tbuckley/cabot-search huggingface dataset:
Unnatural Amino‐Acid‐Based Star‐Shaped Poly(<scp>l</scp>‐Ornithine)s as Emerging Long‐Term and Biofilm‐Disrupting Antimicrobial Peptides to Treat <i>Pseudomonas aeruginosa</i>‐Infected Burn Wounds
Authors: Miao Pan, Chao Lu, Maochao Zheng, Wen Zhou, Fuling Song, Weidong Chen, Fen Yao, Daojun Liu, Jianfeng Cai
Journal: Advanced Healthcare Materials (2020)

Abstract Peptide‐based antimicrobial materials are recognized as promising alternatives to antibiotics to circumvent the emergence of antibiotic‐resistant bacteria or to combat multiple resistant bacteria by targeting the bacterial cell membrane. The components and conformations of antimicrobial peptides are extensively explored to achieve broad‐spectrum and effective antimicrobial activity. Here, star‐shaped antimicrobial polypeptides are fabricated by employing homologs of poly( l ‐lysine)s (i.e., poly( l ‐ornithine)s, poly( l ‐lysine)s, and poly( l ‐ α , ζ ‐diaminoheptylic acid)s) with the aim of modulating their charge/hydrophobicity balance and rationalizing their structure–antimicrobial property relationships. The in vitro antibacterial investigation reveals that unnatural amino‐acid‐based star‐shaped poly( l ‐ornithine)s have remarkable proteolytic stability, excellent biofilm‐disrupting capacity, and broad‐spectrum antimicrobial activity, even against difficult‐to‐kill Gram‐negative Pseudomonas aeruginosa . Furthermore, star‐shaped poly( l ‐ornithine)s significantly reduce the microbial burden and improve the burn wound healing of mouse skin infected with P. aeruginosa . These results demonstrate that unnatural amino‐acid‐based star‐shaped poly( l ‐ornithine)s can serve as emerging long‐term and biofilm‐disrupting antimicrobial agents to treat biofilm‐related infections in burn, especially caused by notorious P. aeruginosa .
Covid-19: Government plans to spend £100bn on expanding testing to 10 million a day
Authors: Gareth Iacobucci, Rebecca Coombes
Journal: BMJ (2020)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Covid-19: Government plans to spend £100bn on expanding testing to 10 million a day Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Circular RNA<i> circPPM1F</i> modulates M1 macrophage activation and pancreatic islet inflammation in type 1 diabetes mellitus
Authors: Caiyan Zhang, Xiao Han, Lan Yang, Jinrong Fu, Chengjun Sun, Saihua Huang, Wenfeng Xiao, Yajing Gao, Qiuyan Liang, Xiang Wang, Feihong Luo, Wei Lu, Yufeng Zhou
Journal: Theranostics (2020)

Rationale: Macrophages play critical roles in the pathogenesis of type 1 diabetes mellitus (T1DM). Circular RNAs (circRNAs) are a novel class of endogenous RNAs with covalently closed loop structures, implicated in various disease processes. However, their impact on macrophage activation and T1DM pathogenesis remains elusive. Methods: circRNA expression profiles of peripheral blood mononuclear cells (PBMCs) from T1DM children were determined by whole transcriptome microarray. Bioinformatics, quantitative real-time PCR, Western blot, RNA immunoprecipitation (RIP), cell co-culture, cell proliferation, and cell apoptosis assays were performed to investigate the expression, function, and regulatory mechanisms of circPPM1F in vitro. The regulatory role of circPPM1F in vivo was evaluated in the streptozocin-induced diabetic mouse model. Results: We identified 27 upregulated and 31 downregulated differentially expressed circRNAs in T1DM patients. circPPM1F, a circRNA with unknown function, was dominantly expressed in monocytes and significantly upregulated in T1DM patients. Functionally, circPPM1F promoted lipopolysaccharide (LPS)-induced M1 macrophage activation via enhancement of the NF-κB signaling pathway. Mechanistically, circPPM1F competitively interacted with HuR to impair the translation of protein phosphatase, Mg2+/Mn2+ dependent 1F (PPM1F), thus alleviating the inhibitory effect of PPM1F on the NF-κB pathway. Moreover, eukaryotic initiation factor 4A-III (EIF4A3) and fused in sarcoma (FUS) coordinately regulated circPPM1F expression during M1 macrophage activation. In addition, circPPM1F could exacerbate pancreas injury in the streptozocin-induced diabetic mice by activation of M1 macrophages in vivo. Conclusions:circPPM1F is a novel positive regulator of M1 macrophage activation through the circPPM1F-HuR-PPM1F-NF-κB axis. Overexpression of circPPM1F could promote pancreatic islet injury by enhancing M1 macrophage activation and circPPM1F may serve as a novel potential therapeutic target for T1DM in children.
Author Correction: High-protein diets increase cardiovascular risk by activating macrophage mTOR to suppress mitophagy
Authors: Xiangyu Zhang, Ismail Sergin, Trent D. Evans, Se-Jin Jeong, Astrid Rodriguez-Velez, Divya Kapoor, Sunny Chen, Eric Song, Karyn B. Holloway, Jan R. Crowley, Slava Epelman, Conrad C. Weihl, Abhinav Diwan, Daping Fan, Bettina Mittendorfer, Nathan O. Stitziel, Joel D. Schilling, Irfan J. Lodhi, Babak Razani
Journal: Nature Metabolism (2020)
Triheptanoin: First Approval
Authors: Matt Shirley
Journal: Drugs (2020)

Triheptanoin (Dojolvi™), a synthetic medium-chain triglyceride, is being developed by Ultragenyx Pharmaceutical as a pharmaceutical-grade anaplerotic compound for use in the treatment of inherited metabolic disorders. In June 2020, triheptanoin received its first regulatory approval, in the USA, for use as a source of calories and fatty acids for the treatment of pediatric and adult patients with molecularly confirmed long-chain fatty acid oxidation disorders (LC-FAOD). Triheptanoin has also been investigated for use as a treatment in a range of other metabolic disorders or other diseases where energy deficiency is implicated. This article summarizes the milestones in the development of triheptanoin leading to this first regulatory approval for use in the treatment of pediatric and adult patients with LC-FAOD.
Peritumoral Radiomics and Predicting Treatment Response
Authors: Ruijiang Li
Journal: JAMA Network Open (2020)

Yihuai Hu, MD; Chenyi Xie, MD; Hong Yang, MD, PhD; Joshua W. K. Ho, PhD; Jing Wen, MD, PhD; Lujun Han, MD, PhD; Keith W. H. Chiu, MBChB; Jianhua Fu, MD, PhD; Varut Vardhanabhuti, MBBS, PhD
Correspondence on ‘Lung involvement in macrophage activation syndrome and severe COVID-19: results from a cross-sectional study to assess clinical, laboratory and artificial intelligence–radiological differences’ by Ruscitti<i>et al</i>
Authors: Acer I-Hung Chen, Sheng-Chieh Lin, James Cheng-Chung Wei
Journal: Annals of the Rheumatic Diseases (2020)

<h3>Objective:</h3> To test whether plasma tau is altered in Alzheimer disease (AD) and whether it is related to changes in cognition, CSF biomarkers of AD pathology (including β-amyloid [Aβ] and tau), brain atrophy, and brain metabolism. <h3>Methods:</h3> This was a study of plasma tau in prospectively followed patients with AD (n = 179), patients with mild cognitive impairment (n = 195), and cognitive healthy controls (n = 189) from the Alzheimer9s Disease Neuroimaging Initiative (ADNI) and cross-sectionally studied patients with AD (n = 61), mild cognitive impairment (n = 212), and subjective cognitive decline (n = 174) and controls (n = 274) from the Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably (BioFINDER) study at Lund University, Sweden. A total of 1284 participants were studied. Associations were tested between plasma tau and diagnosis, CSF biomarkers, MRI measures, <sup>18</sup>fluorodeoxyglucose-PET, and cognition. <h3>Results:</h3> Higher plasma tau was associated with AD dementia, higher CSF tau, and lower CSF Aβ<sub>42</sub>, but the correlations were weak and differed between ADNI and BioFINDER. Longitudinal analysis in ADNI showed significant associations between plasma tau and worse cognition, more atrophy, and more hypometabolism during follow-up. <h3>Conclusions:</h3> Plasma tau partly reflects AD pathology, but the overlap between normal aging and AD is large, especially in patients without dementia. Despite group-level differences, these results do not support plasma tau as an AD biomarker in individual people. Future studies may test longitudinal plasma tau measurements in AD.
Efficacy and safety of first-line avelumab in patients with advanced non-small cell lung cancer: results from a phase Ib cohort of the JAVELIN Solid Tumor study
Authors: Claire F Verschraegen, Guy Jerusalem, Edward F McClay, Nicholas Iannotti, Charles H Redfern, Jaafar Bennouna, Franklin L Chen, Karen Kelly, Janice Mehnert, John C Morris, Matthew Taylor, David Spigel, Ding Wang, Hans Juergen Grote, Dongli Zhou, Neru Munshi, Marcis Bajars, James L Gulley
Journal: Journal for ImmunoTherapy of Cancer (2020)

Introduction Avelumab, an antiprogrammed death ligand-1 antibody, is approved as a monotherapy for treatment of metastatic Merkel cell carcinoma and advanced urothelial carcinoma, and in combination with axitinib for advanced renal cell carcinoma. We report the efficacy and safety of first-line avelumab in advanced non-small cell lung cancer (NSCLC). Methods In a phase I expansion cohort of the JAVELIN Solid Tumor trial, patients with treatment-naive, metastatic, or recurrent NSCLC received 10 mg/kg avelumab intravenously every 2 weeks. Endpoints included best overall response, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Results Overall, 156 patients were enrolled and treated. Median duration of follow-up was 18.6 months (range, 15 to 23 months). The objective response rate was 19.9% (95% CI, 13.9 to 27.0), including complete response in 3 (1.9%) and partial response in 28 (17.9%). Median DOR was 12.0 months (95% CI, 6.9 to not estimable). Median PFS was 4.0 months (95% CI, 2.7 to 5.4) and the 6-month PFS rate was 38.5% (95% CI, 30.7 to 46.3). Median OS was 14.1 months (95% CI, 11.3 to 16.9) and the 12-month OS rate was 56.6% (95% CI, 48.2 to 64.1). Treatment-related adverse events (TRAEs) occurred in 107 patients (68.6%), including grade ≥3 TRAEs in 19 (12.2%). Immune-related adverse events and infusion-related reactions occurred in 31 (19.9%) and 40 patients (25.6%), respectively. No treatment-related deaths occurred. Conclusion Avelumab showed antitumor activity with a tolerable safety profile as a first-line treatment in patients with advanced NSCLC. These data support further investigation of avelumab in the phase III JAVELIN Lung 100 study. Trial registration details ClinicalTrials.gov NCT01772004 ; registered January 21, 2013.
Quantifying national responsibility for climate breakdown: an equality-based attribution approach for carbon dioxide emissions in excess of the planetary boundary
Authors: Jason Hickel
Journal: The Lancet Planetary Health (2020)

BackgroundThis analysis proposes a novel method for quantifying national responsibility for damages related to climate change by looking at national contributions to cumulative CO2 emissions in excess of the planetary boundary of 350 ppm atmospheric CO2 concentration. This approach is rooted in the principle of equal per capita access to atmospheric commons.MethodsFor this analysis, national fair shares of a safe global carbon budget consistent with the planetary boundary of 350 ppm were derived. These fair shares were then subtracted from countries' actual historical emissions (territorial emissions from 1850 to 1969, and consumption-based emissions from 1970 to 2015) to determine the extent to which each country has overshot or undershot its fair share. Through this approach, each country's share of responsibility for global emissions in excess of the planetary boundary was calculated.FindingsAs of 2015, the USA was responsible for 40% of excess global CO2 emissions. The European Union (EU-28) was responsible for 29%. The G8 nations (the USA, EU-28, Russia, Japan, and Canada) were together responsible for 85%. Countries classified by the UN Framework Convention on Climate Change as Annex I nations (ie, most industrialised countries) were responsible for 90% of excess emissions. The Global North was responsible for 92%. By contrast, most countries in the Global South were within their boundary fair shares, including India and China (although China will overshoot soon).InterpretationThese figures indicate that high-income countries have a greater degree of responsibility for climate damages than previous methods have implied. These results offer a just framework for attributing national responsibility for excess emissions, and a guide for determining national liability for damages related to climate change, consistent with the principles of planetary boundaries and equal access to atmospheric commons.FundingNone.
Association of Immunotherapy With Survival Among Patients With Brain Metastases Whose Cancer Was Managed With Definitive Surgery of the Primary Tumor
Authors: Saber Amin, Michael J. Baine, Jane L. Meza, Chi Lin
Journal: JAMA Network Open (2020)

Immunotherapy has shown significant control of intracranial metastases in patients with melanoma. However, the association of immunotherapy combined with other cancer treatments and overall survival (OS) of patients with brain metastases, regardless of primary tumor site, is unknown.To explore the association of immunotherapy with OS in patients with cancer and brain metastases who received definitive surgery of the primary site.This comparative effectiveness study included 3112 adult patients in the National Cancer Database from 2010 to 2016 with non-small cell lung cancer, breast cancer, melanoma, colorectal cancer, or kidney cancer and brain metastases at the time of diagnosis and who received definitive surgery of the primary site. Data analysis was conducted from March to April 2020.Treatment groups were stratified as follows: (1) any treatment with or without immunotherapy, (2) chemotherapy with or without immunotherapy, (3) radiotherapy (RT) with or without immunotherapy, and (4) chemoradiation with or without immunotherapy.The association of immunotherapy with OS was assessed with Cox proportional hazards regression, adjusted for age at diagnosis, race, sex, place of living, income, education, treatment facility type, primary tumor type, and year of diagnosis.Of 3112 patients, 1436 (46.14%) were men, 2714 (87.72%) were White individuals, 257 (8.31%) were Black individuals, and 123 (3.98%) belonged to other racial and ethnic groups. The median (range) age at diagnosis was 61 (19-90) years. Overall, 183 (5.88%) received immunotherapy, 318 (10.22%) received chemotherapy alone, 788 (25.32%) received RT alone, and 1393 (44.76%) received chemoradiation alone; 22 (6.47%) received chemotherapy plus immunotherapy, 72 (8.37%) received RT plus immunotherapy, and 76 (5.17%) received chemoradiation plus immunotherapy. In the multivariable analysis, patients who received immunotherapy had significantly improved OS compared with no immunotherapy (hazard ratio, 0.62; 95% CI, 0.51-0.76; P < .001). Treatment with RT plus immunotherapy was associated with significantly improved OS compared with RT alone (hazard ratio, 0.59; 95% CI, 0.42-0.84; P = .003). Chemotherapy plus immunotherapy or chemoradiation plus immunotherapy were not associated with improved OS in the multivariable analysis.In this study, the addition of immunotherapy to RT was associated with improved OS compared with radiotherapy alone in patients with brain metastases who received definitive surgery of the primary tumor site.
Sociodemographic Disparities in Influenza Vaccination Among Adults With Atherosclerotic Cardiovascular Disease in the United States
Authors: Gowtham R. Grandhi, Reed Mszar, Farhaan Vahidy, Javier Valero-Elizondo, Ron Blankstein, Michael J. Blaha, Salim S. Virani, Julia D. Andrieni, Saad B. Omer, Khurram Nasir
Journal: JAMA Cardiology (2020)

Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of death and disability in the US and worldwide. Influenza vaccination has shown to decrease overall morbidity, mortality, severity of infection, and hospital readmissions among these individuals. However, national estimates of influenza vaccination among individuals with ASCVD in the US are not well studied.To evaluate the prevalence of and sociodemographic disparities in influenza vaccination among a nationally representative sample of individuals with ASCVD.Pooled Medical Expenditure Panel Survey data from 2008 to 2016 were used and included adults 40 years or older with ASCVD. Participants' ASCVD status was ascertained via self-report and/or International Classification of Diseases, Ninth Revision diagnosis of coronary heart disease, peripheral artery disease, and/or cerebrovascular disease. Analysis began April 2020.Prevalence and characteristics of adults with ASCVD who lacked influenza vaccination during the past year. Covariates including age, sex, race/ethnicity, family income, insurance status, education level, and usual source of care were assessed.Of 131 881 adults, 19 793 (15.7%) had ASCVD, corresponding to 22.8 million US adults annually. A total of 7028 adults with ASCVD (32.7%), representing 7.4 million adults, lacked influenza vaccination. The highest odds of lacking vaccination were observed among individuals aged 40 to 64 years (odds ratio [OR], 2.32; 95% CI, 2.06-2.62), without a usual source of care (OR, 2.00; 95% CI, 1.71-2.33), without insurance (OR, 2.05; 95% CI, 1.63-2.58), with a lower education level (OR, 1. 25; 95% CI, 1.12-1.40), with a lower income level (OR, 1.14; 95% CI, 1.01-1.27), and of non-Hispanic Black race/ethnicity (OR, 1.24, 95% CI, 1.10-1.41). A stepwise increase was found in the prevalence and odds of lacking influenza vaccination among individuals with increase in high-risk characteristics. Overall, 1171 individuals (59.7%; 95% CI, 55.8%-63.5%) with 4 or more high-risk characteristics and ASCVD (representing 732 524 US adults annually) reported lack of influenza vaccination (OR, 6.06; 95% CI, 4.88-7.53).Despite current recommendations, a large proportion of US adults with established ASCVD lack influenza vaccination, with several sociodemographic subgroups having greater risk. Focused public health initiatives are needed to increase access to influenza vaccinations for high-risk and underserved populations.
Cystinuria: clinical practice recommendation
Authors: Aude Servais, Kay Thomas, Luca Dello Strologo, John A. Sayer, Soumeya Bekri, Aurelia Bertholet-Thomas, Matthew Bultitude, Giovanna Capolongo, Rimante Cerkauskiene, Michel Daudon, Steeve Doizi, Valentine Gillion, Silvia Gràcia-Garcia, Jan Halbritter, Laurence Heidet, Marleen van den Heijkant, Sandrine Lemoine, Bertrand Knebelmann, Francesco Emma, Elena Levtchenko
Journal: Kidney International (2020)
Erratum to “Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up”
Authors: F. Cardoso, S. Kyriakides, S. Ohno, F. Penault-Llorca, P. Poortmans, I.T. Rubio, S. Zackrisson, E. Senkus
Journal: Annals of Oncology (2020)
Troubleshooting a Transcutaneous Pacemaker
Authors: Emily R. Cedarbaum, Rohit Mital, Nora Goldschlager
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
Inhibition of bacterial adhesion and biofilm formation by a textured fluorinated alkoxyphosphazene surface
Authors: Meixian Tang, Chen Chen, Jieru Zhu, Harry R. Allcock, Christopher A. Siedlecki, Li-Chong Xu
Journal: Bioactive Materials (2020)

The utilization of biomaterials in implanted blood-contacting medical devices often induces a persistent problem of microbial infection, which results from bacterial adhesion and biofilm formation on the surface of biomaterials. In this research, we developed new fluorinated alkoxyphosphazene materials, specifically poly[bis(octafluoropentoxy) phosphazene] (OFP) and crosslinkable OFP (X–OFP), with improved mechanical properties, and further modified the surface topography with ordered pillars to improve the antibacterial properties. Three X–OFP materials, X–OFP3.3, X–OFP8.1, X–OFP13.6, with different crosslinking densities were synthesized, and textured films with patterns of 500/500/600 nm (diameter/spacing/height) were fabricated via a two stage soft lithography molding process. Experiments with 3 bacterial strains: Staphylococcal epidermidis, Staphylococcal aureus, and Pseudomonas aeruginosa showed that bacterial adhesion coefficients were significantly lower on OFP and X–OFP smooth surfaces than on the polyurethane biomaterial, and surface texturing further reduced bacterial adhesion due to the reduction in accessible surface contact area. Furthermore the anti-bacterial adhesion effect shows a positive relationship with the crosslinking degree. Biofilm formation on the substrates was examined using a CDC biofilm reactor for 7 days and no biofilm formation was observed on textured X–OFP biomaterials. The results suggested that the combination of fluorocarbon chemistry and submicron topography modification in textured X–OFP materials may provide a practical approach to improve the biocompatibility of current biomaterials with significant reduction in risk of pathogenic infection.