tbuckley/cabot-search huggingface dataset:
Improvement of lung function measured by AM PEF in patients with severe eosinophilic asthma treated with mepolizumab: A combined analysis of the MENSA and MUSCA studies
Authors: Hector Ortega, Andrew Menzies-Gow, Jean-Pierre Llanos-Ackert, Mark S. Forshag, Frank C. Albers, Necdet Gunsoy, Eric Bradford, Steven W. Yancey, Monica Kraft
Journal: Journal of Allergy and Clinical Immunology (2018)
Human Herpesvirus 8–Associated Inflammatory Cytokine Syndrome
Authors: Marta Prieto-Barrios, Raquel Aragón-Miguel, David Tarragó-Asensio, Antonio Lalueza, Carlos Zarco-Olivo
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
Efficacy and safety of lebrikizumab (an anti-IL-13 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical corticosteroids: A randomized, placebo-controlled phase II trial (TREBLE)
Authors: Eric L. Simpson, Carsten Flohr, Lawrence F. Eichenfield, Thomas Bieber, Howard Sofen, Alain Taïeb, Ryan Owen, Wendy Putnam, Marcela Castro, Kendra DeBusk, Chin-Yu Lin, Athina Voulgari, Karl Yen, Theodore A. Omachi
Journal: Journal of the American Academy of Dermatology (2018)

BackgroundInterleukin (IL)-13 plays a key role in type 2 inflammation and is an emerging pathogenic mediator in atopic dermatitis (AD).ObjectiveWe investigated the efficacy and safety of lebrikizumab, an IL-13 monoclonal antibody, as an add-on to topical corticosteroid (TCS) treatment.MethodsA randomized, placebo-controlled, double-blind, phase 2 study. Adults with moderate-to-severe AD were required to use TCS twice daily and then randomized (1:1:1:1) to lebrikizumab 125 mg single dose, lebrikizumab 250 mg single dose, lebrikizumab 125 mg every 4 weeks for 12 weeks, or placebo every 4 weeks for 12 weeks, after a 2-week TCS run-in. The primary endpoint was percentage of patients achieving Eczema Area and Severity Index (EASI)-50 at week 12.ResultsIn total, 209 patients received the study drug. At week 12, significantly more patients achieved EASI-50 with lebrikizumab 125 mg every 4 weeks (82.4%; P = .026) than placebo every 4 weeks (62.3%); patients receiving a single dose of lebrikizumab showed no statistically significant improvements in EASI-50 compared with placebo. Adverse events were similar between groups (66.7% all lebrikizumab vs 66.0% placebo) and mostly mild or moderate.LimitationsProtocol-mandated twice daily TCS treatment limits our understanding of the efficacy of lebrikizumab as a monotherapy. The short study duration did not enable long-term efficacy or safety evaluations.ConclusionWhen combined with TCS, lebrikizumab 125 mg taken every 4 weeks led to a significant improvement and was well tolerated in patients with moderate-to-severe AD.
Abstract 13444: Decreased REM Sleep is Associated With Higher Risk of Incident Atrial Fibrillation
Authors: Matthew A Christensen, Shalini Dixit, Eric Vittinghoff, Kenneth J Mukamal, Susan Redline, John A Robbins, Anne B Newman, Sanjay R Patel, Jared W Magnani, Bruce M Psaty, Susan R Heckbert, Gregory M Marcus
Journal: Circulation (2016)

Introduction: Reduced sleep quality, beyond that caused by obstructive sleep apnea (OSA), has recently been associated with the development of obesity, hypertension, stroke, and death. While OSA has been shown to predict AF, it remains unknown if sleep disturbances independent of apnea predict the disease. Hypothesis: Reduced sleep quality increases the risk of incident AF independent of OSA Methods: We performed a longitudinal analysis in a sub-set of participants in the Cardiovascular Health Study who were co-enrolled in the Sleep Heart Health Study. Sleep duration, efficiency, latency, and architecture were measured at baseline using at-home polysomnography. Severity of OSA was determined using clinical cut-offs with the apnea-hypopnea-index (AHI), also measured by polysomnography. Cox proportional hazards models were used to obtain effect estimates and adjust for OSA severity and other potential confounders including: age, sex, race, site, BMI, smoking, alcohol use, use of sleeping pills, diabetes, HTN, CHD, and CHF. Results: Among 1,131 participants with a mean age of 77 ± 4.5 years, 665 (59%) were female, and 647 (60%) had at least mild OSA (AHI &gt; 5). Over a median follow-up of 9.8 years (IQR, 5.5 - 11.7), 259 (23%) developed AF. Decreased REM sleep was associated with increased risk of AF before and after adjustment for OSA and other potential confounders ( Figure ). For every standard deviation decrease in the proportion of sleep spent in REM (SD 6.6%) there was an approximate 23% increase in the risk of AF (adjusted hazard ratio 1.23; 95% CI, 1.05 - 1.44, p = .01). Conclusions: Reduced REM sleep was independently associated with greater risk of incident AF among older adults. Aspects of sleep beyond OSA may be involved in the pathogenesis of AF and sleep quality may be an important modifiable risk factor for AF.
Prenatal Transplantation of Placental Cells Engineered to Express FVIII Leads to Corrective Plasma Levels of FVIII after Birth
Authors: M. Graca Almeida-Porada, Sunil George, Alshaima Morsi, Nadia El-Akabawy, Jorge Figueroa, Jordan E Shields, Diane Meares, Andrew M. Farland, Anthony Atala, Christopher B Doering, H. Trent Spencer, Christopher D Porada
Journal: Blood (2017)
Emergency doctors “disappointed” over exclusion from winter pressure panel
Authors: Tom Moberly
Journal: BMJ (2018)

Emergency medicine doctors have expressed surprise and disappointment that the NHS’s winter pressure panel does not include representatives from the Royal College of Emergency Medicine (RCEM).

NHS England’s National Emergency Pressures Panel is chaired by Bruce Keogh, national medical director of NHS England, and met for the first time on 20 December 2017. It includes eight people representing NHS Improvement and NHS England, as well as representatives of Public Health England and the Care Quality Commission (CQC).

The group also has members from the Royal College of Nursing, the Royal College of GPs, the Royal College of …
Sputum Eosinophilia and Magnetic Resonance Imaging Ventilation Heterogeneity in Severe Asthma
Authors: Sarah Svenningsen, Rachel L. Eddy, Hui Fang Lim, P. Gerard Cox, Parameswaran Nair, Grace Parraga
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Inflammation and smooth muscle dysfunction are integral components of severe asthma that contribute to luminal obstruction causing airflow limitation, ventilation heterogeneity, and symptoms. This is important for guiding treatment decisions directed at the inflammatory (e.g., anti-T-helper cell type 2 monoclonal antibodies) and noninflammatory, smooth muscle-mediated (e.g., bronchial thermoplasty) components of severe asthma.To investigate the contribution of eosinophilic bronchitis and smooth muscle dysfunction to magnetic resonance imaging (MRI) ventilation heterogeneity in patients with severe asthma.We measured the inhaled hyperpolarized gas MRI response to salbutamol as a marker of smooth muscle dysfunction, and sputum eosinophils as a marker of airway inflammation, and their contributions to ventilation heterogeneity (quantified as the ventilation defect percent [VDP]) in 27 patients with severe asthma. Spirometry and forced oscillation airway resistance measurements were also acquired pre- and postsalbutamol. Patients were dichotomized on the basis of sputum eosinophilia, and pre- and postsalbutamol VDP and physiological measurements were evaluated.MRI VDP improved with salbutamol inhalation in patients in whom sputum eosinophilia was uncontrolled (≥3%, n = 16) (P = 0.002) and in those in whom it was controlled (<3%, n = 11) (P = 0.02), independent of improvements in FEV1, indicating smooth muscle response. In those patients in whom sputum eosinophilia was uncontrolled, greater VDP persisted postsalbutamol (P = 0.004). Postsalbutamol VDP correlated with sputum eosinophils (r = 0.63; P = 0.005).In patients with severe asthma, MRI regionally identifies the inflammatory and noninflammatory components of airway disease. Ventilation heterogeneity persists postsalbutamol in patients with uncontrolled eosinophilic bronchitis, which may be the functional consequence of airway inflammation.
Impact of race and payer status on the outcome of chronic myeloid leukemia (CML) in the era of tyrosine kinase inhibitors.
Authors: Srinivas S. Devarakonda, Avinash Pasam, Jill Comeau, Binu Sivaraman Nair, Reinhold Munker, Gary Von Burton, Glenn Morris Mills, Nebu V. Koshy
Journal: Journal of Clinical Oncology (2014)

e17568 Background: Race and payer status have been shown to impact the outcome of several hematological malignancies including multiple myeloma and acute leukemia. There is, however, limited information on the impact of these variables on the survival of chronic myeloid leukemia (CML) in the era of tyrosine kinase inhibitors. Methods: We conducted a retrospective chart review of all patients diagnosed and treated at our institution between 2001 and 2013. Electronic health records were used for data collection. Descriptive statistics and cox regression model were used for data analysis. Results: Ninety six patients were included in our review of which 52 were Caucasian and 44 were African American (AA). Mean age at diagnosis was 48 years. Caucasians had a lower median age at diagnosis (45.5 years) compared to AA (51.2 years) p=0.04. More Caucasians were insured than AA (53% vs. 45%). Patients with Medicare or private insurance had higher rates of major molecular response (MMR) as compared to Medicaid or uninsured patients (Mcare-63.1%, private-55.6%, Mcaid-36.3%, uninsured-30.5%). Overall survival (OS) was superior in patients with Medicare and private insurance compared to Medicaid (hazard ratios 0.41 and 0.35 respectively) and patients with private insurance did better than uninsured patients (HR=0.37). Age, race, gender, achievement of MMR had no impact on the survival of patients. Compliance had a non-significant trend towards improved overall survival (p=0.13). Conclusions: Patient outcomes, both MMR and OS, appear to be impacted by payer status with insured and Medicare patients having superior outcomes as compared to Medicaid and uninsured patients. Possible explanations include limited access to medical services, difficulty in obtaining medications and poor treatment compliance. Larger population studies are needed to validate this finding and identify possible interventions to further improve outcomes.
Alpha-band lateralization during auditory selective attention for brain–computer interface control
Authors: Martin Spüler, Simone Kurek
Journal: Brain-Computer Interfaces (2018)

In this paper, we investigated selective attention to auditory stimuli as a control mechanism for a Brain–Computer Interface (BCI). For BCIs using visual stimuli, the use of steady state or code modulated visual evoked potentials yields high performance. In this work, these approaches were transferred and tested in the auditory domain. The attentional modulation of code-modulated auditory evoked potentials (c-AEPs) and steady state auditory evoked potentials (SSAEPs) showed only a small effect, which is not sufficient for BCI control. However, for both kinds of stimuli, we found a spatial attention-related alpha-band lateralization that allows classification accuracies above 70% and thereby can be used for controlling a BCI.
Understanding and removing barriers to physical activity: one key in addressing child obesity
Authors: Lisa Murphy, Alessandro R Demaio
Journal: British Journal of Sports Medicine (2018)

Latest worldwide estimates suggest that by 2016, 41 million children under 5 years and 337 million aged 5–19 years were overweight; obesity rates in the latter population had seen a tenfold increase in just four decades.1 2 Overweight and obesity affect the cardiovascular, respiratory, endocrine and neuromuscular systems. An associated and increasing burden of chronic disease, coupled with the related economic costs of increased disability and reduced productivity, is devastating health systems and hindering socioeconomic development in many nations.

Prevention-focused policy with a particular emphasis on nutrition is key to combating this epidemic. However, this alone will be insufficient; a growing body of evidence now also supports complementary, individual-level, lifestyle interventions to arrest and reverse the established burden. Recently published Cochrane reviews, for example, suggest that multicomponent lifestyle modification may afford small but important reductions in age-standardised body mass index for children and adolescents of all ages.3 In addition, interventions that recruited overweight parents of young children also resulted in a significant and sustainable reduction in parental weight.

At a national level, strong correlations exist between socioeconomic status (SES) and child …
The Debate About Electronic Cigarettes: Harm Minimization or the Precautionary Principle
Authors: Lawrence W. Green, Jonathan E. Fielding, Ross C. Brownson
Journal: Annual Review of Public Health (2018)

Two contrasting reviews (authored by Abrams et al. and Glantz & Bareham) in this volume have reached opposing conclusions on the effects of electronic cigarettes in a debate that is dividing the scientific and professional communities that have devoted careers to controlling the manufacture, advertising, sale, and use of combustible cigarettes. The research on the types, degree, and extent of harm from e-cigarettes is far from complete and, together with trends in teenage smoking and vaping, has raised new questions and prospects about the potential benefits that the new electronic products offer smokers of combustible cigarettes in quitting or at least cutting back on the known risks associated with the traditional forms of smoking. The rapidly morphing forms, constituents, promotions, and uses of the electronic varieties of the new nicotine delivery products (in this case electronic cigarettes) make research on their biological and behavioral effects moving targets. The two sides of this argument have produced a global divide on policy strategies.
Abstract 13837: Adrenergic Receptors β2 and β3 Transduce Differential Signals in Cardiac Fibroblasts
Authors: Kota Tonegawa, Hiroyuki Nakayama, Hiromi Igarashi, Sachi Matsunami, Nao Hayamizu, Masanori Obana, Makiko Maeda, Yasushi Fujio
Journal: Circulation (2015)

Background: Cardiac fibroblasts (CFs) are the most prevalent cell types in heart and play important roles in cardiac remodeling. While the roles of β-adrenergic receptor (βAR) signaling in cardiomyocytes (CMs) are well characterized, those in CFs remain to be elusive due to lack of convenient method to assess those signaling. There are three subtypes of, βAR β1, β2, β3 and β2AR is reported to be expressed in CFs by which enhances cell proliferation and production of inflammatory cytokines. Clinical efficacy of non-selective β blocker carvedilol for heart failure (HF) surpasses that of β1 selective blocker metoprolol, suggesting critical roles of β2 and β3AR in the pathogenesis of HF. Objective: To elucidate the signaling downstream βARs in CFs in heart. Methods and Results: Caveolae is an important microdomain for signal transduction, such as βAR, present in CMs or CFs. To elucidate βAR signaling of caveolae in CFs, we generated a fusion protein composed of phospholamban (PLN) and caveolin3 (Cav3) representing PKA activation as phosphorylation at S16 of PLN and CaMKII as that at T17 in caveolae. Thus, activation of PKA or CaMKII is detectable by anti-phospho-S16 or T17 antibody, respectively. In neonatal rat CFs (NRCFs) infected PLN-Cav3 adenovirus, stimulation by isoproterenol (ISO) led to enhanced phosphorylation of both S16 and T17, suggesting PKA and CaMKII activation in caveolae of CFs. RT-PCR analyses showed β2AR and β3AR were present in NRCFs. Stimulation with β2AR selective agonists activated both PKA and CaMKII, while β3AR elicited solely PKA activation, analyzed by using β3AR selective agonist/antagonist. In addition, in order to examine the significance of βAR stimulation for heart failure, we administered ISO continuously for two weeks in β2ARKO mice. As a result, fibrosis was suppressed in β2ARKO mice compared with wild-type mice (0.35% vs 2.37%, p&lt;0.05) suggesting critical roles of β2AR in development of cardiac fibrosis caused by βAR stimulation in mice. Conclusions: Both β2 and β3AR are expressed in NRCFs and transduce distinct signaling and β2AR selective stimulation elicit development of cardiac fibrosis via activation of CaMKII signaling. Thus, selective βAR regulation could be potential novel anti-fibrotic therapeutics in HF.
Vaccines targeting preS1 domain overcome immune tolerance in hepatitis B virus carrier mice
Authors: Yingjie Bian, Zheng Zhang, Zhichen Sun, Juanjuan Zhao, Danming Zhu, Yang Wang, Sherry Fu, Jingya Guo, Longchao Liu, Lishan Su, Fu‐Sheng Wang, Yang‐Xin Fu, Hua Peng
Journal: Hepatology (2017)

Strong tolerance to hepatitis B virus (HBV) surface antigens limits the therapeutic effect of the conventional hepatitis B surface antigen (HBsAg) vaccination in both preclinical animal models and patients with chronic hepatitis B (CHB) infection. In contrast, we observed that clinical CHB patients presented less immune tolerance to the preS1 domain of HBV large surface antigen. To study whether targeting the weak tolerance of the preS1 region could improve therapy gain, we explored vaccination with the long peptide of preS1 domain for HBV virions clearance. Our study showed that this preS1‐polypeptide rather than HBsAg vaccination induced robust immune responses in HBV carrier mice. The anti‐preS1 rapidly cleared HBV virions in vivo and blocked HBV infection to hepatocytes in vitro . Intriguingly, vaccination of preS1‐polypeptide even reduced the tolerized status of HBsAg, opening a therapeutic window for the host to respond to the HBsAg vaccine. A sequential administration of antigenically distinct preS1‐polypeptide and HBsAg vaccines in HBV carrier mice could finally induce HBsAg/hepatitis B surface antibody serological conversion and clear chronic HBV infection in carrier mice. Conclusion : These results suggest that preS1 can function as a therapeutic vaccine for the control of CHB. (H epatology 2017;66:1067‐1082)
Haploidentical T-Repleted Stem Cell Transplantation (SCT) Has Comparable Survival to 10/10 and 9/10 Unrelated SCT in Poor-Cytogenetics Risk Acute Myeloid Leukemia in First Complete Remission: A Study on Behalf of the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT)
Authors: Francesca Lorentino, Myriam Labopin, Fabio Ciceri, Massimo Bernardi, Jordi Esteve, Liisa Volin, Ibrahim Yakoub-Agha, Charles Craddock, Jakob R. Passweg, Gerard Socie, Jan J Cornelissen, Didier Blaise, Tobias Gedde-Dahl, Nathalie Fegueux, Mohamad Mohty, Arnon Nagler
Journal: Blood (2017)
The role of the gut microbiome in systemic inflammatory disease
Authors: Jose C Clemente, Julia Manasson, Jose U Scher
Journal: BMJ (2018)

<h3>ABSTRACT</h3> The role of the gut microbiome in models of inflammatory and autoimmune disease is now well characterized. Renewed interest in the human microbiome and its metabolites, as well as notable advances in host mucosal immunology, has opened multiple avenues of research to potentially modulate inflammatory responses. The complexity and interdependence of these diet-microbe-metabolite-host interactions are rapidly being unraveled. Importantly, most of the progress in the field comes from new knowledge about the functional properties of these microorganisms in physiology and their effect in mucosal immunity and distal inflammation. This review summarizes the preclinical and clinical evidence on how dietary, probiotic, prebiotic, and microbiome based therapeutics affect our understanding of wellness and disease, particularly in autoimmunity.
Multidimensional endotypes of chronic rhinosinusitis and their association with treatment outcomes
Authors: B. Liao, J.‐X. Liu, Z.‐Y. Li, Z. Zhen, P.‐P. Cao, Y. Yao, X.‐B. Long, H. Wang, Y. Wang, R. Schleimer, Z. Liu
Journal: Allergy (2018)

The expression of chronic rhinosinusitis (CRS) is multidimensional. Disease heterogeneity in patients with CRS remains poorly understood. This study aimed to identify endotypes of CRS using cluster analysis by integrating multidimensional characteristics and to explore their association with treatment outcomes.
Analysis of differential expression of tight junction proteins in cultured oral epithelial cells altered by Porphyromonas gingivalis, Porphyromonas gingivalis lipopolysaccharide, and extracellular adenosine triphosphate
Authors: Wei Guo, Peng Wang, Zhong-Hao Liu, Ping Ye
Journal: International Journal of Oral Science (2018)

Tight junctions (TJs) are the most apical intercellular junctions of epithelial cells formed by occludin, claudins, junctional adhesion molecules (JAMs), and zonula occludens (ZO). Tight junction proteins can sense the presence of bacteria and regulate the transcription of target genes that encode effectors and regulators of the immune response. The aim of this study was to determine the impact of TJ proteins in response to Porphyromonas gingivalis (P. gingivalis), P. gingivalis lipopolysaccharide (P. gingivalis LPS), and extracellular adenosine triphosphate (ATP) in the oral epithelial cell culture model. Quantified real time-polymerase chain reaction (RT-PCR), immunoblots, and immunostaining were performed to assess the gene and protein expression in TJs. It was found that P. gingivalis infection led to transient upregulation of the genes encoding occludin, claudin-1, and claudin-4 but not JAM-A, claudin-15, or ZO-1, while P. gingivalis LPS increased claudin-1, claudin-15, and ZO-1 and decreased occludin, JAM-A, and claudin-4. Tight junction proteins showed significant upregulation in the above two groups when cells were pretreated with ATP for 3 h. The findings indicated that P. gingivalis induced the host defence responses at an early stage. P. gingivalis LPS exerted a more powerful stimulatory effect on the disruption of the epithelial barrier than P. gingivalis. ATP stimulation enhanced the reaction of TJ proteins to P. gingivalis invasion and LPS destruction of the epithelium.International Journal of Oral Science (2018) 10, e8; doi:10.1038/ijos.2017.51; published online 10 January 2018.
Human-Specific Adaptations in Vpu Conferring Anti-tetherin Activity Are Critical for Efficient Early HIV-1 Replication In Vivo
Authors: Eri Yamada, Shinji Nakaoka, Lukas Klein, Elisabeth Reith, Simon Langer, Kristina Hopfensperger, Shingo Iwami, Gideon Schreiber, Frank Kirchhoff, Yoshio Koyanagi, Daniel Sauter, Kei Sato
Journal: Cell Host & Microbe (2018)
Measures of heart rate variability shortly after birth are associated with wheeze and ED visits at age 2-3 years
Authors: Matthew Perzanowski, Khalil W. Savary, Emilio Arteaga-Solis, Natalie H. Brito, Virginia A. Rauh, Laura A. Lautenbacher, Amy J. Elliot, Michael M. Myers, William P. Fifer
Journal: Journal of Allergy and Clinical Immunology (2018)