tbuckley/cabot-search huggingface dataset:
Cytochrome P450 enzyme-mediated auto-enhanced photodynamic cancer therapy of co-nanoassembly between clopidogrel and photosensitizer
Authors: Qiu Wang, Mengchi Sun, Dan Li, Chang Li, Cong Luo, Zhaomeng Wang, Wenjuan Zhang, Zimeng Yang, Yao Feng, Shuang Wang, Zhonggui He, Haotian Zhang, Qiming Kan, Wei Sun, Jin Sun
Journal: Theranostics (2020)

Reactive oxygen species (ROS)-based photodynamic therapy (PDT) has a widespread application in cancer therapy.Nevertheless, the efficiency of PDT is far from satisfactory.One major impediment is the overexpression of glutathione (GSH) in tumor cells, which could deplete the level of PDT-generated ROS.Herein, we develop a novel type of cytochrome P450 enzyme-mediated auto-enhanced photodynamic co-nanoassembly between clopidogrel (CPG) and photosensitizer pyropheophorbide a (PPa).Methods: In this work, we prepare the co-assembled nanoparticles of CPG and PPa (CPG/PPa NPs) by using one-step precipitation method.The assembly mechanism, drug release behavior, GSH consumption, ROS generation, cellular uptake, cytotoxicity of CPG/PPa NPs are investigated in vitro.The mice bearing 4T1 tumor are employed to evaluate in vivo biodistribution and anti-tumor effect of CPG/PPa NPs.Results: Such CPG/PPa NPs could disrupt the intracellular redox homeostasis, resulting from the elimination of GSH by CPG active metabolite mediated by cytochrome P450 enzyme (CYP2C19).The in vivo assays reveal that CPG/PPa NPs not only increase the drug accumulation in tumor sites but also significantly suppress tumor growth in BALB/c mice bearing 4T1 tumor.With CPG-mediated GSH consumption and PPa-triggered ROS generation, CPG/PPa NPs show the enhanced PDT treatment effect by breaking intracellular redox balance.Conclusion: Our findings provide a valuable knowledge for the rational design of the PDT-based combinational cancer therapy.
Athletes as community; athletes in community: covid-19, sporting mega-events and athlete health protection
Authors: Robert H Mann, Bryan C Clift, Jules Boykoff, Sheree Bekker
Journal: British Journal of Sports Medicine (2020)

> ‘This is far bigger than our dreams right now. Now more than ever is a time to think bigger than yourself. Protect yourself, your families and your communities’.
> 
> Melissa Bishop-Nriagu (Canadian 800 m record holder).

The current coronavirus (covid-19) pandemic presents an extraordinary public health challenge. The WHO defines a pandemic as the global spread of a new disease for which there is little or no pre-existing immunity in the human population. Worldwide, we have seen ambitious public health measures implemented by governments, non-governmental organisations and individuals alike. Yet, there is still more to be done to ‘flatten the curve’ and mitigate the impact of this pandemic.

Sporting ‘mega-events’ are international, out of the ordinary and generally large in composition.1 These include the Olympic Games, which provide mass-spectacle for the public2 while producing significant health and socioeconomic impacts for host nation(s),3 including an increased risk for transmission of infectious diseases.4 Therefore, pandemics like covid-19 bring added urgency to examine the impacts of hosting sporting mega-events.

As sporting mega-events have been cancelled and postponed in response to covid-19, the rhetoric emerging from international sporting organisations, such as the International Olympic Committee (IOC), has emphasised the importance of …
Cysteamine prevents asthma development and reduces airway hyperresponsiveness in experimental asthma
Authors: Paige E. Bolcas, Eric B. Brandt, Brandy P. Ruff, Mehak Kalra, Gurjit K. Khurana Hershey
Journal: Allergy (2020)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Comparison of Placebos and Propensity Score Adjustment in Multiple Sclerosis Nonrandomized Studies
Authors: Alessio Signori, Fabio Pellegrini, Francesca Bovis, Luca Carmisciano, Carl de Moor, Maria Pia Sormani
Journal: JAMA Neurology (2020)

This comparative effectiveness research study examines propensity scores adjustment in multiple sclerosis studies comparing disease-modifying treatments.
COVID-19 and rheumatology: first steps towards a different future?
Authors: Iain B McInnes
Journal: Annals of the Rheumatic Diseases (2020)

The eosinophil granule contains a series of basic proteins, including major basic protein, eosinophil peroxidase, eosinophil-derived neurotoxin (EDN), and eosinophil cationic protein (ECP). Both EDN and ECP are neurotoxins and helminthotoxins. Comparison of the partial N-terminal amino acid sequences of EDN and ECP showed 67% identity; surprisingly, they also showed structural homology to pancreatic ribonuclease (RNase). Therefore, we determined whether EDN and ECP possess RNase enzymatic activity. By spectrophotometric assay of acid soluble nucleotides formed from yeast RNA, purified EDN showed RNase activity similar to bovine pancreatic RNase, whereas ECP was 50 to 100 times less active. The RNase activity associated with ECP was not significantly inhibited after exposure of ECP to polyclonal or monoclonal antibody to EDN. These results indicate that EDN and ECP both possess RNase activity, the RNase activity of EDN and ECP is specific, and EDN and ECP have maintained not only structural but also functional homology to pancreatic RNase.
Finding Effective Treatments for COVID-19
Authors: Jesse L. Goodman, Luciana Borio
Journal: JAMA (2020)

Chenguang Shen, PhD; Zhaoqin Wang, PhD; Fang Zhao, PhD; Yang Yang, MD; Jinxiu Li, MD; Jing Yuan, MD; Fuxiang Wang, MD; Delin Li, PhD; Minghui Yang, PhD; Li Xing, MM; Jinli Wei, MM; Haixia Xiao, PhD; Yan Yang, MM; Jiuxin Qu, MD; Ling Qing, MM; Li Chen, MD; Zhixiang Xu, MM; Ling Peng, MM; Yanjie Li, MM; Haixia Zheng, MM; Feng Chen, MM; Kun Huang, MM; Yujing Jiang, MM; Dongjing Liu, MD; Zheng Zhang, MD; Yingxia Liu, MD; Lei Liu, MD
Effect of long-lasting insecticidal nets with and without piperonyl butoxide on malaria indicators in Uganda (LLINEUP): a pragmatic, cluster-randomised trial embedded in a national LLIN distribution campaign
Authors: Sarah G Staedke, Samuel Gonahasa, Grant Dorsey, Moses R Kamya, Catherine Maiteki-Sebuguzi, Amy Lynd, Agaba Katureebe, Mary Kyohere, Peter Mutungi, Simon P Kigozi, Jimmy Opigo, Janet Hemingway, Martin J Donnelly
Journal: The Lancet (2020)

BackgroundLong-lasting insecticidal nets (LLINs) are the primary malaria prevention tool, but their effectiveness is threatened by pyrethroid resistance. We embedded a pragmatic cluster-randomised trial into Uganda's national LLIN campaign to compare conventional LLINs with those containing piperonyl butoxide (PBO), a synergist that can partially restore pyrethroid susceptibility in mosquito vectors.Methods104 health sub-districts, from 48 districts in Uganda, were randomly assigned to LLINs with PBO (PermaNet 3.0 and Olyset Plus) and conventional LLINs (PermaNet 2.0 and Olyset Net) by proportionate randomisation using an iterative process. At baseline 6, 12, and 18 months after LLIN distribution, cross-sectional surveys were done in 50 randomly selected households per cluster (5200 per survey); a subset of ten households per cluster (1040 per survey) were randomly selected for entomological surveys. The primary outcome was parasite prevalence by microscopy in children aged 2–10 years, assessed in the as-treated population at 6, 12, and 18 months. This trial is registered with ISRCTN, ISRCTN17516395.FindingsLLINs were delivered to households from March 25, 2017, to March 18, 2018, 32 clusters were randomly assigned to PermaNet 3.0, 20 to Olyset Plus, 37 to PermaNet 2.0, and 15 to Olyset Net. In the as-treated analysis, three clusters were excluded because no dominant LLIN was received, and four clusters were reassigned, resulting in 49 PBO LLIN clusters (31 received PermaNet 3.0 and 18 received Olyset Plus) and 52 non-PBO LLIN clusters (39 received PermaNet 2.0 and 13 received Olyset Net). At 6 months, parasite prevalence was 11% (386/3614) in the PBO group compared with 15% (556/3844) in the non-PBO group (prevalence ratio [PR] adjusted for baseline values 0·74, 95% CI 0·62–0·87; p=0·0003). Parasite prevalence was similar at month 12 (11% vs 13%; PR 0·73, 95% CI 0·63–0·85; p=0·0001) and month 18 (12% vs 14%; PR 0·84, 95% CI 0·72–0·98; p=0·029).InterpretationIn Uganda, where pyrethroid resistance is high, PBO LLINs reduced parasite prevalence more effectively than did conventional LLINs for up to 18 months. This study provides evidence needed to support WHO's final recommendation on use of PBO LLINs.FundingThe Against Malaria Foundation, UK Department for International Development, Innovative Vector Control Consortium, and Bill and Melinda Gates Foundation.
Re: Couturier et al.: Widefield OCT-angiography and fluorescein angiography assessments of nonperfusion in diabetic retinopathy and edema treated with anti–vascular endothelial growth factor (Ophthalmology. 2019;126:1685–1694)
Authors: Enrico Borrelli, Riccardo Sacconi, Giuseppe Querques
Journal: Ophthalmology (2020)
Abstract A05: Growth rate alterations of human colorectal cancer cells by 157 gut bacteria
Authors: Rahwa Taddese, Daniel R. Garza, Lilian Ruiter, Clara Belzer, Steven Aalvink, Iris D. Nagtegaal, Bas E. Dutilh, Annemarie Boleij
Journal: Cancer Research (2020)

Abstract Several bacteria in the human gut microbiome have been associated with colorectal cancer (CRC) by high-throughput screens. In some cases, molecular mechanisms have been elucidated that drive tumorigenesis, including bacterial membrane proteins or secreted molecules that interact with the human cancer cells. For most gut bacteria, however, it remains unknown if they enhance or inhibit cancer cell growth. Here, we screened bacteria-free supernatants (secretomes) and inactivated cells of over 150 cultured bacterial strains for their effect on CRC cell growth. Five CRC cell lines and one noncancerous kidney cell line were selected based on their differences in mutational landscapes. We observed family-level and strain-level effects that often differed between bacterial cells and secretomes, suggesting that different molecular mechanisms are at play. Secretomes of Bacteroidaceae, Enterobacteriaceae, and Erysipelotrichaceae enhanced CRC cell growth, while most Fusobacteriaceae cells and secretomes inhibited growth, contrasting prior findings. For some bacterial families, strong cell line-dependent effects were obsevered, such as for Streptococcaceae and HT29 cells. In some bacteria, the presence of specific functional genes was associated with CRC cell growth rates, including the virulence genes TcdA in Clostridiales and FadA in Fusobacteriaceae, which both inhibited growth. Bacteroidaceae cells that enhanced growth were enriched for genes of the cobalamin synthesis pathway, while Fusobacteriaceae cells that inhibit growth were enriched for genes in ethanolamine utilization pathway. Together, our results reveal how different gut bacteria have wide-ranging effects on cancer cells, contribute a better understanding of the effects of the gut microbiome on the human host, and provide a valuable resource for identifying candidate target genes for potential microbiome-based diagnostics and treatment strategies. Citation Format: Rahwa Taddese, Daniel R. Garza, Lilian Ruiter, Clara Belzer, Steven Aalvink, Iris D. Nagtegaal, Bas E. Dutilh, Annemarie Boleij. Growth rate alterations of human colorectal cancer cells by 157 gut bacteria [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr A05.
Distinct associations of sputum and oral microbiota with atopic, immunologic, and clinical features in mild asthma
Authors: Juliana Durack, Laura S. Christian, Snehal Nariya, Jeanmarie Gonzalez, Nirav R. Bhakta, K. Mark Ansel, Avraham Beigelman, Mario Castro, Anne-Marie Dyer, Elliot Israel, Monica Kraft, Richard J. Martin, David T. Mauger, Stephen P. Peters, Sharon R. Rosenberg, Christine A. Sorkness, Michael E. Wechsler, Sally E. Wenzel, Steven R. White, Susan V. Lynch, Homer A. Boushey, Yvonne J. Huang
Journal: Journal of Allergy and Clinical Immunology (2020)
Isolation of<i>Borrelia burgdorferi</i>from the Myocardium of a Patient with Long-Standing Cardiomyopathy
Authors: Gerold Stanek, Jutta Klein, Reginald Bittner, Dietmar Glogar
Journal: New England Journal of Medicine (1990)

LYME borreliosis (or Lyme disease) is a systemic disorder caused by the spirochete Borrelia burgdorferi, a newly discovered species of borrelia.1 , 2 The disease usually begins with a characteristic skin lesion; neurologic, cardiac, and joint involvement may develop weeks to months later. Some manifestations may last for years or even decades.3 Lyme borreliosis is transmitted by arthropods, especially by ticks of the genus ixodes and by some tabanid species. The area in which it is endemic includes most of the United States,4 all of Europe,5 the European and Asian parts of Russia,6 China,7 and Japan.8 Cardiac abnormalities induced by Lyme . . .
Which endosurgical treatment for gastroparesis: pyloromyotomy or gastric electrical stimulation?
Authors: Henry P. Parkman
Journal: Endoscopy (2020)

There has been a boom in performing pyloromyotomy for gastroparesis over the past 10 years, particularly since endoscopic pyloromyotomy (gastric peroral endoscopic myotomy [G-POEM] or pyloromyotomy [POP]) was introduced. How do we place the use of pyloromyotomy, particularly G-POEM, with other treatments for gastroparesis, particularly gastric electrical stimulation (GES)?
Techniques for Treatment of Carotid Stenosis
Authors: Sanjiv Sharma, Neil Bhambi, Brijesh Bhambi
Journal: JAMA (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Default polyfunctional T helper 1 response to ample signal 1 alone
Authors: Luca Danelli, Georgina Cornish, Julia Merkenschlager, George Kassiotis
Journal: Cellular and Molecular Immunology (2020)

Abstract CD4 + T cells integrate well-defined signals from the T-cell receptor (TCR) (signal 1) and a host of costimulatory molecules (signal 2) to initiate clonal expansion and differentiation into diverse functional T helper (Th) subsets. However, our ability to guide the expansion of context-appropriate Th subsets by deploying these signals in vaccination remains limited. Using cell-based vaccines, we selectively amplified signal 1 by exclusive presentation of an optimized peptide:MHC II (pMHC II) complex in the absence of classic costimulation. Contrary to expectations, amplified signal 1 alone was strongly immunogenic and selectively expanded high-affinity TCR clonotypes, despite delivering intense TCR signals. In contrast to natural infection or standard vaccines, amplified signal 1, presented by a variety of professional and nonprofessional antigen-presenting cells (APCs), induced exclusively polyfunctional Th1 effector and memory cells, which protected against retroviral infection and tumor challenge, and expanded tumor-reactive CD4 + T cells otherwise rendered unresponsive in tumor-bearing hosts. Together, our findings uncover a default Th1 response to ample signal 1 and offer a means to selectively prime such protective responses by vaccination.
Correction: Reply to Rizzatti et al.
Authors: Juliana Yang, Mouen A. Khashab
Journal: Endoscopy (2020)

Correction Reply to Rizzatti et al. Yang J, Khashab MA. Reply to Rizzatti et al.Endoscopy 2020; 52: 322 In the above-mentioned article, the name of Mouen A. Khashab has been corrected. This was corrected in the online version on April 17, 2020.
Downregulation of a Candidate Myeloid Tumor Suppressor Gene Isolated from 7q21 Induces Abnormal Mitosis Due to Insufficient Centrosome Maturation.
Authors: Hiroya Asou, Hirotaka Matsui, Yuko Ozaki, Akiko Nagamachi, Daisuke Aki, Miho Ohsugi, Toshiya Inaba
Journal: Blood (2007)
Unexpected Heparin-Induced Thrombocytopenia While Bridging—Reply
Authors: Shradha A. Kulkarni, Margaret C. Fang
Journal: JAMA Internal Medicine (2020)

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 Internal Medicine 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 Internal Medicine journal
Daratumumab in Combination with Carfilzomib and Dexamethasone in Patients (pts) with Relapsed Multiple Myeloma (MMY1001): An Open-Label, Phase 1b Study
Authors: Sagar Lonial, Jesus F. San-Miguel, Joaquín Martínez-Lopez, Maria-Victoria Mateos, Joan Blade, Lotfi Benboubker, Albert Oriol, Bertrand Arnulf, Ajai Chari, Luis Pineiro, Kaida Wu, Jianping Wang, Parul Doshi, Jordan Schecter, Philippe Moreau
Journal: Blood (2017)
Targeting potential drivers of COVID-19: Neutrophil extracellular traps
Authors: Betsy J. Barnes, Jose M. Adrover, Amelia Baxter-Stoltzfus, Alain Borczuk, Jonathan Cools-Lartigue, James M. Crawford, Juliane Daßler-Plenker, Philippe Guerci, Caroline Huynh, Jason S. Knight, Massimo Loda, Mark R. Looney, Florencia McAllister, Roni Rayes, Stephane Renaud, Simon Rousseau, Steven Salvatore, Robert E. Schwartz, Jonathan D. Spicer, Christian C. Yost, Andrew Weber, Yu Zuo, Mikala Egeblad
Journal: The Journal of Experimental Medicine (2020)

Coronavirus disease 2019 (COVID-19) is a novel, viral-induced respiratory disease that in ∼10-15% of patients progresses to acute respiratory distress syndrome (ARDS) triggered by a cytokine storm. In this Perspective, autopsy results and literature are presented supporting the hypothesis that a little known yet powerful function of neutrophils-the ability to form neutrophil extracellular traps (NETs)-may contribute to organ damage and mortality in COVID-19. We show lung infiltration of neutrophils in an autopsy specimen from a patient who succumbed to COVID-19. We discuss prior reports linking aberrant NET formation to pulmonary diseases, thrombosis, mucous secretions in the airways, and cytokine production. If our hypothesis is correct, targeting NETs directly and/or indirectly with existing drugs may reduce the clinical severity of COVID-19.
A Multi-Targeting, Nucleoside-Modified mRNA Influenza Virus Vaccine Provides Broad Protection in Mice
Authors: Alec W. Freyn, Jamile Ramos da Silva, Victoria C. Rosado, Carly M. Bliss, Matthew Pine, Barbara L. Mui, Ying K. Tam, Thomas D. Madden, Luís Carlos de Souza Ferreira, Drew Weissman, Florian Krammer, Lynda Coughlan, Peter Palese, Norbert Pardi, Raffael Nachbagauer
Journal: Molecular Therapy (2020)

Influenza viruses are respiratory pathogens of public health concern worldwide with up to 650,000 deaths occurring each year. Seasonal influenza virus vaccines are employed to prevent disease, but with limited effectiveness. Development of a universal influenza virus vaccine with the potential to elicit long-lasting, broadly cross-reactive immune responses is necessary for reducing influenza virus prevalence. In this study, we have utilized lipid nanoparticle-encapsulated, nucleoside-modified mRNA vaccines to intradermally deliver a combination of conserved influenza virus antigens (hemagglutinin stalk, neuraminidase, matrix-2 ion channel, and nucleoprotein) and induce strong immune responses with substantial breadth and potency in a murine model. The immunity conferred by nucleoside-modified mRNA-lipid nanoparticle vaccines provided protection from challenge with pandemic H1N1 virus at 500 times the median lethal dose after administration of a single immunization, and the combination vaccine protected from morbidity at a dose of 50 ng per antigen. The broad protective potential of a single dose of combination vaccine was confirmed by challenge with a panel of group 1 influenza A viruses. These findings support the advancement of nucleoside-modified mRNA-lipid nanoparticle vaccines expressing multiple conserved antigens as universal influenza virus vaccine candidates. Influenza viruses are respiratory pathogens of public health concern worldwide with up to 650,000 deaths occurring each year. Seasonal influenza virus vaccines are employed to prevent disease, but with limited effectiveness. Development of a universal influenza virus vaccine with the potential to elicit long-lasting, broadly cross-reactive immune responses is necessary for reducing influenza virus prevalence. In this study, we have utilized lipid nanoparticle-encapsulated, nucleoside-modified mRNA vaccines to intradermally deliver a combination of conserved influenza virus antigens (hemagglutinin stalk, neuraminidase, matrix-2 ion channel, and nucleoprotein) and induce strong immune responses with substantial breadth and potency in a murine model. The immunity conferred by nucleoside-modified mRNA-lipid nanoparticle vaccines provided protection from challenge with pandemic H1N1 virus at 500 times the median lethal dose after administration of a single immunization, and the combination vaccine protected from morbidity at a dose of 50 ng per antigen. The broad protective potential of a single dose of combination vaccine was confirmed by challenge with a panel of group 1 influenza A viruses. These findings support the advancement of nucleoside-modified mRNA-lipid nanoparticle vaccines expressing multiple conserved antigens as universal influenza virus vaccine candidates.
Deprivation and prognosis in patients with pulmonary arterial hypertension: missing the effect of deprivation on a rare disease?
Authors: Eleni Sofianopoulou, Colin Church, Gerry Coghlan, Luke Howard, Martin Johnson, David G. Kiely, Allan Lawrie, James Lordan, Martin R. Wilkins, Stephen J. Wort, Nicholas W. Morrell, Mark R. Toshner
Journal: European Respiratory Journal (2020)

<b>No association was found between deprivation and mortality for PAH patients in England and Wales. The association found between risk stratification at baseline and deprivation suggests that the issue of deprivation and outcomes in PAH may be more nuanced.</b>https://bit.ly/2y8WgqB