tbuckley/cabot-search huggingface dataset:
Bronchial Inflammation and Airway Responses to Deep Inspiration in Asthma and Chronic Obstructive Pulmonary Disease
Authors: Annelies M. Slats, Kirsten Janssen, Annemarie van Schadewijk, Dirk T. van der Plas, Robert Schot, Joost G. van den Aardweg, Johan C. de Jongste, Pieter S. Hiemstra, Thais Mauad, Klaus F. Rabe, Peter J. Sterk
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Deep inspirations provide physiologic protection against airway narrowing in healthy subjects, which is impaired in asthma and chronic obstructive pulmonary disease (COPD). Airway inflammation has been suggested to alter airway mechanics during deep inspiration.We tested the hypothesis that the number of bronchial inflammatory cells is related to deep inspiration-induced bronchodilation in asthma and COPD.In a cross-sectional study, three modified methacholine challenges were performed in 13 patients with mild, persistent asthma, 12 patients with mild to moderate COPD, and 12 healthy control subjects.After a 20-minute period of deep inspiration avoidance, inhalation of methacholine was followed by either one or five deep inspirations, or preceded by five deep inspirations. The response to deep inspiration was measured by forced oscillation technique. Inflammatory cells were counted within the lamina propria and airway smooth muscle area in bronchial biopsies of patients with asthma and COPD. The reduction in expiratory resistance by one and five deep inspirations was significantly less in asthma (mean change+/-SD: -0.5+/-0.8 and -0.9+/-1.0 cm H2O/L/s, respectively) and COPD (+0.2+/-1.1 and +0.4+/-1.0 cm H2O/L/s, respectively) as compared with healthy subjects (-1.5+/-1.3 and -2.0+/-1.2 cm H2O/L/s, respectively; p=0.05 and p=0.001, respectively). In asthma, this was related to an increase in mast cell numbers within the airway smooth muscle area (r=0.73; p=0.03), and in CD4+ lymphocytes in the lamina propria (r=0.61; p=0.04).Inflammation in the airway smooth muscle bundles and submucosa of bronchial biopsies is positively associated with impaired airway mechanics during deep inspiration in asthma, but not in COPD. Clinical trial registered with www.clinicaltrials.gov (NCT OO279136).
Co-receptor choice by Vα14<i>i</i> NKT cells is driven by Th-POK expression rather than avoidance of CD8-mediated negative selection
Authors: Isaac Engel, Kirsten Hammond, Barbara A. Sullivan, Xi He, Ichiro Taniuchi, Dietmar Kappes, Mitchell Kronenberg
Journal: The Journal of Experimental Medicine (2010)

Mouse natural killer T (NKT) cells with an invariant V alpha14-J alpha18 rearrangement (V alpha14 invariant [V alpha14i] NKT cells) are either CD4(+)CD8(-) or CD4(-)CD8(-). Because transgenic mice with forced CD8 expression in all T cells exhibited a profound NKT cell deficit, the absence of CD8 has been attributed to negative selection. We now present evidence that CD8 does not serve as a coreceptor for CD1d recognition and that the defect in development in CD8 transgene homozygous mice is the result of a reduction in secondary T cell receptor alpha rearrangements. Thymocytes from mice hemizygous for the CD8 transgene have a less severe rearrangement defect and have functional CD8(+) V alpha14i NKT cells. Furthermore, we demonstrate that the transcription factor Th, Poxviruses and Zinc finger, and Krüppel family (Th-POK) is expressed by V alpha14i NKT cells throughout their differentiation and is necessary both to silence CD8 expression and for the functional maturity of V alpha14i NKT cells. We therefore suggest that Th-POK expression is required for the normal development of V alpha14i NKT cells and that the absence of CD8 expression by these cells is a by-product of such expression, as opposed to the result of negative selection of CD8-expressing V alpha14i NKT cells.
Novel methods to deal with publication biases: secondary analysis of antidepressant trials in the FDA trial registry database and related journal publications
Authors: S. G Moreno, A. J Sutton, E. H Turner, K. R Abrams, N. J Cooper, T. M Palmer, A E Ades
Journal: BMJ (2009)

<b>Objective</b> To assess the performance of novel contour enhanced funnel plots and a regression based adjustment method to detect and adjust for publication biases. <b>Design</b> Secondary analysis of a published systematic literature review. <b>Data sources</b> Placebo controlled trials of antidepressants previously submitted to the US Food and Drug Administration (FDA) and matching journal publications. <b>Methods</b> Publication biases were identified using novel contour enhanced funnel plots, a regression based adjustment method, Egger's test, and the trim and fill method. Results were compared with a meta-analysis of the gold standard data submitted to the FDA. <b>Results</b> Severe asymmetry was observed in the contour enhanced funnel plot that appeared to be heavily influenced by the statistical significance of results, suggesting publication biases as the cause of the asymmetry. Applying the regression based adjustment method to the journal data produced a similar pooled effect to that observed by a meta-analysis of the FDA data. Contrasting journal and FDA results suggested that, in addition to other deviations from study protocol, switching from an intention to treat analysis to a per protocol one would contribute to the observed discrepancies between the journal and FDA results. <b>Conclusion</b> Novel contour enhanced funnel plots and a regression based adjustment method worked convincingly and might have an important part to play in combating publication biases.
Incorporating Genomics into Breast Cancer Clinical Trials and Care
Authors: Adel Tabchy, Cynthia X. Ma, Ron Bose, Matthew J. Ellis
Journal: Clinical Cancer Research (2013)

Abstract Advances in DNA sequencing provide the potential for clinical assays that are timely and affordable and use small amounts of clinical material. The hypothesis has therefore been raised that marked improvements in patient outcomes will result when DNA diagnostics are matched to an armamentarium of targeted agents. While this may be partially true, much of the novel biology uncovered by recent sequencing analysis is poorly understood and not druggable with existing agents. Significant other challenges remain before these technologies can be successfully implemented in the clinic, including the predictive accuracy of pathway-based models, distinguishing drivers from passenger mutations, development of rational combinations, addressing genomic heterogeneity, and molecular evolution/resistance mechanisms. Developments in regulatory science will also need to proceed in parallel to scientific advances so that targeted treatment approaches can be delivered to small subsets of patients with defined biology and drug reimbursement is available for individuals whose tumor carries a mutation that has been successfully targeted in another malignancy, as long as they agree to participate in an outcome registry. Clin Cancer Res; 19(23); 6371–9. ©2013 AACR.
The effect of electrical stimulation on recovery from exercise-induced muscle damage
Authors: J Leeder, J Spence, E Taylor, A Harrison, G Howatson
Journal: British Journal of Sports Medicine (2011)

The aim was to investigate the efficacy of a commercially available electrical stimulation device purporting to facilitate recovery from strenuous exercise. Eight participants (5 male and 3 female, age range 23–30 y) volunteered for the study and were familiarised with all exercises involved. Prior to damaging exercise, participants completed tests of maximal isometric voluntary contraction of the knee extensors (MIVC-E) and flexors (MIVC-F) of both legs and perception of delayed-onset muscle soreness (DOMS) was ascertained via a 200 mm visual analogue scale. To induce muscle damage, participants completed 5 sets of 20 drop jumps (10 s between jumps, 2 min between sets) from a 60 cm (males) or 40 cm high (females) platform. Electrical stimulation (Bodyflow, Victoria, Australia) was applied at 1.52 Hz for 3×20 min per day, separated by 5 h, for the next 48 h, randomised into either the dominant ( n = 4) or non-dominant leg ( n = 4), with the contralateral leg acting as the non-treatment control. Participants completed tests of MIVC-E and MIVC-F and a visual analogue scale 24 h and 48 h following the exercise insult. DOMS showed an increase over time ( p &lt;0.05), peaking at 48 h (119±45 mm). MIVC-E showed a reduction over time ( p &lt;0.05), indicating muscle damage was present, but MIVC-F showed no reduction over time ( p &gt;0.05). There were no effects of treatment, or interactions between treatment and time for muscle function or muscle soreness ( p &gt;0.05). At 24 h after exercise, relative reductions in MIVC-E for control and treatment groups were 16±8% and 11±7%, respectively, and at 48 h 8±8% and 5±8%, respectively. Electrical stimulation was not effective at alleviating perceptions of DOMS following muscle damaging exercise, but there was a trend towards accelerated recovery of knee extensor strength. Further research is required to elucidate this finding with a larger and more homogenous sample population.
Mitogen-activated Protein Kinase Phosphatase-1 Modulates Regional Effects of Injurious Mechanical Ventilation in Rodent Lungs
Authors: Moo Suk Park, Qianbin He, Michael G. Edwards, Amen Sergew, David W. H. Riches, Richard K. Albert, Ivor S. Douglas
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Mechanical ventilation induces heterogeneous lung injury by mitogen-activated protein kinase (MAPK) and nuclear factor-κB. Mechanisms regulating regional injury and protective effects of prone positioning are unclear.To determine the key regulators of the lung regional protective effects of prone positioning in rodent lungs exposed to injurious ventilation.Adult rats were ventilated with high (18 ml/kg, positive end-expiratory pressure [PEEP] 0) or low Vt (6 ml/kg; PEEP 3 cm H(2)O; 3 h) in supine or prone position. Dorsal-caudal lung mRNA was analyzed by microarray and MAPK phosphatases (MKP)-1 quantitative polymerase chain reaction. MKP-1(-/-) or wild-type mice were ventilated with very high (24 ml/kg; PEEP 0) or low Vt (6-7 ml/kg; PEEP 3 cm H(2)O). The MKP-1 regulator PG490-88 (MRx-108; 0.75 mg/kg) or phosphate-buffered saline was administered preventilation. Injury was assessed by lung mechanics, bronchioalveolar lavage cell counts, protein content, and lung injury scoring. Immunoblotting for MKP-1, and IκBα and cytokine ELISAs were performed on lung lysates.Prone positioning was protective against injurious ventilation in rats. Expression profiling demonstrated MKP-1 20-fold higher in rats ventilated prone rather than supine and regional reduction in p38 and c-jun N-terminal kinase activation. MKP-1(-/-) mice experienced amplified injury. PG490-88 improved static lung compliance and injury scores, reduced bronchioalveolar lavage cell counts and cytokine levels, and induced MKP-1 and IκBα.Injurious ventilation induces MAPK in an MKP-1-dependent fashion. Prone positioning is protective and induces MKP-1. PG490-88 induced MKP-1 and was protective against high Vt in a nuclear factor-κB-dependent manner. MKP-1 is a potential target for modulating regional effects of injurious ventilation.
<i>BRAF/NRAS</i> Mutation Frequencies Among Primary Tumors and Metastases in Patients With Melanoma
Authors: Maria Colombino, Mariaelena Capone, Amelia Lissia, Antonio Cossu, Corrado Rubino, Vincenzo De Giorgi, Daniela Massi, Ester Fonsatti, Stefania Staibano, Oscar Nappi, Elena Pagani, Milena Casula, Antonella Manca, MariaCristina Sini, Renato Franco, Gerardo Botti, Corrado Caracò, Nicola Mozzillo, Paolo A. Ascierto, Giuseppe Palmieri
Journal: Journal of Clinical Oncology (2012)

Purpose The prevalence of BRAF, NRAS, and p16CDKN2A mutations during melanoma progression remains inconclusive. We investigated the prevalence and distribution of mutations in these genes in different melanoma tissues. Patients and Methods In all, 291 tumor tissues from 132 patients with melanoma were screened. Paired samples of primary melanomas (n = 102) and synchronous or asynchronous metastases from the same patients (n = 165) were included. Tissue samples underwent mutation analysis (automated DNA sequencing). Secondary lesions included lymph nodes (n = 84), and skin (n = 36), visceral (n = 25), and brain (n = 44) sites. Results BRAF/NRAS mutations were identified in 58% of primary melanomas (43% BRAF; 15% NRAS); 62% in lymph nodes, 61% subcutaneous, 56% visceral, and 70% in brain sites. Mutations were observed in 63% of metastases (48% BRAF; 15% NRAS), a nonsignificant increase in mutation frequency after progression from primary melanoma. Of the paired samples, lymph nodes (93% consistency) and visceral metastases (96% consistency) presented a highly similar distribution of BRAF/NRAS mutations versus primary melanomas, with a significantly less consistent pattern in brain (80%) and skin metastases (75%). This suggests that independent subclones are generated in some patients. p16CDKN2A mutations were identified in 7% and 14% of primary melanomas and metastases, with a low consistency (31%) between secondary and primary tumor samples. Conclusion In the era of targeted therapies, assessment of the spectrum and distribution of alterations in molecular targets among patients with melanoma is needed. Our findings about the prevalence of BRAF/NRAS/p16CDKN2A mutations in paired tumor lesions from patients with melanoma may be useful in the management of this disease.
Update in Environmental and Occupational Medicine 2009
Authors: Victor C. Van Hee, Joel D. Kaufman, G. R. Scott Budinger, Gökhan M. Mutlu
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Environmental and occupational health was a major focus of both the scientific and lay press in 2009. Population-based studies confirmed the importance of environmental pollutants in the development of cardiorespiratory morbidity and mortality. Concerns regarding climate change highlighted the important public health consequences of carbon dioxide and methane emissions. The promise of new manufactured nanomaterials has been tempered by emerging concerns regarding their environmental impact. In addition, a ruling by the U.S. Supreme Court in 2009 will force a revision of the U.S. Environmental Protection Agency (EPA) standards for the three major air pollutants, particulate matter, ozone, and nitrogen oxides (NOx), in 2010. In this review on environmental and occupational medicine, we provide an overview of studies in the American Journal of Respiratory and Critical Care Medicine and selected other studies from the literature focused on environmental and occupational health. Although by no means comprehensive, we attempt to highlight the progress that has been made in identifying major health consequences of environmental exposure and understanding the mechanisms by which these occur.
The Coming Plague: Newly Emerging Diseases in a World out of Balance
Authors: K. M De Cock
Journal: BMJ (1995)

Laurie Garrett Virago, pounds sterling20, pp 750 ISBN 1 85381 764 3

Optimism that followed the development of effective antibiotics, vaccines, and ambitious public health programmes has been confounded by the emergence of new infectious diseases and resurgence of old ones, sometimes in impressive epidemics. The changing nature of infectious disease epidemiology results from the altered balance between host (humans), agent (the microbe), and environment; this is the subject matter of this excellent book by the American journalist Laurie Garrett.

The Coming Plague describes for the nonspecialist what several recent official reports in the United States have documented for …
Medical Documentation in the Electronic Era
Authors: C. Jason Wang
Journal: JAMA (2012)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Development and Validation of a Novel Radiosensitivity Signature in Human Breast Cancer
Authors: Corey Speers, Shuang Zhao, Meilan Liu, Harry Bartelink, Lori J. Pierce, Felix Y. Feng
Journal: Clinical Cancer Research (2015)

Abstract Purpose: An unmet clinical need in breast cancer management is the accurate identification of patients who will benefit from adjuvant radiotherapy. We hypothesized that integration of postradiation clonogenic survival data with gene expression data across breast cancer cell (BCC) lines would generate a radiation sensitivity signature (RSS) and identify patients with tumors refractive to conventional therapy. Experimental Design: Using clonogenic survival assays, we identified the surviving fraction (SF-2Gy) after radiation across a range of BCC lines. Intrinsic radiosensitivity was correlated to gene expression using Spearman correlation. Functional analysis was performed in vitro, and enriched biologic concepts were identified. The RSS was generated using a Random Forest model and was refined, cross-validated, and independently validated in additional breast cancer datasets. Results: Clonogenic survival identifies a range of radiosensitivity in human BCC lines (SF-2Gy 77%-17%) with no significant correlation to the intrinsic breast cancer subtypes. One hundred forty-seven genes were correlated with radiosensitivity. Functional analysis of RSS genes identifies previously unreported radioresistance-associated genes. RSS was trained, cross-validated, and further refined to 51 genes that were enriched for concepts involving cell-cycle arrest and DNA damage response. RSS was validated in an independent dataset and was the most significant factor in predicting local recurrence on multivariate analysis, outperfoming all clinically used clinicopathologic features. Conclusions: We derive a human breast cancer–specific RSS with biologic relevance and validate this signature for prediction of locoregional recurrence. By identifying patients with tumors refractory to standard radiation this signature has the potential to allow for personalization of radiotherapy. Clin Cancer Res; 21(16); 3667–77. ©2015 AACR.
Health-related quality of life in patients with idiopathic pulmonary fibrosis: a systematic review
Authors: J J Swigris, W G Kuschner, S S Jacobs, S R Wilson, M K Gould
Journal: Thorax (2005)

<b>Background:</b> Idiopathic pulmonary fibrosis (IPF) profoundly affects the quality of patients’ lives. A systematic review was performed to evaluate critically the published literature and to examine what is known about health-related quality of life (HRQL) in patients with IPF. <b>Methods:</b> The MEDLINE, EMBASE, Health and Psychosocial Instruments, and Cochrane Library databases were searched to 1 April 2004. Abstracts and bibliographies of published articles were scanned and contact was made with investigators. Included studies analysed HRQL (or quality of life) in at least 10 patients with IPF. Two reviewers independently selected studies, evaluated their quality according to predetermined criteria, and abstracted data on study design, patients’ demographic and clinical characteristics, and quality of life outcome measures. <b>Results:</b> Seven studies met the inclusion criteria. The studies enrolled 512 patients with IPF and used three different instruments to measure HRQL. All studies had important limitations in methodological quality; none measured longitudinal changes in HRQL over time. Patients reported substantially impaired HRQL, especially in domains that measured physical health and level of independence. Patients with IPF appear to have similar impairments in HRQL to those with chronic obstructive pulmonary disease. Measures of dyspnoea were moderately correlated with scores from domains that measured physical health (<i>R</i><sup>2</sup> = 0.03–0.66) and energy/fatigue/pep (<i>R</i><sup>2</sup> = 0.19–0.55), but measures of pulmonary function and gas exchange did not correlate as strongly with these and other domains. <b>Conclusion:</b> Studies of HRQL in patients with IPF suggest that, in addition to the obvious effect on physical health, general health, energy level, respiratory symptoms, and level of independence are also impaired. Variability in HRQL among patients is not fully explained by measures of dyspnoea or pulmonary function, suggesting that HRQL measures provide unique information. More research is needed to identify or design appropriate measurement instruments for patients with IPF and to examine changes in HRQL over time or in response to specific treatments.
Transplanted Mesenchymal Stem Cells Accelerate Glomerular Healing in Experimental Glomerulonephritis
Authors: Uta Kunter, Song Rong, Zivka Djuric, Peter Boor, Gerhard Mu[Combining Diaeresis]ller-Newen, Donghai Yu, Ju[Combining Diaeresis]rgen Floege
Journal: Journal of the American Society of Nephrology (2006)

Bone marrow-derived cells contribute to glomerular cell turnover and repair, but the cell types involved are unknown. Whether rat mesenchymal stem cells (MSC) can accelerate recovery from damage in rat mesangioproliferative anti-Thy1.1 glomerulonephritis was studied. After injection into the left renal artery on day 2 after disease induction, fluorescently labeled MSC were detected in 20 to 50% of glomeruli and rare intrarenal vessels but not in the tubulointerstitium, in contralateral kidneys, or in medium controls. In control experiments, injected mesangial cells were detected less frequently in glomeruli in comparison with injected MSC. In nephritic outbred Wistar rats, MSC injection led to an approximately 50% reduction of mesangiolysis on days 4 and 6 after disease induction, accompanied by three- to four-fold higher intraglomerular cell proliferation on day 4 and more rapid mesangial reconstitution as detected by alpha-smooth muscle actin expression. Injection of MSC into tail veins or intra-arterial injection of mesangial cells instead of MSC failed to reproduce any of these findings. In inbred Lewis rats, anti-Thy1.1 nephritis followed an aggravated course with transient acute renal failure. Acute renal failure was ameliorated by MSC injection into the left renal artery on day 2 after disease induction. Again, MSC led to more rapid recovery from mesangiolysis, increased glomerular cell proliferation, and reduction of proteinuria by 28%. Double immunostaining of 5-bromo-2'-deoxyuridine-labeled MSC for endothelial, mesangial, or monocyte/macrophage antigens showed that 85 to 95% of MSC that localized in glomeruli on day 6 failed to express these markers. In vitro, MSC secreted high amounts of vascular endothelial growth factor and TGF-beta1 but not PDGF-BB. In conclusion, even low numbers of MSC can markedly accelerate glomerular recovery from mesangiolytic damage possibly related to paracrine growth factor release and not to differentiation into resident glomerular cell types or monocytes/macrophages.