tbuckley/cabot-search huggingface dataset:
An optimized lentiviral vector system for conditional RNAi and efficient cloning of microRNA embedded short hairpin RNA libraries
Authors: Felix F. Adams, Dirk Heckl, Thomas Hoffmann, Steven R. Talbot, Arnold Kloos, Felicitas Thol, Michael Heuser, Johannes Zuber, Axel Schambach, Adrian Schwarzer
Journal: Biomaterials (2017)
Wet‐AMD on a Chip: Modeling Outer Blood‐Retinal Barrier In Vitro
Authors: Minhwan Chung, Somin Lee, Byung Joo Lee, Kyungmin Son, Noo Li Jeon, Jeong Hun Kim
Journal: Advanced Healthcare Materials (2017)

Choroidal neovascularization (CNV) in the retinal pigment epithelium (RPE)-choroid complex constituting outer blood retinal barrier (oBRB) is a critical pathological step in various ophthalmic diseases, which results in blindness, such as wet type age-related macula degeneration. Current in vitro experimental models using petri dishes or transwell are unable to study CNV morphogenesis. Here, a unique organotypic eye-on-a-chip model is described that mimics the RPE-choroid complex in vitro. This model consists of an RPE monolayer and adjacent perfusable blood vessel network, which is supporting barrier function of oBRB. The intact barrier function of the RPE-choroid complex is reconstituted while maintaining important structural features. Further, this model can successfully mimic the pathogenesis of CNV especially in terms of morphogenesis, which is penetrating angiogenic sprouts from pre-existing choroidal vessels that result in breakdown of RPE monolayer. The alleviation of the pathological angiogenesis can be modeled with bevacizumab, a clinical drug for CNV treatment. It is believed that this model can be used to aid in the development of advanced in vitro eye drug evaluation in conjunction with animal models.
Reply:
Authors: Anna S.F. Lok
Journal: Hepatology (2006)

We are delighted that Lackner et al. provided external validation for our two models for predicting cirrhosis among patients with hepatitis C. Platelet count carried the most weight in both of these models; therefore, it is not surprising that Lackner et al. found that accuracy of platelet count alone approximated the more complex models. Our experience with both treatment-naïve patients and nonresponders with advanced liver disease indicate that platelet count alone was not as accurate as APRI or model 3, because some patients who had histological cirrhosis had normal platelet count, whereas other patients with low platelet count did not have cirrhosis on biopsy. We agree that an ideal model should perform equally well in predicting and excluding cirrhosis, but the latter itself has clinical relevance as indicated by Lackner et al. Anna S.F. Lok*, * University of Michigan, Ann Arbor, MI.
COPD and bronchodilators: should the heart pay the bill for the lung?
Authors: Nera Agabiti, Giuseppe Maria Corbo
Journal: European Respiratory Journal (2017)

The pharmacological treatment of patients with coexisting cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD) is challenging, because some drugs for COPD patients should be used with caution in patients with CVD, and vice versa . The crucial question on cardiovascular safety of long-acting bronchodilators, i.e. long-acting β2-agonists (LABAs) and long-acting anti-muscarinic agents (LAMAs, principally tiotropium), has no definitive answer. Because of different mechanisms of action, the combination of these drugs is expected to be more effective than the individual components in the maintenance treatment of COPD [1]. Evidence available from randomised controlled trails and observational studies on increased risk of cardiovascular adverse events is large but difficult to summarise because of complex methodology, different comparison groups and potential bias in each study [2–5]. Results are controversial and inconclusive. The risks of combining LABAs and tiotropium for the treatment of COPD are still unclear. Whether COPD patients treated with long-acting bronchodilators have increased risk of heart failure, or patients with both COPD and heart failure have higher risk of adverse events, remain open questions. Treatment with bronchodilators in COPD patients should take into account cardiovascular comorbidities <http://ow.ly/gMIG30aAwTK>
Absolute values of lung function explain the sex difference in breathlessness in the general population
Authors: Magnus Ekström, Linus Schiöler, Rune Grønseth, Ane Johannessen, Cecilie Svanes, Benedicte Leynaert, Deborah Jarvis, Thorarinn Gislason, Pascal Demoly, Nicole Probst-Hensch, Isabelle Pin, Angelo G. Corsico, Bertil Forsberg, Joachim Heinrich, Dennis Nowak, Chantal Raherison-Semjen, Shyamali C. Dharmage, Giulia Trucco, Isabel Urrutia, Jesús Martinez-Moratalla Rovira, José Luis Sánchez-Ramos, Christer Janson, Kjell Torén
Journal: European Respiratory Journal (2017)

Activity-related breathlessness is twice as common among females as males in the general population and is associated with adverse health outcomes. We tested whether this sex difference is explained by the lower absolute forced expiratory volume in 1 s (FEV 1 ) or forced vital capacity (FVC) in females. This was a cross-sectional analysis of 3250 subjects (51% female) aged 38−67 years across 13 countries in the population-based third European Community Respiratory Health Survey. Activity-related breathlessness was measured using the modified Medical Research Council (mMRC) scale. Associations with mMRC were analysed using ordered logistic regression clustering on centre, adjusting for post-bronchodilator spirometry, body mass index, pack-years smoking, cardiopulmonary diseases, depression and level of exercise. Activity-related breathlessness (mMRC ≥1) was twice as common in females (27%) as in males (14%) (odds ratio (OR) 2.21, 95% CI 1.79−2.72). The sex difference was not reduced when controlling for FEV 1 % predicted (OR 2.33), but disappeared when controlling for absolute FEV 1 (OR 0.89, 95% CI 0.69−1.14). Absolute FEV 1 explained 98−100% of the sex difference adjusting for confounders. The effect was similar within males and females, when using FVC instead of FEV 1 and in healthy never-smokers. The markedly more severe activity-related breathlessness among females in the general population is explained by their smaller spirometric lung volumes.
Linus Pauling, Ph.D. (1901–1994): From Chemical Bond to Civilization
Authors: Kenneth J. Weiss
Journal: American Journal of Psychiatry (2017)

A scientist from Oregon with an insatiably inquisitive and fertile mind, Linus Pauling tried to refocus psychiatry from psychology to chemistry.Mid-20th century theories abounded, especially about schizophrenia-for example, that methylated catecholamines act as endogenous hallucinogens.Megavitamin therapy with niacin (vitamin B 3 , a methyl acceptor) was the proposed remedy (1).When Pauling, using examples from this theory, published his findings in Science in 1968 (2), orthomolecular psychiatry was born.Some mental diseases, he argued, were the result of localized cerebral deficiencies of nutrients, not appreciable in the bloodstream or directly measurable.The idea rankled the psychiatric establishment.Pauling's personal history may shed light on his interest in molecular disease (3).His mother suffered and died from pernicious anemia, cause then unknown.He was plagued by disabling colds, much improved by his use of vitamin C.And he suffered from Bright's disease (chronic nephritis), battling it with bed rest and severe dietary modifications.His insistence on an orthomolecular approach, coupled with growing popular interest in alternative psychiatry, were dynamics in the creation of the APA task force report Megavitamin and Orthomolecular Therapy in Psychiatry in 1973 (4).Pauling's 1974 rebuttal appeared in the Journal's new Opinion and Comment section (5), followed by commentaries from Drs.Richard Jed Wyatt, Donald Klein, and Morris Lipton (6-8).They rejected Pauling's ideas because of his reliance on the flawed methodology of his sources and his resistance to controlled clinical trials.Pauling did not set out to turn psychiatry on its head.His interest in a simple solution to mental illness grew from his work on the nature of chemical bonds, earning him a Nobel Prize in chemistry in 1954, and on the structure of hemoglobin and its application to understanding sickle cell disease.Whereas the catecholamine-methylation hypothesis of schizophrenia waned, current literature connects DNA methylation to the epigenetics of mental illness (9).Pauling recognized exogenous dynamics in mental illness, but not epigenetics: "Psychoanalysis has failed, and psychiatry is now rapidly returning to the scientific approach, the recognition of the corporeal character of mental illness, with manifestations determined to some extent by environmental stress and past experience" (10, p. vi).
Novel assay reveals a large, inducible, replication-competent HIV-1 reservoir in resting CD4+ T cells
Authors: Anwesha Sanyal, Robbie B Mailliard, Charles R Rinaldo, Deena Ratner, Ming Ding, Yue Chen, Jennifer M Zerbato, Nicholas S Giacobbi, Narasimhan J Venkatachari, Bruce K Patterson, Amanda Chargin, Nicolas Sluis-Cremer, Phalguni Gupta
Journal: Nature Medicine (2017)
GENE-01. TUMOR MUTATION BURDEN AND DRIVER MUTATIONS: FURTHER INSIGHT INTO THE GENOMIC LANDSCAPE OF PEDIATRIC HIGH GRADE GLIOMAS
Authors: Lauren Weintraub, Vikramjit Kanwar, Jeffrey Ross
Journal: Neuro-Oncology (2017)

Pediatric high grade gliomas (HGG) have been described to have a higher tumor mutation burden (TMB) than low grade gliomas. A high TMB has been associated with improved objective immune checkpoint inhibitor (ICPI) response and progression-free survival in adult HGG. There is also data to suggest that tumors with a high TMB are less likely to possess a mutation in a cancer driver gene. To better characterize the range of TMB in pediatric HGG, and the relationship to mutations in cancer driver genes, we analyzed a cohort of HGG tumor specimens. DNA was extracted from 40 microns of formalin-fixed paraffin-embedded (FFPE) specimen from a set of 93 cases of pediatric (≤18 years) HGG. Hybridization capture of 567 cancer-related genes and select introns from genes commonly rearranged in cancer was performed on DNA extracted from 3,983 clinical FFPE specimens and sequenced to high, uniform coverage (>500x). TMB was assessed as the number of somatic coding point mutations per megabase of targeted territory. Cases were analyzed for the presence of known cancer driver gene mutations. Thirteen (14%) tumors had a TMB >10 mutations per megabase, 9 (10%) had a TMB >40, and 7 (7.5%) had a TMB >100. Eighteen (23%) of the 79 patients with a low TMB <10, 3 (23%) of the 13 patients with a TMB >10, and 1 (11%) of the 9 patients with a high TMB >40, had at least one driver mutation. Driver mutations identified included PIK3CA, BRAF, EGFR, IDH1, KRAS, HRAS. A substantial subset of pediatric HGG tumors possess a high TMB and, while it did not reach statistical significance, there was a trend toward decreased incidence of cancer driver mutations in high TMB tumors. Studies are needed to evaluate if TMB and driver mutation status in pediatric HGG is predictive of response to ICPI.
Phenotypes of Atopic Dermatitis Depending on the Timing of Onset and Progression in Childhood
Authors: Caroline Roduit, Remo Frei, Martin Depner, Anne M. Karvonen, Harald Renz, Charlotte Braun-Fahrländer, Elisabeth Schmausser-Hechfellner, Juha Pekkanen, Josef Riedler, Jean-Charles Dalphin, Erika von Mutius, Roger Pascal Lauener, Anne Hyvärinen, Pirkka Kirjavainen, Sami Remes, Marjut Roponen, Marie-Laure Dalphin, Vincent Kaulek, Markus Ege, Jon Genuneit, Sabina Illi, Micahel Kabesch, Bianca Schaub, Petra Ina Pfefferle, Gert Doekes
Journal: JAMA Pediatrics (2017)

Atopic dermatitis is an inflammatory, pruritic skin disease that often occurs in early infancy with a chronic course. However, a specific description of subtypes of atopic dermatitis depending on the timing of onset and progression of the disease in childhood is lacking.To identify different phenotypes of atopic dermatitis using a definition based on symptoms before age 6 years and to determine whether some subtypes are more at risk for developing other allergic diseases.The Protection Against Allergy Study in Rural Environments (PASTURE) is a European birth cohort where pregnant women were recruited between August 2002 and March 2005 and divided in 2 groups dependent on whether they lived on a farm. Children from this cohort with data on atopic dermatitis from birth to 6 years of age were included.Atopic dermatitis, defined as an itchy rash on typical locations from birth to 6 years.The latent class analysis was used to identify subtypes of atopic dermatitis in childhood based on the course of symptoms. Multivariable logistic regressions were used to analyze the association between atopic dermatitis phenotypes and other allergic diseases.We included 1038 children; of these, 506 were girls. The latent class analysis model with the best fit to PASTURE data separated 4 phenotypes of atopic dermatitis in childhood: 2 early phenotypes with onset before age 2 years (early transient [n = 96; 9.2%] and early persistent [n = 67; 6.5%]), the late phenotype with onset at age 2 years or older (n = 50; 4.8%), and the never/infrequent phenotype (n = 825; 79.5%), defined as children with no atopic dermatitis. Children with both parents with history of allergies were 5 times more at risk to develop atopic dermatitis with an early-persistent phenotype compared with children with parents with no history of allergies. Both early phenotypes were strongly associated with food allergy. The risk of developing asthma was significantly increased among the early-persistent phenotype (adjusted odds ratio, 2.87; 95% CI, 1.31-6.31). The late phenotype was only positively associated with allergic rhinitis.Using latent class analysis, 4 phenotypes of atopic dermatitis were identified depending on the onset and course of the disease. The prevalence of asthma and food allergy by 6 years of age was strongly increased among children with early phenotypes (within age 2 years), especially with persistent symptoms. These findings are important for the development of strategies in allergy prevention.
Reflections on Admissions for Heart—and Social System—Failure
Authors: Michelle D. Carlson
Journal: JAMA Cardiology (2017)

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 Cardiology 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 Cardiology journal
Core Outcome Measures for Clinical Research in Acute Respiratory Failure Survivors. An International Modified Delphi Consensus Study
Authors: Dale M. Needham, Kristin A. Sepulveda, Victor D. Dinglas, Caroline M. Chessare, Lisa Aronson Friedman, Clifton O. Bingham, Alison E. Turnbull
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Research evaluating acute respiratory failure (ARF) survivors' outcomes after hospital discharge has substantial heterogeneity in terms of the measurement instruments used, creating barriers to synthesizing study data.To identify a minimum set of core outcome measures that are essential to include in all clinical research studies evaluating ARF survivors after discharge.We conducted a three-round modified Delphi consensus process with 77 participants (47% female, 55% outside the United States), including clinical researchers from more than 16 countries across six continents, patients/caregivers, clinicians, and research funders. Participants reviewed standardized information on measure instruments for seven consensus-derived outcomes plus one recommended outcome.Response rates were 91 to 97% across the three rounds. Among 75 measurement instruments evaluated, the following met a priori consensus criteria: EQ-5D and 36-item Short Form Health Survey version 2 (optional) for the "satisfaction with life and personal enjoyment" and "pain" outcomes, and both the Hospital Anxiety and Depression Scale and the Impact of Events Scale-Revised for the "mental health" outcome. No measures reached consensus for the following outcomes: cognition, muscle and/or nerve function, physical function, and pulmonary function. All measures considered for pulmonary function met consensus criteria for exclusion. The following measures did not reach the threshold for consensus but achieved the highest scores for their respective outcomes: the Montreal Cognitive Assessment (cognition), manual muscle testing and handgrip dynamometry (muscle and/or nerve function), and 6-minute-walk test (physical function).This Core Outcome Measurement Set is recommended for use in all clinical research evaluating ARF survivors after hospital discharge. In the future, researchers should evaluate measures for outcomes not reaching consensus.
Descriptive analysis of head impact kinetics in a simulated rugby union tackle: preliminary findings
Authors: Salmon Danielle, Jayden Pinfold, S John Sullivan, Gray Andrew, Ed Lodge, Osborne Hamish, Tong Darryl
Journal: British Journal of Sports Medicine (2017)

Objective The tackle is a key component in rugby union and carries some of the highest risk for concussions. The purpose this study was to observe the acceleration profile of the head during a simulated tackle and to determine if these forces vary by playing position. Design Observational. Setting Laboratory. Participants Male rugby players (n=41) age 21.8±3.4 years. Protocol Participants were asked to perform 5 tackles with each shoulder. For each tackle the 50 kg bag was released on a pendulum and the players completed a 3 m run-up to make contact with the bag at its peak speed (4.3 ±.13 m/s). For each tackle the linear and rotational acceleration were captured using a head positioning system (HPS) anchored over the mastoid bone. Outcome measures The magnitude and variability of the mean resultant linear and rotational acceleration forces over the 10 tackles were examined using the peak acceleration values and were compared with Mann-Whitney-Wilcoxon tests. Main results The overall mean peak linear force was 82.9 Gz with a range of 20.1–236.6 Gz. For the forwards (n=23) the peak linear and rotational accelerations were 83.0±36.3 Gz and 2537.8±477.7 m/s 2 , while for the backs (n=18) were 77.6±33.8 Gz and 2501.9±519.6 m/s 2 . There were no significant differences between forwards/backs, or those with a history of concussion (p≥0.054). Conclusions With growing evidence implicating the importance of sub-concussive impacts in later brain health, understanding the exposure load of players during trainings and games is essential. This is the first study to document the impact forces recorded at the head during a simulated rugby tackle. Competing interests None. Ed Lodge is CEO of CSx Concussion Management Systems, who developed and provided the Head positioning system that was used to measure head impact kinetics in real time.
Tolerogenic insulin peptide therapy precipitates type 1 diabetes
Authors: Marie-Louise Bergman, Thiago Lopes-Carvalho, Ana-Catarina Martins, Fabio A. Grieco, Décio L. Eizirik, Jocelyne Demengeot
Journal: The Journal of Experimental Medicine (2017)

Daniel et al. (https://doi.org/10.1084/jem.20110574) have previously published in JEM a study on the preventive effect of tolerogenic vaccination with a strong agonist insulin mimetope in type 1 diabetes. Our study now challenges these results and shows that osmotic pump delivery of the modified insulin peptide R22E did not prevent hyperglycemia, accelerated disease onset, increased its incidence, and worsened insulitis.
Surface De-PEGylation Controls Nanoparticle-Mediated siRNA Delivery <i>In Vitro</i> and <i>In Vivo</i>
Authors: Xi Zhu, Wei Tao, Danny Liu, Jun Wu, Zilei Guo, Xiaoyuan Ji, Zameer Bharwani, Lili Zhao, Xiaoping Zhao, Omid C. Farokhzad, Jinjun Shi
Journal: Theranostics (2017)

The present work proposes a unique de-PEGylation strategy for controllable delivery of small interfering RNA (siRNA) using a robust lipid-polymer hybrid nanoparticle (NP) platform. The self-assembled hybrid NPs are composed of a lipid-poly(ethylene glycol) (lipid-PEG) shell and a polymer/cationic lipid solid core, wherein the lipid-PEG molecules can gradually dissociate from NP surface in the presence of serum albumin. The de-PEGylation kinetics of a series of different lipid-PEGs is measured with their respective NPs, and the NP performance is comprehensively investigated in vitro and in vivo. This systematic study reveals that the lipophilic tails of lipid-PEG dictate its dissociation rate from NP surface, determining the uptake by tumor cells and macrophages, pharmacokinetics, biodistribution, and gene silencing efficacy of these hybrid siRNA NPs. Based on our observations, we here propose that lipid-PEGs with long and saturated lipophilic tails might be required for effective siRNA delivery to tumor cells and gene silencing of the lipid-polymer hybrid NPs after systemic administration.
연구논문 : 간세포암종에 대한 간절제술 후 조기재발에 영향을 미치는 위험인자
Authors: 박의준 ( Ui Jun Park ), 김용훈 ( Yong Hoon Kim ), 강구정 ( Koo Jeong Kang ), 임태진 ( Tae Jin Lim )
Journal: Clinical and Molecular Hepatology (2008)
Research and development in the NHS
Authors: John Swales
Journal: Journal of the Royal Society of Medicine (1998)

J D Swales is Professor of Medicine, University of Leicester from 1974 to present. He is on secondment as Director of Research &amp; Development (1996 to present) Department of Health. Professor Swales' main research interest is in the processes which cause high blood pressure and methods of treatment. In his present post he is responsible for research and development within the NHS. He has written and edited several books including Platt versus Pickering (1985), Textbook of Hypertension (1994) and Manual of Hypertension (1995). He is an ex-President of the British Hypertension Society and has been Editor of Clinical Science, The Journal of Hypertension and The Journal of the Royal Society of Medicine. He has been Bradshaw, Croonian and Harveian Lecturer of the Royal College of Physicians.