blazes, Wirichada Pan-ngum, Alessandro Vespigiani, Suzanne E. Mate, Sheetal P. Silal, Sasikiran Kandula, Rachel Sippy, Talia M. Quandelacy, Jeffrey J. Morgan, Jacob Ball, Lindsay C. Morton, Benjamin M. Althouse, Julie Pavlin, Wilbert van Panhuis, Steven Riley, Matthew Biggerstaff, Cecile Viboud, Oliver Brady, Caitlin Rivers
Journal: PLoS Medicine (2021)

The importance of infectious disease epidemic forecasting and prediction research is underscored by decades of communicable disease outbreaks, including COVID-19. Unlike other fields of medical research, such as clinical trials and systematic reviews, no reporting guidelines exist for reporting epidemic forecasting and prediction research despite their utility. We therefore developed the EPIFORGE checklist, a guideline for standardized reporting of epidemic forecasting research.We developed this checklist using a best-practice process for development of reporting guidelines, involving a Delphi process and broad consultation with an international panel of infectious disease modelers and model end users. The objectives of these guidelines are to improve the consistency, reproducibility, comparability, and quality of epidemic forecasting reporting. The guidelines are not designed to advise scientists on how to perform epidemic forecasting and prediction research, but rather to serve as a standard for reporting critical methodological details of such studies.These guidelines have been submitted to the EQUATOR network, in addition to hosting by other dedicated webpages to facilitate feedback and journal endorsement.
Shear stress–induced cellular senescence blunts liver regeneration through Notch–sirtuin 1–P21/P16 axis
Authors: Juan‐Li Duan, Bai Ruan, Ping Song, Zhi‐Qiang Fang, Zhen‐Sheng Yue, Jing‐Jing Liu, Guo‐Rui Dou, Hua Han, Lin Wang
Journal: Hepatology (2021)

The mechanisms involved in liver regeneration after partial hepatectomy (pHx) are complicated. Cellular senescence, once linked to aging, plays a pivotal role in wound repair. However, the regulatory effects of cellular senescence on liver regeneration have not been fully elucidated.Mice subjected to pHx were analyzed 14 days after surgery. The incomplete remodeling of liver sinusoids affected shear stress-induced endothelial nitric oxide synthase (eNOS) signaling on day 14, resulting in the accumulation of senescent LSECs. Removing macrophages to augment LSEC senescence led to a malfunction of the regenerating liver. A dynamic fluctuation in Notch activity accompanied senescent LSEC accumulation during liver regeneration. Endothelial Notch activation by using Cdh5-CreERT NICeCA mice triggered LSEC senescence and senescence-associated secretory phenotype, which disrupted liver regeneration. Blocking the Notch by γ-secretase inhibitor (GSI) diminished senescence and promoted LSEC expansion. Mechanically, Notch-hairy and enhancer of split 1 signaling inhibited sirtuin 1 (Sirt1) transcription by binding to its promoter region. Activation of Sirt1 by SRT1720 neutralized the up-regulation of P53, P21, and P16 caused by Notch activation and eliminated Notch-driven LSEC senescence. Finally, Sirt1 activator promoted liver regeneration by abrogating LSEC senescence and improving sinusoid remodeling.Shear stress-induced LSEC senescence driven by Notch interferes with liver regeneration after pHx. Sirt1 inhibition accelerates liver regeneration by abrogating Notch-driven senescence, providing a potential opportunity to target senescent cells and facilitate liver repair after injury.
MA13.06 Improved Outcomes for Patients Developing Any Immune-Related Adverse Events in Advanced NSCLC Treated With Pembrolizumab Monotherapy
Authors: A. Lee, B. Girling, G. Patel, P. Sawhney, M. Luong, D. Ohana, M. Forster, S. Lee
Journal: Journal of Thoracic Oncology (2021)
Lymphatics in the broken heart
Authors: Ebba Bråkenhielm, Yuguo Chen, Yihai Cao
Journal: Journal of Clinical Investigation (2021)

Cardiac lymphatics have emerged as a therapeutic target in cardiovascular diseases to limit myocardial edema and inflammation, notably after myocardial infarction (MI). While most experimental therapeutic approaches have focused on vascular endothelial growth factor C (VEGF-C) delivery, it remains uncertain to what degree the beneficial cardiac effects are related to lymphatic expansion in the heart. In this issue of the JCI, Keller, Lim, et al. reexamined the acute functional impact of endogenous cardiac lymphangiogenesis in the infarct zone after MI in mice. Their data, obtained by elegant comparisons of several complementary genetic mouse models, indicate that infarct expansion and left ventricular dilation and function after MI are unaffected by infarct lymphangiogenesis. This Commentary places the results into the context of previous findings. We believe these data will help further advance the research field of cardiac lymphatics to guide better clinical translation and benefit patients with ischemic heart disease.
P68.04 Molecular Mechanism of MK2 Promoting Lung Adenocarcinoma Progression by Phosphorylating Transcription Regulator CRABP2
Authors: J. Deng, J. Xu, F. Zhong, J. Tang, K. Fang, F. Yu, G. Zhang, J. Lai, F. Qiu
Journal: Journal of Thoracic Oncology (2021)
Astrocyte dysfunction in Parkinson's disease: from the perspectives of transmitted α-synuclein and genetic modulation
Authors: Changjing Wang, Tongtong Yang, Meiyu Liang, Junxia Xie, Ning Song
Journal: Translational Neurodegeneration (2021)

Abstract Parkinson’s disease (PD) is a common neurodegenerative disorder that primarily affects the elderly. While the etiology of PD is likely multifactorial with the involvement of genetic, environmental, aging and other factors, α-synuclein (α-syn) pathology is a pivotal mechanism underlying the development of PD. In recent years, astrocytes have attracted considerable attention in the field. Although astrocytes perform a variety of physiological functions in the brain, they are pivotal mediators of α-syn toxicity since they internalize α-syn released from damaged neurons, and this triggers an inflammatory response, protein degradation dysfunction, mitochondrial dysfunction and endoplasmic reticulum stress. Astrocytes are indispensable coordinators in the background of several genetic mutations, including PARK7, GBA1, LRRK2, ATP13A2, PINK1, PRKN and PLA2G6 . As the most abundant glial cells in the brain, functional astrocytes can be replenished and even converted to functional neurons. In this review, we discuss astrocyte dysfunction in PD with an emphasis on α-syn toxicity and genetic modulation and conclude that astrocyte replenishment is a valuable therapeutic approach in PD.
A global screening identifies chromatin-enriched RNA-binding proteins and the transcriptional regulatory activity of QKI5 during monocytic differentiation
Authors: Yue Ren, Yue Huo, Weiqian Li, Manman He, Siqi Liu, Jiabin Yang, Hongmei Zhao, Lingjie Xu, Yuehong Guo, Yanmin Si, Hualu Zhao, Shuan Rao, Jing Wang, Yanni Ma, Xiaoshuang Wang, Jia Yu, Fang Wang
Journal: Genome biology (2021)

Abstract Background Cellular RNA-binding proteins (RBPs) have multiple roles in post-transcriptional control, and some are shown to bind DNA. However, the global localization and the general chromatin-binding ability of RBPs are not well-characterized and remain undefined in hematopoietic cells. Results We first provide a full view of RBPs’ distribution pattern in the nucleus and screen for chromatin-enriched RBPs (Che-RBPs) in different human cells. Subsequently, by generating ChIP-seq, CLIP-seq, and RNA-seq datasets and conducting combined analysis, the transcriptional regulatory potentials of certain hematopoietic Che-RBPs are predicted. From this analysis, quaking (QKI5) emerges as a potential transcriptional activator during monocytic differentiation. QKI5 is over-represented in gene promoter regions, independent of RNA or transcription factors. Furthermore, DNA-bound QKI5 activates the transcription of several critical monocytic differentiation-associated genes, including CXCL2, IL16, and PTPN6. Finally, we show that the differentiation-promoting activity of QKI5 is largely dependent on CXCL2, irrespective of its RNA-binding capacity. Conclusions Our study indicates that Che-RBPs are versatile factors that orchestrate gene expression in different cellular contexts, and identifies QKI5, a classic RBP regulating RNA processing, as a novel transcriptional activator during monocytic differentiation.
MA17.06 Nodal Upstaging Comparison of Open, Video-Assisted Thoracoscopic, and Robotic Lung Resections Form﻿ Non–Small Cell Lung Cancer
Authors: R. Terra, A. Dela Vega, L. Lauricella, E. Rocha, L. Lima, M. Cremonese, P. Pêgo-Fernandes
Journal: Journal of Thoracic Oncology (2021)
Nivolumab versus placebo in patients with relapsed malignant mesothelioma (CONFIRM): a multicentre, double-blind, randomised, phase 3 trial
Authors: Dean A Fennell, Sean Ewings, Christian Ottensmeier, Raffaele Califano, Gerard G Hanna, Kayleigh Hill, Sarah Danson, Nicola Steele, Mavis Nye, Lucy Johnson, Joanne Lord, Calley Middleton, Peter Szlosarek, Sam Chan, Aarti Gaba, Liz Darlison, Peter Wells-Jordan, Cathy Richards, Charlotte Poile, Jason F Lester, Gareth Griffiths, Gillian Price, Paul Shaw, Judith Cave, Jay Naik, Amy Ford, Tom Geldhart, Gairin Dancey, Dionysis Papadatos, Andy Polychronis, Petra Jankowska, Angela Scott, Jill Gardiner, Mathilda Cominos, Lynn Campbell, Carol MacGregor, Lois Mullholand, Meenali Chitnis, Gary Dougherty
Journal: The Lancet Oncology (2021)

No phase 3 trial has yet shown improved survival for patients with pleural or peritoneal malignant mesothelioma who have progressed following platinum-based chemotherapy. The aim of this study was to assess the efficacy and safety of nivolumab, an anti-PD-1 antibody, in these patients.
Metabolic regulation by PD-1 signaling promotes long-lived quiescent CD8 T cell memory in mice
Authors: Vandana Kalia, Yevgeniy Yuzefpolskiy, Adithya Vegaraju, Hanxi Xiao, Florian Baumann, Shashank Jatav, Candice Church, Martin Prlic, Abhishek Jha, Paul Nghiem, Stanley Riddell, Surojit Sarkar
Journal: Science Translational Medicine (2021)

PD-1 signals promote development of long-lived quiescent memory CD8 T cells by regulating the balance of glycolysis and fatty acid oxidation.
Delta Variant Linked With Spike in Youth Hospitalizations
Authors: Bridget M. Kuehn
Journal: JAMA (2021)

Weekly COVID-19 hospitalization rates among US children and adolescents increased 5-fold this past summer as the B.1.617.2 (Delta) variant became the dominant circulating strain, according to data from the Coronavirus Disease 2019–Associated Hospitalization Surveillance Network (COVID-NET).