tbuckley/cabot-search huggingface dataset:
Influence of Race, Ethnicity, and Culture on Childhood Obesity: Implications for Prevention and Treatment
Authors: Sonia Caprio, Stephen R. Daniels, Adam Drewnowski, Francine R. Kaufman, Lawrence A. Palinkas, Arlan L. Rosenbloom, Jeffrey B. Schwimmer
Journal: Diabetes Care (2008)

Obesity may be thought of as a body weight that conveys significant risk for adverse health outcomes. In children, obesity is defined as a BMI at or above the 95th percentile for age and sex, based on population data from the 1970s (1,2). The prevalence of obesity has increased markedly in U.S. children and adolescents in the past 30 years. Obesity-related risk factors and diseases formerly seen only in adults are increasingly being recognized in obese adolescents and even younger children.

Race and ethnicity are terms used to categorize populations on the basis of shared characteristics. Race has traditionally been used to categorize populations on the basis of shared biological characteristics such as genes, skin color, and other observable features. Ethnicity is used to categorize on the basis of cultural characteristics such as shared language, ancestry, religious traditions, dietary preferences, and history. Although ethnic groups can share a range of phenotypic characteristics due to their shared ancestry, the term is typically used to highlight cultural and social characteristics instead of biological ones (3).

Both race and ethnicity are, in fact, social constructs. The assumption that race reflects only biological distinctions is inaccurate. Categories based on race account for only 3–7% of total human genetic diversity, are not reliably measured, and are not always biologically meaningful (3,4). Furthermore, both race and ethnicity are constantly evolving concepts, making the task of comparing groups or following the same group over time quite challenging. For instance, the increasing proportion of the U.S. population describing their race as “mixed” or “other,” as well as changes in ethnic self-identification across generations and occasionally even within the same generation, makes it difficult to assign individuals to invariant categories of race or ethnicity. Nevertheless, the social importance given to these constructs to describe …
Chemical pleurodesis in malignant pleural effusions: a randomised prospective study of mepacrine versus bleomycin.
Authors: S Koldsland, J L Svennevig, G Lehne, E Johnson
Journal: Thorax (1993)

BACKGROUND--The treatment of recurrent pleural effusion in advanced malignant disease should be efficient and with tolerable side effects. Since 1983 intrathoracic instillation of the anti-malaria drug mepacrine has been used to achieve pleurodesis. The cytotoxic drug bleomycin has been claimed to be equally effective and with fewer side effects. The present study was designed to compare these two agents. METHODS--Forty patients with carcinoma and pleural effusions refractory to repeated pleural aspirations over the previous 12 weeks were randomised to receive treatment with intrathoracic instillation of mepacrine or bleomycin. Fluid volumes before and after pleurodesis, drainage time, and side effects were registered and analysed, and the response to treatment was evaluated by clinical examination and chest radiography. RESULTS--The amount of fluid produced after treatment in the patients receiving mepacrine was lower than in those receiving bleomycin, and the duration of chest drainage was shorter. After 30 days 16 of 20 in the mepacrine group responded to treatment and 10 of 20 in the bleomycin group. Most patients died during the three months observation period. Moderate side effects occurred equally in both groups. CONCLUSIONS--Chemical pleurodesis can reduce or stop pleural effusion in many patients, and in this study mepacrine appeared to be more efficient than bleomycin. A prospective study with a larger number of patients is now warranted.
Stable Expression and Somatic Hypermutation of Antibody V Regions in B-Cell Developmental Pathways
Authors: C Kocks, K Rajewsky
Journal: Annual Review of Immunology (1989)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
The effects of tocilizumab on osteitis, synovitis and erosion progression in rheumatoid arthritis: results from the ACT-RAY MRI substudy
Authors: Philip G Conaghan, Charles Peterfy, Ewa Olech, Jeffrey Kaine, David Ridley, Julie DiCarlo, Josh Friedman, Jenny Devenport, Orrin Troum
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objective</h3> To examine the imaging-detected mechanism of reduction of structural joint damage progression by tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) using MRI. <h3>Methods</h3> In a substudy of a randomised, double-blind, phase 3b study (ACT-RAY) of biologic-naïve patients with RA who were methotrexate (MTX)-inadequate responders, 63 patients were randomised to continue MTX or receive placebo (PBO), both in combination with TCZ 8 mg/kg every 4 weeks, with optional additional disease-modifying antirheumatic drugs at week 24 if Disease Activity Score of 28 joints &lt; 3.2. The most symptomatic hand was imaged with 0.2 Tesla extremity MRI at weeks 0, 2, 12 and 52. MR images were scored using Outcome Measures in Rheumatology–Rheumatoid Arthritis Magnetic Resonance Imaging Score. Predictors of week 52 erosion progression were determined by logistic regression analysis. <h3>Results</h3> TCZ + PBO (n=32) demonstrated mean improvements in synovitis from baseline to weeks 2 (−0.92; p=0.0011), 12 (−1.86; p&lt;0.0001) and 52 (−3.35; p&lt;0.0001), while TCZ + MTX (n=31) had mean improvements in synovitis at week 12 (−0.88; p=0.0074), but not week 52 (−1.00; p=0.0711). TCZ+PBO demonstrated mean reductions in osteitis at weeks 12 (−5.10; p=0.0022) and 52 (−8.56; p=0.0006), while TCZ+MTX had mean reductions at weeks 2 (−0.21; p&lt;0.05) and 12 (−3.63; p=0.0008), but not week 52 (−2.31; p=0.9749). Mean erosion scores did not worsen in either group. MRI erosion scores at weeks 12 and 52 correlated strongly with radiography erosion scores at week 52 (r&gt;0.80). Baseline synovitis and worsening of osteitis predicted erosion progression. <h3>Conclusions</h3> Rapid suppression of synovitis and osteitis with reduction in structural joint damage progression occurred with TCZ, as monotherapy or in combination with MTX, through week 52.
Calsarcin-2 deficiency increases exercise capacity in mice through calcineurin/NFAT activation
Authors: Norbert Frey, Derk Frank, Stefanie Lippl, Christian Kuhn, Harald Kögler, Tomasa Barrientos, Claudia Rohr, Rainer Will, Oliver J. Müller, Hartmut Weiler, Rhonda Bassel-Duby, Hugo A. Katus, Eric N. Olson
Journal: Journal of Clinical Investigation (2008)

The composition of skeletal muscle, in terms of the relative number of slow- and fast-twitch fibers, is tightly regulated to enable an organism to respond and adapt to changing physical demands. The phosphatase calcineurin and its downstream targets, transcription factors of the nuclear factor of activated T cells (NFAT) family, play a critical role in this process by promoting the formation of slow-twitch, oxidative fibers. Calcineurin binds to calsarcins, a family of striated muscle-specific proteins of the sarcomeric Z-disc. We show here that mice deficient in calsarcin-2, which is expressed exclusively by fast-twitch muscle and encoded by the myozenin 1 (Myoz1) gene, have substantially reduced body weight and fast-twitch muscle mass in the absence of an overt myopathic phenotype. Additionally, Myoz1 KO mice displayed markedly improved performance and enhanced running distances in exercise studies. Analysis of fiber type composition of calsarcin-2-deficient skeletal muscles showed a switch toward slow-twitch, oxidative fibers. Reporter assays in cultured myoblasts indicated an inhibitory role for calsarcin-2 on calcineurin, and Myoz1 KO mice exhibited both an excess of NFAT activity and an increase in expression of regulator of calcineurin 1-4 (RCAN1-4), indicating enhanced calcineurin signaling in vivo. Taken together, these results suggest that calsarcin-2 modulates exercise performance in vivo through regulation of calcineurin/NFAT activity and subsequent alteration of the fiber type composition of skeletal muscle.
Re: Dormancy of Mammary Carcinoma After Mastectomy
Authors: J. S. Spratt
Journal: JNCI Journal of the National Cancer Institute (2000)

Carcinoma After MastectomyThe article by Karrison et al. (1) argues incorrectly that the long, latent period before the recurrence of breast cancer after mastectomy is due to dormant cells.An alternate and better documented explanation is the extreme variation in the actual tumor volume doubling time.How the variation in actual growth rates affects the extremes of disease duration has been well documented in previous publications and has been reviewed recently (2-5).
Current and Future Utilization of Services From Medical Oncologists
Authors: Joan L. Warren, Angela B. Mariotto, Angela Meekins, Marie Topor, Martin L. Brown
Journal: Journal of Clinical Oncology (2008)

There is limited information on the current use of oncologists and projections of future need. This analysis assesses current utilization patterns and projects the number of people with cancer and their use of oncologists' services through 2020.Data from the Surveillance, Epidemiology, and End Results cancer registries and Medicare physician claims were used to estimate oncologists' services from 1998 to 2003. We estimated the portion of patients with cancer who saw an oncologist, the mean number of visits, and the clinical setting where care was provided. Care was divided into initial, continuing, and last-year-of-life phases. Projections for future number of patients with cancer and visits were calculated by applying incidence and prevalence rates derived from Surveillance, Epidemiology, and End Results data to census population projections through 2020.The percentage of patients who saw an oncologist was 47% during the initial-care phase, 36% during the continuing-care phase, and 70% in the last year of life. The number of visits varied by age, sex, cancer site, and phase. The total number of cancer patients in the United States is projected to increase 55%, from 11.8 million in 2005 to 18.2 million in 2020. Total oncology visits are projected to increase from 38 million in 2005 to 57 million in 2020.Utilization of oncologists' services will increase appreciably between 2005 and 2020; this will be driven predominantly by an increase in survivors of cancer and by the aging of the population. The United States may face an acute shortage of medical oncologists if efforts are not taken to meet this growing need.
Identification of genes involved in ceramide-dependent neuronal apoptosis using cDNA arrays
Authors: Charles Decraene, Bernard Brugg, Merle Ruberg, Eric Eveno, Christiane Matingou, Fariza Tahi, Jean Mariani, Charles Auffray, Geneviève Pietu
Journal: Genome biology (2002)

Ceramide is important in many cell responses, such as proliferation, differentiation, growth arrest and apoptosis. Elevated ceramide levels have been shown to induce apoptosis in primary neuronal cultures and neuronally differentiated PC 12 cells. To investigate gene expression during ceramide-dependent apoptosis, we carried out a global study of gene expression in neuronally differentiated PC 12 cells treated with C2-ceramide using an array of 9,120 cDNA clones. Although the criteria adopted for differential hybridization were stringent, modulation of expression of 239 genes was identified during the effector phase of C2-ceramide-induced cell death. We have made an attempt at classifying these genes on the basis of their putative functions, first with respect to known effects of ceramide or ceramide-mediated transduction systems, and then with respect to regulation of cell growth and apoptosis. Our cell-culture model has enabled us to establish a profile of gene expression during the effector phase of ceramide-mediated cell death. Of the 239 genes that met the criteria for differential hybridization, 10 correspond to genes previously involved in C2-ceramide or TNF-α signaling pathways and 20 in neuronal disorders, oncogenesis or more broadly in the regulation of proliferation. The remaining 209 genes, with or without known functions, constitute a pool of genes potentially implicated in the regulation of neuronal cell death.
Unusual phenotype of B cells in the thymus of normal mice.
Authors: M Miyama-Inaba, S Kuma, K Inaba, H Ogata, H Iwai, R Yasumizu, S Muramatsu, R M Steinman, S Ikehara
Journal: The Journal of Experimental Medicine (1988)

A small number of B cells are found in the thymus of normal mice. A population of B lymphocytes could be enriched to greater than 90% purity by isolating a low-density fraction on Percoll density gradients and then depleting T cells with a mixture of anti-Thy-1, CD4, and CD8 mAbs and complement. Enrichment was monitored by surface Ig staining and by functional studies (responsiveness to LPS, and to anti-mu plus IL-4). When the phenotype of these B cells was studied by flow cytometry, 60-80% had the phenotype Ly-1+ (CD5), Ia+, B220low (CD45R), and Mac-1+ (CD 11b). In contrast, splenic B cells lacked CD5 and CD11b and expressed higher levels of B220 and Ia antigens. These results indicate that most thymic B cells have the phenotype of the Ly-1 B cell subset, which was identified previously as a trace subpopulation in some peripheral tissues and is thought to play a role in autoantibody formation.
Overdiagnosis in publicly organised mammography screening programmes: systematic review of incidence trends
Authors: K. J. Jorgensen, P. C Gotzsche
Journal: BMJ (2009)

<b>Objective</b> To estimate the extent of overdiagnosis (the detection of cancers that will not cause death or symptoms) in publicly organised screening programmes. <b>Design</b> Systematic review of published trends in incidence of breast cancer before and after the introduction of mammography screening. <b>Data sources</b> PubMed (April 2007), reference lists, and authors. <b>Review methods</b> One author extracted data on incidence of breast cancer (including carcinoma in situ), population size, screening uptake, time periods, and age groups, which were checked independently by the other author. Linear regression was used to estimate trends in incidence before and after the introduction of screening and in older, previously screened women. Meta-analysis was used to estimate the extent of overdiagnosis. <b>Results</b> Incidence data covering at least seven years before screening and seven years after screening had been fully implemented, and including both screened and non-screened age groups, were available from the United Kingdom; Manitoba, Canada; New South Wales, Australia; Sweden; and parts of Norway. The implementation phase with its prevalence peak was excluded and adjustment made for changing background incidence and compensatory drops in incidence among older, previously screened women. Overdiagnosis was estimated at 52% (95% confidence interval 46% to 58%). Data from three countries showed a drop in incidence as the women exceeded the age limit for screening, but the reduction was small and the estimate of overdiagnosis was compensated for in this review. <b>Conclusions</b> The increase in incidence of breast cancer was closely related to the introduction of screening and little of this increase was compensated for by a drop in incidence of breast cancer in previously screened women. One in three breast cancers detected in a population offered organised screening is overdiagnosed.
Health secretary announces plan to cut NHS litigation costs
Authors: C. Dyer
Journal: BMJ (2014)

A new drive to save lives and cut litigation costs by reducing avoidable harm in the NHS by half over the next three years has been unveiled by the health secretary for England, Jeremy Hunt.

Hunt also announced that a full duty of candour would be imposed on NHS providers, requiring them to tell patients and apologise to those who suffer even moderate harm at the hands of the health service, not just severe harm.

The initiatives have their roots in the findings of Robert Francis QC’s inquiry into systemic failures at Mid Staffordshire NHS Foundation Trust and the NHS patient safety review by the US healthcare expert Don Berwick. Both called for a new culture of openness and readiness …
Cancer Incidence in Denmark Following Exposure to Poliovirus Vaccine Contaminated With Simian Virus 40
Authors: Eric A Engels, Hormuzd A Katki, Nete M Nielsen, Jeanette F Winther, Henrik Hjalgrim, Flemming Gjerris, Philip S Rosenberg, Morten Frisch
Journal: JNCI Journal of the National Cancer Institute (2003)

Background: Early poliovirus vaccines were accidentally contaminated with simian virus 40 (SV40). In Denmark, poliovirus vaccine was administered to most children from 1955 through 1961. SV40 DNA sequences have been detected in several human malignancies, including mesothelioma, ependymoma, choroid plexus tumors, and non-Hodgkin's lymphoma. To clarify whether SV40 infection increases risk of these cancers or of cancers arising in children, we examined cancer incidence in three Danish birth cohorts. Methods: Population-based cancer incidence data from 1943 through 1997 were obtained from the Danish Cancer Registry. The relationship between exposure to SV40-contaminated vaccine and cancer incidence was evaluated by examining incidence in birth cohorts that differed in exposure to SV40-contaminated vaccine. In addition, cancer incidence was examined in children who were 0–4 years of age before, during, and after the period of vaccine contamination. Incidence was compared using Poisson regression, adjusting for age differences. All statistical tests were two-sided. Results: After 69.5 million person-years of follow-up, individuals exposed to SV40-contaminated poliovirus vaccine as infants (i.e., born 1955–1961) or children (i.e., born 1946–1952) had lower overall cancer risk (age-adjusted relative risk [RR] = 0.86, 95% confidence interval [CI] = 0.81 to 0.91 and RR = 0.79, 95% CI = 0.75 to 0.84, respectively; P<.001 for both) than unexposed individuals (i.e., born 1964–1970, after the vaccine was cleared of SV40 contamination). Specifically, SV40 exposure was not associated with increased incidence of mesothelioma, ependymoma, choroid plexus tumor, or non-Hodgkin's lymphoma. After 19.5 million person-years of follow-up, incidence of all cancers combined, of intracranial tumors, and of leukemia among children aged 0–4 years was also not associated with SV40 exposure. Ependymoma incidence was higher during the exposed period than during the unexposed period (RR = 2.59, 95%CI = 1.36 to 4.92; P = .004 versus the period before contamination); however, incidence peaked in 1969, after the vaccine was cleared of SV40. Conclusion: Exposure to SV40-contaminated poliovirus vaccine in Denmark was not associated with increased cancer incidence.
Longer term follow up of aerobic capacity in children affected by severe acute respiratory syndrome (SARS)
Authors: C C W Yu
Journal: Thorax (2006)

A study was undertaken to investigate the aerobic capacity and pulmonary function of children 6 and 15 months after the diagnosis of severe acute respiratory syndrome (SARS).Thirty four patients of mean age 14.7 years completed both pulmonary function and maximal aerobic capacity tests at 6 months. All had normal clinical examination and were asymptomatic. Their exercise responses were compared with a group of healthy controls. Complete data were collected on 27 of the original 34 cases at 15 months.Compared with normal controls, the patient group had significantly lower absolute and mass related peak oxygen consumption (peak V o(2) (p<0.01)), higher ventilatory equivalent for oxygen (p<0.01), lower oxygen pulse (p<0.01), and a lower oxygen uptake efficiency slope (p<0.01) at 6 months. This impairment was unexpected and out of proportion with the degree of lung function abnormality. Residual high resolution computed tomography of thorax (HRCT) abnormalities were present in 14 patients. Those with abnormal HRCT findings had significantly lower mass related peak V o(2) than subjects with normal radiology (p<0.01). Absolute and mass related peak V o(2) in the patient group remained impaired at 15 months despite normalisation of lung function in all patients.The mechanism for the reduced aerobic capacity in children following SARS is not fully understood, but it is probably a consequence of impaired perfusion to the lungs at peak exercise and deconditioning.
Small Molecule Agonists of PPAR-γ Exert Therapeutic Effects in Esophageal Cancer
Authors: Hiroshi Sawayama, Takatsugu Ishimoto, Masayuki Watanabe, Naoya Yoshida, Hidetaka Sugihara, Junji Kurashige, Kotaro Hirashima, Masaaki Iwatsuki, Yoshifumi Baba, Eiji Oki, Masaru Morita, Yoshinobu Shiose, Hideo Baba
Journal: Cancer Research (2013)

The transcription factor PPAR-γ plays various roles in lipid metabolism, inflammation, cellular differentiation, and apoptosis. PPAR-γ agonists used to treat diabetes may have utility in cancer treatment. Efatutazone is a novel later generation PPAR-γ agonist that selectively activates PPAR-γ target genes and has antiproliferative effects in a range of malignancies. In this study, we investigated PPAR-γ status in esophageal squamous cell carcinoma (ESCC) and investigated the antiproliferative effects of efatutazone. PPAR-γ was expressed heterogeneously in ESCC, in which it exhibited an inverse relationship with Ki-67 expression. PPAR-γ expression was associated independently with good prognosis in ESCC. Efatutazone, but not the conventional PPAR-γ agonist troglitazone, inhibited ESCC cell proliferation in vitro and in vivo. Mechanistic investigations suggested that efatutazone acted by upregulating p21Cip1 protein in the nucleus through inactivation of the Akt pathway and dephosphorylation of p21Cip1 at Thr145 without affecting the transcriptional activity of p21Cip1. We also found that treatment with efatutazone led to phosphorylation of the EGF receptor and activation of the mitogen-activated protein kinase (MAPK) pathway. Accordingly, the combination of efatutazone with the antiepithelial growth factor receptor antibody cetuximab synergized to negatively regulate the phosphoinositide 3-kinase-Akt and MAPK pathways. Together, our results suggest that efatutazone, alone or in combination with cetuximab, may offer therapeutic effects in ESCC.