tbuckley/cabot-search huggingface dataset:
P33.02 Comparison of PD-L1 Protein Expression Between Primary and Metastatic Lesions in Lung Cancer Patients
Authors: M. Moutafi, W. Tao, R. Huang, J. Haberberger, B. Alexander, S. Ramkissoon, J. Ross, K. Syrigos, W. Wei, L. Pusztai, D. Rimm, I. Vathiotis
Journal: Journal of Thoracic Oncology (2021)
Abstract 16126: Cumulative Impact of Social Determinants of Health Risk Score on Obesity Among Young Adults in the United States
Authors: Muhammad Haisum Maqsood, Javier Valero-Elizondo, Rahul Singh, Karan Shah, Maryam Hyder, Garima Sharma, Michael J Blaha, Ron Blankstein, Salim S Virani, Miguel Cainzos Achirica, Khurram Nasir
Journal: Circulation (2020)

Introduction: The growing prevalence of obesity has created a major burden on the health care system. To date, studies examining social determinants of obesity in adults have mostly focused on individual social determinants of health (SDOH) components. In this study, we explore the influence of cumulative SDOH on obesity among young adults (&lt; 45) as compared with middle- aged (45-64) and elderly (≥ 65) populations in the US. Methods: We examined cross-sectional data on 164,696 adult participants from the National Health Interview Survey (2013-17). For each individual, the unfavorable SDOH risk factor was identified from 39 sub-components, stemming from 6 general domains (economic stability, neighborhood and physical environment, community and social context, food, education, and healthcare system access). Risk factors were then aggregated to develop a cumulative score, wherein individuals were divided into quartiles. Obesity was calculated from self-reported height and weight and defined as BMI ≥ 30 kg/m 2 . Adults with a BMI &lt;18.5 kg/m 2 were excluded from the analysis. Results: The age-adjusted prevalence of obesity was 32.5%, which translates to 78 million US adults annually. A linear increase in the prevalence of age-adjusted obesity was noted with increasing unfavorable SDOH prevalence across all age groups. In the overall population, those with the worst (4 th quartile) vs best (1 st quartile) SDOH profile had 1.47 higher odds of being obese in adjusted models. There was evidence, however, of effect modification by age (p-value for interaction &lt; 0.001), with a stronger association of unfavorable SDOH risk with obesity in the young (&lt;45 years) as compared with middle age and elderly (Table). Conclusions: A higher burden of SDOH is more strongly associated with obesity in young adults. Estimating and understanding the impact of SDOH may have practical implications for informing effective interventions to combat early adulthood obesity and its ensuing complications.
4SCAR2.0: a multi-CAR-T therapy regimen for the treatment of relapsed/refractory B cell lymphomas
Authors: Cheng Jiao, Eugene Zvonkov, Xun Lai, Rui Zhang, Yuchen Liu, Yue Qin, Valery Savchenko, Nelly Gabeeva, Tsai-Hua Chung, Liyuan Sheng, Lung-Ji Chang
Journal: Blood Cancer Journal (2021)
Precision Dosing
Authors: Kimberly Maxfield, Issam Zineh
Journal: JAMA (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
FP14.17 Efficacy and Safety of Pralsetinib in Chinese Patients with Advanced RET Fusion+ Non-Small Cell Lung Cancer after Platinum-Based Chemotherapy
Authors: Q. Zhou, Y. Wu, J. Chang, Y. Fan, J. Zhao, G. Wu, Y. Sun, X. Wang, W. Nian, K. Wang, X. Zheng, L. Qu, S. Yao, K. Liu, P. Li, J. Yang
Journal: Journal of Thoracic Oncology (2021)
Construction of acetyl-CoA and DBAT hybrid metabolic pathway for acetylation of 10-deacetylbaccatin III to baccatin III
Authors: Hao Wang, Bo-Yong Zhang, Ting Gong, Tian-Jiao Chen, Jing-Jing Chen, Jin-Ling Yang, Ping Zhu
Journal: Acta Pharmaceutica Sinica B (2021)

10-Deacetylbaccatin III (10-DAB) C10 acetylation is an indispensable procedure for Taxol semi-synthesis, which often requires harsh conditions. 10-Deacetylbaccatin III-10-β-O-acetyltransferase (DBAT) catalyzes the acetylation but acetyl-CoA supply remains a key limiting factor. Here we refactored the innate biosynthetic pathway of acetyl-CoA in Escherichia coli and obtained a chassis with acetyl-CoA productivity over three times higher than that of the host cell. Then, we constructed a microbial cell factory by introducing DBAT gene into this chassis for efficiently converting 10-DAB into baccatin III. We found that baccatin III could be efficiently deacetylated into 10-DAB by DBAT with CoASH and K+ under alkaline condition. Thus, we fed acetic acid to the engineered strain both for serving as a substrate of acetyl-CoA biosynthesis and for alleviating the deacetylation of baccatin III. The fermentation conditions were optimized and the baccatin III titers reached 2, 3 and 4.6 g/L, respectively, in a 3-L bioreactor culture when 2, 3 and 6 g/L of 10-DAB were supplied. Our study provides an environment-friendly approach for the large scale 10-DAB acetylation without addition of acetyl-CoA in the industrial Taxol semi-synthesis. The finding of DBAT deacetylase activity may broaden its application in the structural modification of pharmaceutically important lead compounds.
P19.03 Operative Outcomes of Local Consolidation with Cytoreductive Surgery for Oncogenic-Driven Advanced NSCLC
Authors: B.J. Park, S.Y. Park, M.H. Hong, Y.H. Yang, H.E. Kim, C.Y. Lee, J.G. Lee, D.J. Kim, H.C. Paik, K.Y. Chung
Journal: Journal of Thoracic Oncology (2021)
Patient e-Visit Use and Outcomes for Common Symptoms in an Integrated Health Care Delivery System
Authors: Reena Bhargava, Gregg Gayre, Jie Huang, Evangeline Sievers, Mary Reed
Journal: JAMA Network Open (2021)

Electronic physician visits, or e-visits, use a digital virtual care platform with structured, asynchronous exchange between patients and clinicians to provide care without scheduled appointments.1 e-Visits can be an efficient model for receiving care during pandemics such as coronavirus disease 2019 (COVID-19).2

Through a patient portal, e-visits collect clinician-developed, internet-based questionnaires for physician management with clinical decision support tools and electronic health record (EHR) order sets. Little evidence exists on characteristics of patients using e-visits and success in managing patients’ concerns. We evaluated patients’ adoption and success of primary care e-visits by monitoring the 7-day follow-up care needed within an integrated health care delivery system.
FP14.13 Molecular Characterisation and Clinical Outcomes in RET Rearranged Non-Small Cell Lung Cancer (NSCLC)
Authors: A. Tan, G. Lai, G.S. Tan, A. Seet, A. Takano, J. Alvarez, A. Skanderup, W. Tan, M. Ang, R. Kanesvaran, Q.S. Ng, A. Jain, T. Rajasekaran, W. Lim, E. Tan, K.H.T. Lim, D. Tan
Journal: Journal of Thoracic Oncology (2021)
Burden of Heart Failure Signs and Symptoms, Prognosis, and Response to Therapy
Authors: Karola Jering, Brian Claggett, Margaret M. Redfield, Sanjiv J. Shah, Inder S. Anand, Felipe Martinez, Shalini V. Sabarwal, Petar M. Seferović, Jose F. Kerr Saraiva, Tzvetana Katova, Marty P. Lefkowitz, Marc A. Pfeffer, John J.V. McMurray, Scott D. Solomon
Journal: JACC Heart Failure (2021)
Attention to Immortal Time Bias in Critical Care Research
Authors: Emily A. Vail, Hayley B. Gershengorn, Hannah Wunsch, Allan J. Walkey
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Section:ChooseTop of pageAbstract <<Immortal Time Bias and It...Study Reporting Elements ...Susceptibility of Observa...Persistence of Unaddresse...Conclusions and Future Di...ReferencesCITING ARTICLES
Stabilization of Damaged Articular Cartilage with Hydrogel‐Mediated Reinforcement and Sealing
Authors: Jay M. Patel, Claudia Loebel, Kamiel S. Saleh, Brian C. Wise, Edward D. Bonnevie, Liane M. Miller, James L. Carey, Jason A. Burdick, Robert L. Mauck
Journal: Advanced Healthcare Materials (2021)

Abstract Cartilage injuries and subsequent tissue deterioration impact millions of patients. Since the regeneration of functional hyaline cartilage remains elusive, methods to stabilize the remaining tissue, and prevent further deterioration, would be of significant clinical utility and prolong joint function. Finite element modeling shows that fortification of the degenerate cartilage (Reinforcement) and reestablishment of a superficial zone (Sealing) are both required to restore fluid pressurization within the tissue and restrict fluid flow and matrix loss from the defect surface. Here, a hyaluronic acid (HA) hydrogel system is designed to both interdigitate with and promote the sealing of the degenerated cartilage. Interdigitating fortification restores both bulk and local pericellular tissue mechanics, reestablishing the homeostatic mechanotransduction of endogenous chondrocytes within the tissue. This HA therapy is further functionalized to present chemo mechanical cues that improve the attachment and direct the response of mesenchymal stem/stromal cells at the defect site, guiding localized extracellular matrix deposition to “seal” the defect. Together, these results support the therapeutic potential, across cell and tissue length scales, of an innovative hydrogel therapy for the treatment of damaged cartilage.
Genomic Signatures for Species-Specific Adaptation in Lake Victoria Cichlids Derived from Large-Scale Standing Genetic Variation
Authors: Haruna Nakamura, Mitsuto Aibara, Rei Kajitani, Hillary D J Mrosso, Semvua I Mzighani, Atsushi Toyoda, Takehiko Itoh, Norihiro Okada, Masato Nikaido
Journal: Molecular Biology and Evolution (2021)

Abstract The cichlids of Lake Victoria are a textbook example of adaptive radiation, as &amp;gt;500 endemic species arose in just 14,600 years. The degree of genetic differentiation among species is very low due to the short period of time after the radiation, which allows us to ascertain highly differentiated genes that are strong candidates for driving speciation and adaptation. Previous studies have revealed the critical contribution of vision to speciation by showing the existence of highly differentiated alleles in the visual opsin gene among species with different habitat depths. In contrast, the processes of species-specific adaptation to different ecological backgrounds remain to be investigated. Here, we used genome-wide comparative analyses of three species of Lake Victoria cichlids that inhabit different environments—Haplochromis chilotes, H. sauvagei, and Lithochromis rufus—to elucidate the processes of adaptation by estimating population history and by searching for candidate genes that contribute to adaptation. The patterns of changes in population size were quite distinct among the species according to their habitats. We identified many novel adaptive candidate genes, some of which had surprisingly long divergent haplotypes between species, thus showing the footprint of selective sweep events. Molecular phylogenetic analyses revealed that a large fraction of the allelic diversity among Lake Victoria cichlids was derived from standing genetic variation that originated before the adaptive radiation. Our analyses uncovered the processes of species-specific adaptation of Lake Victoria cichlids and the complexity of the genomic substrate that facilitated this adaptation.
Myocardial Flow Reserve and Coronary Calcification in Prognosis of Patients With Suspected Coronary Artery Disease
Authors: Ahmed Aljizeeri, Ahmed Ibrahim Ahmed, Mousa Alali Alfaris, Dalia Ahmed, Jabir Farea, Awadelkarim Elneama, Ihab Suliman, Mohsen Alharthi, Amjad Ahmed, Ahmed Alsaileek, Mouaz H Al-Mallah
Journal: JACC. Cardiovascular imaging (2021)
Timing and Origins of Local and Distant Metastases in Lung Cancer
Authors: Wen-Fang Tang, Min Wu, Hua Bao, Yang Xu, Jie-Shan Lin, Yi Liang, Yu Zhang, Xiang-Peng Chu, Zhen-Bin Qiu, Jian Su, Jia-Tao Zhang, Chao Zhang, Fang-Ping Xu, Jing-Hua Chen, Rui Fu, Ying Chen, Tao Yang, Qing-Ke Chen, Ting-Ting Wu, Xue Wu, Yang Shao, Jian-Tao Zheng, Zhi Xie, Zhi-Yi Lv, Song Dong, Yi-Long Wu, Wen-Zhao Zhong
Journal: Journal of Thoracic Oncology (2021)

<h2>Abstract</h2><h3>Introduction</h3> Metastasis is the primary cause of lung cancer-related death. Nevertheless, the underlying molecular mechanisms and evolutionary patterns of lung cancer metastases are still elusive. <h3>Methods</h3> We performed whole-exome sequencing for 40 primary tumors (PTs) and 61 metastases from 47 patients with lung cancer, of which 40 patients had paired PTs and metastases. The PT-metastasis genomic divergence, metastatic drivers, timing of metastatic dissemination, and evolutionary origins were analyzed using appropriate statistical tools and mathematical models. <h3>Results</h3> There were various degrees of genomic heterogeneity when comparing the paired primary and metastatic lesions or comparing metastases of different sites. Multiple metastasis-selected/enriched genetic alterations were found, such as <i>MYC</i> amplification, NKX2-1 amplification, <i>RICTOR</i> amplification, arm 20p gain, and arm 11p loss, and these results were were also featured in a meta-analysis cross-validated using an independent cohort from Memorial Sloan-Kettering Cancer Center database. To elucidate the metastatic seeding time, we applied a metastatic model and found 61.1% of the tumors were late dissemination, in which the metastatic seeding happened approximately 2.74 years before clinical detection. One exception was lymph node metastases whose dissemination time was relatively early. By analyzing the evolutionary origins, we reported that nonlymph node metastases were mainly seeded by the PT (87.5%) rather than the earlier colonized lymph node metastases. <h3>Conclusions</h3> Our results shed light on the molecular features that potentially drive lung cancer metastases. The distinct temporospatial pattern of disease progression revealed that lung cancer was susceptible to either late dissemination or indolent early lymph node metastases, leaving a potential time window to minimize metastases by early cancer detection.
P62.09 PLGF Regulates Stimulation of Cell Proliferation and Glycolysis of Lung Adenocarcinoma Through Wnt/β-catenin Pathway
Authors: B. Han, W. Zhang, Y. Zhang, F. Qian, W. Zhou, Y. Chen, M. Hu, J. Lu, Y. Lou
Journal: Journal of Thoracic Oncology (2021)
A comprehensive analysis and resource to use CRISPR-Cas13 for broad-spectrum targeting of RNA viruses
Authors: Xueqiu Lin, Yanxia Liu, Augustine Chemparathy, Tara Pande, Marie La Russa, Lei S. Qi
Journal: Cell Reports Medicine (2021)

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and variants has led to significant mortality. We recently reported that an RNA-targeting CRISPR-Cas13 system, called prophylactic antiviral CRISPR in human cells (PAC-MAN), offered an antiviral strategy against SARS-CoV-2 and influenza A virus. Here, we expand in silico analysis to use PAC-MAN to target a broad spectrum of human- or livestock-infectious RNA viruses with high specificity, coverage, and predicted efficiency. Our analysis reveals that a minimal set of 14 CRISPR RNAs (crRNAs) is able to target >90% of human-infectious viruses across 10 RNA virus families. We predict that a set of 5 experimentally validated crRNAs can target new SARS-CoV-2 variant sequences with zero mismatches. We also build an online resource (crispr-pacman.stanford.edu) to support community use of CRISPR-Cas13 for broad-spectrum RNA virus targeting. Our work provides a new bioinformatic resource for using CRISPR-Cas13 to target diverse RNA viruses to facilitate the development of CRISPR-based antivirals.
A single-cell atlas of the healthy breast tissues reveals clinically relevant clusters of breast epithelial cells
Authors: Poornima Bhat-Nakshatri, Hongyu Gao, Liu Sheng, Patrick C. McGuire, Xiaoling Xuei, Jun Wan, Yunlong Liu, Sandra K. Althouse, Austyn Colter, George Sandusky, Anna Maria Storniolo, Harikrishna Nakshatri
Journal: Cell Reports Medicine (2021)

Single-cell RNA sequencing (scRNA-seq) is an evolving technology used to elucidate the cellular architecture of adult organs. Previous scRNA-seq on breast tissue utilized reduction mammoplasty samples, which are often histologically abnormal. We report a rapid tissue collection/processing protocol to perform scRNA-seq of breast biopsies of healthy women and identify 23 breast epithelial cell clusters. Putative cell-of-origin signatures derived from these clusters are applied to analyze transcriptomes of ~3,000 breast cancers. Gene signatures derived from mature luminal cell clusters are enriched in ~68% of breast cancers, whereas a signature from a luminal progenitor cluster is enriched in ~20% of breast cancers. Overexpression of luminal progenitor cluster-derived signatures in HER2+, but not in other subtypes, is associated with unfavorable outcome. We identify TBX3 and PDK4 as genes co-expressed with estrogen receptor (ER) in the normal breasts, and their expression analyses in >550 breast cancers enable prognostically relevant subclassification of ER+ breast cancers.
P62.05 Identifying Therapeutic Approaches to Treat KEAP1-Mutant Lung Adenocarcinoma
Authors: S. Best, S. Ding, A. Kersbergen, B. Reljic, G. Wright, V. Rathi, D. Desouza, M. Mcconville, M. Ritchie, K. Sutherland
Journal: Journal of Thoracic Oncology (2021)
Reduction of RUNX1 transcription factor activity by a CBFA2T3-mimicking peptide: application to B cell precursor acute lymphoblastic leukemia
Authors: Hélène Jakobczyk, Lydie Debaize, Benoit Soubise, Stéphane Avner, Jérémie Rouger-Gaudichon, Séverine Commet, Yan Jiang, Aurélien A. Sérandour, Anne-Gaëlle Rio, Jason S. Carroll, Christian Wichmann, Michael Lie-a-Ling, Georges Lacaud, Laurent Corcos, Gilles Salbert, Marie-Dominique Galibert, Virginie Gandemer, Marie-Bérengère Troadec
Journal: Journal of Hematology & Oncology (2021)

Abstract Background B Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) is the most common pediatric cancer. Identifying key players involved in proliferation of BCP-ALL cells is crucial to propose new therapeutic targets. Runt Related Transcription Factor 1 (RUNX1) and Core-Binding Factor Runt Domain Alpha Subunit 2 Translocated To 3 (CBFA2T3, ETO2, MTG16) are master regulators of hematopoiesis and are implicated in leukemia. Methods We worked with BCP-ALL mononuclear bone marrow patients’ cells and BCP-ALL cell lines, and performed Chromatin Immunoprecipitations followed by Sequencing (ChIP-Seq), co-immunoprecipitations (co-IP), proximity ligation assays (PLA), luciferase reporter assays and mouse xenograft models. Results We demonstrated that CBFA2T3 transcript levels correlate with RUNX1 expression in the pediatric t(12;21) ETV6-RUNX1 BCP-ALL. By ChIP-Seq in BCP-ALL patients’ cells and cell lines, we found that RUNX1 is recruited on its promoter and on an enhancer of CBFA2T3 located − 2 kb upstream CBFA2T3 promoter and that, subsequently, the transcription factor RUNX1 drives both RUNX1 and CBFA2T3 expression. We demonstrated that, mechanistically, RUNX1 and CBFA2T3 can be part of the same complex allowing CBFA2T3 to strongly potentiate the activity of the transcription factor RUNX1. Finally, we characterized a CBFA2T3-mimicking peptide that inhibits the interaction between RUNX1 and CBFA2T3, abrogating the activity of this transcription complex and reducing BCP-ALL lymphoblast proliferation. Conclusions Altogether, our findings reveal a novel and important activation loop between the transcription regulator CBFA2T3 and the transcription factor RUNX1 that promotes BCP-ALL proliferation, supporting the development of an innovative therapeutic approach based on the NHR2 subdomain of CBFA2T3 protein.
Mouse multipotent progenitor 5 cells are located at the interphase between hematopoietic stem and progenitor cells
Authors: Pia Sommerkamp, Mari Carmen Romero-Mulero, Andreas Narr, Luisa Ladel, Lucie Hustin, Katharina Schönberger, Simon Renders, Sandro Altamura, Petra Zeisberger, Karin Jäcklein, Daniel Klimmeck, Alejo Rodriguez-Fraticelli, Fernando D. Camargo, Leïla Perié, Andreas Trumpp, Nina Cabezas-Wallscheid
Journal: Blood (2021)
P48.19 Outcomes of Patients Treated with First Line Immunotherapy Plus Chemotherapy for ES-SCLC: Real World Outcomes from a Tertiary Academic Center
Authors: S. Patel, S. Zhao, L. Wei, M. Smith, G. Lopez, E. Bertino, K. He, C. Presley, M. Welliver, K. Haglund, J. Palmer, A. Arnett, S. Beyer, J. Elder, D. Hardesty, P. Shields, T. Williams, D. Carbone, G. Otterson, D. Owen
Journal: Journal of Thoracic Oncology (2021)