tbuckley/cabot-search huggingface dataset:
A Phase Ib/IIa Study of the Pan-BET Inhibitor ZEN-3694 in Combination with Enzalutamide in Patients with Metastatic Castration-resistant Prostate Cancer
Authors: Rahul R. Aggarwal, Michael T. Schweizer, David M. Nanus, Allan J. Pantuck, Elisabeth I. Heath, Eric Campeau, Sarah Attwell, Karen Norek, Margo Snyder, Lisa Bauman, Sanjay Lakhotia, Felix Y. Feng, Eric J. Small, Wassim Abida, Joshi J. Alumkal
Journal: Clinical Cancer Research (2020)

ZEN-3694 is a bromodomain extraterminal inhibitor (BETi) with activity in androgen-signaling inhibitor (ASI)-resistant models. The safety and efficacy of ZEN-3694 plus enzalutamide was evaluated in a phase Ib/IIa study in metastatic castration-resistant prostate cancer (mCRPC).
Abstract 14862: Nogo-B Regulates Mitochondria Associated Membrane Remodeling in Hyperglycemia Induced Endothelium Dysfunction
Authors: Cheng Zhang, Yaru Cui, Dan Shan, Telushi Ajdora, Chao Zhong, Jun Yu
Journal: Circulation (2019)

Objective: The endothelium plays essential roles in regulating vascular homeostasis and diseases. Endothelial cell (EC) dysfunction is associated with several pathologies including diabetes, hypert...
Tape strips detect distinct immune and barrier profiles in atopic dermatitis and psoriasis
Authors: Helen He, Robert Bissonnette, Jianni Wu, Aisleen Diaz, Etienne Saint-Cyr Proulx, Catherine Maari, Carolyn Jack, Maudeline Louis, Yeriel Estrada, James G. Krueger, Ning Zhang, Ana B. Pavel, Emma Guttman-Yassky
Journal: Journal of Allergy and Clinical Immunology (2020)
Nanosized zeolites as a gas delivery platform in a glioblastoma model
Authors: Clément Anfray, Sarah Komaty, Aurélien Corroyer-Dulmont, Moussa Zaarour, Charly Helaine, Hayriye Ozcelik, Clélia Allioux, Jérôme Toutain, Kamila Goldyn, Edwige Petit, Karim Bordji, Myriam Bernaudin, Valentin Valtchev, Omar Touzani, Svetlana Mintova, Samuel Valable
Journal: Biomaterials (2020)
RNA helicase p68 inhibits the transcription and post-transcription of <i>Pkd1</i> in ADPKD
Authors: Lu Zhang, Linda Xiaoyan Li, Julie Xia Zhou, Peter C. Harris, James P. Calvet, Xiaogang Li
Journal: Theranostics (2020)

Background: Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations of the PKD1 and PKD2 genes. Dysregulation of the expression of PKD genes, the abnormal activation of PKD associated signaling pathways, and the expression and maturation of miRNAs regulates cyst progression. However, the upstream factors regulating these abnormal processes in ADPKD remain elusive. Methods: To investigate the roles of an RNA helicase, p68, in ADPKD, we performed Western blot and qRT-PCR analysis, immunostaining and ChIP assay in cystic renal epithelium cells and tissues. Results: We found that p68 was upregulated in cystic renal epithelial cells and tissues. p68 represses Pkd1 gene expression via transcriptional and posttranscriptional mechanisms in renal epithelial cells, in that 1) p68 binds to the promoter of the Pkd1 gene together with p53 to repress transcription; and 2) p68 promotes the expression and maturation of miR-17, miR-200c and miR-182 and via these miRNAs, post-transcriptionally regulates the expression of Pkd1 mRNA. Drosha is involved in this process by forming a complex with p68. p68 also regulates the phosphorylation and activation of PKD proliferation associated signaling and the expression of fibrotic markers in Pkd1 mutant renal epithelial cells. Silence of p68 delays cyst formation in collecting duct cell mediated 3D cultures. In addition, the expression of p68 is induced by H2O2-dependent oxidative stress and DNA damage which causes downregulation of Pkd1 transcription in cystic renal epithelial cells and tissues. Conclusions: p68 plays a critical role in negatively regulating the expression of the PKD1 gene along with positively regulating the expression and maturation of miRNAs and activation of PKD associated signaling pathways to cause renal cyst progression and fibrosis in ADPKD.
Proliferation of Endothelial and Tumor Epithelial Cells by Progestin- Induced VEGF from Human Breast Cancer Cells: Paracrine and Autocrine Effects
Authors: Yayun Liang, Sandra L. Brandt, Salman M. Hyder
Journal: Cancer Research (2005)

1290  Angiogenesis or the formation of new blood vessels is essential for tumor expansion, and vascular endothelial growth factor (VEGF) is one of the most potent angiogenic growth factors known. We recently discovered that natural and synthetic progestins induce VEGF in a sub-set of breast cancer cells in a progesterone receptor (PR) dependent manner. This observation could be very significant since a vast majority of all breast tumors are estrogen receptor and PR-positive. It is known that tumor-secreted VEGF can diffuse from tumor cells and increase the proliferation of surrounding endothelial cells. However, it is not known if hormone-induced VEGF from tumor cells can also regulate angiogenesis, thereby leading to tissue expansion. It is thus critical to investigate the functional role of progestin-induced VEGF in promoting angiogenesis and breast cancer cell growth, since PR could be considered a target for therapeutic intervention of VEGF production. In the present study, we investigated whether progestin-induced VEGF from breast tumor cell lines can function in a paracrine manner to induce proliferation of endothelial cells, and in addition if hormone induced VEGF can function in a paracrine/autocrine manner to increase the proliferation of tumor epithelial cells. Our novel findings indicate that conditioned medium from a sub-set of progestin-treated breast tumor cells can induce proliferation of endothelial cells in a paracrine manner and can induce proliferation of tumor epithelial cells in a paracrine and an autocrine manner. The use of an anti-VEGF antibody and SU-1498, an inhibitor of the VEGF receptor-2 (VEGFR-2 or flk/kdr) demonstrated that these proliferative effects involve interactions between VEGF and VEGFR-2. Also, blockage of progestin-induced VEGF by the anti-progestin RU-486 eliminated VEGF-induced proliferative effects. The ability of VEGF to increase proliferation of endothelial cells and tumor cells, including tumor cells that do not release VEGF in response to progestins, suggests that these effects are mediated by amplification of the progestin signal, which ultimately results in angiogenesis and tumor growth. These novel findings suggest that targeting the release of VEGF from tumor epithelial cells and blocking interactions between VEGF and VEGFR-2 on both endothelial and tumor epithelial cells may lead to the development of new anti-angiogenic therapies for progestin-dependent breast tumors. Furthermore, these data indicate that PR is a molecular target for anti-angiogenic therapy and that selective PR modulators should be developed to block release of angiogenic growth factors from the breast cancer cells. Supported by NIH grant CA-86916. SMH is the Zalk Missouri Professor of Tumor Angiogenesis.
AB0087 Takayasu’s arteritis: review and four clinical cases
Authors: G Sequeira, F Saraiva, A Marques, J Romeu, T Costa, V Queiroz
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Takayasu's arteritis is a rare disease, mainly affecting young women. The authors describe four cases of Takayasu's disease from the rheumatology outpatient clinic of Hospital de Santa Maria in Portugal. A revision of the disease is made concerning it's clinical manifestations, laboratory, diagnosis, treatment and prognosis. <h3>Objectives</h3> <h3>Methods</h3> <h3>Results</h3> All patients were female, three were white and one black. Begining of symptoms was between 7 and 56 years, satisfying the American College of Rheumatology criteria for the classification of Takayasu's arteritis. The spectrum of presentation, disease activity and pace of disease progression were very variable. The delay between the onset of first symptoms and diagnosis was less than three years in three patients and twenty in the other. The first symptoms of disease were in two patients systemic reactions such as malaise, fever and anorexia, absent pulses in the lower limbs in another and claudication of the upper extremities in the last. Vascular ischaemic symptoms, hallmark of the disease, were present in the four patients and all of them had angiograms that involved visualisation of at least primary tributaries that showed lesions of the aortic arch and its branches. All patients needed corticosteroid treatment in the acute inflammatory phase of the disease. Cytotoxic agents were used in three of them and in two cases vascular surgery was done because of fear of occlusion of the involved vessels. <h3>Conclusion</h3> Females and caucasian race predominated. The diagnosis of Takayasu's arteritis should be considered in the presence of symptoms of vascular ischemia such as pulse defects or signs of bruits and in the angiografic study. The prominence of inflammatory features antedating obvious symptoms often delayed diagnosis for substantial periods of time. Fever, myalgia/arthralgia with no identified cause, elevated erythrocyte sedimentation rate, claudication, diminished or absent pulses, bruits, vascular pain and the typical angiographic features are criteria for disease activity. The mainstay of treatment is oral corticosteroids. They are very effective in controlling clinical manifestations and arresting disease progression and sometimes in achieving return of previously absent pulses. Cytotoxic therapy has been helpful in patients failing to respond to corticosteroids.
OP0064 Genetic markers for the efficacy of tnf blocking therapy of rheumatoid arthritis
Authors: L Padyukov, J Lampa, M Heimbürger, S Ernestam, T Cederholm, I Lundkvist, P Andersson, Y Hermansson, A Harju, O Olerup, L Klareskog, J Bratt
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> The regulation of cytokine production on the level of the gene transcription may involve several types of polymorphisms in promoter/enhancer region. The aim of this study was to evaluate if polymorphism in several genes could associate with the responsiveness to TNF blocking therapy with etanercept (Enbrel®) in patients with rheumatoid arthritis from Eastern Sweden. <h3>Methods</h3> 124 patients with active RA were treated with subcutaneous etanercept 25 mg twice a week. The efficacy measures included ACR and DAS28 response rates after treatment for 3 months. The ?308 TNFA, -1082 IL10 and codon 25 TGFB1 gene polymorphisms were detected by combination of PCR and restriction endonuclease mapping. VNTRs in intron 2 of IL1RN gene were detected by PCR and HLA-DQB1 and HLA-DRB1 were typed and subtyped by PCR-SSP. <h3>Results</h3> 24 patients (19%) were non-responders according to both ACR and DAS28 criteria. We found significant association of one group, composite of TNF1/TNF1 and G/G genotypes, with positive responsiveness to etanercept (p &lt; 0.05). Non-responders with TNF2 allele had relatively low ESR before treatment (mean ± SE = 25 ± 5 mm/min) in comparison with other groups (p &lt; 0.05, Fisher's PLSD). Individuals with non-shared epitope genes showed approximately 2 times more frequent fail of the therapy if ACR criteria was used. <h3>Conclusion</h3> We find strong evidence for association of certain genetic markers with efficacy of etanercept treatment in RA patients. Combined ?308 TNFA and ?1082 IL10 genotype may predispose for the response to etanercept therapy, while ?308 TNFA genotype in combination with ESR may be used for the selection of potential non-responders. These results may provide information for future improvement of treatment of RA.
Knowledge gaps in oncoplastic breast surgery
Authors: Walter P Weber, Monica Morrow, Jana de Boniface, Andrea Pusic, Giacomo Montagna, Elisabeth A Kappos, Mathilde Ritter, Martin Haug, Christian Kurzeder, Ramon Saccilotto, Alexandra Schulz, John Benson, Florian Fitzal, Zoltan Matrai, Jane Shaw, Marie-Jeanne Vrancken Peeters, Shelley Potter, Joerg Heil, Eduardo González, Mona Elzayat, Rupert Koller, Michael Gnant, Fabricio Brenelli, Regis Resende Paulinelli, Vappu Zobel, Sarianna Joukainen, Ulla Karhunen-Enckell, Susanna Kauhanen, Jean-Marc Piat, Vesna Bjelic-Radisic, Andree Faridi, Christoph Heitmann, Juergen Hoffmann, Ulrich Kneser, Sherko Kümmel, Thorsten Kühn, Michalis Kontos, Ekaterini Christina Tampaki, Mitchel Barry, Tanir M Allweis, Moshe Carmon, Tal Hadar, Giuseppe Catanuto, Carlos A Garcia-Etienne, Oreste D Gentilini, Susan Knox, Barbara Klein, Linetta Koppert, Pedro F Gouveia, Tor Svensjö, Heiner C Bucher, Silvia Ess, Ursula Ganz-Blättler, Andreas Günthert, Nik Hauser, Nancy Hynes, Michael Knauer, Marlen Pfeiffer, Christoph Rochlitz, Christoph Tausch, Yves Harder, Frank Zimmermann, Fabienne D Schwab, Veronica D'Amico, Savas D Soysal, Liliana Castrezana Lopez, Ilario Fulco, Lars G Hemkens, Visnu Lohsiriwat, Bahadir M Gulluoglu, Guldeniz Karadeniz, Hasan Karanlik, Atakan Sezer, Mehmet Ali Gulcelik, Mustafa Emiroglu, Tibor Kovacs, Tim Rattay, Laszlo Romics, Raghavan Vidya, Lynda Wyld, Mahmoud El-Tamer, Virgilio Sacchini
Journal: The Lancet Oncology (2020)
Using a Public Health Ethics Framework to Unpick Discrimination in COVID-19 Responses
Authors: Roger Yat-Nork Chung, Alexandre Erler, Hon-Lam Li, Derrick Au
Journal: The American Journal of Bioethics (2020)

In the face of a pandemic of such epic proportions as Coronavirus Disease 2019 (COVID-19), public health has become the foremost concern of literally all people, establishments, and governments aro...
<i>C</i><i>hlamydia trachomatis</i> during pregnancy and childhood asthma-related morbidity: a population-based prospective cohort
Authors: Evelien R. van Meel, Marina Attanasi, Vincent W.V. Jaddoe, Irwin K.M. Reiss, Henriëtte A. Moll, Johan C. de Jongste, Liesbeth Duijts
Journal: European Respiratory Journal (2020)

Introduction Chlamydia trachomatis is the most commonly reported sexually transmitted disease and although infection during pregnancy is associated with neonatal complications, long-term respiratory consequences are unknown. We aimed to determine whether C. trachomatis infection during pregnancy is associated with asthma-related symptoms across childhood Methods This study among 2475 children and their mothers was embedded in a population-based prospective cohort study. Maternal urine samples were tested for C. trachomatis infection during pregnancy. Questionnaires provided information on childhood physician-attended lower respiratory tract infections and wheezing, and current asthma at age 10 years. Lung function was measured by spirometry at age 10 years. Results The prevalence of C. trachomatis infection during pregnancy was 3.2% (78 out of 2475). C. trachomatis infection during pregnancy was not associated with lower respiratory tract infections until age 6 years, but was associated with a higher odds of wheezing in children until age 10 years (OR 1.50 (95% CI 1.10–2.03)). C. trachomatis infection during pregnancy was associated with an increased odds of asthma (OR 2.29 (95% CI 1.02–5.13)), and with a lower forced expiratory volume in 1 s/forced vital capacity and forced expiratory flow at 75% of forced vital capacity (z-score difference −0.28 (95% CI −0.52– −0.04) and −0.24 (95% CI −0.46– −0.01), respectively) in children at age 10 years. The observed associations were only partly explained by mode of delivery, gestational age at birth or birthweight. Conclusions C. trachomatis infection during pregnancy is associated with increased odds of wheezing, asthma and impaired lung function. The causality of the observed associations and potential underlying mechanisms need to be explored.
Pandemic science and politics
Authors: Philip Ball
Journal: The Lancet (2020)

In 2019, the Global Health Security Alliance assessed worldwide adherence to the International Health Regulations (2005), which supposedly commit nations to measures that prevent or control the spread of infectious diseases and mitigate their effects. The study found that no nation was fully prepared, and many countries—rich or poor—fell woefully short. This finding is only one of the many indications that we could have been ready, nationally and globally, to deal with a crisis like COVID-19, but were not.
COVID-19, Pandemic Triage, and the Polymorphism of Justice
Authors: Jonathan H. Marks
Journal: The American Journal of Bioethics (2020)

This article refers to:Ethics Lessons From Seattle’s Early Experience With COVID-19Ethical Challenges Arising in the COVID-19 Pandemic: An Overview from the Association of Bioethics Program Directors (ABPD) Task ForcePositive Public Health Ethics: Toward Flourishing and Resilient Communities and Individuals
Silver nanoparticles: Synthesis, medical applications and biosafety
Authors: Li Xu, Yi-Yi Wang, Jie Huang, Chun-Yuan Chen, Zhen-Xing Wang, Hui Xie
Journal: Theranostics (2020)

Silver nanoparticles (AgNPs) have been one of the most attractive nanomaterials in biomedicine due to their unique physicochemical properties. In this paper, we review the state-of-the-art advances of AgNPs in the synthesis methods, medical applications and biosafety of AgNPs. The synthesis methods of AgNPs include physical, chemical and biological routes. AgNPs are mainly used for antimicrobial and anticancer therapy, and also applied in the promotion of wound repair and bone healing, or as the vaccine adjuvant, anti-diabetic agent and biosensors. This review also summarizes the biological action mechanisms of AgNPs, which mainly involve the release of silver ions (Ag+), generation of reactive oxygen species (ROS), destruction of membrane structure. Despite these therapeutic benefits, their biological safety problems such as potential toxicity on cells, tissue, and organs should be paid enough attention. Besides, we briefly introduce a new type of Ag particles smaller than AgNPs, silver Ångstrom (Å, 1 Å = 0.1 nm) particles (AgÅPs), which exhibit better biological activity and lower toxicity compared with AgNPs. Finally, we conclude the current challenges and point out the future development direction of AgNPs.
Computational technology for nasal cartilage-related clinical research and application
Authors: Bing Shi, Hanyao Huang
Journal: International Journal of Oral Science (2020)

Surgeons need to understand the effects of the nasal cartilage on facial morphology, the function of both soft tissues and hard tissues and nasal function when performing nasal surgery. In nasal cartilage-related surgery, the main goals for clinical research should include clarification of surgical goals, rationalization of surgical methods, precision and personalization of surgical design and preparation and improved convenience of doctor-patient communication. Computational technology has become an effective way to achieve these goals. Advances in three-dimensional (3D) imaging technology will promote nasal cartilage-related applications, including research on computational modelling technology, computational simulation technology, virtual surgery planning and 3D printing technology. These technologies are destined to revolutionize nasal surgery further. In this review, we summarize the advantages, latest findings and application progress of various computational technologies used in clinical nasal cartilage-related work and research. The application prospects of each technique are also discussed.
Measuring SARS-CoV-2 neutralizing antibody activity using pseudotyped and chimeric viruses
Authors: Fabian Schmidt, Yiska Weisblum, Frauke Muecksch, Hans-Heinrich Hoffmann, Eleftherios Michailidis, Julio C.C. Lorenzi, Pilar Mendoza, Magdalena Rutkowska, Eva Bednarski, Christian Gaebler, Marianna Agudelo, Alice Cho, Zijun Wang, Anna Gazumyan, Melissa Cipolla, Marina Caskey, Davide F. Robbiani, Michel C. Nussenzweig, Charles M. Rice, Theodora Hatziioannou, Paul D. Bieniasz
Journal: The Journal of Experimental Medicine (2020)

The emergence of SARS-CoV-2 and the ensuing explosive epidemic of COVID-19 disease has generated a need for assays to rapidly and conveniently measure the antiviral activity of SARS-CoV-2–specific antibodies. Here, we describe a collection of approaches based on SARS-CoV-2 spike-pseudotyped, single-cycle, replication-defective human immunodeficiency virus type-1 (HIV-1), and vesicular stomatitis virus (VSV), as well as a replication-competent VSV/SARS-CoV-2 chimeric virus. While each surrogate virus exhibited subtle differences in the sensitivity with which neutralizing activity was detected, the neutralizing activity of both convalescent plasma and human monoclonal antibodies measured using each virus correlated quantitatively with neutralizing activity measured using an authentic SARS-CoV-2 neutralization assay. The assays described herein are adaptable to high throughput and are useful tools in the evaluation of serologic immunity conferred by vaccination or prior SARS-CoV-2 infection, as well as the potency of convalescent plasma or human monoclonal antibodies.
USEFULNESS OF SALIVA SAMPLES FOR DETECTING SARS-CoV-2 RNA AMONG LIVER DISEASE PATIENTS
Authors: Livia Melo Villar, Vanessa Duarte da Costa, Bianca Cristina Leires Marques, Lucas Lima da Silva, Alanna Calheiros Santos, Ana Carolina da Fonseca Mendonça, Vanessa Alves Marques, Giselle Prado do Nascimento, Lia Laura Lewis-Ximenez, Vanessa Salete de Paula
Journal: Journal of Infection (2020)
Reactive mesoporous silica nanoparticles loaded with limonene for improving physical and mental health of mice at simulated microgravity condition
Authors: Zhiguo Lu, Jianze Wang, Lina Qu, Guanghan Kan, Tianlu Zhang, Jie Shen, Yan Li, Jun Yang, Yunwei Niu, Zuobing Xiao, Yinghui Li, Xin Zhang
Journal: Bioactive Materials (2020)

Astronauts are under high stress for a long time because of the microgravity condition, which leads to anxiety, affects their learning and memory abilities, and seriously impairs the health of astronauts. Aromatherapy can improve the physical and mental health of astronauts in a way that moisturizes them softly and silently. However, the strong volatility of fragrances and inconvenience of aroma treatment greatly limit their application in the field of spaceflight. In this study, reactive mesoporous silica nanoparticles were prepared to encapsulate and slowly release limonene. The limonene loaded nanoparticles were named limonene@mesoporous silica nanoparticles-cyanuric chloride (LE@MSNs-CYC). LE@MSNs-CYC were then applied to wallpaper to improve the convenience of aromatherapy. LE@MSNs-CYC could chemically react with the wallpaper, thus firmly adsorbed on the wallpaper. In the following, the mice were treated with hindlimb unloading (HU) to simulate a microgravity environment. The results showed that 28-day HU led to an increase in the level of anxiety and declines in learning, memory, and physical health in mice. LE@MSNs-CYC showed significant relief effects on anxiety, learning, memory, and physical health of HU treated mice. Subsequently, the molecular mechanisms were explored by hypothalamic-pituitary-adrenal axis related hormones, immune-related cytokines, learning, and memory-related neurotransmitters and proteins.