tbuckley/cabot-search huggingface dataset:
Posttranslational Regulation of the Exon Skipping Machinery Controls Aberrant Splicing in Leukemia
Authors: Yalu Zhou, Cuijuan Han, Eric Wang, Adam H. Lorch, Valentina Serafin, Byoung-Kyu Cho, Blanca T. Gutierrez Diaz, Julien Calvo, Celestia Fang, Alireza Khodadadi-Jamayran, Tommaso Tabaglio, Christian Marier, Anna Kuchmiy, Limin Sun, George Yacu, Szymon K. Filip, Qi Jin, Yoh-Hei Takahashi, David R. Amici, Emily J. Rendleman, Radhika Rawat, Silvia Bresolin, Maddalena Paganin, Cheng Zhang, Hu Li, Irawati Kandela, Yuliya Politanska, Hiam Abdala-Valencia, Marc L. Mendillo, Ping Zhu, Bruno Palhais, Pieter Van Vlierberghe, Tom Taghon, Iannis Aifantis, Young Ah Goo, Ernesto Guccione, Adriana Heguy, Aristotelis Tsirigos, Keng Boon Wee, Rama K. Mishra, Francoise Pflumio, Benedetta Accordi, Giuseppe Basso, Panagiotis Ntziachristos
Journal: Cancer Discovery (2020)

Abstract Splicing alterations are common in diseases such as cancer, where mutations in splicing factor genes are frequently responsible for aberrant splicing. Here we present an alternative mechanism for splicing regulation in T-cell acute lymphoblastic leukemia (T-ALL) that involves posttranslational stabilization of the splicing machinery via deubiquitination. We demonstrate there are extensive exon skipping changes in disease, affecting proteasomal subunits, cell-cycle regulators, and the RNA machinery. We present that the serine/arginine-rich splicing factors (SRSF), controlling exon skipping, are critical for leukemia cell survival. The ubiquitin-specific peptidase 7 (USP7) regulates SRSF6 protein levels via active deubiquitination, and USP7 inhibition alters the exon skipping pattern and blocks T-ALL growth. The splicing inhibitor H3B-8800 affects splicing of proteasomal transcripts and proteasome activity and acts synergistically with proteasome inhibitors in inhibiting T-ALL growth. Our study provides the proof-of-principle for regulation of splicing factors via deubiquitination and suggests new therapeutic modalities in T-ALL. Significance: Our study provides a new proof-of-principle for posttranslational regulation of splicing factors independently of mutations in aggressive T-cell leukemia. It further suggests a new drug combination of splicing and proteasomal inhibitors, a concept that might apply to other diseases with or without mutations affecting the splicing machinery. This article is highlighted in the In This Issue feature, p. 1241
98O The immunomodulatory (IM) signature enhances prediction of pathologic complete response (pCR) to neoadjuvant therapy (NAT) in triple negative breast cancers (TNBC) with moderate stromal tumour infiltrating lymphocytes (sTIL)
Authors: N. Abuhadra, R. Sun, J.K. Litton, G. Rauch, A.M. Thompson, B. Lim, B. Adrada, E. Mittendorf, S. Damodaran, R. Pitpitan, B. Arun, J. White, E. Ravenberg, L. Santiago, A. Sahin, R. Murthy, N.T. Ueno, N. Ibrahim, S. Moulder, L. Huo
Journal: Annals of Oncology (2020)
Human amniotic mesenchymal stromal cells promote bone regeneration via activating endogenous regeneration
Authors: Fei Jiang, Wenjie Zhang, Mingliang Zhou, Zhixuan Zhou, Ming Shen, Ning Chen, Xinquan Jiang
Journal: Theranostics (2020)

Rationale: The effectiveness of stem cell based-therapy for bone regeneration has been demonstrated; yet, clinical application of autologous stem cells is still limited by invasive acquisition, long culture processes, and high cost. Besides, it remains controversial whether autologous stem cells could directly participate in tissue repair after differentiation. Thus, increasing allogeneic stem cells have been developed into drugs to indirectly activate endogenous regeneration and induce tissue regeneration. Human amniotic mesenchymal stromal cells (HAMSCs) have been extensively studied, showing multiple regulatory functions, but mechanisms of HAMSCs in promoting bone regeneration are remain unclear. Methods: Proteome profile of HAMSCs and their functions on vascularized bone regeneration were investigated in vitro, while rabbit cranial defect model was used to further detect the effects of bone formation in vivo. Results: HAMSCs secrete many osteogenic, angiogenic, and immunomodulatory cytokines. In vitro, HAMSCs can promote human bone-marrow mesenchymal stromal cells (HBMSCs) migration and osteogenic differentiation; promote the capillary-tube formation of human umbilical vascular endothelial cells (HUVECs), induce HUVECs migration and pro-angiogenic genes expression, and promote M2 macrophage polarization. Further, in vivo studies suggested that transplanted HAMSCs could survive and induce M2 macrophages to secrete bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) in rabbits' skull defects at an early stage, and, in turn, promote more new bone formation. Conclusion: HAMSCs have good biocompatibility and paracrine function to promote bone repair by stimulating endogenous regeneration.
Recommended Treatment Schedules for Gonorrhea
Authors: VENEREAL DISEASES BRANCH, STATE AND COMMUNITY SERVICES DIVISION, CENTER FOR DISEASE CONTROL
Journal: Annals of Internal Medicine (1972)

ExcerptThe preferred drug for Neisseria gonorrhoeae infection is penicillin or ampicillin. Physicians are cautioned to use no less than the recommended doses of antibiotics.For Treatment of Uncomplicated Gonorrhea (Urethral, Cervical, Pharyngeal, or Rectal)PARENTERALMen or women: aqueous procaine penicillin G, 4.8 million units intramuscularly divided into at least two doses and injected at different sites at one visit, together with 1 g of oral probenecid, preferably given at least 30 minutes before the injection.ORALMen or women: ampicillin, 3.5 g, with probenecid, 1 g, administered simultaneously.Treatment of ContactsPatients with known exposure to gonorrhea should receive...
MGAT3-mediated glycosylation of tetraspanin CD82 at asparagine 157 suppresses ovarian cancer metastasis by inhibiting the integrin signaling pathway
Authors: Jun Li, Jiawen Xu, Luhan Li, Alessandro Ianni, Poonam Kumari, Shuo Liu, Peiqing Sun, Thomas Braun, Xiaoyue Tan, Rong Xiang, Shijing Yue
Journal: Theranostics (2020)

Background: Tetraspanins constitute a family of transmembrane spanning proteins that function mainly by organizing the plasma membrane into micro-domains. CD82, a member of tetraspanins, is a potent inhibitor of cancer metastasis in numerous malignancies. CD82 is a highly glycosylated protein, however, it is still unknown whether and how this post-translational modification affects CD82 function and cancer metastasis. Methods: The glycosylation of CD82 profiles are checked in the paired human ovarian primary and metastatic cancer tissues. The functional studies on the various glycosylation sites of CD82 are performed in vitro and in vivo. Results: We demonstrate that CD82 glycosylation at Asn157 is necessary for CD82-mediated inhibition of ovarian cancer cells migration and metastasis in vitro and in vivo. Mechanistically, we discover that CD82 glycosylation is pivotal to disrupt integrin α5β1-mediated cellular adhesion to the abundant extracellular matrix protein fibronectin. Thereby the glycosylated CD82 inhibits the integrin signaling pathway responsible for the induction of the cytoskeleton rearrangements required for cellular migration. Furthermore, we reveal that the glycosyltransferase MGAT3 is responsible for CD82 glycosylation in ovarian cancer cells. Metastatic ovarian cancers express reduced levels of MGAT3 which in turn may result in impaired CD82 glycosylation. Conclusions: Our work implicates a pathway for ovarian cancers metastasis regulation via MGAT3 mediated glycosylation of tetraspanin CD82 at asparagine 157.
Abstract 13631: PPARalpha-Sirt1 Complex Mediates Metabolic Adaptation in Response to Starvation in the Heart
Authors: Shinichi Oka, Peiyong Zhai, Takanobu Yamamoto, Dan Shao, Junichi Sadoshima
Journal: Circulation (2011)

Minimizing energy consumption contributes to survival in organisms under starved conditions, such as fasting and hibernation. The heart consumes a large amount of nutrition and oxygen in the proces...
157P Germline BRCA1/2 (gBRCA1/2) testing patterns among oncologists (ONC) treating HER2- advanced breast cancer (ABC): Results from a multi-country real-world study
Authors: R. Mahtani, A. Niyazov, K. Lewis, R. Wild, A. Rider, B. Arondekar, M.P. Lux
Journal: Annals of Oncology (2020)
Who Cares About Care? Family Members as Moral Actors in Treatment Decision Making
Authors: Anna-Henrikje Seidlein, Sabine Salloch
Journal: The American Journal of Bioethics (2020)

In illuminating patients and families’ ethical concerns, the descriptive data of Cho and colleagues (2020) shed light on an important and, so far, widely neglected topic in empirical bioethics rese...
Autophagy-modulating phytochemicals in cancer therapeutics: Current evidences and future perspectives
Authors: Srimanta Patra, Soumya R. Mishra, Bishnu P. Behera, Kewal K. Mahapatra, Debasna P. Panigrahi, Chandra S. Bhol, Prakash P. Praharaj, Gautam Sethi, Samir K. Patra, Sujit K. Bhutia
Journal: Seminars in Cancer Biology (2020)
Sustained-Release Bupropion for Pharmacologic Relapse Prevention after Smoking Cessation
Authors: J. Taylor Hays, Richard D. Hurt, Nancy A. Rigotti, Raymond Niaura, David Gonzales, Michael J. Durcan, David P.L. Sachs, Troy D. Wolter, A. Sonia Buist, J. Andrew Johnston, Jonathan D. White
Journal: Annals of Internal Medicine (2001)

In persons who had stopped smoking during 7 weeks of bupropion treatment, sustained-release bupropion for 12 months delayed smoking relapse and resulted in less weight gain compared with patients w...
Treatment of Obesity in Mitigating Metabolic Risk
Authors: Sean P. Heffron, Johnathon S. Parham, Jay Pendse, José O. Alemán
Journal: Circulation Research (2020)

Through diverse mechanisms, obesity contributes to worsened cardiometabolic health and increases rates of cardiovascular events. Effective treatment of obesity is necessary to reduce the associated burdens of diabetes mellitus, cardiovascular disease, and death. Despite increasing cardiovascular outcome data on obesity interventions, only a small fraction of the population with obesity are optimally treated. This is a primary impetus for this article in which we describe the typical weight loss, as well as the associated impact on both traditional and novel cardiovascular disease risk factors, provided by the 4 primary modalities for obtaining weight loss in obesity—dietary modification, increasing physical activity, pharmacotherapy, and surgery. We also attempt to highlight instances where changes in metabolic risk are relatively specific to particular interventions and appear at least somewhat independent of weight loss. Finally, we suggest important areas for further research to reduce and prevent adverse cardiovascular consequences due to obesity.
Contributing to health security in Europe since 2005 – ECDC’s 15th anniversary
Authors: Andrea Ammon
Journal: Eurosurveillance (2020)

Preview this article: Contributing to health security in Europe since 2005 – ECDC’s 15th anniversary, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/25/20/eurosurv-25-20-1-1.gif
147P Pharmacokinetics, safety, and efficacy of trastuzumab deruxtecan (T-DXd) with OATP1B/CYP3A inhibitors in patients with HER2-expressing advanced solid tumours
Authors: M. Takahashi, Y-J. Bang, M. Karayama, J. Watanabe, H. Minami, N. Yamamoto, I. Kinoshita, C.C. Lin, Y-H. Im, T. Fujiki, I. Achiwa, E. Kamiyama, Y. Okuda, C. Lee, S. Takahashi
Journal: Annals of Oncology (2020)
Integrated and patient-centred management of Parkinson's disease: a network model for reshaping chronic neurological care
Authors: Bastiaan R Bloem, Emily J Henderson, E Ray Dorsey, Michael S Okun, Njideka Okubadejo, Piu Chan, John Andrejack, Sirwan K L Darweesh, Marten Munneke
Journal: The Lancet Neurology (2020)
Response to: “Missed induced bullous pemphigoid: When the anamnesis is the cure,” a comment on “Missed drug-induced bullous pemphigoid leads to longer immunosuppression than recognized cases: A 9-year retrospective review”
Authors: Gabriel E. Molina, Rebecca L. Yanovsky, Erin X. Wei, Steven T. Chen
Journal: Journal of the American Academy of Dermatology (2020)
Early Predictors of Arteriovenous Fistula Maturation: A Novel Perspective on an Enduring Problem
Authors: Crystal A. Farrington, Michelle L. Robbin, Timmy Lee, Jill Barker-Finkel, Michael Allon
Journal: Journal of the American Society of Nephrology (2020)

Preoperative ultrasound mapping is routinely used to select vessels meeting minimal threshold diameters for surgical arteriovenous fistula (AVF) creation but fails to improve AVF maturation rates. This suggests a need to reassess the preoperative ultrasound criteria used to optimize AVF maturation.We retrospectively identified 300 catheter-dependent patients on hemodialysis with a new AVF created between 2010 and 2016. We then evaluated the associations of preoperative vascular measurements and hemodynamic factors with unassisted AVF maturation (successful use for dialysis without prior intervention) and overall maturation (successful use with or without prior intervention). Multivariable logistic regression was used to identify preoperative factors associated with unassisted and overall AVF maturation.Unassisted AVF maturation associated with preoperative arterial diameter (adjusted odds ratio [aOR], 1.50 per 1-mm increase; 95% confidence interval [95% CI], 1.23 to 1.83), preoperative systolic BP (aOR, 1.16 per 10-mm Hg increase; 95% CI, 1.05 to 1.28), and left ventricular ejection fraction (aOR, 1.07 per 5% increase; 95% CI, 1.01 to 1.13). Overall AVF maturation associated with preoperative arterial diameter (aOR, 1.36 per 1-mm increase; 95% CI, 1.10 to 1.66) and preoperative systolic BP (aOR, 1.17; 95% CI, 1.06 to 1.30). Using receiver operating curves, the combination of preoperative arterial diameter, systolic BP, and left ventricular ejection fraction was fairly predictive of unassisted maturation (area under the curve, 0.69). Patient age, sex, race, diabetes, vascular disease, obesity, and AVF location were not associated with maturation.Preoperative arterial diameter may be an under-recognized predictor of AVF maturation. Further study evaluating the effect of preoperative arterial diameter and other hemodynamic factors on AVF maturation is needed.
Anticancer drug R&amp;D landscape in China
Authors: Shen Zhao, Hongyun Zhao, Cheng Lv, Jifang Gong, Jian Zhang, Wenfeng Fang, Jin Li, Xichun Hu, Yi Ba, Binghe Xu, Yanqiao Zhang, Yun Fan, Kunyan Li, Xiaoyuan Chen, Zhimin Yang, Lin Shen, Li Zhang
Journal: Journal of Hematology & Oncology (2020)
HMGB1 promotes ductular reaction and tumorigenesis in autophagy-deficient livers
Authors: Bilon Khambu, Nazmul Huda, Xiaoyun Chen, Daniel J. Antoine, Yong Li, Guoli Dai, Ulrike A. Köhler, Wei-Xing Zong, Satoshi Waguri, Sabine Werner, Tim D. Oury, Zheng Dong, Xiao-Ming Yin
Journal: Journal of Clinical Investigation (2019)
Controlled Release of Stem Cell Secretome Attenuates Inflammatory Response against Implanted Biomaterials
Authors: Mohammadreza Mohammadi, Jennifer Cam Luong, Samuel Mathew Rodriguez, Rui Cao, Ashlyn Elizabeth Wheeler, Hien Lau, Shiri Li, Sepideh Kiani Shabestari, Jean Paul Chadarevian, Michael Alexander, Paul de Vos, Weian Zhao, Jonathan Robert Tod Lakey
Journal: Advanced Healthcare Materials (2020)

Inflammatory response against implanted biomaterials impairs their functional integration and induces medical complications in the host's body. To suppress such immune responses, one approach is the administration of multiple drugs to halt inflammatory pathways. This challenges patient's adherence and can cause additional complications such as infection. Alternatively, biologics that regulate multiple inflammatory pathways are attractive agents in addressing the implants immune complications. Secretome of mesenchymal stromal cells (MSCs) is a multipotent biologic, regulating the homeostasis of lymphocytes and leukocytes. Here, it is reported that alginate microcapsules loaded with processed conditioned media (pCM-Alg) reduces the infiltration and/or expression of CD68+ macrophages likely through the controlled release of pCM. In vitro cultures revealed that alginate can dose dependently induce macrophages to secrete TNFα, IL-6, IL-1β, and GM-CSF. Addition of pCM to the cultures attenuates the secretion of TNFα (p = 0.023) and IL-6 (p < 0.0001) by alginate or lipopolysaccharide (LPS) stimulations. Mechanistically, pCM suppressed the NfκB pathway activation of macrophages in response to LPS (p < 0.0001) in vitro and cathepsin activity (p = 0.005) in response to alginate in vivo. These observations suggest the efficacy of using MSC-derived secretome to prevent or delay the host rejection of implants.
Perspective from Singapore and China on the COVID-19 Pandemic: The New World Order for Ophthalmic Practice
Authors: Adrian Koh, Youxin Chen
Journal: Ophthalmology (2020)

The coronavirus 2019 (COVID-19) outbreak hit Asia with little warning. The first cluster of cases was reported in Wuhan, China, on December 31, 2019. By January 23, 2020, Singapore had recorded its first case. The painful memories and experience with the severe acute respiratory syndrome outbreak in 2003 had prepared Asia for this eventuality. Our immediate priorities were to protect the health and safety of patients and staff, to defer nonurgent cases and prioritize visits and treatment, to continue managing sight-threatening conditions, to provide continuity of care for existing patients unable to come for their appointments, and to ensure business continuity.
Immunogenicity of three sequential schedules with Sabin inactivated poliovirus vaccine and bivalent oral poliovirus vaccine in Zhejiang, China: an open-label, randomised, controlled trial
Authors: Hanqing He, Yamin Wang, Xuan Deng, Chenyan Yue, Xuewen Tang, Yan Li, Yan Liu, Zhiying Yin, Guoping Zhang, Zhongbing Chen, Shuyun Xie, Ning Wen, Zhijie An, Zhiping Chen, Huaqing Wang
Journal: The Lancet Infectious Diseases (2020)
Abstract 17443: Targeting Pyruvate Dehydrogenase Kinase With Dichloroacetate in Pulmonary Arterial Hypertension: A Variable Clinical Response Driven by Genetic Polymorphisms in Sirtuin-3 and Uncoupling Protein-2
Authors: Vikram Gurtu, Linda Webster, Adam Kinnaird, Aristeidis Boukouris, Christopher White, Jayan Nagendran, Darren H Freed, Martin R Wilkins, Evangelos Michelakis
Journal: Circulation (2017)

Introduction: Suppressed mitochondrial function inhibits apoptosis, partly due to inhibition of pyruvate dehydrogenase (PDH) by PDH kinase (PDK) induction in pulmonary artery (PA) vascular cells in...
Response to Comment on Lee et al. The Impact of Medicaid Expansion on Diabetes Management. Diabetes Care 2020;43:1094–1101
Authors: Jusung Lee, Timothy Callaghan
Journal: Diabetes Care (2020)

We welcome the letter by Chen and Parikh (1) sharing their perspective on our study (2) and presenting their recent work on the association of the Affordable Care Act (ACA) Medicaid expansion with dilated eye exams (3).

Joint efforts by providers and patients are vital for successful diabetes management, and the ACA Medicaid expansion could expand the utilization of routine checkups for diabetes care. Through increased access to medical providers and increased attention to self-monitoring behaviors, we believe that the ACA could be leading to important improvements in diabetes management (4). In response to the integrated diabetes management strategy, our research identified diabetes care activities led by providers, such as doctor visits, …
A piece of my mind. Messages from afar
Authors: G. G. Kardos
Journal: JAMA (1988)

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
Interventions for Preventing Thromboembolic Events in Patients With Atrial Fibrillation
Authors: Angela Lowenstern, Sana M. Al-Khatib, Lauren Sharan, Ranee Chatterjee, Nancy M. Allen LaPointe, Bimal Shah, Ethan D. Borre, Giselle Raitz, Adam Goode, Roshini Yapa, J. Kelly Davis, Kathryn Lallinger, Robyn Schmidt, Andrzej S. Kosinski, Gillian D. Sanders
Journal: Annals of Internal Medicine (2018)

This systematic review of 220 comparative studies examines the effectiveness of medical and procedural treatments for patients with nonvalvular atrial fibrillation.
Activation of p38α stress-activated protein kinase drives the formation of the pre-metastatic niche in the lungs
Authors: Jun Gui, Farima Zahedi, Angelica Ortiz, Christina Cho, Kanstantsin V. Katlinski, Kevin Alicea-Torres, Jinyang Li, Leslie Todd, Hongru Zhang, Daniel P. Beiting, Cindy Sander, John M. Kirkwood, Bryan E. Snow, Andrew C. Wakeham, Tak W. Mak, J. Alan Diehl, Constantinos Koumenis, Sandra W. Ryeom, Ben Z. Stanger, Ellen Puré, Dmitry I. Gabrilovich, Serge Y. Fuchs
Journal: Nature Cancer (2020)
62P XRCC1 (Arg194Trp), Palb2 T1100T (3300T&gt;G), HMMR (V353A), TNF (aG308A) polymorphisms as diagnostic markers of breast cancer in the Kyrgyz ethnic group
Authors: A. Semetei kyzy, E. Makimbetov, J. Isakova
Journal: Annals of Oncology (2020)
Novel Approaches Towards a Functional Cure of HIV/AIDS
Authors: Lucia Bailon, Beatriz Mothe, Lance Berman, Christian Brander
Journal: Drugs (2020)

Therapeutic approaches towards a functional cure or eradication of HIV have gained renewed momentum upon encouraging data emerging from studies in SIV monkey models and recent results from human clinical studies. However, a multitude of questions remain to be addressed, including how to deal with the latent viral reservoir, how to boost the host immune response to the virus and what the hurdles are to reach relevant viral compartments in the body. Advances have been made especially with regard to identifying agents that can reactivate the latent virus in vivo and boost the cellular and humoral immunity, but it remains largely unclear whether any of these strategies can awaken a sufficiently large fraction of the viral reservoir and whether the boosted immunity can prevent rapid viral replication once antiretroviral treatments are stopped.