tbuckley/cabot-search huggingface dataset:
Abstract 20450: Aryl Hydrocarbon Receptor Nuclear Translocator in Vascular Smooth Muscle Cells is Required for Optimal Peripheral Perfusion Recovery
Authors: Anna H Borton, Lee Neilson, M. Amer Alaiti, Aaron Proweller, Diana Ramirez-Bergeron
Journal: Circulation (2017)

Background: Occlusive peripheral vascular diseases (PVDs) are common causes of morbidity. Lesions limit blood flow creating a hypoxic environment that damages distal tissue and can require therapeutic revascularization. Angiogenic growth of new vessels and arteriogenic remodeling of existing vessels attempt to restore perfusion to depleted tissues. Hypoxia inducible factors (HIFs) are key transcriptional regulators of vascular responses. Despite vascular smooth muscle cells (VSMCs) importance in vessel integrity, little is known about their responses to hypoxia in PVDs. We hypothesize that HIF in VSMCs plays a critical role in reperfusion of peripheral tissues via arteriogenesis and angiogenesis. Methods and Results: The role of VSMC HIF in regulating adult responses to peripheral ischemia was examined in a murine femoral artery ligation model. Mice with smooth muscle specific deletion of Aryl Hydrocarbon Receptor Nuclear Translocator (ARNT, HIF1B), required for HIF transcriptional activity, (ArntSMKO) de...
Unmet Needs in Severe Asthma Subtyping and Precision Medicine Trials. Bridging Clinical and Patient Perspectives
Authors: Salman Siddiqui, Loren C. Denlinger, Stephen J. Fowler, Praveen Akuthota, Dominick E. Shaw, Liam G. Heaney, Louise Brown, Mario Castro, Tonya A. Winders, Monica Kraft, Scott Wagers, Michael C. Peters, Ian D. Pavord, Samantha Walker, Nizar N. Jarjour
Journal: American Journal of Respiratory and Critical Care Medicine (2019)
Abstract 19631: Scleraxis Regulates Pressure Overload-Induced Cardiac Fibrosis
Authors: Raghu S Nagalingam, David Y Cheung, Nina Aroutiounova, Davinder S Jassal, Michael P Czubryt
Journal: Circulation (2017)

Introduction: Cardiac fibrosis is an independent risk factor for heart failure and death that currently lacks any specific treatment. Fibrosis is the uncontrolled synthesis of matrix components such as collagen and fibronectin, elevating myocardial wall stiffness, decreasing compliance, increasing arrhythmogenesis, and contributing to heart failure. Proliferation and phenotype conversion of fibroblasts to myofibroblasts contributes critically to the progression of fibrosis. Restricting the activation of myofibroblasts could thus be beneficial for restoring the function of the fibrotic heart. Our previous studies have shown that the transcription factor scleraxis governs the production of major matrix proteins including collagen, α-smooth muscle actin and fibronectin, and regulates fibroblast to myofibroblast phenoconversion. Scleraxis knockout animals exhibit a 50% reduction in the resident cardiac fibroblast population and decreased basal extracellular matrix production, but the role of scleraxis in card...
Effect of Augmenting Standard Care for Military Personnel With Brief Caring Text Messages for Suicide Prevention
Authors: Katherine Anne Comtois, Amanda H. Kerbrat, Christopher R. DeCou, David C. Atkins, Justine J. Majeres, Justin C. Baker, Richard K. Ries
Journal: JAMA Psychiatry (2019)

Accessible and cost-effective interventions for suicidality are needed to address high rates of suicidal behavior among military service members. Caring Contacts are brief periodic messages that express unconditional care and concern and have been previously shown to prevent suicide deaths, attempts, ideation, and hospitalizations.To test the effectiveness of augmenting standard military health care with Caring Contacts delivered via text message to reduce suicidal thoughts and behaviors over 12 months.This randomized clinical trial was conducted at 3 military installations in the southern and western United States. Soldiers and Marines identified as being at risk of suicide were recruited between April 2013 and September 2016. The final follow-up was in September 2017.Both groups received standard care, and the Caring Contacts group also received consisted of 11 text messages delivered on day 1, at week 1, at months 1, 2, 3, 4, 6, 8, 10, and 12, and on participants' birthdays.Primary outcomes were current suicidal ideation and suicide risk incidents (hospitalization or medical evacuation). Secondary outcomes were worst-point suicidal ideation, emergency department visits, and suicide attempts. Suicidal ideation was measured by the Scale for Suicide Ideation, suicide risk incidents, and emergency department visits by the Treatment History Interview; attempted suicide was measured by the Suicide Attempt Self-Injury Count.Among 658 randomized participants (329 randomizely assigned to each group), data were analyzed for 657 individuals (mean [SD] age, 25.2 [6.1] years; 539 men [82.0%]). All participants reported suicidal ideation at baseline, and 291 (44.3%) had previously attempted suicide. Of the 657 participants, 461 (70.2%) were assessed at 12 months. Primary outcomes were nonsignificant. There was no significant effect on likelihood or severity of current suicidal ideation or likelihood of a suicide risk incident; there was also no effect on emergency department visits. However, participants who received Caring Contacts (172 of 216 participants [79.6%]) had lower odds than those receiving standard care alone (179 of 204 participants [87.7%]) of experiencing any suicidal ideation between baseline and follow-up (odds ratio, 0.56 [95% CI, 0.33-0.95]; P = .03) and fewer had attempted suicide since baseline (21 of 233 [9.0%] in the group receiving Caring Contacts vs 34 of 228 [14.9%] in the standard-care group; odds ratio, 0.52 [95% CI, 0.29-0.92]; P = .03).This trial provides inconsistent results on the effectiveness of caring text messages between primary and secondary outcomes, but this inexpensive and scalable intervention offers promise for preventing suicide attempts and ideation in military personnel. Additional research is needed.ClinicalTrials.gov identifier: NCT01829620.
A phase I/II multicenter study of ABI-009 (<i>nab</i>-sirolimus) combined with FOLFOX and bevacizumab as first-line (1L) therapy in patients (pts) with metastatic colorectal cancer (mCRC) with or without PTEN loss.
Authors: Sunil Sharma, Carlos Roberto Becerra, Marc Ryan Matrana, Angela Tatiana Alistar, E. Gabriela Chiorean, Anita Nagypal Schmid, Berta Grigorian, Shihe Hou, Neil Desai
Journal: Journal of Clinical Oncology (2019)

TPS730 Background: Very few treatment options are available for pts with mCRC beside the standard of care (SOC), 5-FU based chemotherapy + bevacizumab. Immunotherapy is an option for pts with microsatellite instability (~5% of mCRC). The central role of the PI3K/mTOR pathway in cancer biology, including CRC, suggests that mTOR inhibition along with chemotherapy may improve antitumor activity in the metastatic setting. A recent phase I/II study showed promising antitumor activity of everolimus + SOC as 1L treatment for mCRC (96% progression-free [PF] rate at six months at the maximum tolerated dose (MTD), and 86% ORR for pts with PTEN loss (Gilcrease, ASCO 2012). The goal of this prospective, single arm phase I/II study is to evaluate the efficacy and safety of ABI-009, a novel mTOR inhibitor, + SOC as 1L treatment for mCRC. Methods: Eligible pts have an ECOG performance status of 0-2 and histologically confirmed measurable metastatic disease. PTEN loss (by IHC) and mutational status for PIK3CA, KRAS, NRAS, BRAF by NGS is evaluated for all pts. ABI-009 is given weekly x3 every four weeks starting at 30 mg/m 2 and can escalate to 45 and 60 mg/m 2 (3+3 design); mFOLFOX6 + bevacizumab is given every two weeks. After six cycles of therapy, cycles may change to 21-days: ABI-009 weekly x2 every three weeks and mFOLFOX6 + bevacizumab every three weeks. Pts are treated until disease progression. Tumor response is assessed by CT at baseline then every eight weeks for one year, then every 12 weeks thereafter. Phase I will enroll up to 18 pts; the primary endpoints are dose-limiting toxicities and MTD, secondary endpoints include disease control rate (DCR). Phase II will enroll 40 pts; the primary endpoint is PF rate at six months, and secondary endpoints are median PF survival, overall survival, duration of response, and DCR in the intent-to-treat population and based on PTEN status. This study is now active, with first pt enrolled. The anticipated enrollment period is 12 months. This prospective phase I/II study may show evidence of efficacy and safety of ABI-009 combined with the SOC in pts with mCRC with or without PTEN loss to warrant a larger clinical study. Results: N/A. Conclusions: N/A. Clinical trial information: NCT03439462.
Risk of lymphoma in patients with chronic hepatitis C: A retrospective analysis on East Harlem population.
Authors: Juan Pablo Alderuccio, Luis Quiel, Themis Ntalageorgos, Andrea M. Popescu-Martinez, Nora V. Bergasa
Journal: Journal of Clinical Oncology (2013)

e12526 Background: The association between chronic hepatitis C (HCV) and lymphoma, especially non-Hodgkin lymphoma (NHL), has been conflicting, varies among different geographical regions, and its prevalence has been calculated to be 10-15%. It is postulated that HCV may produce a sustained stimulation of B-cells, providing a rationale for a potential association between this virus and NHL. Accordingly, the aim of this study was to explore the prevalence of NHL on HCV patients in a population subgroup of New York City. Methods: IRB approved retrospective study of adult patients with HCV seen at our Institution from January 2001 to July 2006 with at least one year of follow-up. HCV serology data were collected. Pathology reports were reviewed. Patients on chronic immunosuppressive therapy, previous oncologic treatment, autoimmune disease or HIV with CD4 count &lt;200/mm3 for two years were excluded. Results: 510 patients were included, 3 of which (0.6%) developed NHL after the HCV diagnosis. NHL subtypes were marginal zone and diffuse large B-cell (2 patients). 354(69.4%) were men and median age was 58 years (29-96). Ethnicity distribution was Hispanic 303(59.4%), Black 150(29.4%), Caucasian 49(9.6%) and Asian 8(1.6%). Risks for viral hepatitis were IV drugs 393(77%), not identified 92(18%) and 25(5%) had others factors including hemodialysis, sex and blood transfusion. 504(98.8%) patients had positive HCV antibodies, 6(1.2%) with only positive PCR and 402(78.8%) with both positive. HCV-PCR was not performed in 102(20%) subjects with positive antibodies. Hepatitis B surface antigen was also positive in 7(1.3%) patients. Median follow-up was 72 months (12-468) with an interquartile range of 68.8, 181(35.6%) patients were alive, 90(17.6%) had died and 239(46.8%) were not seen for 2 or more years. The margin of error of the study was 0.04(4%). Conclusions: The prevalence of NHL in our population was 0.6% and is lower than current published data. This finding may be explained by the high prevalence of Hispanics in our study and their known lower incidence of lymphoma respect to Caucasians. Longer periods of follow-up and further investigations in environmental and genetic factors are necessary to confirm these results.
Abstract 15590: Intracranial Hemorrhage in Patients Receiving Non-Vitamin K Oral Anticoagulants
Authors: Taku Inohara, Ying Xian, Li Liang, Roland Matsouaka, Jeffrey L Saver, Eric E Smith, Lee H Schwamm, Mathew J Reeves, Adrian F Hernandez, Deepak L Bhatt, Eric D Peterson, Gregg C Fonarow
Journal: Circulation (2017)

Background: Non-vitamin K oral anticoagulants (NOACs) are increasingly used in clinical practice. While they are effective in preventing thromboembolic disease, NOACs may also cause bleeding. NOACs-related intracerebral hemorrhage (ICH) has not been well investigated. Methods: We analyzed 138,834 patients presenting with ICH between October 2013 and December 2016 from 1661 hospitals participating in the Get With The Guidelines–Stroke program. Multivariable logistic regression with generalized estimating equation was used to evaluate the association between preceding oral anticoagulant (warfarin, NOACs, and no oral anticoagulants [OAC]) and in-hospital outcomes. Results: Of 138,834 patients (mean [SD] age 67.2 [15.5] years; 48.1% women), 15,777 (11.4%) were receiving warfarin and 4,838 (3.5%) were receiving NOACs preceding ICH. Patients with preceding warfarin or NOACs were more likely to be older, and have higher prevalence of atrial fibrillation and prior stroke. Stroke severity as measured by NIHSS was ...
Liver and spleen stiffness in predicting the recurrence of hepatocellular carcinoma after resection: A comment for moving forward
Authors: Xiao Xiang, Yang Wang, Dun-Chang Mo, Si-Qi Wang, Xiao-Dong Xun, Shi-Hua Hu, Qian Cheng, Zhao Li, Ji-Ye Zhu
Journal: Journal of Hepatology (2019)
Laparoscopic versus open pancreatoduodenectomy for pancreatic or periampullary tumours (LEOPARD-2): a multicentre, patient-blinded, randomised controlled phase 2/3 trial
Authors: Jony van Hilst, Thijs de Rooij, Koop Bosscha, David J Brinkman, Susan van Dieren, Marcel G Dijkgraaf, Michael F Gerhards, Ignace H de Hingh, Tom M Karsten, Daniel J Lips, Misha D Luyer, Olivier R Busch, Sebastiaan Festen, Marc G Besselink, Jony Van Hilst, Thijs De Rooij, Koop Bosscha, David J Brinkman, Susan Van Dieren, Marcel G Dijkgraaf, Michael F Gerhards, Ignace H De Hingh, Tom M Karsten, Daniel J Lips, Misha D Luyer, Olivier R Busch, Sebastiaan Festen, Marc G Besselink, Hendrik A Marsman, Thomas M Van Gulik, Dennis A Wicherts, Wietse J Eshuis, Luna A Stibbe, Els JM Nieveen van Dijkum, Janine E Van Hooft, Paul Fockens, Hanneke W Van Laarhoven, Johanna W Wilmink, Marcel J Van de Vijver, Maarten F Bijlsma, Joanne Verheij, C Yung Nio, Krijn P Van Lienden, Geertjan Van Tienhoven, Annuska Schoorlemmer, Geert-Jan Creemers, Casper HJ Van Eijck, Bas Groot Koerkamp, Marco J Bruno, Ferry Eskens, Joost J Nuyttens, Chulja Pek, George P Van der Schelling, Tom C Seerden, Gijs A Patijn, Vincent B Nieuwenhuijs, Jan W De Groot, Bert A Bonsing, Alexander Vahrmeijer, Rutger J Swijnenburg, J Sven D Mieog, Erwin Van der Harst, Marcel Den Dulk, Steven Olde Damink, Cees HC Dejong, Ronald Van Dam, Judith MPGM De Vos, Mike SL Liem, Cees JHM Van Laarhoven, Harry Van Goor, Peter B Van den Boezem, B Marion Van der Kolk, Martijn WJ Stommel, John J Hermans, Erwin JM Van Geenen, Sandra A Radema, Lodewijk A Brosens, Joris JG Scheepers, Daphne Roos, Djamilla Boerma, Wouter Te Riele, Hjalmar C Van Santvoort, Thomas L Bollen, Fanny Wit, I Quintus Molenaar, Nadia Haj Mohammad, Maarten S Van Leeuwen, Annemarie Roele, Kees P De Jong, Vincent E De Meijer, Joost M Klaase, Geert Kazemier, Babs Zonderhuis, Freek Daams, Martijn R Meijerink, Anouk Latenstein, L Bengt Van Rijssen, Carolijn Nota, Emo Van Halsema, Eran Van Veldhuisen, Jantien Vogel, Kiki Janssen, Lianne Scholten, Lois Daamen, Marieke Walma, Marin Strijker, Mariska Prins, Maurice Zwart, Mustafa Suker, Steffi Rombouts, Timothy Mungroop, Frederique Vissers, Maarten Korrel
Journal: The Lancet. Gastroenterology & hepatology (2019)
Spleen Tyrosine Kinase–Mediated Autophagy Is Required for Epithelial–Mesenchymal Plasticity and Metastasis in Breast Cancer
Authors: Aparna Shinde, Shana D. Hardy, Dongwook Kim, Saeed Salehin Akhand, Mohit Kumar Jolly, Wen-Hung Wang, Joshua C. Anderson, Ryan B. Khodadadi, Wells S. Brown, Jason T. George, Sheng Liu, Jun Wan, Herbert Levine, Christopher D. Willey, Casey J. Krusemark, Robert L. Geahlen, Michael K. Wendt
Journal: Cancer Research (2019)

Abstract The ability of breast cancer cells to transiently transition between epithelial and mesenchymal states contributes to their metastatic potential. Therefore, driving tumor cells into a stable mesenchymal state, as opposed to complete tumor cell eradication, presents an opportunity to pharmacologically limit disease progression by promoting an asymptomatic state of dormancy. Here, we compare a reversible model of epithelial–mesenchymal transition (EMT) induced by TGFβ to a stable mesenchymal phenotype induced by chronic exposure to the ErbB kinase inhibitor lapatinib. Only cells capable of returning to an epithelial phenotype resulted in skeletal metastasis. Gene expression analyses of the two mesenchymal states indicated similar transition expression profiles. A potently downregulated gene in both datasets was spleen tyrosine kinase (SYK). In contrast to this similar diminution in mRNA, kinome analyses using a peptide array and DNA-conjugated peptide substrates showed a robust increase in SYK activity upon TGFβ-induced EMT only. SYK was present in cytoplasmic RNA processing depots known as P-bodies formed during the onset of EMT, and SYK activity was required for autophagy-mediated clearance of P-bodies during mesenchymal–epithelial transition (MET). Genetic knockout of autophagy-related 7 (ATG7) or pharmacologic inhibition of SYK activity with fostamatinib, a clinically approved inhibitor of SYK, prevented P-body clearance and MET, inhibiting metastatic tumor outgrowth. Overall, this study suggests assessment of SYK activity as a biomarker for metastatic disease and the use of fostamatinib as a means to stabilize the latency of disseminated tumor cells. Significance: These findings present inhibition of spleen tyrosine kinase as a therapeutic option to limit breast cancer metastasis by promoting systemic tumor dormancy. See related commentary by Farrington and Narla, p. 1756
Near-infrared light remotely up-regulate autophagy with spatiotemporal precision via upconversion optogenetic nanosystem
Authors: Huizhuo Pan, Hanjie Wang, Jingxian Yu, Xian Huang, Yafeng Hao, Chaonan Zhang, Wanying Ji, Minye Yang, Xiaoqun Gong, Xiaoli Wu, Jin Chang
Journal: Biomaterials (2019)
Immunogenicity and safety of an accelerated hepatitis E vaccination schedule in healthy adults: a randomized, controlled, open-label, phase IV trial
Authors: Z. Chen, S. Lin, J. Duan, Y. Luo, S. Wang, Z. Gan, H. Yi, T. Wu, S. Huang, Q. Zhang, H. Lv
Journal: Clinical Microbiology and Infection (2019)
A Murine Model of Chronic Lymphocytic Leukemia Based on B Cell-Restricted Expression of Sf3b1 Mutation and Atm Deletion
Authors: Shanye Yin, Rutendo G. Gambe, Jing Sun, Aina Zurita Martinez, Zachary J. Cartun, Fara Faye D. Regis, Youzhong Wan, Jean Fan, Angela N. Brooks, Sarah E.M. Herman, Elisa ten Hacken, Amaro Taylor-Weiner, Laura Z. Rassenti, Emanuela M. Ghia, Thomas J. Kipps, Esther A. Obeng, Carrie L. Cibulskis, Donna Neuberg, Dean R. Campagna, Mark D. Fleming, Benjamin L. Ebert, Adrian Wiestner, Ignaty Leshchiner, James A. DeCaprio, Gad Getz, Robin Reed, Ruben D. Carrasco, Catherine J. Wu, Lili Wang
Journal: Cancer Cell (2019)

Highlights•Sf3b1-K700E mutation impairs 3′ splice site selection and induces cellular senescence•Sf3b1-K700E mutation in combination with Atm deletion causes CLL•CLL cells show genome instability and dysregulated BCR signaling•Human CLL cells with SF3B1 mutations show dysregulation of BCR signalingSummarySF3B1 is recurrently mutated in chronic lymphocytic leukemia (CLL), but its role in the pathogenesis of CLL remains elusive. Here, we show that conditional expression of Sf3b1-K700E mutation in mouse B cells disrupts pre-mRNA splicing, alters cell development, and induces a state of cellular senescence. Combination with Atm deletion leads to the overcoming of cellular senescence and the development of CLL-like disease in elderly mice. These CLL-like cells show genome instability and dysregulation of multiple CLL-associated cellular processes, including deregulated B cell receptor signaling, which we also identified in human CLL cases. Notably, human CLLs harboring SF3B1 mutations exhibit altered response to BTK inhibition. Our murine model of CLL thus provides insights into human CLL disease mechanisms and treatment.Graphical abstract
Molecular Engineering of Functional Nucleic Acid Nanomaterials toward In Vivo Applications
Authors: JingJing Zhang, Tian Lan, Yi Lu
Journal: Advanced Healthcare Materials (2019)

Recent advances in nanotechnology and engineering have generated many nanomaterials with unique physical and chemical properties. Over the past decade, numerous nanomaterials are introduced into many research areas, such as sensors for environmental monitoring, food safety, point-of-care diagnostics, and as transducers for solar energy transfer. Meanwhile, functional nucleic acids (FNAs), including nucleic acid enzymes, aptamers, and aptazymes, have attracted major attention from the biomedical community due to their unique target recognition and catalytic properties. Benefiting from the recent progress of molecular engineering strategies, the physicochemical properties of nanomaterials are endowed by the target recognition and catalytic activity of FNAs in the presence of a target analyte, resulting in numerous smart nanoprobes for diverse applications including intracellular imaging, drug delivery, in vivo imaging, and tumor therapy. This progress report focuses on the recent advances in designing and engineering FNA-based nanomaterials, highlighting the functional outcomes toward in vivo applications. The challenges and opportunities for the future translation of FNA-based nanomaterials into clinical applications are also discussed.
Aging-like Spontaneous Epigenetic Silencing Facilitates Wnt Activation, Stemness, and BrafV600E-Induced Tumorigenesis
Authors: Yong Tao, Byunghak Kang, Daniel A. Petkovich, Yuba R. Bhandari, Julie In, Genevieve Stein-O'Brien, Xiangqian Kong, Wenbing Xie, Nicholas Zachos, Shinji Maegawa, Himani Vaidya, Stephen Brown, Ray-Whay Chiu Yen, Xiaojian Shao, Jai Thakor, Zhihao Lu, Yi Cai, Yuezheng Zhang, Izaskun Mallona, Miguel Angel Peinado, Cynthia A. Zahnow, Nita Ahuja, Elana Fertig, Jean-Pierre Issa, Stephen B. Baylin, Hariharan Easwaran
Journal: Cancer Cell (2019)
Abstract 16478: The Pattern of Amplitude-Integrated Electroencephalography Successfully Categorizes Post-Cardiac Arrest Patients and Could Guide Treatment
Authors: Kazuhiro Sugiyama, Kazuki Miyazaki, Toshinobu Yamagishi, Takahiro Tanabe, Yuichi Hamabe
Journal: Circulation (2017)

Introduction: Predicting the neurological outcome of post-cardiac arrest patients remains a challenge. We can individualize post-cardiac arrest care by estimating the severity of hypoxic encephalopathy at an early stage after ROSC. Amplitude-integrated electroencephalography (aEEG), a type of quantitative EEG, is easily interpreted by emergency physicians and intensivists. In this study, we categorized post-cardiac arrest patients according to the pattern of aEEG after ROSC and evaluated the neurological outcome of patients in each category. Methods: We assessed the patients who received post-cardiac arrest care including TTM with midazolam-based sedation in our emergency and intensive care center. They were monitored with aEEG from March 2013 to April 2017. Both out-of-hospital and in-hospital cardiac arrest patients were included. We categorized the patients into categories 1 (C1) to 4 (C4). C1 included the patients who gained normal continuous voltage (CNV), the best pattern of aEEG in post-cardiac arr...