tbuckley/cabot-search huggingface dataset:
Scavenging Reactive Lipids to Prevent Oxidative Injury
Authors: Linda S. May-Zhang, Annet Kirabo, Jiansheng Huang, MacRae F. Linton, Sean S. Davies, Katherine T. Murray
Journal: The Annual Review of Pharmacology and Toxicology (2020)

Oxidative injury due to elevated levels of reactive oxygen species is implicated in cardiovascular diseases, Alzheimer's disease, lung and liver diseases, and many cancers. Antioxidant therapies have generally been ineffective at treating these diseases, potentially due to ineffective doses but also due to interference with critical host defense and signaling processes. Therefore, alternative strategies to prevent oxidative injury are needed. Elevated levels of reactive oxygen species induce lipid peroxidation, generating reactive lipid dicarbonyls. These lipid oxidation products may be the most salient mediators of oxidative injury, as they cause cellular and organ dysfunction by adducting to proteins, lipids, and DNA. Small-molecule compounds have been developed in the past decade to selectively and effectively scavenge these reactive lipid dicarbonyls. This review outlines evidence supporting the role of lipid dicarbonyls in disease pathogenesis, as well as preclinical data supporting the efficacy of novel dicarbonyl scavengers in treating or preventing disease.
Advances and recent developments in asthma in 2020
Authors: Lacin Cevhertas, Ismail Ogulur, Debbie J. Maurer, Daniel Burla, Mei Ding, Kirstin Jansen, Jana Koch, Chengyao Liu, Siyuan Ma, Yasutaka Mitamura, Yaqi Peng, Urszula Radzikowska, Arturo O. Rinaldi, Pattraporn Satitsuksanoa, Anna Globinska, Willem van de Veen, Milena Sokolowska, Katja Baerenfaller, Ya‐dong Gao, Ioana Agache, Mübeccel Akdis, Cezmi A. Akdis
Journal: Allergy (2020)

In this review, we discuss recent publications on asthma and review the studies that have reported on the different aspects of the prevalence, risk factors and prevention, mechanisms, diagnosis, and treatment of asthma. Many risk and protective factors and molecular mechanisms are involved in the development of asthma. Emerging concepts and challenges in implementing the exposome paradigm and its application in allergic diseases and asthma are reviewed, including genetic and epigenetic factors, microbial dysbiosis, and environmental exposure, particularly to indoor and outdoor substances. The most relevant experimental studies further advancing the understanding of molecular and immune mechanisms with potential new targets for the development of therapeutics are discussed. A reliable diagnosis of asthma, disease endotyping, and monitoring its severity are of great importance in the management of asthma. Correct evaluation and management of asthma comorbidity/multimorbidity, including interaction with asthma phenotypes and its value for the precision medicine approach and validation of predictive biomarkers, are further detailed. Novel approaches and strategies in asthma treatment linked to mechanisms and endotypes of asthma, particularly biologicals, are critically appraised. Finally, due to the recent pandemics and its impact on patient management, we discuss the challenges, relationships, and molecular mechanisms between asthma, allergies, SARS-CoV-2, and COVID-19.
INFECTIOUS ECZEMATOID DERMATITIS
Authors: M J COSTELLO
Journal: JAMA (1920)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
2-year remission of type 2 diabetes and pancreas morphology: a post-hoc analysis of the DiRECT open-label, cluster-randomised trial
Authors: Ahmad Al-Mrabeh, Kieren G Hollingsworth, James A M Shaw, Alex McConnachie, Naveed Sattar, Michael E J Lean, Roy Taylor
Journal: The Lancet Diabetes & Endocrinology (2020)
Whole genome, transcriptome and methylome profiling enhances actionable target discovery in high-risk pediatric cancer
Authors: Marie Wong, Chelsea Mayoh, Loretta M. S. Lau, Dong-Anh Khuong-Quang, Mark Pinese, Amit Kumar, Paulette Barahona, Emilie E. Wilkie, Patricia Sullivan, Rachel Bowen-James, Mustafa Syed, Iñigo Martincorena, Federico Abascal, Alexandra Sherstyuk, Noemi A. Bolanos, Jonathan Baber, Peter Priestley, M. Emmy M. Dolman, Emmy D. G. Fleuren, Marie-Emilie Gauthier, Emily V. A. Mould, Velimir Gayevskiy, Andrew J. Gifford, Dylan Grebert-Wade, Patrick A. Strong, Elodie Manouvrier, Meera Warby, David M. Thomas, Judy Kirk, Katherine Tucker, Tracey O’Brien, Frank Alvaro, Geoffry B. McCowage, Luciano Dalla-Pozza, Nicholas G. Gottardo, Heather Tapp, Paul Wood, Seong-Lin Khaw, Jordan R. Hansford, Andrew S. Moore, Murray D. Norris, Toby N. Trahair, Richard B. Lock, Vanessa Tyrrell, Michelle Haber, Glenn M. Marshall, David S. Ziegler, Paul G. Ekert, Mark J. Cowley
Journal: Nature Medicine (2020)
Response to: ‘Correspondence on ‘EULAR recommendations for the management of antiphospholipid syndrome in adults’ by Zhouet al
Authors: Maria G Tektonidou, Angela Tincani, Michael M Ward
Journal: Annals of the Rheumatic Diseases (2020)

We thank Zhou et al 1 for their interest in the 2019 European League Against Rheumatism (EULAR) recommendations for the management of antiphospholipid syndrome (APS) in adults.2

Although glucocorticoids (GC) are widely used in systemic lupus erythematous-associated APS, there is some uncertainty about their use in primary APS, and more specifically, about their use and dosage in the second and third trimester of pregnancy. In the EULAR recommendations for APS management, the use of GC in patients with primary APS is recommended only in catastrophic APS (CAPS), and may be considered in refractory cases of obstetric APS at low-doses (≤10 mg prednisolone daily) and for only the first trimester.2 The latter statement is based on expert opinion due to the limited evidence. The only retrospective cohort study that addressed this question is described in the accompanying article with the results of the systematic literature review …
Covid-19: We need to understand the risks to tackle them
Authors: Fiona Godlee
Journal: BMJ (2020)

The emergence of dexamethasone as an effective treatment for people seriously ill with covid-19 has been a welcome sign that we are starting to get a handle on this disease that has so quickly and radically changed all our lives. The BMJ ’s rapid recommendation on dexamethasone has been produced in partnership with MAGIC and WHO.1 Based on a “living” network meta-analysis,2 it and the linked infographic will be regularly updated to include new data on direct comparisons with other treatments.

Meanwhile, the world has passed the …
Education disruption in response to a positive covid-19 PCR test must be proportionate and consistent
Authors: Sunil S Bhopal, Ellie Cannon
Journal: BMJ (2020)

We are delighted that most pupils in the United Kingdom have returned to school, but aghast to have parents tell us about the mass exclusion and 14 day home imprisonment without exercise ("self isolation") of children in the opening weeks of term, given that so few develop severe covid-19 1 and that children do not seem to be primary drivers of disease spread. 2 Reasons for exclusion have included one child in a school year group being PCR test positive, without symptoms.
Facilities for investigation and treatment of Sleep Apnoea in the UK
Authors: G J Gibson, N J Douglas, Stradling
Journal: Thorax (1996)

We have surveyed the current facilities for investigation and treatment of obstructive sleep apnoea (OSA) in the UK by sending a questionnaire to all physicians known to be offering this service in the financial year 1995-6. Replies were received from 42 of the 45 physicians approached. The number of diagnostic sleep studies performed over 12 months was 11, 486. The total number of patients receiving treatment with nasal continuous positive airway pressure (CPAP) was 7006. Of these, CPAP treatment had been initiated in 2288 (32.7%) during the year surveyed. Based on the conservative estimates of prevalence of OSA used in the Royal College of Physicians Report on Sleep Apnoea (1993), the approximate number of patients with symptomatic OSA who might benefit from CPAP treatment in the UK is at least 51, 480. Of the 42 physicians who responded, the numbers reporting problems with NHS funding for sleep apnoea services in relation to diagnostic studies, CPAP systems and support staff were respectively 23, 25 and 24. Only 9 physicians experienced no financial problems related to the service in 1995-6. We conclude that less than 1 in 7 of potentially suitable patients with OSA in the UK are currently being treated with CPAP and that major problems of funding are being faced by the majority of physicians attempting to provide an appropriate level of service.
<sup>89</sup>Zr-pembrolizumab biodistribution is influenced by PD-1-mediated uptake in lymphoid organs
Authors: Elly L van der Veen, Danique Giesen, Linda Pot-de Jong, Annelies Jorritsma-Smit, Elisabeth G E De Vries, Marjolijn N Lub-de Hooge
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background To better predict response to immune checkpoint therapy and toxicity in healthy tissues, insight in the in vivo behavior of immune checkpoint targeting monoclonal antibodies is essential. Therefore, we aimed to study in vivo pharmacokinetics and whole-body distribution of zirconium-89 ( 89 Zr) labeled programmed cell death protein-1 (PD-1) targeting pembrolizumab with positron-emission tomography (PET) in humanized mice. Methods Humanized (huNOG) and non-humanized NOG mice were xenografted with human A375M melanoma cells. PET imaging was performed on day 7 post 89 Zr-pembrolizumab (10 µg, 2.5 MBq) administration, followed by ex vivo biodistribution studies. Other huNOG mice bearing A375M tumors received a co-injection of excess (90 µg) unlabeled pembrolizumab or 89 Zr-IgG 4 control (10 µg, 2.5 MBq). Tumor and spleen tissue were studied with autoradiography and immunohistochemically including PD-1. Results PET imaging and biodistribution studies showed high 89 Zr-pembrolizumab uptake in tissues containing human immune cells, including spleen, lymph nodes and bone marrow. Tumor uptake of 89 Zr-pembrolizumab was lower than uptake in lymphoid tissues, but higher than uptake in other organs. High uptake in lymphoid tissues could be reduced by excess unlabeled pembrolizumab. Tracer activity in blood pool was increased by addition of unlabeled pembrolizumab, but tumor uptake was not affected. Autoradiography supported PET findings and immunohistochemical staining on spleen and lymph node tissue showed PD-1 positive cells, whereas tumor tissue was PD-1 negative. Conclusion 89 Zr-pembrolizumab whole-body biodistribution showed high PD-1-mediated uptake in lymphoid tissues, such as spleen, lymph nodes and bone marrow, and modest tumor uptake. Our data may enable evaluation of 89 Zr-pembrolizumab whole-body distribution in patients.
Physical Therapy Referral From Primary Care for Acute Back Pain With Sciatica
Authors: Julie M. Fritz, Elizabeth Lane, Molly McFadden, Gerard Brennan, John S. Magel, Anne Thackeray, Kate Minick, Whitney Meier, Tom Greene
Journal: Annals of Internal Medicine (2020)

Few studies have examined primary care management for acute sciatica, including referral to physical therapy.To evaluate whether early referral to physical therapy reduced disability more than usual care (UC) alone for patients with acute sciatica.Randomized controlled clinical trial. (ClinicalTrials.gov: NCT02391350).2 health care systems in Salt Lake City, Utah.220 adults aged 18 to 60 years with sciatica of less than 90 days' duration who were making an initial primary care consultation.All participants received imaging and medication at the discretion of the primary care provider before enrollment. A total of 110 participants randomly assigned to UC were provided 1 session of education, and 110 participants randomly assigned to early physical therapy (EPT) were provided 1 education session and then referred for 4 weeks of physical therapy, including exercise and manual therapy.The primary outcome was the Oswestry Disability Index (OSW) score after 6 months. Secondary outcomes were pain intensity, patient-reported treatment success, health care use, and missed workdays.Participants in the EPT group had greater improvement from baseline to 6 months for the primary outcome (relative difference, -5.4 points [95% CI, -9.4 to -1.3 points]; P = 0.009). The OSW and several secondary outcomes favored EPT after 4 weeks. After 1 year, between-group differences favored EPT for the OSW (relative difference, -4.8 points [CI, -8.9 to -0.7 points]) and back pain intensity (relative difference, -1.0 points [CI, -1.6 to -0.4 points]). The EPT group was more likely to self-report treatment success after 1 year (45.2%) than the UC group (27.6%) (relative risk, 1.6 [CI, 1.1 to 2.4]). There were no significant differences in health care use or missed workdays.The patients and providers were unblinded, and specific physical therapy interventions responsible for effects could not be determined.Referral from primary care to physical therapy for recent-onset sciatica improved disability and other outcomes compared with UC.Agency for Healthcare Research and Quality.
Cross-Sectional Evaluation of Humoral Responses against SARS-CoV-2 Spike
Authors: Jérémie Prévost, Romain Gasser, Guillaume Beaudoin-Bussières, Jonathan Richard, Ralf Duerr, Annemarie Laumaea, Sai Priya Anand, Guillaume Goyette, Mehdi Benlarbi, Shilei Ding, Halima Medjahed, Antoine Lewin, Josée Perreault, Tony Tremblay, Gabrielle Gendron-Lepage, Nicolas Gauthier, Marc Carrier, Diane Marcoux, Alain Piché, Myriam Lavoie, Alexandre Benoit, Vilayvong Loungnarath, Gino Brochu, Elie Haddad, Hannah D. Stacey, Matthew S. Miller, Marc Desforges, Pierre J. Talbot, Graham T. Gould Maule, Marceline Côté, Christian Therrien, Bouchra Serhir, Renée Bazin, Michel Roger, Andrés Finzi
Journal: Cell Reports Medicine (2020)

HighlightsAntibodies against SARS-CoV-2 Spike correlate with COVID-19 severityRBD-specific IgM and IgA decline more rapidly than IgGSARS-CoV-2 neutralizing antibodies are elicited within 2 weeks of infectionNeutralizing antibodies decline significantly after resolution of the infectionSummarySARS-CoV-2 is responsible for the coronavirus disease 2019 (COVID-19) pandemic, infecting millions of people and causing hundreds of thousands of deaths. The Spike glycoproteins of SARS-CoV-2 mediate viral entry and are the main targets for neutralizing antibodies. Understanding the antibody response directed against SARS-CoV-2 is crucial for the development of vaccine, therapeutic, and public health interventions. Here, we perform a cross-sectional study on 106 SARS-CoV-2-infected individuals to evaluate humoral responses against SARS-CoV-2 Spike. Most infected individuals elicit anti-Spike antibodies within 2 weeks of the onset of symptoms. The levels of receptor binding domain (RBD)-specific immunoglobulin G (IgG) persist over time, and the levels of anti-RBD IgM decrease after symptom resolution. Although most individuals develop neutralizing antibodies within 2 weeks of infection, the level of neutralizing activity is significantly decreased over time. Our results highlight the importance of studying the persistence of neutralizing activity upon natural SARS-CoV-2 infection.Graphical abstract
ESC-sEVs Rejuvenate Aging Hippocampal NSCs by Transferring SMADs to Regulate the MYT1-Egln3-Sirt1 Axis
Authors: Guowen Hu, Yuguo Xia, Bi Chen, Juntao Zhang, Liangzhi Gong, Yu Chen, Qing Li, Yang Wang, Zhifeng Deng
Journal: Molecular Therapy (2020)

Tissue stem cell senescence leads to stem cell exhaustion, which results in tissue homeostasis imbalance and a decline in regeneration capacity. However, whether neural stem cell (NSC) senescence occurs and causes neurogenesis reduction during aging is unknown. In this study, mice at different ages were used to detect age-related hippocampal NSC (H-NSC) senescence, as well as the function and mechanism of embryonic stem cell-derived small extracellular vesicles (ESC-sEVs) in rejuvenating H-NSC senescence. We found a progressive cognitive impairment, as well as age-related H-NSC senescence, in mice. ESC-sEV treatment significantly alleviated H-NSC senescence, recovered compromised self-renewal and neurogenesis capacities, and reversed cognitive impairment. Transcriptome analysis revealed that myelin transcription factor 1 (MYT1) is downregulated in senescent H-NSCs but upregulated by ESC-sEV treatment. In addition, knockdown of MYT1 in young H-NSCs accelerated age-related phenotypes and impaired proliferation and differentiation capacities. Mechanistically, ESC-sEVs rejuvenated senescent H-NSCs partly by transferring SMAD family members 4 (SMAD4) and 5 (SMAD5) to activate MYT1, which downregulated egl-9 family hypoxia inducible factor 3 (Egln3), followed by activation of hypoxia inducible factor 2 subunit α (HIF-2α), nicotinamide phosphoribosyl transferase (NAMPT), and sirtuin 1 (Sirt1) successively. Taken together, our results indicated that H-NSC senescence caused cellular exhaustion, neurogenesis reduction, and cognitive impairment during aging, which can be reversed by ESC-sEVs. Thus, ESC-sEVs may be promising therapeutic candidates for age-related diseases.
Digestive Manifestations in Patients Hospitalized With Coronavirus Disease 2019
Authors: B. Joseph Elmunzer, Rebecca L. Spitzer, Lydia D. Foster, Ambreen A. Merchant, Eric F. Howard, Vaishali A. Patel, Mary K. West, Emad Qayed, Rosemary Nustas, Ali Zakaria, Marc S. Piper, Jason R. Taylor, Lujain Jaza, Nauzer Forbes, Millie Chau, Luis F. Lara, Georgios I. Papachristou, Michael L. Volk, Liam G. Hilson, Selena Zhou, Vladimir M. Kushnir, Alexandria M. Lenyo, Caroline G. McLeod, Sunil Amin, Gabriela N. Kuftinec, Dhiraj Yadav, Charlie Fox, Jennifer M. Kolb, Swati Pawa, Rishi Pawa, Andrew Canakis, Christopher Huang, Laith H. Jamil, Andrew M. Aneese, Benita K. Glamour, Zachary L. Smith, Katherine A. Hanley, Jordan Wood, Harsh K. Patel, Janak N. Shah, Emil Agarunov, Amrita Sethi, Evan L. Fogel, Gail McNulty, Abdul Haseeb, Judy A. Trieu, Rebekah E. Dixon, Jeong Yun Yang, Robin B. Mendelsohn, Delia Calo, Olga C. Aroniadis, Joseph F. LaComb, James M. Scheiman, Bryan G. Sauer, Duyen T. Dang, Cyrus R. Piraka, Eric D. Shah, Heiko Pohl, William M. Tierney, Stephanie Mitchell, Ashwinee Condon, Adrienne Lenhart, Kulwinder S. Dua, Vikram S. Kanagala, Ayesha Kamal, Vikesh K. Singh, Maria Ines Pinto-Sanchez, Joy M. Hutchinson, Richard S. Kwon, Sheryl J. Korsnes, Harminder Singh, Zahra Solati, Field F. Willingham, Patrick S. Yachimski, Darwin L. Conwell, Evan Mosier, Mohamed Azab, Anish Patel, James Buxbaum, Sachin Wani, Amitabh Chak, Amy E. Hosmer, Rajesh N. Keswani, Christopher J. DiMaio, Michael S. Bronze, Raman Muthusamy, Marcia I. Canto, V. Mihajlo Gjeorgjievski, Zaid Imam, Fadi Odish, Ahmed I. Edhi, Molly Orosey, Abhinav Tiwari, Soumil Patwardhan, Nicholas G. Brown, Anish A. Patel, Collins O. Ordiah, Ian P. Sloan, Lilian Cruz, Casey L. Koza, Uchechi Okafor, Thomas Hollander, Nancy Furey, Olga Reykhart, Natalia H. Zbib, John A. Damianos, James Esteban, Nick Hajidiacos, Melissa Saul, Melanie Mays, Gulsum Anderson, Kelley Wood, Laura Mathews, Galina Diakova, Molly Caisse, Lauren Wakefield, Haley Nitchie, Akbar K. Waljee, Weijing Tang, Yueyang Zhang, Ji Zhu, Amar R. Deshpande, Don C. Rockey, Teldon B. Alford, Valerie Durkalski
Journal: Clinical Gastroenterology and Hepatology (2020)
Bismuth‐Based Mesoporous Nanoball Carrying Sorafenib for Computed Tomography Imaging and Synergetic Chemoradiotherapy of Hepatocellular Carcinoma
Authors: Guang‐Cong Zhang, Jie Liu, Xiang‐Nan Yu, Yong Deng, Yun Sun, Tao‐Tao Liu, Ling Dong, Chang‐Feng Zhu, Xi‐Zhong Shen, Ji‐Min Zhu, Shu‐Qiang Weng, Yuhao Li
Journal: Advanced Healthcare Materials (2020)

Abstract Sorafenib (SOR), a multi‐kinase inhibitor for advanced hepatocellular carcinoma (HCC), reveals a limited therapeutic effect due to a lack of selectivity and evident drug resistance. In the present study, bismuth‐based mesoporous nanomaterial (NBOF) is loaded with SOR and then coated with polyethylene glycol and folic acid conjugates (P‐FA) to form an NBOF@SOR‐P‐FA nanocarrier system. The system achieves significantly enhanced anti‐cancer efficacy by combining chemotherapy with radiotherapy. To evaluate the effect of synergistic treatment, cytotoxicity detection, Live/Dead staining, apoptotic assay, and Western blot analysis are performed. The results suggest that NBOF@SOR‐P‐FA significantly inhibits HCC cell proliferation and promotes cell apoptosis. Also, the NBOF@SOR‐P‐FA exhibits excellent biocompatibility by hemolysis and serum biochemical tests and produces a substantially enhanced contrast efficiency as compared to iohexol by computed tomography imaging. More importantly, the profound suppression of tumor growth and potentiation of apoptosis are observed in a mouse subcutaneous tumor model. Collectively, these results indicate that the bismuth‐based nanotheranostic platform could enhance the therapeutic effect of sorafenib and serve as an innovative method for HCC treatment.
Comparison of indocyanine green and methylene blue use for axillary reverse mapping during axillary lymph node dissection
Authors: Jun‐Dong Wu, Zun Wang, Huan‐Cheng Zeng, Li‐Fang He, Yong‐Qu Zhang, Guang‐Sheng Huang, Fan Zhang, Xiao‐Long Wei, Wen‐He Huang, Guo‐Jun Zhang
Journal: MedComm (2020)

Axillary reverse mapping (ARM) is a technique to identify arm lymphatic drainage during axillary lymph node dissection (ALND). This study compared the feasibility of ARM using indocyanine green (ICG) or methylene blue (MB), and accessed the oncologic safety of the procedure. Overall, 158 patients qualified for ALND were enrolled. The characteristics of ARM-identified nodes were recorded with ICG (n = 78) or MB (n = 80) visualization. Fine-needle aspiration cytology (FNAC) of the nodes were performed and validated by histologic analysis. The nodal identification rate in the ICG group significantly surpassed that of the MB group (87.2% vs 52.5%, P < .05) with fewer complications. Note that 10.9% of the patients had metastatic involvement of the ARM-identified nodes. Also 80% of the positive nodes were found in areas B and D, while the ARM-identified nodes mainly located in area A. All the 51 nodes diagnosed as negative of malignancy by FNAC were free of metastasis. Nodal metastasis was significantly correlated with extensive nodel involvement, advanced disease, and the characteristics of identified nodes. In conclusion, ICG appears superior to MB for ARM nodes identification. FNAC, together with the features of primary tumors and ARM nodes, can delineate which nodes could be preserved during ALND.