tbuckley/cabot-search huggingface dataset:
Comparative effectiveness and safety of anticoagulants for the treatment of heparin‐induced thrombocytopenia
Authors: Henning Nilius, Jonas Kaufmann, Adam Cuker, Michael Nagler
Journal: American Journal of Hematology (2021)

The effectiveness and safety of non-heparin anticoagulants for the treatment of heparin-induced thrombocytopenia (HIT) are not fully established, and the optimal treatment strategy is unknown. In a systematic review and meta-analysis, we aimed to determine precise rates of platelet recovery, new or progressive thromboembolism (TE), major bleeding, and death for all non-heparin anticoagulants and to study potential sources of variability.
Abstract 15698: Structural Mechanism for the Mechanical Rupture of Fibrin Blood Clots
Authors: Valerie Tutwiler, Farkhad Maksudov, Rustem Litvinov, Valeri Barsegov, John W Weisel
Journal: Circulation (2019)

Fibrin is a primary component of blood clots/thrombi and the major contributor to their mechanical stability and integrity, including propensity for thrombotic embolization. We examined the mechani...
Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons
Authors: Tom T Shimabukuro, Shin Y Kim, Tanya R Myers, Pedro L Moro, Titilope Oduyebo, Lakshmi Panagiotakopoulos, Paige L Marquez, Christine K Olson, Ruiling Liu, Karen T Chang, Sascha R Ellington, Veronica K Burkel, Ashley N Smoots, Caitlin J Green, Charles Licata, Bicheng C Zhang, Meghna Alimchandani, Adamma Mba-Jonas, Stacey W Martin, Julianne M Gee, Dana M Meaney-Delman
Journal: New England Journal of Medicine (2021)

Many pregnant persons in the United States are receiving messenger RNA (mRNA) coronavirus disease 2019 (Covid-19) vaccines, but data are limited on their safety in pregnancy.From December 14, 2020, to February 28, 2021, we used data from the "v-safe after vaccination health checker" surveillance system, the v-safe pregnancy registry, and the Vaccine Adverse Event Reporting System (VAERS) to characterize the initial safety of mRNA Covid-19 vaccines in pregnant persons.A total of 35,691 v-safe participants 16 to 54 years of age identified as pregnant. Injection-site pain was reported more frequently among pregnant persons than among nonpregnant women, whereas headache, myalgia, chills, and fever were reported less frequently. Among 3958 participants enrolled in the v-safe pregnancy registry, 827 had a completed pregnancy, of which 115 (13.9%) resulted in a pregnancy loss and 712 (86.1%) resulted in a live birth (mostly among participants with vaccination in the third trimester). Adverse neonatal outcomes included preterm birth (in 9.4%) and small size for gestational age (in 3.2%); no neonatal deaths were reported. Although not directly comparable, calculated proportions of adverse pregnancy and neonatal outcomes in persons vaccinated against Covid-19 who had a completed pregnancy were similar to incidences reported in studies involving pregnant women that were conducted before the Covid-19 pandemic. Among 221 pregnancy-related adverse events reported to the VAERS, the most frequently reported event was spontaneous abortion (46 cases).Preliminary findings did not show obvious safety signals among pregnant persons who received mRNA Covid-19 vaccines. However, more longitudinal follow-up, including follow-up of large numbers of women vaccinated earlier in pregnancy, is necessary to inform maternal, pregnancy, and infant outcomes.
Protecting Adolescents During a Sexually Transmitted Infection Testing Shortage
Authors: Fareeda W. Haamid, Andrea E. Bonny, Cynthia Holland-Hall
Journal: JAMA Pediatrics (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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Pediatrics journal
Abstract IA-024: Sirt2: A tumor suppressor or promotor?
Authors: Fen Xia
Journal: Clinical Cancer Research (2021)

Abstract SIRT2, an NAD+-dependent histone deacetylase, has been shown to play a pivotal role in various physiological processes, however, its role in cancer is currently controversial. In recent years, SIRT2 has been described as both a tumor suppressor and oncogene with divergent expression and function in various malignancies. Using murine xenograft melanoma models, our results suggest increased systemic expression of SIRT2 promotes tumor progression. In this study, SIRT2-overexpressing mice exhibited enhanced tumor growth and larger tumor volumes compared to their wild-type littermates. Mechanistically, systemic overexpression of SIRT2 reduces the number of tumor-infiltrating natural killer (NK) cells and suppresses NK cell activation and proliferation within tumor microenvironment (TME). Furthermore, despite the effect of increased tumor growth rate and tumor volume in wild-type littermate mice, NK cell depletion does not affect that in SIRT2-overexpressing mice. Lastly, pharmacological inhibition of SIRT2 increases NK cell tumor infiltration and suppresses melanoma tumor growth in mice. The findings of this study identify a dynamic functional interaction between systemic SIRT2 and NK cell activity, which promotes melanoma tumor progression. Given the recent renewed interest in NK-cell-mediated immunotherapy response, SIRT2 could present a new opportunity to mediate immunotherapy response and resistance. Citation Format: Fen Xia. Sirt2: A tumor suppressor or promotor? [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr IA-024.
Low-dose decitabine modulates T-cell homeostasis and restores immune tolerance in immune thrombocytopenia
Authors: Panpan Han, Yu Hou, Yajing Zhao, Yang Liu, Tianshu Yu, Yunqi Sun, Haoyi Wang, Pengcheng Xu, Guosheng Li, Tao Sun, Xiang Hu, Xinguang Liu, Lizhen Li, Jun Peng, Hai Zhou, Ming Hou
Journal: Blood (2021)
Pure photosensitizer-driven nanoassembly with core-matched PEGylation for imaging-guided photodynamic therapy
Authors: Shenwu Zhang, Yuequan Wang, Zhiqiang Kong, Xuanbo Zhang, Bingjun Sun, Han Yu, Qin Chen, Cong Luo, Jin Sun, Zhonggui He
Journal: Acta Pharmaceutica Sinica B (2021)

Pure drug-assembled nanomedicines (PDANs) are currently under intensive investigation as promising nanoplatforms for cancer therapy. However, poor colloidal stability and less tumor-homing ability remain critical unresolved problems that impede their clinical translation. Herein, we report a core-matched nanoassembly of pyropheophorbide a (PPa) for photodynamic therapy (PDT). Pure PPa molecules are found to self-assemble into nanoparticles (NPs), and an amphiphilic PEG polymer (PPa-PEG2K) is utilized to achieve core-matched PEGylating modification via the π‒π stacking effect and hydrophobic interaction between the PPa core and the PPa-PEG2K shell. Compared to PCL-PEG2K with similar molecular weight, PPa-PEG2K significantly increases the stability, prolongs the systemic circulation and improves the tumor-homing ability and ROS generation efficiency of PPa-nanoassembly. As a result, PPa/PPa-PEG2K NPs exert potent antitumor activity in a 4T1 breast tumor-bearing BALB/c mouse xenograft model. Together, such a core-matched nanoassembly of pure photosensitizer provides a new strategy for the development of imaging-guided theragnostic nanomedicines.
The effect of environmental degradation and land use change on malaria re-emergence in south Venezuela: a spatiotemporal modelling study
Authors: Isabel K Fletcher, Juan Hernández-Villena, Jorge E Moreno, Chris Drakeley, Kate Jones, Maria Eugenia Grillet, Rachel Lowe
Journal: The Lancet Planetary Health (2021)

BackgroundMalaria transmission is highly dependent on environmental conditions. The association between climatic variables and malaria transmission is well established, but the interaction between variations in climate and land use change, such as deforestation, is less well understood. Earth observation data provide a valuable and accessible resource to investigate these environment–malaria associations, in particular where little ground truth data are available. Progress towards malaria elimination in Latin America is being hindered by a surge of cases in Venezuela, a country that accounted for 53% of cases in the region in 2019. The country's economic and political crisis has fuelled economic migration to gold mining areas in the south, where extraction activities are expanding malaria vector habitats and sustaining disease transmission.MethodsIn this spatiotemporal modelling study, we used multisource Earth observation data, including meteorological, land use change, and socioeconomic factors, and data on mining activity, to investigate how changes in the ecological landscape might have facilitated increases in the incidence of malaria in the past 20 years. We modelled spatiotemporal malaria case data for 1996–2016 using a Bayesian hierarchical mixed-model framework for Bolívar state in Venezuela, a malaria foci where approximately 60% of national cases occur annually. We examined how mining activities were associated with malaria hotspots and also considered the potential effects of climate variation, seasonality, and spatial dependency structures.FindingsWe found that malaria risk was increased in mining hotspots, which were important in sustaining transmission in Bolívar state. We also found that the effect of temperature and rainfall variation differed depending on the level of deforestation in Bolívar, where the increased risk of malaria with temperature was greatest in areas that were more deforested.InterpretationOur findings provide important evidence of environmentally driven re-emergence of malaria and highlight the advantages of using Earth observation data for understanding malaria dynamics in areas with sparse or incomplete data records.FundingThe Biotechnology and Biological Sciences Research Council and Royal Society Dorothy Hodgkin Fellowship.
Health Economic Aspects of Chimeric Antigen Receptor T-cell Therapies for Hematological Cancers: Present and Future
Authors: Renaud Heine, Frederick W. Thielen, Marc Koopmanschap, Marie José Kersten, Hermann Einsele, Ulrich Jaeger, Pieter Sonneveld, Jorge Sierra, Carin Smand, Carin A. Uyl-de Groot
Journal: HemaSphere (2021)

Since 2018, 2 chimeric antigen receptor (CAR) T-cell therapies received approval from the European Medicine Agency, with list prices around 320 000 Euro (€) (EUR) per treatment. These high prices raise concerns for patient access and the sustainability of healthcare systems. We aimed to estimate the costs and budget impact associated with CAR T-cell therapies for current and future indications in hematological cancers from 2019 to 2029. We focused on the former France, Germany, Spain, Italy and the United Kingdom (EU-5) and the Netherlands. We conducted a review of list prices, health technology assessment reports, budget impact analysis dossiers, and published cost-effectiveness analyses. We forecasted the 10-year health expenditures on CAR T-cells for several hematological cancers in selected European Union countries. Nine cost-effectiveness studies were identified and list prices for CAR T-cell therapies ranged between 307 200 EUR and 350 000 EUR. Estimated additional costs for pre- and post-treatment were 50 359 EUR per patient, whereas the incremental costs of CAR T-cell therapy (when compared with care as usual) ranged between 276 086 EUR and 328 727 EUR. We estimated market entry of CAR T-cell therapies for chronic mantle cell lymphoma, follicular lymphoma, chronic lymphocytic leukemia, multiple myeloma, and acute myeloid leukemia in 2021, 2022, 2022, 2022, and 2025, respectively. Cumulative expenditure estimates for existing and future indications from 2019 to 2029 were on average 28.5 billion EUR, 32.8 billion EUR, and 28.9 billion EUR when considering CAR T-cell therapy costs only, CAR T-cell therapy costs including pre- and post-treatment, and incremental CAR T-cell therapy costs, respectively. CAR T-cell therapies seem to be promising treatment options for hematological cancers but the financial burden on healthcare systems in the former EU-5 and the Netherlands will contribute to a substantial rise in healthcare expenditure in the field of hematology.
Abstract 17184: Characteristics of Purkinje Fiber Triggered Ventricular Fibrillation Storm
Authors: James Coromilas, Amardeep Saluja, Theodore Maglione, John Kassotis, William J Kostis
Journal: Circulation (2019)

Introduction: It has been recognized that patients that ventricular fibrillation storm can be induced by PVC arising from Purkinje fibers and successfully treated by ablating these Purkinje fiber t...
The role of PTEN in pancreatic ductal adenocarcinoma
Authors: Michael J. Mendoza, Bangyan L. Stiles, Yuval Dor, Ben Stanger, Douglas A. Melton, Hong Wu
Journal: Cancer Research (2005)

1101  Pancreatic Ductal Adenocarcinoma (PDA) is the fourth most common cause of cancer related deaths annually and has a dismal five-year survival of only 5%. Presently little is known about PDA pathogenesis, though activated K-Ras is found in greater than 90% of cases. It is known that K-Ras can activate PI3K by binding to the p110 catalytic subunit and 32% of human pancreatic tumor samples have been shown to have increased Akt2 activity, a downstream signaling molecule of the PI3K pathway. More recently, Pten expression was shown to be absent or significantly decreased in 71% of human PDA samples. In order to further delineate the pathogenetic pathways involved in PDA, we are studying the involvement of the PI3K-Akt pathway utilizing pancreatic cancer cell lines and tissue specific mouse models. We demonstrated reduced PTEN levels in poorly differentiated pancreatic cancer cell lines by western blot analysis. Moreover, in vivo studies reveal that Pdx1-Cre, PtenLox/Lox mice develop Pancreatic Intraepithelial Neoplastic (PanIN) lesions as early as 8 weeks of age. We plan to further evaluate the differential PTEN levels in various cells lines and evaluate downstream effectors that are mediating increased Akt activity. Lastly, we are evaluating the role of PTEN in PDA development and the cellular origin of PanIN lesions using a pancreas specific PTEN knockout containing a LacZ reporter.
Evaluating Cancer Drugs in Patients With Central Nervous System Metastases
Authors: Shanthi Marur, Julia A. Beaver, Richard Pazdur
Journal: JAMA Oncology (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 Oncology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Oncology journal
Blocking endothelial lipase with monoclonal antibody MEDI5884 durably increases high density lipoprotein in nonhuman primates and in a phase 1 trial
Authors: John E. Le Lay, Qun Du, Minal B. Mehta, Nicholas Bhagroo, B. Timothy Hummer, Judith Falloon, Glenn Carlson, Anton I. Rosenbaum, ChaoYu Jin, Holly Kimko, Lan-Feng Tsai, Steven Novick, Bill Cook, David Han, Chang Yeop Han, Tomas Vaisar, Alan Chait, Sotirios K. Karathanasis, Christopher J. Rhodes, Boaz Hirshberg, Melissa M. Damschroder, Judith Hsia, Joseph S. Grimsby
Journal: Science Translational Medicine (2021)

Neutralization of endothelial lipase with a monoclonal antibody raises functional HDL in both nonhuman primates and in healthy humans.
Correction: ER+ Breast Cancers Resistant to Prolonged Neoadjuvant Letrozole Exhibit an E2F4 Transcriptional Program Sensitive to CDK4/6 Inhibitors
Authors: Angel L. Guerrero-Zotano, Thomas P. Stricker, Luigi Formisano, Katherine E. Hutchinson, Daniel G. Stover, Kyung-Min Lee, Luis J. Schwarz, Jennifer M. Giltnane, Monica V. Estrada, Valerie M. Jansen, Alberto Servetto, Joaquín Gavilá, J. Alejandro Perez-Fidalgo, Ana Lluch, Antonio Llombart-Cussac, Mohamed Amine Bayar, Stefan Michiels, Fabrice André, Mónica Arnedos, Vicente Guillem, Amparo Ruiz-Simon, Carlos L. Arteaga
Journal: Clinical Cancer Research (2019)

In the original version of this article (1), the stated disclosure of the author Carlos L. Arteaga is incorrect. The error has been corrected in the latest online HTML and PDF versions of the article. The authors regret this error.
Multi‐Dimensional Printing for Bone Tissue Engineering
Authors: Moyuan Qu, Canran Wang, Xingwu Zhou, Alberto Libanori, Xing Jiang, Weizhe Xu, Songsong Zhu, Qianming Chen, Wujin Sun, Ali Khademhosseini
Journal: Advanced Healthcare Materials (2021)

Abstract The development of 3D printing has significantly advanced the field of bone tissue engineering by enabling the fabrication of scaffolds that faithfully recapitulate desired mechanical properties and architectures. In addition, computer‐based manufacturing relying on patient‐derived medical images permits the fabrication of customized modules in a patient‐specific manner. In addition to conventional 3D fabrication, progress in materials engineering has led to the development of 4D printing, allowing time‐sensitive interventions such as programed therapeutics delivery and modulable mechanical features. Therapeutic interventions established via multi‐dimensional engineering are expected to enhance the development of personalized treatment in various fields, including bone tissue regeneration. Here, recent studies utilizing 3D printed systems for bone tissue regeneration are summarized and advances in 4D printed systems are highlighted. Challenges and perspectives for the future development of multi‐dimensional printed systems toward personalized bone regeneration are also discussed.
Down but far from out: The durability of SARS-CoV-2 immunity after asymptomatic infection
Authors: Ross M. Kedl
Journal: The Journal of Experimental Medicine (2021)

The dynamics of immune responses in asymptomatic SARS-CoV-2–infected subjects remain to be fully characterized. The work presented in this issue of JEM by Le Bert et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20202617) sheds some light on these issues and ultimately provides some degree of confidence in the magnitude and persistence of immunity over time after asymptomatic infection with SARS-CoV-2.
Oxygen Pathway Limitations in Patients With Chronic Thromboembolic Pulmonary Hypertension
Authors: Erin J. Howden, Sergio Ruiz-Carmona, Mathias Claeys, Ruben De Bosscher, Rik Willems, Bart Meyns, Tom Verbelen, Geert Maleux, Laurent Godinas, Catharina Belge, Jan Bogaert, Piet Claus, Andre La Gerche, Marion Delcroix, Guido Claessen
Journal: Circulation (2021)

Exertional intolerance is a limiting and often crippling symptom in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Traditionally the pathogenesis has been attributed to central factors, including ventilation/perfusion mismatch, increased pulmonary vascular resistance, and right heart dysfunction and uncoupling. Pulmonary endarterectomy and balloon pulmonary angioplasty provide substantial improvement of functional status and hemodynamics. However, despite normalization of pulmonary hemodynamics, exercise capacity often does not return to age-predicted levels. By systematically evaluating the oxygen pathway, we aimed to elucidate the causes of functional limitations in patients with CTEPH before and after pulmonary vascular intervention.Using exercise cardiac magnetic resonance imaging with simultaneous invasive hemodynamic monitoring, we sought to quantify the steps of the O2 transport cascade from the mouth to the mitochondria in patients with CTEPH (n=20) as compared with healthy participants (n=10). Furthermore, we evaluated the effect of pulmonary vascular intervention (pulmonary endarterectomy or balloon angioplasty) on the individual components of the cascade (n=10).Peak Vo2 (oxygen uptake) was significantly reduced in patients with CTEPH relative to controls (56±17 versus 112±20% of predicted; P<0.0001). The difference was attributable to impairments in multiple steps of the O2 cascade, including O2 delivery (product of cardiac output and arterial O2 content), skeletal muscle diffusion capacity, and pulmonary diffusion. The total O2 extracted in the periphery (ie, ΔAVo2 [arteriovenous O2 content difference]) was not different. After pulmonary vascular intervention, peak Vo2 increased significantly (from 12.5±4.0 to 17.8±7.5 mL/[kg·min]; P=0.036) but remained below age-predicted levels (70±11%). The O2 delivery was improved owing to an increase in peak cardiac output and lung diffusion capacity. However, peak exercise ΔAVo2 was unchanged, as was skeletal muscle diffusion capacity.We demonstrated that patients with CTEPH have significant impairment of all steps in the O2 use cascade, resulting in markedly impaired exercise capacity. Pulmonary vascular intervention increased peak Vo2 by partly correcting O2 delivery but had no effect on abnormalities in peripheral O2 extraction. This suggests that current interventions only partially address patients' limitations and that additional therapies may improve functional capacity.
Circulating microbial cell-free DNA is associated with inflammatory host-responses in severe pneumonia
Authors: Haopu Yang, Ghady Haidar, Nameer S Al-Yousif, Haris Zia, Daniel Kotok, Asim A Ahmed, Lily Blair, Sudeb Dalai, Sivan Bercovici, Carine Ho, Bryan J McVerry, Alison Morris, Georgios D Kitsios
Journal: Thorax (2021)

Host inflammatory responses predict worse outcome in severe pneumonia, yet little is known about what drives dysregulated inflammation. We performed metagenomic sequencing of microbial cell-free DNA (mcfDNA) in 83 mechanically ventilated patients (26 culture-positive, 41 culture-negative pneumonia, 16 uninfected controls). Culture-positive patients had higher levels of mcfDNA than those with culture-negative pneumonia and uninfected controls (p&lt;0.005). Plasma levels of inflammatory biomarkers (fractalkine, procalcitonin, pentraxin-3 and suppression of tumorigenicity-2) were independently associated with mcfDNA levels (adjusted p&lt;0.05) among all patients with pneumonia. Such host–microbe interactions in the systemic circulation of patients with severe pneumonia warrant further large-scale clinical and mechanistic investigations.