tbuckley/cabot-search huggingface dataset:
Power-maximized experimental design and combination index surface analysis for evaluating interactions of drug combinations, with applications to suberoylanilide hydroxamic acid (SAHA) combined with etoposide (VP-16) in HL-60 human acute myeloid leukemia cells
Authors: Hong-Bin Fang, Takeo Nakanishi, Ken Shiozawa, Edward Sausville, Douglas Ross, Ming Tan
Journal: Cancer Research (2007)

5592  Abstract  Although a number of methods for assessing drug interactions are available, most methods lack a means of selecting combinations of doses efficiently in planning such experiments. The power-maximized design, derived based on the uniform measures of all possible dose combinations of interest, is able to select the drug combinations (doses of each constituent drug) and to determine the required number of replicates at each combination in order to detect synergy, additivity or antagonism, with pre-specified statistical power for the experiment. An F-test is proposed to detect departures from additivity for combinations of two drugs. To explore the joint effect of the combination, a 3-dimensional combination index surface characterizes the interaction of a two-drug combination estimated using the B-splines. Synergism is manifested as a substantial drop in the combination index which is a 2-dimensional slice of the combination index surface. These methods were applied to evaluate SAHA treatment combined with VP-16 in HL-60 human acute myeloid leukemia cells. The implementation will be illustrated through the companion computer program for the design and analysis of combination studies.
2D Gadolinium Oxide Nanoplates as<i>T</i><sub>1</sub>Magnetic Resonance Imaging Contrast Agents
Authors: Gary Stinnett, Nasim Taheri, Jake Villanova, Arash Bohloul, Xiaoting Guo, Edward P. Esposito, Zhen Xiao, Deanna Stueber, Carolina Avendano, Paolo Decuzzi, Robia G. Pautler, Vicki L. Colvin
Journal: Advanced Healthcare Materials (2021)

Millions of people a year receive magnetic resonance imaging (MRI) contrast agents for the diagnosis of conditions as diverse as fatty liver disease and cancer. Gadolinium chelates, which provide preferred T1 contrast, are the current standard but face an uncertain future due to increasing concerns about their nephrogenic toxicity as well as poor performance in high-field MRI scanners. Gadolinium-containing nanocrystals are interesting alternatives as they bypass the kidneys and can offer the possibility of both intracellular accumulation and active targeting. Nanocrystal contrast performance is notably limited, however, as their organic coatings block water from close interactions with surface Gadoliniums. Here, these steric barriers to water exchange are minimized through shape engineering of plate-like nanocrystals that possess accessible Gadoliniums at their edges. Sulfonated surface polymers promote second-sphere relaxation processes that contribute remarkable contrast even at the highest fields (r1 = 32.6 × 10-3 m Gd-1 s-1 at 9.4 T). These noncytotoxic materials release no detectable free Gadolinium even under mild acidic conditions. They preferentially accumulate in the liver of mice with a circulation half-life 50% longer than commercial agents. These features allow these T1 MRI contrast agents to be applied for the first time to the ex vivo detection of nonalcoholic fatty liver disease in mice.
Early clinical experience of a large hospital trust virtual COVID-19 follow up clinic
Authors: R. R. Taylor, R. Singh, S. Quantrill, A. Beverly, H. Shaw, H. Hylton, C. Francis, R. McGuckin, B. Trivedi, P. E. Pfeffer
Journal: Gut (2021)

Introduction A Virtual Covid-19 Follow-up Clinic was designed in response to the need to review a large number of in-patients, at a large hospital trust, recovering from Covid-19 but without any significant increase in resources  Methods Patients complete a structured online/telephone symptom and psychological health questionnaire and have a chest x-ray 12 weeks after their illness  These results, and their medical records, are reviewed asynchronously by the medical team in a virtual clinic  Patients are then triaged to further virtual review, telephone review, face to face review, or are discharged  All patients receive comprehensive written information to aid their recovery  Results During the first 8 weeks of the service, 388 patients have completed the questionnaire (63% online) and been reviewed  Current symptoms are shown in figure 1  The questionnaire has identified the holistic needs of patients and allowed triaged follow-up with 122 discharged and 53 urgent face-to-face review appointments completed  25 CT pulmonary angiogram scans were arranged for patients with typical symptoms of pulmonary emboli;no thromboembolic disease was identified  Conclusion This early experience of a new service has highlighted 5 learning points:
Activity of venetoclax-based therapy in chronic myelomonocytic leukemia
Authors: Guillermo Montalban-Bravo, Danielle Hammond, Courtney D. DiNardo, Marina Konopleva, Gautam Borthakur, Nicholas J. Short, Jorge Ramos-Perez, Veronica Guerra, Rashmi Kanagal-Shamanna, Kiran Naqvi, Koji Sasaki, Elias Jabbour, Naveen Pemmaraju, Tapan M. Kadia, Farhad Ravandi, Naval Daver, Zeev Estrov, Sherry Pierce, Hagop Kantarjian, Guillermo Garcia-Manero
Journal: Leukemia (2021)
miR-145 micelles mitigate atherosclerosis by modulating vascular smooth muscle cell phenotype
Authors: Deborah D. Chin, Christopher Poon, Jonathan Wang, Johan Joo, Victor Ong, Zhangjingyi Jiang, Kayley Cheng, Anastasia Plotkin, Gregory A. Magee, Eun Ji Chung
Journal: Biomaterials (2021)
Green tea polyphenols inhibit photocarcinogenesis in mice through induction of IL-12, and IL-12-mediated immune responses in skin tumors
Authors: Santosh K. Katiyar, Anshu M. Roy, Craig A. Elmets
Journal: Cancer Research (2005)

4303  Chronic exposure of solar ultraviolet (UV) radiation is the major etiologic agent for over one million new cases of non-melanoma skin cancers in the United States each year. These cutaneous malignancies thus have a tremendous impact on public health and healthcare expenditures. The use of dietary botanical supplements has received considerable interest to protect human skin from adverse biological effects of UV radiation since the protective clothing and use of sunscreens are not adequate to protect the skin. The use of green tea polyphenols (GTP) is one of them, and has been shown to prevent UV carcinogenesis in animal models but their mechanism of photoprotection is not clearly understood specifically when administered in drinking water (d.w.). To determine the skin cancer chemopreventive mechanism of GTP in in vivo mouse model, the SKH-1 hairless mice were given GTP (0.2%, w/v) in d.w. throughout the photocarcinogenesis protocol. Oral administration of GTP resulted in prevention of UV carcinogenesis in mice in terms of tumor incidence, tumor multiplicity and tumor growth. Since UV-induced suppression of immune responses is considered as a risk factor for skin cancer, we examined the effect of GTP on various immunological parameters in tumors using immunostaining and Western blotting. Our data revealed that administration of GTP resulted in inhibition of immunosuppressive cytokine, interleukin (IL)-10, whereas increased the production of IL-12 in UV-induced tumors compared with non-GTP treated animals. The inhibition of IL-10 and induction of IL-12 was associated with the inhibition of PGE2 production in tumors. Since, IL-12 has been shown to have anti-tumor immune responses, we extended our study to examine its effect on various immunological and angiogenic biomarkers. We found that GTP down-regulated the expressions of vascular endothelial cell antigens, such as CD31 and VEGF, which are essential for tumor growth and angiogenesis. GTP inhibited the expression of PCNA in tumor cells. In further studies, GTP treatment markedly down-regulated UV-induced expression of matrix metalloproteinase (MMP)-2 and MMP-9 which play a crucial role in tumor growth, invasion and metastasis, however increased the expression of its inhibitor TIMP1. Additionally, a higher number of cytotoxic T lymphocytes (CD8+ T cells) were detected by immunofluorescence staining in GTP+UV treated tumors which indicated that GTP enhances the development of CD8+ T cells in tumor microenvironment. CD8+ T cells are tumoricidal and thus may result in the inhibition of tumor growth. Since anti-tumor immune response or activity of IL-12 has been associated with above mentioned biomarkers, our data suggest that skin cancer chemopreventive effect of GTP may be mediated through the induction of IL-12 in tumors.
COVID-19 information retrieval with deep-learning based semantic search, question answering, and abstractive summarization
Authors: Andre Esteva, Anuprit Kale, Romain Paulus, Kazuma Hashimoto, Wenpeng Yin, Dragomir Radev, Richard Socher
Journal: npj Digital Medicine (2021)

Abstract The COVID-19 global pandemic has resulted in international efforts to understand, track, and mitigate the disease, yielding a significant corpus of COVID-19 and SARS-CoV-2-related publications across scientific disciplines. Throughout 2020, over 400,000 coronavirus-related publications have been collected through the COVID-19 Open Research Dataset. Here, we present CO-Search, a semantic, multi-stage, search engine designed to handle complex queries over the COVID-19 literature, potentially aiding overburdened health workers in finding scientific answers and avoiding misinformation during a time of crisis. CO-Search is built from two sequential parts: a hybrid semantic-keyword retriever, which takes an input query and returns a sorted list of the 1000 most relevant documents, and a re-ranker, which further orders them by relevance. The retriever is composed of a deep learning model (Siamese-BERT) that encodes query-level meaning, along with two keyword-based models (BM25, TF-IDF) that emphasize the most important words of a query. The re-ranker assigns a relevance score to each document, computed from the outputs of (1) a question–answering module which gauges how much each document answers the query, and (2) an abstractive summarization module which determines how well a query matches a generated summary of the document. To account for the relatively limited dataset, we develop a text augmentation technique which splits the documents into pairs of paragraphs and the citations contained in them, creating millions of (citation title, paragraph) tuples for training the retriever. We evaluate our system ( http://einstein.ai/covid ) on the data of the TREC-COVID information retrieval challenge, obtaining strong performance across multiple key information retrieval metrics.
Post-exercise recovery for the endurance athlete with type 1 diabetes: a consensus statement
Authors: Sam N Scott, Federico Y Fontana, Matt Cocks, James P Morton, Asker Jeukendrup, Radu Dragulin, Jørgen F P Wojtaszewski, Jørgen Jensen, Rafael Castol, Michael C Riddell, Christoph Stettler
Journal: The Lancet Diabetes & Endocrinology (2021)
Is Treatment Inertia Unique to Publicly Funded Healthcare? Insights from the Guidelines Oriented Approach to Lipid lowering (GOAL) Canada Program
Authors: Anatoly Langer
Journal: Clinical Cardiology and Cardiovascular Interventions (2021)

Background: We compared the use of lipid lowering therapy, low density-lipoprotein cholesterol (LDL-C) levels, and proportion achieving guideline-recommended LDL-C levels in patients with private vs. public insurance coverage for their lipid lowering treatment. Materials and Methods: Guidelines Oriented Approach to Lipid lowering (GOAL) Canada enrolled 2009 patients with cardiovascular disease (CVD) or heterozygous familial hypercholesterolemia (FH) and an LDL-C above the guideline-recommended target of &lt;2.0 mmol/L despite maximally tolerated statin therapy. During two follow-up visits physicians received online reminders of treatment recommendations. Results: Of 2009 patients enrolled (median age 63 years, 42% female), there were 1284 (64%) patients with private and 725 (36%) with public insurance for lipid lowering therapy. Patients with private insurance were younger and less likely to have a history of heart failure or to be on bile acid sequestrants. There was no difference between the groups in their lipid levels or lipid lowering therapy at baseline. During the follow up, there was no difference in the use of ezetimibe; however, the use of PCSK9i was more frequent in patients with private insurance (31.7 % vs. 21%, p&lt;0.0001), the mean LDL-C level was slightly lower (2.11±1.17 vs. 2.31±1.17 mmol/L, p = 0.001), and the proportion of patients achieving the guideline-recommended LDL-C level was greater (54% vs. 45.5%, p = 0.001). After adjustment for other factors in a multivariable model, private insurance was not a significant predictor of achieving the guideline-recommended LDL-C level in a multivariable model. Conclusion: While PCSK9i use was higher in patients with private insurance, the majority of patients with either private or public insurance experienced similar treatment inertia. The cost of non-generic medications does not appear to be the dominant reason for the continued care gap in lipid lowering of high-risk patients.
Pre-Clinical Activity of SN37169, a Novel Hypoxia-Activated FLT3 Inhibitor Prodrug in FLT3-Mutated AML
Authors: Antonio Cavazos, Helen Ma, Lina Han, Tianyu Cai, Qi Zhang, Karine Harutyunyan, Natalia Baran, Weiguo Zhang, Naval Daver, Michael Andreeff, Amir Ashoorzadeth, Robert Anderson, Adam Patterson, Jeffrey B Smaill, Marina Konopleva
Journal: Blood (2017)
Inhibition of NF-kB enhances chemotherapy induced apoptosis in ovarian cancer cells
Authors: Sarah Fogoros, Milheon Choi, J. Rebecca Liu
Journal: Cancer Research (2005)

4932  Objectives: The NF-kB transcription factors can both promote cell survival and induce apoptosis depending on cell type and context. It is thought that inhibition of NF-kB may differentially affect tumors that retain wt-p53, as compared to tumors with mutant p53. We sought to determine if the NF-kB inhibitors curcumin, resveratrol, and pyrrolidine dithiocarbamate (PDTC) could enhance cisplatin induced apoptosis in ovarian cancer cells. Methods: Constitutive activation of endogenous NF-kB was determined in a panel of 8 ovarian cancer cell lines by immunoblotting for IKBα. NF-kB is present in the majority of cells as an inactive cytoplasmic precursor complexed with the inhibitory subunit IkBα. Upon activation of NF-kB, IkBα is degraded. Consequently, cells with constitutive activation of NF-kB have low IkBα expression levels. Cell lines with wt-p53 (A2780, OVCAR4) and mutant/null p53 (SKOV3, CaOV3) were treated with the NF-kB inhibitors (curcumin, resveratrol, and PDTC) alone, or in combination with cisplatin. Cell viability was determined by sulforhodamine. Apoptotic fraction was determined by staining with propidium iodide and analyzing subGo content by flow cytometry. NF-kB activation was determined by transfecting cells with a NF-kB-dependent reporter plasmid, and measuring luciferase activity. Results: The NF-kB inhibitors used in this study induced cell death in ovarian cancer cell lines with wt and mutant/null p53 expression, suggesting that constitutive NF-kB activity is required for survival. NF-kB inhibition following treatment with curcumin, resveratrol, and PDTC was confirmed using the NF-kB-dependent reporter assay. All NF-kB inhibitors enhanced cisplatin induced apoptosis. Conclusions: Most ovarian cancer patients die of chemoresistant recurrent disease. Conventional chemotherapeutic agents induce apoptosis, and resistance to chemotherapy can be promoted by constitutive activation of NF-kB. We have shown that inhibition of NF-kB enhances chemotherapy induced apoptosis in ovarian cancer cells regardless of p53 status. These results suggest that the use of NF-kB inhibitors in combination with conventional chemotherapy may have broad clinical benefits to ovarian cancer patients.
US National Trends in Vascular Surgical Practice During the COVID-19 Pandemic
Authors: Vy Thuy Ho, Anne V. Eberhard, Steven M. Asch, Nicholas J. Leeper, Eri Fukaya, Shipra Arya, Elsie Gyang Ross
Journal: JAMA Surgery (2021)

This national cohort study examines changes in the number of vascular surgical procedures completed in the US before and during the COVID-19 pandemic.
Questionable Conceptualizations of Nonmedical Use Can Contribute to Needless Distress—Reply
Authors: Sriram Yennurajalingam, Eduardo Bruera
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
Covid-19: Infections fell by 65% after first dose of AstraZeneca or Pfizer vaccine, data show
Authors: Gareth Iacobucci
Journal: BMJ (2021)

Covid-19: Infections fell by 65% after first dose of AstraZeneca or Pfizer vaccine, data show Gareth IacobucciInfections of SARS-CoV-2 fell by 65% after a first dose of the Oxford-AstraZeneca or Pfizer-BioNTech vaccines, preliminary results from a large UK surveillance study indicate.Reductions increased to 70% after a second dose of the Pfizer vaccine, data from the UK Covid-19 Infection Survey show.Not enough people had yet received two doses of the AstraZeneca vaccine to assess this.The survey, carried out by the University of Oxford in partnership with the Office for National Statistics and the Department of Health and Social Care for England, included data from 1.7 million self-reported swab test results taken from 370 000 UK adults between 1 December 2020 and 3 April 2021.The results, published in two preprint papers, 1 2 show that two doses of the Pfizer vaccine offered levels of protection against covid-19 that were similar to levels from previous SARS-CoV-2 infection.1 Pritchard E, Matthews PC, Stoesser N, Eyre DW, Gethings O. Impact of vaccination on SARS-CoV-2 cases in the community: a population-based study using the UK's Covid-19 Infection Survey.https://www.ndm.ox.ac.uk/covid-19/covid-19-infection-survey/results/longer-articles/vaccine-effectiveness. 2 Wei J, Stoesser N, Matthews PC, Studley R, Bell I.The impact of SARS-CoV-2 vaccines on antibody responses
Abstract PO-065: ATRXLoss and IDH1R132H impair self-renewal of glioma stem cells after proton radiotherapy
Authors: Angel A. Garces, Lawrence Bronk, Krishna P.L. Bhat, David R. Grosshans
Journal: Clinical Cancer Research (2021)

Abstract Background: Glioblastoma Multiforme (GBM-Grade IV) is the most aggressive form of glioma in the USA carrying only a 15-month median survival time. IDH1R132H is an early onset mutation present in 70-80% of low grade gliomas (LGG-Grade I and II) and secondary GBM patients that causes intracellular oxidative stress and impairment of post-radiation DNA damage repair (DDR) via Homologous Recombination (HR). Although IDH1R132H is associated with improved patient survival and clinical response to chemotherapy, astrocytoma (LGG) patients specifically also harbor ATRXLoss, a genetic alteration that inactivates the ATRX chromatin remodeling protein and impairs DDR via non-homologous end joining (NHEJ). Importantly, the recent discovery of glioma stem cells (GSCs), a subpopulation of chemoradioresistant, self-renewable, tumor initiating cells known to promote tumor recurrence, presents a new target for therapeutic intervention. However, the mechanisms by which IDH1R132H and ATRXLoss contribute to GSC sensitivity to proton radiotherapy (PRT), a more tumor specific and cytotoxic form of radiation therapy than conventional X-rays (XRT), is not well understood. We hypothesize that both IDH1R132H and ATRXLoss contribute to the impairment of GSC self-renewal after PRT, but not after XRT. Methods: Isogenic MGG18-IDH1WT, MGG18-IDH1R132H, TS543-ATRXWT, and TS543-ATRXLoss patient derived glioma cells were cultured as neurospheres and treated with 3-6 Gy of XRT or PRT. GSC self-renewal, based on neurosphere formation frequency, was quantified using extreme limiting dilution analysis (ELDA). Results: TS543-ATRXLoss significantly inhibited GSC self-renewal over TS543-ATRXWT when subject to PRT (Pairwise Testing Pr(&amp;gt;χ2)&amp;lt;0.01). However, TS543-ATRXWT displayed lower GSC self-renewal compared to TS543-ATRXLoss when subject to XRT (Pr(&amp;gt;χ2)&amp;lt;0.0001). Interestingly, similar results were found in the isogenic MGG18 cell lines. MGG18-IDH1R132H displayed higher radiosensitivity to PRT (Pr(&amp;gt;χ2)&amp;lt;0.05) while MGG18-IDH1WT displayed higher radiosensitivity to XRT (Pr(&amp;gt;χ2)&amp;lt;0.01), as defined by GSC self-renewal. Conclusions: We conclude that ATRXLoss and IDH1R132H both substantially contribute to PRT sensitivity in GSCs, thereby supporting the benefits of PRT for astrocytoma patients. Our future experiments will further elucidate the biological mechanisms by which ATRXLoss and IDH1R132H confer PRT sensitivity, especially via dsDNA damage and apoptosis. Citation Format: Angel A. Garces, Lawrence Bronk, Krishna P.L. Bhat, David R. Grosshans. ATRXLoss and IDH1R132H impair self-renewal of glioma stem cells after proton radiotherapy [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 PO-065.
Is IL-6 a key cytokine target for therapy in COVID-19?
Authors: Simon A. Jones, Christopher A. Hunter
Journal: Nature reviews. Immunology (2021)

The identification of elevated IL-6 levels in patients with severe COVID-19 led to the rapid development of clinical trials targeting this cytokine. Overall, these trials do not support the widespread use of IL-6 antagonists in hospitalized patients with mild-to-moderate disease, but IL-6 antagonists may be beneficial when rapidly deployed in patients with severe COVID-19, as we discuss here.
Therapeutic targeting of ATR yields durable regressions in small cell lung cancers with high replication stress
Authors: Anish Thomas, Nobuyuki Takahashi, Vinodh N. Rajapakse, Xiaohu Zhang, Yilun Sun, Michele Ceribelli, Kelli M. Wilson, Yang Zhang, Erin Beck, Linda Sciuto, Samantha Nichols, Brian Elenbaas, Janusz Puc, Heike Dahmen, Astrid Zimmermann, Jillian Varonin, Christopher W. Schultz, Sehyun Kim, Hirity Shimellis, Parth Desai, Carleen Klumpp-Thomas, Lu Chen, Jameson Travers, Crystal McKnight, Sam Michael, Zina Itkin, Sunmin Lee, Akira Yuno, Min-Jung Lee, Christophe E. Redon, Jessica D. Kindrick, Cody J. Peer, Jun S. Wei, Mirit I. Aladjem, William Douglas Figg, Seth M. Steinberg, Jane B. Trepel, Frank T. Zenke, Yves Pommier, Javed Khan, Craig J. Thomas
Journal: Cancer Cell (2021)