tbuckley/cabot-search huggingface dataset:
Pentraxin‐3 modulates lipopolysaccharide‐induced inflammatory response and attenuates liver injury
Authors: Luis Perea, Mar Coll, Lucia Sanjurjo, Delia Blaya, Adil El Taghdouini, Daniel Rodrigo‐Torres, José Altamirano, Isabel Graupera, Beatriz Aguilar‐Bravo, Marta Llopis, Julia Vallverdú, Joan Caballeria, Leo A. van Grunsven, Maria‐Rosa Sarrias, Pere Ginès, Pau Sancho‐Bru
Journal: Hepatology (2017)

Acute‐on‐chronic liver injury is characterized by an important inflammatory response frequently associated with endotoxemia. In this context, acute‐phase proteins such as Pentraxin‐3 (PTX3) are released; however, little is known about their role in chronic liver disease. The aim of this study was to elucidate the role of PTX3 in liver injury. The role of PTX3 was evaluated in cultured human cells, liver tissue slices, and mice with acute‐on‐chronic liver injury. PTX3 expression was assessed in tissue and serum samples from 54 patients with alcoholic hepatitis. PTX3 expression was up‐regulated in animal models of liver injury and strongly induced by lipopolysaccharide (LPS). Liver cell fractionation showed that macrophages and activated hepatic stellate cells were the main cell types expressing PTX3 in liver injury. Ex vivo and in vivo studies showed that PTX3 treatment attenuated LPS‐induced liver injury, inflammation, and cell recruitment. Mechanistically, PTX3 mediated the hepatic stellate cell wound‐healing response. Moreover, PTX3 modulated LPS‐induced inflammation in human primary liver macrophages and peripheral monocytes by enhancing a TIR domain–containing adapter‐inducing interferon–dependent response and favoring a macrophage interleukin‐10‐like phenotype. Additionally, hepatic and plasma PTX3 levels were increased in patients with alcoholic hepatitis, a prototypic acute‐on‐chronic condition; and its expression correlated with disease severity scores, endotoxemia, infections, and short‐term mortality, thus suggesting that expression of PTX3 found in patients could be a counterregulatory response to injury. Conclusion : Experimental and human evidence suggests that, in addition to being a potential biomarker for alcoholic hepatitis, PTX3 participates in the wound‐healing response and attenuates LPS‐induced liver injury and inflammation; therefore, administration of PTX3 could be a promising therapeutic strategy in acute‐on‐chronic conditions, particularly those associated with endotoxemia. (H epatology 2017;66:953–968).
Charlie Gard and the Limits of the Harm Principle—Reply
Authors: Seema K. Shah, Abby R. Rosenberg, Douglas S. Diekema
Journal: JAMA Pediatrics (2018)

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 Pediatrics 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 Pediatrics journal
CAR-T Cells Targeting BAFF-Receptor for B-Cell Malignancies: A Potential Alternative to CD19
Authors: Hong Qin, Zhenyuan Dong, Fen Wen, Wesley Cheng, Han Sun, Guowei Wei, Diane Lynne Smith, Sattva S. Neelapu, Xiuli Wang, Stephen J. Forman, Larry W Kwak
Journal: Blood (2017)
Nitric Oxide Dependent Degradation of Polyethylene Glycol‐Modified Single‐Walled Carbon Nanotubes: Implications for Intra‐Articular Delivery
Authors: Kunal Bhattacharya, Cristiano Sacchetti, Pedro M. Costa, Jens Sommertune, Birgit D. Brandner, Andrea Magrini, Nicola Rosato, Nunzio Bottini, Massimo Bottini, Bengt Fadeel
Journal: Advanced Healthcare Materials (2018)

Abstract Polyethylene glycol (PEG)‐modified carbon nanotubes have been successfully employed for intra‐articular delivery in mice without systemic or local toxicity. However, the fate of the delivery system itself remains to be understood. In this study 2 kDa PEG‐modified single‐walled carbon nanotubes (PNTs) are synthesized, and trafficking and degradation following intra‐articular injection into the knee‐joint of healthy mice are studied. Using confocal Raman microspectroscopy, PNTs can be imaged in the knee‐joint and are found to either egress from the synovial cavity or undergo biodegradation over a period of 3 weeks. Raman analysis discloses that PNTs are oxidatively degraded mainly in the chondrocyte‐rich cartilage and meniscus regions while PNTs can also be detected in the synovial membrane regions, where macrophages can be found. Furthermore, using murine chondrocyte (ATDC‐5) and macrophage (RAW264.7) cell lines, biodegradation of PNTs in activated, nitric oxide (NO)‐producing chondrocytes, which is blocked upon pharmacological inhibition of inducible nitric oxide synthase (iNOS), can be shown. Biodegradation of PNTs in macrophages is also noted, but after a longer period of incubation. Finally, cell‐free degradation of PNTs upon incubation with the peroxynitrite‐generating compound, SIN‐1 is demonstrated. The present study paves the way for the use of PNTs as delivery systems in the treatment of diseases of the joint.
Axillary vs Sentinel Lymph Node Dissection in Women With Invasive Breast Cancer
Authors: Hajime Uno, Michael J. Hassett, Lee-Jen Wei
Journal: JAMA (2018)

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
MSCT,経食道エコー,MRIを用いた心アミロイドーシスの画像診断
Authors: 金枝朋宜, 野島愛佳, 宮内秀行, 三上陽子, 関根有希子, 椎名由美, 李光浩, 上原雅恵, 鳴海浩也, 小林欣夫, 高野博之, 船橋伸禎, 小室一成
Journal: Circulation (2008)
Worsening Renal Function in Patients With Acute Heart Failure Undergoing Aggressive Diuresis Is Not Associated With Tubular Injury
Authors: Tariq Ahmad, Keyanna Jackson, Veena S. Rao, W.H. Wilson Tang, Meredith A. Brisco-Bacik, Horng H. Chen, G. Michael Felker, Adrian F. Hernandez, Christopher M. O’Connor, Venkata S. Sabbisetti, Joseph V. Bonventre, F. Perry Wilson, Steven G. Coca, Jeffrey M. Testani
Journal: Circulation (2018)

Background: Worsening renal function (WRF) in the setting of aggressive diuresis for acute heart failure treatment may reflect renal tubular injury or simply indicate a hemodynamic or functional change in glomerular filtration. Well-validated tubular injury biomarkers, N -acetyl-β- d -glucosaminidase, neutrophil gelatinase-associated lipocalin, and kidney injury molecule 1, are now available that can quantify the degree of renal tubular injury. The ROSE-AHF trial (Renal Optimization Strategies Evaluation–Acute Heart Failure) provides an experimental platform for the study of mechanisms of WRF during aggressive diuresis for acute heart failure because the ROSE-AHF protocol dictated high-dose loop diuretic therapy in all patients. We sought to determine whether tubular injury biomarkers are associated with WRF in the setting of aggressive diuresis and its association with prognosis. Methods: Patients in the multicenter ROSE-AHF trial with baseline and 72-hour urine tubular injury biomarkers were analyzed (n=283). WRF was defined as a ≥20% decrease in glomerular filtration rate estimated with cystatin C. Results: Consistent with protocol-driven aggressive dosing of loop diuretics, participants received a median 560 mg IV furosemide equivalents (interquartile range, 300–815 mg), which induced a urine output of 8425 mL (interquartile range, 6341–10 528 mL) over the 72-hour intervention period. Levels of N -acetyl-β- d -glucosaminidase and kidney injury molecule 1 did not change with aggressive diuresis (both P &gt;0.59), whereas levels of neutrophil gelatinase-associated lipocalin decreased slightly (−8.7 ng/mg; interquartile range, −169 to 35 ng/mg; P &lt;0.001). WRF occurred in 21.2% of the population and was not associated with an increase in any marker of renal tubular injury: neutrophil gelatinase-associated lipocalin ( P =0.21), N -acetyl-β- d -glucosaminidase ( P =0.46), or kidney injury molecule 1 ( P =0.22). Increases in neutrophil gelatinase-associated lipocalin, N -acetyl-β- d -glucosaminidase, and kidney injury molecule 1 were paradoxically associated with improved survival (adjusted hazard ratio, 0.80 per 10 percentile increase; 95% confidence interval, 0.69–0.91; P =0.001). Conclusions: Kidney tubular injury does not appear to have an association with WRF in the context of aggressive diuresis of patients with acute heart failure. These findings reinforce the notion that the small to moderate deteriorations in renal function commonly encountered with aggressive diuresis are dissimilar from traditional causes of acute kidney injury.
Detection of early neoplasia in Barrett’s esophagus using lectin-based near-infrared imaging: an ex vivo study on human tissue
Authors: André Neves, Massimiliano Di Pietro, Maria O’Donovan, Dale Waterhouse, Sarah Bohndiek, Kevin Brindle, Rebecca Fitzgerald
Journal: Endoscopy (2018)

Abstract Background and study aims Endoscopic surveillance for Barrett’s esophagus (BE) is limited by long procedure times and sampling error. Near-infrared (NIR) fluorescence imaging minimizes tissue autofluorescence and optical scattering. We assessed the feasibility of a topically applied NIR dye-labeled lectin for the detection of early neoplasia in BE in an ex vivo setting. Methods Consecutive patients undergoing endoscopic mucosal resection (EMR) for BE-related early neoplasia were recruited. Freshly collected EMR specimens were sprayed at the bedside with fluorescent lectin and then imaged. Punch biopsies were collected from each EMR under NIR light guidance. We compared the fluorescence intensity from dysplastic and nondysplastic areas within EMRs and from punch biopsies with different histological grades. Results 29 EMR specimens were included from 17 patients. A significantly lower fluorescence was found for dysplastic regions across whole EMR specimens (P &lt; 0.001). We found a 41 % reduction in the fluorescence of dysplastic compared to nondysplastic punch biopsies (P &lt; 0.001), with a sensitivity and specificity for dysplasia detection of 80 % and 82.9 %, respectively. Conclusion Lectin-based NIR imaging can differentiate dysplastic from nondysplastic Barrett’s mucosa ex vivo.
The views of children and young people on the use of silk garments for the treatment of eczema: a nested qualitative study within the <scp>CLOTH</scp> ing for the relief of Eczema Symptoms ( <scp>CLOTHES</scp> ) randomized controlled trial
Authors: E.V. Wake, J. Batchelor, S. Lawton, K.S. Thomas, E.F. Harrison, F.C. Cowdell, Hywel Williams, Jo Llewellyn, Taraneh Dean, Jane Grundy, Ian Pollock, Juliet Guinness, Nigel Burrows, Clare Crang, Andrew Gribbin, Lelia Duley, Lucy Bradshaw, Eleanor Mitchell, Andrew Jadowski, Jennifer White, Sarah Walker, Tessa Clarke, Trish Hepburn, Justin Fenty, Lucinda Murphy, Daniel Simpkins, Chris Rumsey, Hannah Buckley, Sharon McCready, Rachel Watson, Gill Glasbey, Rachel Harding, Jo Aspland, Tracey Sach, Amina Ahmed
Journal: British Journal of Dermatology (2017)

Many children suffer with skin diseases but to date most dermatological research has been done 'on' rather than 'with' children; in this study we actively sought the experiences of children and young people. Atopic eczema (AE) is a chronic, itchy, inflammatory skin condition that affects around 20% of children and can impact on the health and wellbeing of children and their families. The role of specialist clothing in the management of AE is poorly understood. The aim of this study, which was nested in a randomized controlled trial, was to qualitatively examine child participants' experiences of using silk garments for the treatment of AE. Eighteen children aged 5–15 years, who took part in the CLOTHing for the relief of Eczema Symptoms (CLOTHES) trial, participated in age‐appropriate individual interviews or focus groups. Thematic analysis generated four themes directly related to the silk garments: (i) expectations of the garments; (ii) wearing the garments; (iii) asking if the garments helped; and (iv) thoughts about the garments. The conclusions from this nested qualitative study are that there was some limited improvement in eczema for some children but that the hoped‐for 'miracle cure' did not transpire. A mixed picture of knowledge, beliefs and experiences of using the silk garments emerged. Engaging children in the evaluation of the garments provided first‐hand nuanced insights that enhanced understanding of the CLOTHES study as a whole. This nested study demonstrates that children can and indeed want to be engaged in dermatological research in meaningful ways that add to our understanding of treatment options.
New tools for old drugs: Functional genetic screens to optimize current chemotherapy
Authors: Nora M. Gerhards, Sven Rottenberg
Journal: Drug Resistance Updates (2018)

Despite substantial advances in the treatment of various cancers, many patients still receive anti-cancer therapies that hardly eradicate tumor cells but inflict considerable side effects. To provide the best treatment regimen for an individual patient, a major goal in molecular oncology is to identify predictive markers for a personalized therapeutic strategy. Regarding novel targeted anti-cancer therapies, there are usually good markers available. Unfortunately, however, targeted therapies alone often result in rather short remissions and little cytotoxic effect on the cancer cells. Therefore, classical chemotherapy with frequent long remissions, cures, and a clear effect on cancer cell eradication remains a corner stone in current anti-cancer therapy. Reliable biomarkers which predict the response of tumors to classical chemotherapy are rare, in contrast to the situation for targeted therapy. For the bulk of cytotoxic therapeutic agents, including DNA-damaging drugs, drugs targeting microtubules or antimetabolites, there are still no reliable biomarkers used in the clinic to predict tumor response. To make progress in this direction, meticulous studies of classical chemotherapeutic drug action and resistance mechanisms are required. For this purpose, novel functional screening technologies have emerged as successful technologies to study chemotherapeutic drug response in a variety of models. They allow a systematic analysis of genetic contributions to a drug-responsive or -sensitive phenotype and facilitate a better understanding of the mode of action of these drugs. These functional genomic approaches are not only useful for the development of novel targeted anti-cancer drugs but may also guide the use of classical chemotherapeutic drugs by deciphering novel mechanisms influencing a tumor's drug response. Moreover, due to the advances of 3D organoid cultures from patient tumors and in vivo screens in mice, these genetic screens can be applied using conditions that are more representative of the clinical setting. Patient-derived 3D organoid lines furthermore allow the characterization of the "essentialome", the specific set of genes required for survival of these cells, of an individual tumor, which could be monitored over the course of treatment and help understanding how drug resistance evolves in clinical tumors. Thus, we expect that these functional screens will enable the discovery of novel cancer-specific vulnerabilities, and through clinical validation, move the field of predictive biomarkers forward. This review focuses on novel advanced techniques to decipher the interplay between genetic alterations and drug response.
Environmental Influences on the Epigenome: Exposure- Associated DNA Methylation in Human Populations
Authors: Elizabeth M. Martin, Rebecca C. Fry
Journal: Annual Review of Public Health (2018)

DNA methylation is the most well studied of the epigenetic regulators in relation to environmental exposures. To date, numerous studies have detailed the manner by which DNA methylation is influenced by the environment, resulting in altered global and gene-specific DNA methylation. These studies have focused on prenatal, early-life, and adult exposure scenarios. The present review summarizes currently available literature that demonstrates a relationship between DNA methylation and environmental exposures. It includes studies on aflatoxin B1, air pollution, arsenic, bisphenol A, cadmium, chromium, lead, mercury, polycyclic aromatic hydrocarbons, persistent organic pollutants, tobacco smoke, and nutritional factors. It also addresses gaps in the literature and future directions for research. These gaps include studies of mixtures, sexual dimorphisms with respect to environmentally associated methylation changes, tissue specificity, and temporal stability of the methylation marks.
Decrease in early basophil sensitivity to Ara h 2 correlates with sustained unresponsiveness in peanut oral immunotherapy
Authors: Colby P. Rondeau, Agustin Calatroni, Neal Smith, Huong Tang, Yamini V. Virkud, Bert Ruiter, Wayne G. Shreffler, Sarita U. Patil
Journal: Journal of Allergy and Clinical Immunology (2018)
Addendum: Deep brain stimulation restores frontostriatal network activity in obsessive-compulsive disorder
Authors: Martijn Figee, Judy Luigjes, Ruud Smolders, Carlos-Eduardo Valencia-Alfonso, Guido van Wingen, Bart de Kwaasteniet, Mariska Mantione, Pieter Ooms, Pelle de Koning, Nienke Vulink, Nina Levar, Lukas Droge, Pepijn van den Munckhof, P Richard Schuurman, Aart Nederveen, Wim van den Brink, Ali Mazaheri, Matthijs Vink, Damiaan Denys
Journal: Nature Neuroscience (2014)
Lack of Benefit With Idalopirdine for Alzheimer Disease
Authors: David A. Bennett
Journal: JAMA (2018)

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
Meta-Analysis of Complex Interventions
Authors: Emily E. Tanner-Smith, Sean Grant
Journal: Annual Review of Public Health (2018)

Meta-analysis is a prominent method for estimating the effects of public health interventions, yet these interventions are often complex in ways that pose challenges to using conventional meta-analytic methods. This article discusses meta-analytic techniques that can be used in research syntheses on the effects of complex public health interventions. We first introduce the use of complexity frameworks to conceptualize public health interventions. We then present a menu of meta-analytic procedures for addressing various sources of complexity when answering questions about the effects of public health interventions in research syntheses. We conclude with a review of important practices and key resources for conducting meta-analyses on complex interventions, as well as future directions for research synthesis more generally. Overall, we argue that it is possible to conduct meaningful quantitative syntheses of research on the effects of public health interventions, though these meta-analyses may require the use of advanced techniques to properly consider and attend to issues of complexity.
Osimertinib as First-Line Treatment in <i>EGFR</i>-Mutated Non–Small-Cell Lung Cancer
Authors: Sanjay Popat
Journal: New England Journal of Medicine (2018)

Genetic analysis is now routine in metastatic non–small-cell lung cancer (NSCLC) to identify somatic sensitizing mutations in EGFR, typically L858R and exon 19 deletion (Ex19del). Patients with these genotypes are treated with first- or second-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) (e.g., erlotinib, gefitinib, and afatinib) preferentially over chemotherapy owing to their marked superiority in tumor response, progression-free survival, and quality of life. Such molecular selection has seen median overall survival increase among patients with such genetic variants, from a median of 7.9 months in 20021 to 27.3 months in 2015.2 However, despite rapid and durable responses, acquired . . .