tbuckley/cabot-search huggingface dataset:
Early stage nonclinical pulmonary disorder in COVID-19 may present asymptomatic and fuel the contagion
Authors: Kamoru Ademola Adedokun
Journal: Military Medical Research (2021)

Abstract Evidence shows that pulmonary problems in coronavirus disease 2019 (COVID-19) may set off from vascular injury that progresses to physiological disturbances through a compromised gas exchange, following an infection with the severe acute respiratory syndrome coronavirus 2. In this process, inefficient gas exchange in the alveolar could precipitate silent nonclinical hypoxemia. Unfortunately, patients with “silent hypoxemia” do not necessarily experience any breathing difficulty (dyspnea) at the early stage of COVID-19 while the disease progresses. As a result, several asymptomatic, presymptomatic and patients with mild symptoms may escape quarantine measure and thus continue to spread the virus through contacts. Therefore, early diagnosis of “silent hypoxemia”, which attracts no clinical warnings, could be an important diagnostic measure to prevent acute respiratory distress syndrome from the risk of pulmonary failure among the presymptomatic and as a screening tool in the asymptomatic who are hitherto potential spreaders of the virus.
Aberrant Level of Estrogen Correlates with Defective Thrombopoiesis during Pregnancy in Patients with Immune Thrombocytopenia
Authors: Qi Chen, Xiao Liu, Jing-Zhong Zhao, Chen-Cong Wang, Ya-Nan Wang, Jing Xue, Jia-Min Zhang, Xiao-Lu Zhu, Yun He, Qian-Ming Wang, Hai-Xia Fu, Lan-Ping Xu, Kai-Yan Liu, Xiao-Jun Huang, Xiaohui Zhang
Journal: Blood (2017)
Why translation from basic discoveries to clinical applications is so difficult for atrial fibrillation and possible approaches to improving it
Authors: Stanley Nattel, Philip T Sager, Jörg Hüser, Jordi Heijman, Dobromir Dobrev
Journal: Cardiovascular Research (2021)

Atrial fibrillation (AF) is the most common sustained clinical arrhythmia, with a lifetime incidence of up to 37%, and is a major contributor to population morbidity and mortality. Important components of AF management include control of cardiac rhythm, rate, and thromboembolic risk. In this narrative review article, we focus on rhythm-control therapy. The available therapies for cardiac rhythm control include antiarrhythmic drugs and catheter-based ablation procedures; both of these are presently neither optimally effective nor safe. In order to develop improved treatment options, it is necessary to use preclinical models, both to identify novel mechanism-based therapeutic targets and to test the effects of putative therapies before initiating clinical trials. Extensive research over the past 30 years has provided many insights into AF mechanisms that can be used to design new rhythm-maintenance approaches. However, it has proven very difficult to translate these mechanistic discoveries into clinically applicable safe and effective new therapies. The aim of this article is to explore the challenges that underlie this phenomenon. We begin by considering the basic problem of AF, including its clinical importance, the current therapeutic landscape, the drug development pipeline, and the notion of upstream therapy. We then discuss the currently available preclinical models of AF and their limitations, and move on to regulatory hurdles and considerations and then review industry concerns and strategies. Finally, we evaluate potential paths forward, attempting to derive insights from the developmental history of currently used approaches and suggesting possible paths for the future. While the introduction of successful conceptually innovative new treatments for AF control is proving extremely difficult, one significant breakthrough is likely to revolutionize both AF management and the therapeutic development landscape.
Therapeutic Agent Delivery Across the Blood–Brain Barrier Using Focused Ultrasound
Authors: Dallan McMahon, Meaghan A. O'Reilly, Kullervo Hynynen
Journal: Annual Review of Biomedical Engineering (2021)

Specialized features of vasculature in the central nervous system greatly limit therapeutic treatment options for many neuropathologies. Focused ultrasound, in combination with circulating microbubbles, can be used to transiently and noninvasively increase cerebrovascular permeability with a high level of spatial precision. For minutes to hours following sonication, drugs can be administered systemically to extravasate in the targeted brain regions and exert a therapeutic effect, after which permeability returns to baseline levels. With the wide range of therapeutic agents that can be delivered using this approach and the growing clinical need, focused ultrasound and microbubble (FUS+MB) exposure in the brain has entered human testing to assess safety. This review outlines the use of FUS+MB-mediated cerebrovascular permeability enhancement as a drug delivery technique, details several technical and biological considerations of this approach, summarizes results from the clinical trials conducted to date, and discusses the future direction of the field.
Abstract P27: Effect of paclitaxel in gefitinib-resistant non-small cell lung cancer (NSCLC) treatment during the COVID-19 pandemic
Authors: Md Mohiuddin, Kazuo Kasahara
Journal: Clinical Cancer Research (2021)

Abstract Background: For cancer patients' treatment, coronavirus disease 2019 (COVID-19) poses a great challenge. COVID-19 presents as a severe respiratory infection in aging individuals, including patients with lung cancer. COVID-19 may be linked to the progression of aggressive lung cancer. Conversely, chemotherapy's side effects, such as chemotherapy resistance, acceleration of cellular senescence, could worsen COVID-19. Considering the above-mentioned facts, our present work was aimed to investigate the role of paclitaxel (a chemotherapy drug) in cell proliferation, apoptosis, and cellular senescence of gefitinib-resistant NSCLC cells (PC9-MET) and reveal the underlying mechanisms. Methods: PC9-MET cells were treated with paclitaxel for 72 h and then evaluated by cell viability assay, DAPI staining, Giemsa staining, apoptosis assay, ROS assay, SA-β-Gal staining, TUNEL assay and western blotting. Results: Our results revealed that paclitaxel significantly reduced the viability of PC9-MET cells and induced morphological signs of apoptosis. The apoptotic effects of paclitaxel were observed by increased levels of cleaved caspase-3, cleaved caspase-9 and cleaved PARP. Additionally, paclitaxel increased ROS production, leading to DNA damage. Importantly, paclitaxel eliminated cellular senescence, which was observed by SA-β-Gal staining. Conclusion: In light of these findings, paclitaxel could be a promising anticancer drug and could offer a new therapeutic strategy for gefitinib-resistant non-small cell lung cancer (NSCLC) during the COVID-19 pandemic. Citation Format: Md Mohiuddin, Kazuo Kasahara. Effect of paclitaxel in gefitinib-resistant non-small cell lung cancer (NSCLC) treatment during the COVID-19 pandemic [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2021 Feb 3-5. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(6_Suppl):Abstract nr P27.
Single-Cell RNA Sequencing Uncovers Paracrine Functions of the Epicardial-Derived Cells in Arrhythmogenic Cardiomyopathy
Authors: Ping Yuan, Sirisha M. Cheedipudi, Leila Rouhi, Siyang Fan, Lukas Simon, Zhongming Zhao, Kui Hong, Priyatansh Gurha, Ali J. Marian
Journal: Circulation (2021)

Arrhythmogenic cardiomyopathy (ACM) manifests with sudden death, arrhythmias, heart failure, apoptosis, and myocardial fibro-adipogenesis. The phenotype typically starts at the epicardium and advances transmurally. Mutations in genes encoding desmosome proteins, including DSP (desmoplakin), are major causes of ACM.To delineate contributions of the epicardium to the pathogenesis of ACM, the Dsp allele was conditionally deleted in the epicardial cells in mice upon expression of tamoxifen-inducible Cre from the Wt1 locus. Wild type (WT) and Wt1-CreERT2:DspW/F were crossed to Rosa26mT/mG (R26mT/mG) dual reporter mice to tag the epicardial-derived cells with the EGFP (enhanced green fluorescent protein) reporter protein. Tagged epicardial-derived cells from adult Wt1-CreERT2:R26mT/mG and Wt1-CreERT2: R26mT/mG:DspW/F mouse hearts were isolated by fluorescence-activated cell staining and sequenced by single-cell RNA sequencing.WT1 (Wilms tumor 1) expression was progressively restricted postnatally and was exclusive to the epicardium by postnatal day 21. Expression of Dsp was reduced in the epicardial cells but not in cardiac myocytes in the Wt1-CreERT2:DspW/F mice. The Wt1-CreERT2:DspW/F mice exhibited premature death, cardiac dysfunction, arrhythmias, myocardial fibro-adipogenesis, and apoptosis. Single-cell RNA sequencing of ≈18 000 EGFP-tagged epicardial-derived cells identified genotype-independent clusters of endothelial cells, fibroblasts, epithelial cells, and a very small cluster of cardiac myocytes, which were confirmed on coimmunofluorescence staining of the myocardial sections. Differentially expressed genes between the paired clusters in the 2 genotypes predicted activation of the inflammatory and mitotic pathways-including the TGFβ1 (transforming growth factor β1) and fibroblast growth factors-in the epicardial-derived fibroblast and epithelial clusters, but predicted their suppression in the endothelial cell cluster. The findings were corroborated by analysis of gene expression in the pooled RNA-sequencing data, which identified predominant dysregulation of genes involved in epithelial-mesenchymal transition, and dysregulation of 146 genes encoding the secreted proteins (secretome), including genes in the TGFβ1 pathway. Activation of the TGFβ1 and its colocalization with fibrosis in the Wt1-CreERT2:R26mT/mG:DspW/F mouse heart was validated by complementary methods.Epicardial-derived cardiac fibroblasts and epithelial cells express paracrine factors, including TGFβ1 and fibroblast growth factors, which mediate epithelial-mesenchymal transition, and contribute to the pathogenesis of myocardial fibrosis, apoptosis, arrhythmias, and cardiac dysfunction in a mouse model of ACM. The findings uncover contributions of the epicardial-derived cells to the pathogenesis of ACM.
Abstract 14224: Glycemic Variability is a Strong Predictor in Patients With Impaired Glucose Tolerance After First Episode of Acute Coronary Syndrome
Authors: Yohei Hanajima, Noriaki Iwahashi, Jin Kirigaya, Hironori Takahashi, Yugo Minamimoto, Eiichi Akiyama, Kozo Okada, Nobuhiko Maejima, Yasushi Matsuzawa, Kiyoshi Hibi, Masami Kosuge, Toshiaki Ebina, Kouichi Tamura, Kazuo Kimura
Journal: Circulation (2019)

Background: We explored the effect of glycemic variability (GV) on prognosis in patients with impaired glucose tolerance (IGT) after first acute coronary syndrome (ACS). Methods: We studied 202 pat...
Relevance of Molecular Groups in Children with Newly Diagnosed Atypical Teratoid Rhabdoid Tumor: Results from Prospective St. Jude Multi-institutional Trials
Authors: Santhosh A. Upadhyaya, Giles W. Robinson, Arzu Onar-Thomas, Brent A. Orr, Pascal Johann, Gang Wu, Catherine A. Billups, Ruth G. Tatevossian, Sandeep Kumar Dhanda, Ashok Srinivasan, Alberto Broniscer, Ibrahim Qaddoumi, Anna Vinitsky, Gregory T. Armstrong, Anne E. Bendel, Tim Hassall, Sonia Partap, Paul G. Fisher, John R. Crawford, Murali Chintagumpala, Eric Bouffet, Sridharan Gururangan, Roya Mostafavi, Robert P. Sanders, Paul Klimo, Zoltan Patay, Daniel J. Indelicato, Kim E. Nichols, Frederick A. Boop, Thomas E. Merchant, Marcel Kool, David W. Ellison, Amar Gajjar
Journal: Clinical Cancer Research (2021)

Report relevance of molecular groups to clinicopathologic features, germline
P33.14 STK11/LKB1, KRAS Mutations and Immune-Related Adverse Events as Predictors of Response to Immunotherapy in Lung Cancer
Authors: L. Raez, R. Uba, A. North, K. Dumais, H. Powery, G. Domingo, P. Izquierdo, F. Gentile
Journal: Journal of Thoracic Oncology (2021)
P76.09 A Comparison of Sequential EGFR-TKI Therapy Versus First-Line Osimertinib in NSCLC: A Multi-Center, Retrospective Study
Authors: C. Lee, E. Miao, S. Chung, I. Ahmed, N. Kohn, K. Patel, D. Stefanov, N. Seetharamu
Journal: Journal of Thoracic Oncology (2021)
P76.94 Survival Analyses and Molecular Predictors of Outcomes in Patients Treated with Osimertinib for Metastatic NSCLC Harboring EGFR Mutation
Authors: D. Giffoni M. M. Mata, M. Romero, I. Menjak, A. Thawer, M. Doherty
Journal: Journal of Thoracic Oncology (2021)
The impact of the gut microbiota on the reproductive and metabolic endocrine system
Authors: Xinyu Qi, Chuyu Yun, Yanli Pang, Jie Qiao
Journal: Gut Microbes (2021)

As the gut microbiota exerts various effects on the intestinal milieu which influences distant organs and pathways, it is considered to be a full-fledged endocrine organ. The microbiota plays a major role in the reproductive endocrine system throughout a woman's lifetime by interacting with estrogen, androgens, insulin, and other hormones. Imbalance of the gut microbiota composition can lead to several diseases and conditions, such as pregnancy complications, adverse pregnancy outcomes, polycystic ovary syndrome (PCOS), endometriosis, and cancer; however, research on the mechanisms is limited. More effort should be concentrated on exploring the potential causes and underlying the mechanisms of microbiota-hormone-mediated disease, and providing novel therapeutic and preventive strategies.As the gut microbiota exerts various effects on the intestinal milieu which influences distant organs and pathways, it is considered to be a full-fledged endocrine organ. The microbiota plays a major role in the reproductive endocrine system throughout a woman's lifetime by interacting with estrogen, androgens, insulin, and other hormones. Imbalance of the gut microbiota composition can lead to several diseases and conditions, such as pregnancy complications, adverse pregnancy outcomes, polycystic ovary syndrome (PCOS), endometriosis, and cancer; however, research on the mechanisms is limited. More effort should be concentrated on exploring the potential causes and underlying the mechanisms of microbiota-hormone-mediated disease, and providing novel therapeutic and preventive strategies.
Cancer and Neurofibromatosis Type 1—Confirming What We Knew and Telling Us Something New
Authors: Thierry Alcindor
Journal: JAMA Network Open (2021)

Jace P. Landry, MD; Kelsey L. Schertz, BS; Yi-Ju Chiang, MSPH; Angela D. Bhalla, PhD; Min Yi, MD, PhD; Emily Z. Keung, MD; Christopher P. Scally, MD; Barry W. Feig, MD; Kelly K. Hunt, MD; Christina L. Roland, MD; Ashleigh Guadagnolo, MD; Andrew J. Bishop, MD; Alexander J. Lazar, MD, PhD; John M. Slopis, MD, MPH; Ian E. McCutcheon, MD; Keila E. Torres, MD, PhD
Graft-derived extracellular vesicles transported across subcapsular sinus macrophages elicit B cell alloimmunity after transplantation
Authors: Furong Zeng, Zhizhao Chen, Rao Chen, William J. Shufesky, Mohna Bandyopadhyay, Geoffrey Camirand, Martin H. Oberbarnscheidt, Mara L. G. Sullivan, Catherine J. Baty, Mu-qing Yang, Michel Calderon, Donna Beer Stolz, Geza Erdos, Roberta Pelanda, Todd V. Brennan, Sergio D. Catz, Simon C. Watkins, Adriana T. Larregina, Adrian E. Morelli
Journal: Science Translational Medicine (2021)

Despite the role of donor-specific antibodies (DSAs) in recognizing major histocompatibility complex (MHC) antigens and mediating transplant rejection, how and where recipient B cells in lymphoid tissues encounter donor MHC antigens remains unclear. Contrary to the dogma, we demonstrated here that migration of donor leukocytes out of skin or heart allografts is not necessary for B or T cell allosensitization in mice. We found that mouse skin and cardiac allografts and human skin grafts release cell-free donor MHC antigens via extracellular vesicles (EVs) that are captured by subcapsular sinus (SCS) macrophages in lymph nodes or analog macrophages in the spleen. Donor EVs were transported across the SCS macrophages, and donor MHC molecules on the EVs were recognized by alloreactive B cells. This triggered B cell activation and DSA production, which were both prevented by SCS macrophage depletion. These results reveal an unexpected role for graft-derived EVs and open venues to interfere with EV biogenesis, trafficking, or function to restrain priming or reactivation of alloreactive B cells.
N-Acetyl-L-Cysteine Improves Mesenchymal Stem Cell Function in Prolonged Isolated Thrombocytopenia Post-Allotransplant
Authors: Yuan Kong, Song Yang, Fei-Fei Tang, Hong-Yan Zhao, Yu-Hong Chen, Wei Han, Chen-Hua Yan, Yu Wang, Xiaohui Zhang, Xiao-Jun Huang
Journal: Blood (2017)
FP09.01 Economic Impact of Screening Selection with the PLCOm2012 Risk Model Versus USPSTF-Guidelines in the International Lung Screening Trial (ILST)
Authors: S. Cressman, M. Tammemagi, R. Myers, J. Yee, J. English, J. Mayo, S. Atkar-Khattra, R. Yuan, A. Fernandes, S. Lam
Journal: Journal of Thoracic Oncology (2021)
SARM1 promotes neuroinflammation and inhibits neural regeneration after spinal cord injury through NF-κB signaling
Authors: Huitao Liu, Jingjing Zhang, Xingxing Xu, Sheng Lu, Danlu Yang, Changnan Xie, Mengxian Jia, Wenbin Zhang, Lingting Jin, Xiwu Wang, Xiya Shen, Fayi Li, Wangfei Wang, Xiaomei Bao, Sijia Li, Minyu Zhu, Wei Wang, Ying Wang, Zhihui Huang, Honglin Teng
Journal: Theranostics (2021)

Axonal degeneration is a common pathological feature in many acute and chronic neurological diseases such as spinal cord injury (SCI). SARM1 (sterile alpha and TIR motif-containing 1), the fifth TLR (Toll-like receptor) adaptor, has diverse functions in the immune and nervous systems, and recently has been identified as a key mediator of Wallerian degeneration (WD). However, the detailed functions of SARM1 after SCI still remain unclear. Methods: Modified Allen's method was used to establish a contusion model of SCI in mice. Furthermore, to address the function of SARM1 after SCI, conditional knockout (CKO) mice in the central nervous system (CNS), SARM1Nestin-CKO mice, and SARM1GFAP-CKO mice were successfully generated by Nestin-Cre and GFAP-Cre transgenic mice crossed with SARM1flox/flox mice, respectively. Immunostaining, Hematoxylin-Eosin (HE) staining, Nissl staining and behavioral test assays such as footprint and Basso Mouse Scale (BMS) scoring were used to examine the roles of SARM1 pathway in SCI based on these conditional knockout mice. Drugs such as FK866, an inhibitor of SARM1, and apoptozole, an inhibitor of heat shock protein 70 (HSP70), were used to further explore the molecular mechanism of SARM1 in neural regeneration after SCI. Results: We found that SARM1 was upregulated in neurons and astrocytes at early stage after SCI. SARM1Nestin-CKO and SARM1GFAP-CKO mice displayed normal development of the spinal cords and motor function. Interestingly, conditional deletion of SARM1 in neurons and astrocytes promoted the functional recovery of behavior performance after SCI. Mechanistically, conditional deletion of SARM1 in neurons and astrocytes promoted neuronal regeneration at intermediate phase after SCI, and reduced neuroinflammation at SCI early phase through downregulation of NF-κB signaling after SCI, which may be due to upregulation of HSP70. Finally, FK866, an inhibitor of SARM1, reduced the neuroinflammation and promoted the neuronal regeneration after SCI. Conclusion: Our results indicate that SARM1-mediated prodegenerative pathway and neuroinflammation promotes the pathological progress of SCI and anti-SARM1 therapeutics are viable and promising approaches for preserving neuronal function after SCI.
Declines in Prevalence of Human Papillomavirus Vaccine-Type Infection Among Females after Introduction of Vaccine — United States, 2003–2018
Authors: Hannah G. Rosenblum, Rayleen M. Lewis, Julia W. Gargano, Troy D. Querec, Elizabeth R. Unger, Lauri E. Markowitz
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States (1). Although most infections resolve without clinical sequalae, persistent HPV infection can cause cervical, other anogenital, and oropharyngeal cancers and anogenital warts. HPV vaccination has been recommended in the United States at age 11-12 years since 2006 for females and since 2011 for males. Catch-up vaccination is recommended through age 26 years.* A quadrivalent vaccine (4vHPV) targeting types 6, 11, 16, and 18 was mainly used until 2015, when a 9-valent vaccine (9vHPV), targeting the same four types as 4vHPV and five additional types (31, 33, 45, 52, and 58), was introduced; 9vHPV has been the only vaccine available in the United States since the end of 2016 (2). HPV vaccination coverage has increased but remains lower than that of other vaccinations recommended for adolescents (3). A decrease in prevalence of 4vHPV types detected in cervicovaginal swabs among young females from the prevaccine era (2003-2006) to 2007-2010 in the National Health and Nutrition Examination Survey (NHANES) was an early indicator of vaccine impact (2) and was also observed in later periods (4,5). NHANES data from 2017-2018 were included in this analysis to update HPV prevalence estimates among females aged 14-34 years. From the prevaccine era to 2015-2018, significant decreases in 4vHPV-type prevalence occurred among females aged 14-19 years (88%) and 20-24 years (81%). In sexually experienced females, 4vHPV-type prevalence decreased in those who reported receiving ≥1 HPV vaccine dose (97% among those aged 14-19 years, 86% among those aged 20-24 years) and in those who reported no vaccination (87% among those aged 14-19 years, 65% among those aged 20-24 years). Significant declines among unvaccinated females suggest herd effects. These data show increasing impact of HPV vaccination in the United States. HPV vaccination is a critical prevention tool against HPV infection, anogenital warts, and HPV-attributable precancers and cancers. HPV vaccination is highly effective and is recommended routinely at age 11-12 years and through 26 years for persons not already vaccinated.
Abstract 380: Mapping the i <i>n vitro</i> Interactome of the Cardiac Sodium-Calcium Exchanger 1
Authors: Cathrine R Carlson, Tandekile L Hafver, Pimthanya Wanichawan, Marianne Lunde, Marita Martinsen, Gustavo A de Souza, Ole M Sejersted
Journal: Circulation Research (2017)

The sodium (Na + )-calcium (Ca 2+ ) exchanger 1 (NCX1) is an antiporter membrane protein encoded by the SLC8A1 gene. In the heart, it maintains cytosolic Ca 2+ homeostasis, serving as the primary mechanism for Ca 2+ extrusion during relaxation. Dysregulation of NCX1 is observed in end-stage human heart failure. In this study we used affinity purification coupled with mass spectrometry in rat left ventricle lysates to identify novel NCX1 interacting proteins in the heart. Two screens were conducted using: 1) anti-NCX1 against endogenous NCX1 and 2) anti-His with His-TF-NCX1 cyt recombinant protein as bait. The respective methods identified 112 and 350 protein partners, of which several were known NCX1 partners from the literature and 29 occurred in both screens. Selected protein partners were validated for binding to NCX1 expressed in HEK293 cells. A cardiac NCX1 protein-protein interaction map was constructed. The map was highly connected, containing distinct clusters of proteins with different biological functions, where cell communication and signal transduction formed the largest clusters. The NCX1 interactome was also significantly enriched with proteins/genes involved in cardiovascular disease. Exploring the molecular mechanisms of these protein partners in future studies may aid in elucidation of NCX1 regulation and facilitate selective therapeutic targeting of NCX1.
P08.06 Factors Associated with the Diagnosis of Lymphatic Vascular Invasion and its Impact on Prognosis
Authors: J. Varlotto, C. Hebert, M. Griffin, R. Voland, N. Rassaei, D. Zander, K. Uy, M. Maxfield, J. Flickinger, F. Lou, T. Fitzgerald, P. Rava, I. Emmerick, P. Oliveira, R. Sood, R. Sood, M. Decamp, W. Walsh
Journal: Journal of Thoracic Oncology (2021)