tbuckley/cabot-search huggingface dataset:
Severe Obesity in Children and Adolescents: Identification, Associated Health Risks, and Treatment Approaches
Authors: Aaron S. Kelly, Sarah E. Barlow, Goutham Rao, Thomas H. Inge, Laura L. Hayman, Julia Steinberger, Elaine M. Urbina, Linda J. Ewing, Stephen R. Daniels
Journal: Circulation (2013)

Severe obesity afflicts between 4% and 6% of all youth in the United States, and the prevalence is increasing. Despite the serious immediate and long-term cardiovascular, metabolic, and other health consequences of severe pediatric obesity, current treatments are limited in effectiveness and lack widespread availability. Lifestyle modification/behavior-based treatment interventions in youth with severe obesity have demonstrated modest improvement in body mass index status, but participants have generally remained severely obese and often regained weight after the conclusion of the treatment programs. The role of medical management is minimal, because only 1 medication is currently approved for the treatment of obesity in adolescents. Bariatric surgery has generally been effective in reducing body mass index and improving cardiovascular and metabolic risk factors; however, reports of long-term outcomes are few, many youth with severe obesity do not qualify for surgery, and access is limited by lack of insurance coverage. To begin to address these challenges, the purposes of this scientific statement are to (1) provide justification for and recommend a standardized definition of severe obesity in children and adolescents; (2) raise awareness of this serious and growing problem by summarizing the current literature in this area in terms of the epidemiology and trends, associated health risks (immediate and long-term), and challenges and shortcomings of currently available treatment options; and (3) highlight areas in need of future research. Innovative behavior-based treatment, minimally invasive procedures, and medications currently under development all need to be evaluated for their efficacy and safety in this group of patients with high medical and psychosocial risks.
Lung-resident tissue macrophages generate Foxp3+ regulatory T cells and promote airway tolerance
Authors: Pejman Soroosh, Taylor A. Doherty, Wei Duan, Amit Kumar Mehta, Heonsik Choi, Yan Fei Adams, Zbigniew Mikulski, Naseem Khorram, Peter Rosenthal, David H. Broide, Michael Croft
Journal: The Journal of Experimental Medicine (2013)

Airway tolerance is the usual outcome of inhalation of harmless antigens. Although T cell deletion and anergy are likely components of tolerogenic mechanisms in the lung, increasing evidence indicates that antigen-specific regulatory T cells (inducible Treg cells [iTreg cells]) that express Foxp3 are also critical. Several lung antigen-presenting cells have been suggested to contribute to tolerance, including alveolar macrophages (MØs), classical dendritic cells (DCs), and plasmacytoid DCs, but whether these possess the attributes required to directly promote the development of Foxp3+ iTreg cells is unclear. Here, we show that lung-resident tissue MØs coexpress TGF-β and retinal dehydrogenases (RALDH1 and RALDH 2) under steady-state conditions and that their sampling of harmless airborne antigen and presentation to antigen-specific CD4 T cells resulted in the generation of Foxp3+ Treg cells. Treg cell induction in this model depended on both TGF-β and retinoic acid. Transfer of the antigen-pulsed tissue MØs into the airways correspondingly prevented the development of asthmatic lung inflammation upon subsequent challenge with antigen. Moreover, exposure of lung tissue MØs to allergens suppressed their ability to generate iTreg cells coincident with blocking airway tolerance. Suppression of Treg cell generation required proteases and TLR-mediated signals. Therefore, lung-resident tissue MØs have regulatory functions, and strategies to target these cells might hold promise for prevention or treatment of allergic asthma.
SCANNING ELECTRON MICROSCOPY OF DERMAL FIBROUS TISSUE NETWORKS IN NORMAL SKIN, SOLAR ELASTOSIS AND PSEUD0-XANTH0MA ELASTICUM
Authors: RODNEY DAWBER, SAM SHUSTER
Journal: British Journal of Dermatology (1971)

Journal Article SCANNING ELECTRON MICROSCOPY OF DERMAL FIBROUS TISSUE NETWORKS IN NORMAL SKIN, SOLAR ELASTOSIS AND PSEUD0‐XANTH0MA ELASTICUM Get access RODNEY DAWBER, RODNEY DAWBER University Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne Search for other works by this author on: Oxford Academic Google Scholar SAM SHUSTER SAM SHUSTER University Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 84, Issue 2, 1 February 1971, Pages 130–134, https://doi.org/10.1111/j.1365-2133.1971.tb06855.x Published: 01 February 1971 Article history Accepted: 19 September 1970 Published: 01 February 1971
Redirecting Specificity of T-Cell Populations For CD19 Using the <i>Sleeping Beauty</i> System
Authors: Harjeet Singh, Pallavi R. Manuri, Simon Olivares, Navid Dara, Margaret J. Dawson, Helen Huls, Perry B. Hackett, Donald B. Kohn, Elizabeth J. Shpall, Richard E. Champlin, Laurence J.N. Cooper
Journal: Cancer Research (2008)

Abstract Genetic modification of clinical-grade T cells is undertaken to augment function, including redirecting specificity for desired antigen. We and others have introduced a chimeric antigen receptor (CAR) to enable T cells to recognize lineage-specific tumor antigen, such as CD19, and early-phase human trials are currently assessing safety and feasibility. However, a significant barrier to next-generation clinical studies is developing a suitable CAR expression vector capable of genetically modifying a broad population of T cells. Transduction of T cells is relatively efficient but it requires specialized manufacture of expensive clinical grade recombinant virus. Electrotransfer of naked DNA plasmid offers a cost-effective alternative approach, but the inefficiency of transgene integration mandates ex vivo selection under cytocidal concentrations of drug to enforce expression of selection genes to achieve clinically meaningful numbers of CAR+ T cells. We report a new approach to efficiently generating T cells with redirected specificity, introducing DNA plasmids from the Sleeping Beauty transposon/transposase system to directly express a CD19-specific CAR in memory and effector T cells without drug selection. When coupled with numerical expansion on CD19+ artificial antigen-presenting cells, this gene transfer method results in rapid outgrowth of CD4+ and CD8+ T cells expressing CAR to redirect specificity for CD19+ tumor cells. [Cancer Res 2008;68(8):2961–71]
<i>CHEK2</i>*1100delC Heterozygosity in Women With Breast Cancer Associated With Early Death, Breast Cancer–Specific Death, and Increased Risk of a Second Breast Cancer
Authors: Maren Weischer, Børge G. Nordestgaard, Paul Pharoah, Manjeet K. Bolla, Heli Nevanlinna, Laura J. van't Veer, Montserrat Garcia-Closas, John L. Hopper, Per Hall, Irene L. Andrulis, Peter Devilee, Peter A. Fasching, Hoda Anton-Culver, Diether Lambrechts, Maartje Hooning, Angela Cox, Graham G. Giles, Barbara Burwinkel, Annika Lindblom, Fergus J. Couch, Arto Mannermaa, Grethe Grenaker Alnæs, Esther M. John, Thilo Dörk, Henrik Flyger, Alison M. Dunning, Qin Wang, Taru A. Muranen, Richard van Hien, Jonine Figueroa, Melissa C. Southey, Kamila Czene, Julia A. Knight, Rob A.E.M. Tollenaar, Matthias W. Beckmann, Argyrios Ziogas, Marie-Rose Christiaens, Johanna Margriet Collée, Malcolm W.R. Reed, Gianluca Severi, Frederik Marme, Sara Margolin, Janet E. Olson, Veli-Matti Kosma, Vessela N. Kristensen, Alexander Miron, Natalia Bogdanova, Mitul Shah, Carl Blomqvist, Annegien Broeks, Mark Sherman, Kelly-Anne Phillips, Jingmei Li, Jianjun Liu, Gord Glendon, Caroline Seynaeve, Arif B. Ekici, Karin Leunen, Mieke Kriege, Simon S. Cross, Laura Baglietto, Christof Sohn, Xianshu Wang, Vesa Kataja, Anne-Lise Børresen-Dale, Andreas Meyer, Douglas F. Easton, Marjanka K. Schmidt, Stig E. Bojesen
Journal: Journal of Clinical Oncology (2012)

We tested the hypotheses that CHEK2*1100delC heterozygosity is associated with increased risk of early death, breast cancer-specific death, and risk of a second breast cancer in women with a first breast cancer.From 22 studies participating in the Breast Cancer Association Consortium, 25,571 white women with invasive breast cancer were genotyped for CHEK2*1100delC and observed for up to 20 years (median, 6.6 years). We examined risk of early death and breast cancer-specific death by estrogen receptor status and risk of a second breast cancer after a first breast cancer in prospective studies.CHEK2*1100delC heterozygosity was found in 459 patients (1.8%). In women with estrogen receptor-positive breast cancer, multifactorially adjusted hazard ratios for heterozygotes versus noncarriers were 1.43 (95% CI, 1.12 to 1.82; log-rank P = .004) for early death and 1.63 (95% CI, 1.24 to 2.15; log-rank P < .001) for breast cancer-specific death. In all women, hazard ratio for a second breast cancer was 2.77 (95% CI, 2.00 to 3.83; log-rank P < .001) increasing to 3.52 (95% CI, 2.35 to 5.27; log-rank P < .001) in women with estrogen receptor-positive first breast cancer only.Among women with estrogen receptor-positive breast cancer, CHEK2*1100delC heterozygosity was associated with a 1.4-fold risk of early death, a 1.6-fold risk of breast cancer-specific death, and a 3.5-fold risk of a second breast cancer. This is one of the few examples of a genetic factor that influences long-term prognosis being documented in an extensive series of women with breast cancer.
Bispecific T-Cell Engaging Antibodies for Cancer Therapy
Authors: Patrick A. Baeuerle, Carsten Reinhardt
Journal: Cancer Research (2009)

There is increasing evidence that T cells are able to control tumor growth and survival in cancer patients, both in early and late stages of the disease. However, tumor-specific T-cell responses are difficult to mount and sustain in cancer patients, and are limited by numerous immune escape mechanisms of tumor cells selected during immunoediting. An alternative approach to engage T cells for cancer therapy are antibodies, which are bispecific for a surface target antigen on cancer cells, and for CD3 on T cells. These are capable of connecting any kind of cytotoxic T cell to a cancer cell, independently of T-cell receptor specificity, costimulation, or peptide antigen presentation. Here, we review the principle of a new class of bispecific antibodies called BiTE (for "bispecific T-cell engager") antibodies. Recent results from clinical studies with a CD19/CD3-bispecific BiTE antibody suggest that this therapeutic paradigm is finally showing promise for treatment of both bulky and minimal residual disease.
Problems Reported by Parents of Children in Multiple Cultures: The Child Behavior Checklist Syndrome Constructs
Authors: Alfons A.M. Crijnen, Thomas M. Achenbach, Frank C. Verhulst
Journal: American Journal of Psychiatry (1999)

The purpose of this study was to compare syndromes of parent-reported problems for children in 12 cultures.Child Behavior Checklists were analyzed for 13,697 children and adolescents, ages 6 through 17 years, from general population samples in Australia, Belgium, China, Germany, Greece, Israel, Jamaica, the Netherlands, Puerto Rico, Sweden, Thailand, and the United States.Comparisons of nine cultures for subjects ages 6 through 17 gave medium effect sizes for cross-cultural variations in withdrawn and social problems and small effect sizes for somatic complaints, anxious/depressed, thought problems, attention problems, delinquent behavior, and aggressive behavior. Scores of Puerto Rican subjects were the highest, whereas Swedish subjects had the lowest scores on almost all syndromes. With great cross-cultural consistency, girls obtained higher scores than boys on somatic complaints and anxious/depressed but lower scores on attention problems, delinquent behavior, and aggressive behavior. Although remarkably consistent across cultures, the developmental trends differed according to syndrome. Comparison of the 12 cultures across ages 6 through 11 supported these results.Empirically based assessment in terms of Child Behavior Checklist syndromes permits comparisons of problems reported for children from diverse cultures.
Open science versus commercialization: a modern research conflict?
Authors: Timothy Caulfield, Shawn HE Harmon, Yann Joly
Journal: Genome Medicine (2012)

Efforts to improve research outcomes have resulted in genomic researchers being confronted with complex and seemingly contradictory instructions about how to perform their tasks. Over the past decade, there has been increasing pressure on university researchers to commercialize their work. Concurrently, they are encouraged to collaborate, share data and disseminate new knowledge quickly (that is, to adopt an open science model) in order to foster scientific progress, meet humanitarian goals, and to maximize the impact of their research.We present selected guidelines from three countries (Canada, United States, and United Kingdom) situated at the forefront of genomics to illustrate this potential policy conflict. Examining the innovation ecosystem and the messages conveyed by the different policies surveyed, we further investigate the inconsistencies between open science and commercialization policies.Commercialization and open science are not necessarily irreconcilable and could instead be envisioned as complementary elements of a more holistic innovation framework. Given the exploratory nature of our study, we wish to point out the need to gather additional evidence on the coexistence of open science and commercialization policies and on its impact, both positive and negative, on genomics academic research.
Randomized, Phase II, Placebo-Controlled, Double-Blind Study With and Without Enzastaurin in Combination With Paclitaxel and Carboplatin As First-Line Treatment Followed by Maintenance Treatment in Advanced Ovarian Cancer
Authors: Ignace B. Vergote, Radoslav Chekerov, Frederic Amant, Philipp Harter, Antonio Casado, Janusz Emerich, Thomas Bauknecht, Kambiz Mansouri, Scott P. Myrand, Tuan S. Nguyen, Peipei Shi, Jalid Sehouli
Journal: Journal of Clinical Oncology (2013)

Purpose Enzastaurin is an oral serine/threonine kinase inhibitor antitumor agent. Our phase II trial tested the efficacy and safety of enzastaurin added to a standard carboplatin/paclitaxel chemotherapy regimen in patients with newly diagnosed advanced ovarian cancer. Patients and Methods This was a randomized, placebo-controlled study in patients with International Federation of Gynecology and Obstetrics stage IIB to IV ovarian, fallopian tube, or peritoneal epithelial carcinoma. Patients were randomly assigned to six cycles of chemotherapy (paclitaxel/carboplatin ± enzastaurin [PCE/PC]) followed by maintenance therapy (enzastaurin/placebo). Primary end point was progression-free survival (PFS). Secondary measures included response rate, safety assessment, and translational research. Results A total of 142 patients were randomly assigned to PCE (n = 69) or PC (n = 73). Patients in the PCE group had a 3.7-month longer median PFS compared with patients in the PC group; this was not statistically significant (hazard ratio [HR], 0.80; 95% CI, 0.50 to 1.29; P = .37). Safety profiles of the treatment arms were comparable. Frequency of discontinuation because of adverse events was similar (PCE, 11.9%; PC, 9.7%). Multivariate analyses confirmed the importance of optimal debulking with regard to PFS (debulking optimal v suboptimal: HR, 0.51; 95% CI, 0.30 to 0.85; P = .009). HR for covariate stage (stage IIB to IIIB v IIIC to IV) was not statistically significant (0.75; 95% CI, 0.38 to 1.47; P = .40). Translational research of immunohistochemistry protein assays did not identify any markers significantly associated with treatment difference regarding PFS. Conclusion The PCE combination increased PFS, but it was not significantly superior to PC in this phase II study.
Joint segmentation of anatomical and functional images: Applications in quantification of lesions from PET, PET-CT, MRI-PET, and MRI-PET-CT images
Authors: Ulas Bagci, Jayaram K. Udupa, Neil Mendhiratta, Brent Foster, Ziyue Xu, Jianhua Yao, Xinjian Chen, Daniel J. Mollura
Journal: Medical Image Analysis (2013)
Design Considerations for Dose-Expansion Cohorts in Phase I Trials
Authors: Alexia Iasonos, John O'Quigley
Journal: Journal of Clinical Oncology (2013)

Phase I trials are increasingly including dose-expansion cohorts after the maximum-tolerated dose (MTD) has been reached to better characterize the toxicity profile or identify early signs of efficacy within a specific disease population. This article provides guidelines on how to monitor safety and re-evaluate the MTD using data obtained from expansion cohorts of phase I protocols. We illustrate how to implement a sequential monitoring rule for safety using a completed phase I trial that included an expansion cohort. We compare the accuracy of the revised MTD with the MTD obtained before expansion and with the true MTD based on simulated trials. The percent of trials that led to a change in the MTD, how far the revised MTD was from the true MTD, and the toxicity rates associated with each level are reported. When toxicity outcomes from the expansion cohort are taken into account, there is a 50% chance that a new, higher MTD will be recommended. Significant improvement in the accuracy of the MTD is obtained 30% of the time (ie, revised MTD is exactly the true MTD), and moderate improvement is obtained 80% of the time when the revised MTD is within a level from true MTD. Failure to include toxicity outcomes from additional patients treated during the expansion phase may result in a less accurate estimate of the MTD. This article provides investigators of phase I protocols with methodological tools to monitor safety and/or efficacy for patients accrued during the expansion phase and to update or confirm the established MTD.
Nitric oxide and penile erection: Is erectile dysfunction another manifestation of vascular disease?
Authors: M Sullivan
Journal: Cardiovascular Research (1999)

There is convincing evidence that the prevalence of erectile dysfunction is increased among men with ischaemic heart disease. This association may be attributed to the fact that both erectile dysfunction and ischaemic heart disease share similar risk factors (e.g. hypertension, dyslipidaemia, diabetes and smoking). Nitric oxide (NO) activity is adversely affected, in penile and vascular tissue, by these risk factors. It is therefore not surprising that a defect in NO activity is thought to play a role in the pathogenesis of both erectile dysfunction and ischaemic heart disease. We consider this evidence and propose that defective NO activity provides a unifying explanation for the association between these two conditions. Further research in this area may improve our understanding of the pathogenesis of cardiovascular diseases as a whole.
Standardization of Alternaria alternata: Extraction and quantification of Alt a 1 by using an mAb-based 2-site binding assay☆☆☆
Authors: Elke Aden, Bernhard Weber, Jochen Bossert, Manfred Teppke, Edda Frank, Rüdiger Wahl, Helmut Fiebig, Oliver Cromwell
Journal: Journal of Allergy and Clinical Immunology (1999)
Cellular reaction to complexes formed between rheumatoid factor and aggregated human gamma globulin.
Authors: N Williamson, N R Ling
Journal: Annals of the Rheumatic Diseases (1965)

<b>Objective:</b> To compare dedicated low-field MRI (lfMRI) with conventional MRI (cMRI) in the detection and scoring of synovitis, tenosynovitis and erosions in patients with rheumatoid arthritis. <b>Patients and methods:</b> The wrist and finger joints of 17 patients with rheumatoid arthritis (median (range) disease duration 8 years (7–12); Disease Activity Score 3.3 (2.6–4.5)) were examined by 0.2 T lfMRI and 1.5 TcMRI. The protocols comprised coronal spin-echo and three-dimensional gradient-echo sequences before and after contrast medium administration. Synovitis of the metacarpophalangeal and proximal interphalangeal joints 2–5 and the wrist joints was scored according to Outcome Measures in Rheumatology recommendations. Tenosynovitis and erosions were scored using 4-point and 6-point scales, respectively. The results were analysed by calculating κ values and performing McNemar’s test intra-individually on a joint-by-joint basis. <b>Results:</b> Agreement between the two MRI techniques was good to excellent for synovitis and erosions, and moderate for tenosynovitis. Of the 306 joints evaluated, 245 and 200 joints showed synovitis in lfMRI and cMRI, respectively. Scoring of synovitis of the finger joints yielded κ values from 0.69 to 0.94. Of the 68 flexor tendons evaluated, tenosynovitis was diagnosed by lfMRI in 24 and by cMRI in 33 instances. Of the 391 bones evaluated, 154 and 139 showed erosions in lfMRI and cMRI, respectively. κ values for erosion scores were between 0.65 and 1. <b>Conclusion:</b> Dedicated, lfMRI shows high agreement with cMRI in diagnosing and scoring synovitis, tenosynovitis and erosions in rheumatoid arthritis when using standardised scoring systems.
Rescue of the Hypoplastic Lung by Prenatal Cyclical Strain
Authors: Scott M. Nelson, Constantinos A. Hajivassiliou, Graham Haddock, Alan D. Cameron, Lindsay Robertson, Richard E. Olver, Robert Hume
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

We determined the effects of sustained and cyclical prenatal mechanical strain on the hypoplastic lung of the ovine model of congenital diaphragmatic hernia. Over a period of 4 weeks in late gestation, repeated cyclical tracheal occlusion for 23 hours with 1-hour release stimulated minimal growth, but promoted maturation with the development of a saccular lung. In contrast, a cycle consisting of 47 hours with 1-hour release induced optimal lung growth and morphologic maturation of the hypoplastic lung parenchyma. Sustained occlusion resulted in exaggerated lung growth, exceeding that of unaffected controls, and abnormal alveolar development. The extent of induction of lung growth by mechanical strain was inversely proportional to the number of alveolar type II cells remaining in the lung epithelium. These studies show that, although mechanical strain is capable of inducing lung growth and differentiation, cyclical strain is a prerequisite for normal development and that mechanically induced growth occurs at the expense of the alveolar type II cell. We conclude that cyclical strain may allow optimal alveolar development while maintaining a population of alveolar type II cells and may thus facilitate an improvement in postnatal lung function in infants with congenital diaphragmatic hernia.