tbuckley/cabot-search huggingface dataset:
The COX-2 inhibitor celecoxib and its use in the management of prostate cancer.
Authors: Prasanna Sooriakumaran, Ayaz Mehar, Patricia Macanas-Pirard, Stephen Langley, Robert Laing, David Lovell, Helen Coley
Journal: Cancer Research (2006)

5287  We have been exploring the role of COX-2 in prostate cancer and subsequently have looked at the effects of COX-2 inhibitors as a possible treatment modality for the management of this disease.This has involved examination of the role of the COX-2 inhibitor celecoxib (Celebrex™) both in in vitro studies and in a randomized clinical trial. Using the LNCap prostate cancer model transfected with COX-2, showing overexpression at the level of the COX-2 protein, we have demonstrated a number of molecular features to be attentuated, relative to the control (empty vector) cells. Gene expression profiling using cDNA microarrays revealed a number of genes to be overexpressed in COX-2 overexpressing cells including those involved with signal transduction pathways and also the anti-apototic factor Survivin. Western blot analysis with the LNCap prostate cancer model transfected with COX-2 revealed increased constitutive p-AKT, Bcl2 and survivin levels, relative to control LNCap cells. Interestingly, with celecoxib treatment COX-2 expressing LNCap cells were shown to down-regulate their levels of p-AKT and Bcl2, seen up to 24h of celecoxib exposure. We could ascribe many of the effects we saw as COX-2 independent, as the levels used were far in excess of the dose required to cause inhibition of the COX-2 enzyme itself. In conjunction with laboratory studies we have conducted a randomized clinical trial in 45 patients (2:1 drug vs placebo) with newly diagnosed prostate cancer treated for 4 weeks with celecoxib 400mg b.d. prior to radical prostatectomy. Pre- and post operative examination of biopsies to look at possible effects mediated by celecoxib treatment has involved immunohistochemistry to assess markers of angiogenesis, proliferation and apoptosis: COX-2, VEGF, Kdr2, CD31, HIF-1, Ki-67 and TUNEL. In addition, we have looked at gene expression profiles of control (placebo group) versus celecoxib treated patients. The data analysis is on-going and the conclusions from this study are eagerly awaited and will be presented. We conclude that use of COX-2 inhibitors in the management of prostate cancer is an exciting new area and the effects we see may be representative of both COX-2-dependent and independent processes.
An mRNA Vaccine against SARS-CoV-2 — Preliminary Report
Authors: Lisa A Jackson, Evan J Anderson, Nadine G Rouphael, Paul C Roberts, Mamodikoe Makhene, Rhea N Coler, Michele P McCullough, James D Chappell, Mark R Denison, Laura J Stevens, Andrea J Pruijssers, Adrian McDermott, Britta Flach, Nicole A Doria-Rose, Kizzmekia S Corbett, Kaitlyn M Morabito, Sijy O'Dell, Stephen D Schmidt, Phillip A Swanson, Marcelino Padilla, John R Mascola, Kathleen M Neuzil, Hamilton Bennett, Wellington Sun, Etza Peters, Mat Makowski, Jim Albert, Kaitlyn Cross, Wendy Buchanan, Rhonda Pikaart-Tautges, Julie E Ledgerwood, Barney S Graham, John H Beigel
Journal: New England Journal of Medicine (2020)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally, prompting an international effort to accelerate development of a vaccine. The candidate vaccine mRNA-1273 encodes the stabilized prefusion SARS-CoV-2 spike protein. We conducted a phase 1, dose-escalation, open-label trial including 45 healthy adults, 18 to 55 years of age, who received two vaccinations, 28 days apart, with mRNA-1273 in a dose of 25 μg, 100 μg, or 250 μg. There were 15 participants in each dose group. After the first vaccination, antibody responses were higher with higher dose (day 29 enzyme-linked immunosorbent assay anti-S-2P antibody geometric mean titer [GMT], 40,227 in the 25-μg group, 109,209 in the 100-μg group, and 213,526 in the 250-μg group). After the second vaccination, the titers increased (day 57 GMT, 299,751, 782,719, and 1,192,154, respectively). After the second vaccination, serum-neutralizing activity was detected by two methods in all participants evaluated, with values generally similar to those in the upper half of the distribution of a panel of control convalescent serum specimens. Solicited adverse events that occurred in more than half the participants included fatigue, chills, headache, myalgia, and pain at the injection site. Systemic adverse events were more common after the second vaccination, particularly with the highest dose, and three participants (21%) in the 250-μg dose group reported one or more severe adverse events. The mRNA-1273 vaccine induced anti-SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified. These findings support further development of this vaccine. (Funded by the National Institute of Allergy and Infectious Diseases and others; mRNA-1273 ClinicalTrials.gov number, NCT04283461).
THU0145 Hyperhomocysteinemia in rheumatoid arthritis
Authors: B Seriolo, V Ferretti, D Fasciolo, M Cutolo
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Recent reports have suggested that elevated total circulating homocysteine levels are important risk factor for vascular diseases, stroke, and thrombotic events in patients with atherosclerosis and in patients with systemic lupus erythematosus. <h3>Objectives</h3> The aim of our study was to analyse the relationship between plasma homocysteine levels and thrombotic events in a select population of rheumatoid arthritis (RA) patients with or without antiphospholipid antibody (aPL) positivity. <h3>Methods</h3> 168 female RA patients attending the Extra-articular Involvement RA Clinic of University of Genova and 72 female subjects matched for age and vascular diseases as controls were included in the study. 30 of the RA patients showed aPL antibody positivity and 138 were found aPL antibody negativity on the basis of the concomitant presence or absence of high concentrations of anticardiolipin (aCL) antibodies or presence of Lupus Anticoagulant (LA). All subjects were evaluated for plasma homocysteine concentrations and for the occurrence of thrombotic events. <h3>Results</h3> Twenty-five RA patients and five controls reported a history of thrombotic events. Eleven and nine of RA patients with aPL antibody positivity were found previously affected by venous and arterial thrombosis, respectively. Plasma levels of homocysteine in aPL antibody positive patients with thrombosis were found significantly higher than in aPL antibody positive RA patients without thrombosis (p &lt; 0.001). When RA patients with thrombosis were analysed a significant increase of plasma homocysteine levels was found in aPL antibody positive RA patients versus aPL antibody negative RA patients (p &lt; 0.04) and versus related controls (p &lt; 0.003). <h3>Conclusion</h3> The association observed between aPL antibody positivity and high levels of plasma homocysteine in RA patients may represent a possible risk factor for thrombotic events. Therefore, it is suggested that hyperhomocysteinemia might be involved in vascular-related mortality observed in RA patients with a history of thrombosis.
Covid-19: Study reveals six clusters of symptoms that could be used as a clinical prediction tool
Authors: Jacqui Wise
Journal: BMJ (2020)

Covid-19: Study reveals six clusters of symptoms that could be used as a clinical prediction tool Jacqui WiseAn analysis of data obtained from a symptom tracker app has shown that there are six distinct "types" of covid-19, each distinguished by a cluster of symptoms.The researchers said that these types could be used to predict the need for respiratory support in severe covid-19.The study is available online as a preprint and has been submitted to a scientific journal for rapid peer review and publication. 1 The Covid Symptom Study app was developed by King's College London in conjunction with the health technology company ZOE and has more than 4 million users.Users of the app are asked to log their health and any new potential symptoms of covid-19 daily.A machine learning algorithm analysed data from a subset of 1653 users of the app in the UK and US with confirmed covid-19 who had regularly logged their symptoms in March and April.Of the sample, 383 reported at least one hospital visit and 107 reported respiratory support.The algorithm revealed six distinct groupings of symptoms.This was then tested by running it on a second independent dataset of 1000 users in the UK, US, and Sweden who had logged their symptoms in May.The six clusters are
Completion of Advance Directives and Documented Care Preferences During the Coronavirus Disease 2019 (COVID-19) Pandemic
Authors: Catherine L. Auriemma, Scott D. Halpern, Jeremy M. Asch, Matthew Van Der Tuyn, David A. Asch
Journal: JAMA Network Open (2020)

Fewer than one-third of US residents have completed an advance directive (AD) to guide care when seriously ill.1 Clinician-focused efforts to increase AD completion, such as Medicare payments for advance care planning (ACP), have been ineffective.2 In contrast, patient-facing interventions that enable independent completion of ADs show early promise.3 Self-service platforms also reveal changes in demand for ADs and preferences for future care. We sought to quantify changes in patient completion of ADs and expressed preferences during the coronavirus disease 2019 (COVID-19) pandemic by monitoring users of a web-based AD platform from January 2019 to April 2020.
TET repression and increased DNMT activity synergistically induce aberrant DNA methylation
Authors: Hideyuki Takeshima, Tohru Niwa, Satoshi Yamashita, Takeji Takamura-Enya, Naoko Iida, Mika Wakabayashi, Sohachi Nanjo, Masanobu Abe, Toshiro Sugiyama, Young-Joon Kim, Toshikazu Ushijima
Journal: Journal of Clinical Investigation (2020)

Chronic inflammation is deeply involved in various human disorders, such as cancer, neurodegenerative disorders, and metabolic disorders. Induction of epigenetic alterations, especially aberrant DNA methylation, is one of the major mechanisms, but how it is induced is still unclear. Here, we found that expression of TET genes, methylation erasers, was downregulated in inflamed mouse and human tissues, and that this was caused by upregulation of TET-targeting miRNAs such as MIR20A, MIR26B, and MIR29C, likely due to activation of NF-κB signaling downstream of IL-1β and TNF-α. However, TET knockdown induced only mild aberrant methylation. Nitric oxide (NO), produced by NOS2, enhanced enzymatic activity of DNA methyltransferases (DNMTs), methylation writers, and NO exposure induced minimal aberrant methylation. In contrast, a combination of TET knockdown and NO exposure synergistically induced aberrant methylation, involving genomic regions not methylated by either alone. The results showed that a vicious combination of TET repression, due to NF-κB activation, and DNMT activation, due to NO production, is responsible for aberrant methylation induction in human tissues.
Abstract 13793: Implantation of Adipose-Derived Regenerative Cells Promotes Coordinated Angiogenesis and Lymphangiogenesis in Reparative Hind Limb Ischemia Model
Authors: Zhongyue Pu, Yuuki Shimizu, Kazuhito Tsuzuki, Junya Suzuki, Toyoaki Murohara
Journal: Circulation (2019)

Introduction: Lymphatic vessels collaborate with blood vessels to maintain tissue integrity by draining interstitial fluid and by controlling inflammatory cell infiltration. However, little is know...
A Neural Network for Wind-Guided Compass Navigation
Authors: Tatsuo S. Okubo, Paola Patella, Isabel D’Alessandro, Rachel I. Wilson
Journal: Neuron (2020)

Spatial maps in the brain are most accurate when they are linked to external sensory cues. Here, we show that the compass in the Drosophila brain is linked to the direction of the wind. Shifting the wind rightward rotates the compass as if the fly were turning leftward, and vice versa. We describe the mechanisms of several computations that integrate wind information into the compass. First, an intensity-invariant representation of wind direction is computed by comparing left-right mechanosensory signals. Then, signals are reformatted to reduce the coding biases inherent in peripheral mechanics, and wind cues are brought into the same circular coordinate system that represents visual cues and self-motion signals. Because the compass incorporates both mechanosensory and visual cues, it should enable navigation under conditions where no single cue is consistently reliable. These results show how local sensory signals can be transformed into a global, multimodal, abstract representation of space.
Dynamic changes in glioma macrophage populations after radiotherapy reveal CSF-1R inhibition as a strategy to overcome resistance
Authors: Leila Akkari, Robert L. Bowman, Jeremy Tessier, Florian Klemm, Shanna M. Handgraaf, Marnix de Groot, Daniela F. Quail, Lucie Tillard, Jules Gadiot, Jason T. Huse, Dieta Brandsma, Johan Westerga, Colin Watts, Johanna A. Joyce
Journal: Science Translational Medicine (2020)

Macrophage subsets are dynamically altered during glioma response to radiotherapy, and their targeting delays tumor recurrence in preclinical trials.
Whole Genome Sequencing to Detect Small Deletions in Ribosomal Protein Genes in Diamond Blackfan Anemia Patients
Authors: Jens Lichtenberg, Jason E. Farrar, David Chelimo, Frederick Horne, Nisc Comparative Sequencing Program, Steven Ellis, Adrianna Vlachos, Jeffrey H. Lipton, David M. Bodine
Journal: Blood (2017)
Recommendations for caring for patients with severe and nonsevere COVID-19
Authors: Susmita Paladugu, Anthony A. Donato
Journal: Annals of Internal Medicine (2020)

Ye Z, Rochwerg B, Wang Y, et al. Treatment of patients with nonsevere and severe coronavirus disease 2019: an evidence-based guideline. CMAJ. 2020;192:E536-45. 32350002.
Abstract 13555: Adverse Effect of Hepatitis C Virus Positivity on Cardiac Function and Long-term Prognosis in Patients With Adult Congenital Heart Disease
Authors: Ryo Konno, Shunsuke Tatebe, Koichiro Sugimura, Kimio Satoh, Tatsuo Aoki, Saori Yamamoto, Toru Shimizu, Haruka Sato, Katsuya Kozu, Osamu Adachi, Masato Kimura, Yoshikatsu Saiki, Hiroaki Shimokawa
Journal: Circulation (2017)

Background: It was previously suggested that hepatitis C virus (HCV) positivity affects cardiac function. As the screening for HCV began in 1992 in Japan, we hypothesized that HCV positive rate wou...
AKI in Hospitalized Patients with and without COVID-19: A Comparison Study
Authors: Molly Fisher, Joel Neugarten, Eran Bellin, Milagros Yunes, Lindsay Stahl, Tanya S. Johns, Matthew K. Abramowitz, Rebecca Levy, Neelja Kumar, Michele H. Mokrzycki, Maria Coco, Mary Dominguez, Kalyan Prudhvi, Ladan Golestaneh
Journal: Journal of the American Society of Nephrology (2020)

Significance Statement Centers have reported a wide range of AKI incidence rates among patients hospitalized with coronavirus disease 2019 (COVID-19). In a retrospective observational study, the authors compared the incidence, risk factors, and outcomes of AKI in hospitalized adults with and without COVID-19 in a large New York City health system. Compared with patients without COVID-19 and with historical controls, patients with COVID-19 had a significantly higher incidence of AKI; were more likely to require RRT, intensive care unit admission, and mechanical ventilation; and were more likely to experience in-hospital death. Male sex, Black race, and older age were associated with AKI, but these associations were not unique to COVID-19. Select initial vital signs at hospital admission and inflammatory markers were predictors of severe AKI. Background Reports from centers treating patients with coronavirus disease 2019 (COVID-19) have noted that such patients frequently develop AKI. However, there have been no direct comparisons of AKI in hospitalized patients with and without COVID-19 that would reveal whether there are aspects of AKI risk, course, and outcomes unique to this infection. Methods In a retrospective observational study, we evaluated AKI incidence, risk factors, and outcomes for 3345 adults with COVID-19 and 1265 without COVID-19 who were hospitalized in a large New York City health system and compared them with a historical cohort of 9859 individuals hospitalized a year earlier in the same health system. We also developed a model to identify predictors of stage 2 or 3 AKI in our COVID-19. Results We found higher AKI incidence among patients with COVID-19 compared with the historical cohort (56.9% versus 25.1%, respectively). Patients with AKI and COVID-19 were more likely than those without COVID-19 to require RRT and were less likely to recover kidney function. Development of AKI was significantly associated with male sex, Black race, and older age (&gt;50 years). Male sex and age &gt;50 years associated with the composite outcome of RRT or mortality, regardless of COVID-19 status. Factors that were predictive of stage 2 or 3 AKI included initial respiratory rate, white blood cell count, neutrophil/lymphocyte ratio, and lactate dehydrogenase level. Conclusions Patients hospitalized with COVID-19 had a higher incidence of severe AKI compared with controls. Vital signs at admission and laboratory data may be useful for risk stratification to predict severe AKI. Although male sex, Black race, and older age associated with development of AKI, these associations were not unique to COVID-19.
Sports Medicine Australia and COVID-19: providing ‘virtual’ support to the sports community
Authors: Andrea Britt Mosler, Liam Richard West
Journal: British Journal of Sports Medicine (2020)

The COVID-19 pandemic has sent shockwaves through the global sporting world with events and competitions postponed or cancelled. The impact on elite athletes, sporting organisations, people working in sport, and community-level sport has been extraordinary. While Sports Medicine Australia (SMA) has similarly faced considerable challenges, opportunities for the organisation to adapt and redirect its focus have presented as a result of the pandemic.

The cancellation of the 2020 annual SMA Conference was a difficult, but essential decision as the health and welfare of attendees was prioritised. The next annual conference will be held in Melbourne in October 2021, with dates soon to be confirmed. Additionally, all face-to-face service and education delivery was suspended during the lockdown empowering SMA to explore online professional development options.

At the commencement of the COVID-19 shutdown, SMA recognised the need to support and provide opportunities for engagement within the sports community. SMA has provided freely accessible, high quality online education content through pre-recorded …
Beyond thrombosis: the impact of tissue factor signaling in cancer
Authors: Dusten Unruh, Craig Horbinski
Journal: Journal of Hematology & Oncology (2020)

Tissue factor (TF) is the primary initiator of the coagulation cascade, though its effects extend well beyond hemostasis. When TF binds to Factor VII, the resulting TF:FVIIa complex can proteolytically cleave transmembrane G protein-coupled protease-activated receptors (PARs). In addition to activating PARs, TF:FVIIa complex can also activate receptor tyrosine kinases (RTKs) and integrins. These signaling pathways are utilized by tumors to increase cell proliferation, angiogenesis, metastasis, and cancer stem-like cell maintenance. Herein, we review in detail the regulation of TF expression, mechanisms of TF signaling, their pathological consequences, and how it is being targeted in experimental cancer therapeutics.
IC4R-2.0: Rice Genome Reannotation Using Massive RNA-Seq Data
Authors: Jian Sang, Dong Zou, Zhennan Wang, Fan Wang, Yuansheng Zhang, Lin Xia, Zhaohua Li, Lina Ma, Mengwei Li, Bingxiang Xu, Xiaonan Liu, Shuangyang Wu, Lin Liu, Guangyi Niu, Man Li, Yingfeng Luo, Songnian Hu, Lili Hao, Zhang Zhang
Journal: Genomics Proteomics & Bioinformatics (2020)

Abstract Genome reannotation aims for complete and accurate characterization of gene models and thus is of critical significance for in-depth exploration of gene function. Although the availability of massive RNA-seq data provides great opportunities for gene model refinement, few efforts have been made to adopt these precious data in rice genome reannotation. Here we reannotate the rice (Oryza sativa L. ssp. japonica) genome based on integration of large-scale RNA-seq data and release a new annotation system IC4R-2.0. In general, IC4R-2.0 significantly improves the completeness of gene structure, identifies a number of novel genes, and integrates a variety of functional annotations. Furthermore, long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) are systematically characterized in the rice genome. Performance evaluation shows that compared to previous annotation systems, IC4R-2.0 achieves higher integrity and quality, primarily attributable to massive RNA-seq data applied in genome annotation. Consequently, we incorporate the improved annotations into the Information Commons for Rice (IC4R), a database integrating multiple omics data of rice, and accordingly update IC4R by providing more user-friendly web interfaces and implementing a series of practical online tools. Together, the updated IC4R, which is equipped with the improved annotations, bears great promise for comparative and functional genomic studies in rice and other monocotyledonous species. The IC4R-2.0 annotation system and related resources are freely accessible at http://ic4r.org/.
Follicular lymphoma in the modern era: survival, treatment outcomes, and identification of high-risk subgroups
Authors: Connie L. Batlevi, Fushen Sha, Anna Alperovich, Ai Ni, Katy Smith, Zhitao Ying, Jacob D. Soumerai, Philip C. Caron, Lorenzo Falchi, Audrey Hamilton, Paul A. Hamlin, Steven M. Horwitz, Erel Joffe, Anita Kumar, Matthew J. Matasar, Alison J. Moskowitz, Craig H. Moskowitz, Ariela Noy, Colette Owens, Lia M. Palomba, David Straus, Gottfried von Keudell, Andrew D. Zelenetz, Venkatraman E. Seshan, Anas Younes
Journal: Blood Cancer Journal (2020)

Patients with follicular lymphoma (FL) frequently require multiple treatments during their disease course; however, survival based on lines of treatment remains poorly described in the post-rituximab era. Also, the Follicular Lymphoma International Prognostic Index (FLIPI) score was developed to predict survival at diagnosis, yet it remains unknown whether increase in FLIPI score following an initial observation period is associated with less-favorable outcomes. To address these knowledge gaps, we retrospectively studied 1088 patients with FL grade 1-3A managed between 1998 and 2009 at our institution. Median overall survival (OS) and progression-free survival (PFS) after first-line treatment were not reached and 4.73 years, respectively. Following successive lines of treatment, years of median OS and PFS were, respectively: after second-line, 11.7 and 1.5; third-line, 8.8 and 1.1; fourth-line, 5.3 and 0.9; fifth-line, 3.1 and 0.6; sixth-line, 1.9 and 0.5. In initially observed, subsequently treated patients, FLIPI score increase after observation was associated with inferior survival following first-line treatment. The reduced survival we observed after second-line and later therapy supports the development of new treatments for relapsed patients and benchmarks historical targets for clinical endpoints. This study also highlights the utility of changes in FLIPI score at diagnosis and after observation in identifying patients likely to have worse outcomes.