tbuckley/cabot-search huggingface dataset:
Smoking and leanness: evidence for change in Finland.
Authors: B. Marti, J. Tuomilehto, H. J. Korhonen, L. Kartovaara, E. Vartiainen, P. Pietinen, P. Puska
Journal: BMJ (1989)

Many studies have shown smokers to weigh less than non-smokers, which is plausible given the metabolic effects of cigarette smoke. The interrelation between smoking and relative body weight and its change over time were analysed by using data from Finnish population based surveys from 1982 and 1987. Among both men and women the inverse association between smoking and body mass index was clearly weakened between 1982 and 1987. In 1987 among men aged 25-44 smoking was positively related to body mass index. Moreover, the relation between smoking and waist to hip girth ratio was positive in both sexes at all ages. Years of smoking was nevertheless confirmed as a significant inverse predictor of relative weight. A cluster of unfavourable health habits, including high consumption of alcohol and saturated fats, especially emerged among younger smokers. This may have been due to different selection of smokers in Finland, where smoking increasingly seems to be a form of deviant or risk taking behaviour. It is concluded that at a population level the metabolic effects of smoking seem to be increasingly overridden by several other unfavourable health behaviours of smokers.
BIOSYNTHETIC HUMAN INSULIN IN THE TREATMENT OF DIABETES
Authors: AdrianJ.L Clark, Graham Knight, PhilipG Wiles, Harry Keen, JohnD Ward, JoanM Cauldwell, RodneyO Adeniyi-Jones, JamesM Leiper, RichardH Jones, AngusC Maccuish, PeterJ Watkins, Alan Glynne, JanetB Scotton
Journal: The Lancet (1982)
Effects of Fish Oil Supplementation on Kidney Transplantation
Authors: Athina Tatsioni, Mei Chung, Yannan Sun, Bruce Kupelnick, Alice H. Lichtenstein, Ronald Perrone, Priscilla Chew, Joseph Lau, Peter A. Bonis
Journal: Journal of the American Society of Nephrology (2005)

The objective of this study was to assess the effects of omega-3 fatty acid supplementation on various kidney transplant–related outcomes. A systematic review and meta-analysis was performed of published randomized, controlled trials (RCT). There were 16 kidney transplant RCT with a total of 812 patients. All trials evaluated fish oil with dosages that ranged from 1.2 to 5.4 g/d. No consistent benefits were observed for any outcome with the exception of a modest benefit on triglycerides. A meta-analysis of rejection episodes found no significant benefit on either early (<6 mo posttransplantation) or late episodes. The overall relative risk of having at least one rejection episode in those who received fish oil was 0.91 (95% confidence interval 0.74 to 1.10) in four studies with a follow-up of 1 yr. A meta-analysis of eight RCT of graft survival found no significant benefit (relative risk 1.00, 95% confidence interval 0.96 to 1.05). The available data (mostly derived from older studies with important methodologic limitations) do not demonstrate a consistent, clinically important benefit of fish oil in kidney transplantation.
Likelihood of early detection of breast cancer in relation to false-positive risk in life-time mammographic screening: population-based cohort study
Authors: J.D.M. Otten, J. Fracheboud, G.J. den Heeten, S.J. Otto, R. Holland, H.J. de Koning, M.J.M. Broeders, A.L.M. Verbeek
Journal: Annals of Oncology (2013)
Randomized Trial of Radiation Therapy Versus Concomitant Chemotherapy and Radiation Therapy for Advanced-Stage Oropharynx Carcinoma
Authors: Gilles Calais, Marc Alfonsi, Etienne Bardet, Christian Sire, Thierry Germain, Philippe Bergerot, Béatrix Rhein, Jacques Tortochaux, Patrick Oudinot, Philippe Bertrand
Journal: JNCI Journal of the National Cancer Institute (1999)

We designed a randomized clinical trial to test whether the addition of three cycles of chemotherapy during standard radiation therapy would improve disease-free survival in patients with stages III and IV (i.e., advanced oropharynx carcinoma).A total of 226 patients have been entered in a phase III multicenter, randomized trial comparing radiotherapy alone (arm A) with radiotherapy with concomitant chemotherapy (arm B). Radiotherapy was identical in the two arms, delivering, with conventional fractionation, 70 Gy in 35 fractions. In arm B, patients received during the period of radiotherapy three cycles of a 4-day regimen containing carboplatin (70 mg/m(2) per day) and 5-fluorouracil (600 mg/m(2) per day) by continuous infusion. The two arms were equally balanced with regard to age, sex, stage, performance status, histology, and primary tumor site.Radiotherapy compliance was similar in the two arms with respect to total dose, treatment duration, and treatment interruption. The rate of grades 3 and 4 mucositis was statistically significantly higher in arm B (71%; 95% confidence interval [CI] = 54%-85%) than in arm A (39%; 95% CI = 29%-56%). Skin toxicity was not different between the two arms. Hematologic toxicity was higher in arm B as measured by neutrophil count and hemoglobin level. Three-year overall actuarial survival and disease-free survival rates were, respectively, 51% (95% CI = 39%-68%) versus 31% (95% CI = 18%-49%) and 42% (95% CI = 30%-57%) versus 20% (95% CI = 10%-33%) for patients treated with combined modality versus radiation therapy alone (P =.02 and.04, respectively). The locoregional control rate was improved in arm B (66%; 95% CI = 51%-78%) versus arm A (42%; 95% CI = 31%-56%).The statistically significant improvement in overall survival that was obtained supports the use of concomitant chemotherapy as an adjunct to radiotherapy in the management of carcinoma of the oropharynx.
New Frontiers in Translational Research in Neuro-oncology and the Blood-Brain Barrier: Report of the Tenth Annual Blood-Brain Barrier Disruption Consortium Meeting
Authors: Nancy D. Doolittle, Lauren E. Abrey, W. Archie Bleyer, Steven Brem, Thomas P. Davis, Paula Dore-Duffy, Lester R. Drewes, Walter A. Hall, John M. Hoffman, Agnieszka Korfel, Robert Martuza, Leslie L. Muldoon, David Peereboom, Darryl R. Peterson, Samuel D. Rabkin, Quentin Smith, Glen H.J. Stevens, Edward A. Neuwelt
Journal: Clinical Cancer Research (2005)

The blood-brain barrier (BBB) presents a major obstacle to the treatment of malignant brain tumors and other central nervous system (CNS) diseases. For this reason, a meeting partially funded by an NIH R13 grant was convened to discuss recent advances and future directions in translational research in neuro-oncology and the BBB. Cell biology and transport across the BBB, delivery of agents to the CNS, neuroimaging, angiogenesis, immunotherapy, and gene therapy, as well as glioma, primary CNS lymphoma, and metastases to the CNS were discussed. Transport across the BBB relates to the neurovascular unit, which consists not only of endothelial cells but also of pericyte, glia, and neuronal elements.
Hairy-Related Transcription Factors Inhibit Notch-Induced Smooth Muscle α-Actin Expression by Interfering With Notch Intracellular Domain/CBF-1 Complex Interaction With the CBF-1–Binding Site
Authors: Yuefeng Tang, Sumithra Urs, Lucy Liaw
Journal: Circulation Research (2008)

Notch signaling regulates smooth muscle cell phenotype and is critical for vascular development. One Notch target is smooth muscle α-actin (SMA), a differentiated smooth muscle cell marker. The Notch intracellular domain (NotchICD) forms a complex with CBF-1 (C-promoter–binding factor-1) and directly induces SMA expression. Using primary human smooth muscle cells, we show that expression of the constitutive active ICD of human Notch1, Notch2, or Notch4 receptors increase SMA levels. NotchICD also induce expression of the transcriptional repressors HRT1 (Hairy-related transcription factor 1) and HRT2, in a CBF-1–dependent manner. However, unlike the activating effects of NotchICD, HRT1 or HRT2 represses basal SMA expression, and both are strong antagonists of NotchICD-induced SMA upregulation. This antagonism does not depend on histone deacetylase activity and occurs at the transcriptional level. Competitive coimmunoprecipitation experiments demonstrate that HRT does not disrupt the association of NotchICD and CBF-1, which form a complex in the presence or absence of HRTs. However, HRT suppresses NotchICD/CBF-1 binding to the SMA promoter, as measured by chromatin immunoprecipitation, and transactivation of an SMA promoter reporter spanning sequences −124/+32. SMA expression was regulated similarly following endogenous Notch activation in smooth muscle cells by coculture with endothelial cells, and this effect was also sensitive to HRT inhibition. Temporally defined HRT activity may constitute a negative feedback mechanism of Notch signaling. Our study presents a novel mechanism by which a balance between Notch signaling and HRT activity determines the expression of smooth muscle differentiation markers including SMA.
EGFR, KRAS, BRAF and ALK gene alterations in lung adenocarcinomas: patient outcome, interplay with morphology and immunophenotype
Authors: A. Warth, R. Penzel, H. Lindenmaier, R. Brandt, A. Stenzinger, E. Herpel, B. Goeppert, M. Thomas, F. J. F. Herth, H. Dienemann, P. A. Schnabel, P. Schirmacher, H. Hoffmann, T. Muley, W. Weichert
Journal: European Respiratory Journal (2013)

Numerous studies have been published on single aspects of pulmonary adenocarcinoma (ADC). To comprehensively link clinically relevant ADC characteristics, we evaluated established morphological, diagnostic and predictive biomarkers in 425 resected ADCs. Morphology was reclassified. Cytokeratin-7, thyroid transcription factor (TTF)1, napsin A, thymidylate synthase and excision repair cross-complementing rodent repair deficiency complementation group-1 expression, anaplastic lymphoma kinase rearrangements as well as epidermal growth factor receptor (<i>EGFR</i>), V-Ki-ras2 Kirsten rat sarcoma viral oncogene homologue (<i>KRAS</i>) and v-Raf murine sarcoma viral oncogene homologue B1 (<i>BRAF</i>) mutations were analysed. All characteristics were correlated with clinical and survival parameters. Morphological ADC subtypes were significantly associated with smoking history and distinct patterns of diagnostic biomarkers. <i>KRAS</i> mutations were prevalent in male smokers, while <i>EGFR</i> mutations were associated with female sex, nonsmoking and lepidic as well as micropapillary growth patterns. TTF1 expression (hazard ratio (HR) for overall survival 0.61, p=0.021) and <i>BRAF</i> mutations (HR for disease-free survival 2.0, p=0.046) were found to be morphology- and stage-independent predictors of survival in multivariate analysis. Adjuvant radio-/chemotherapy, in some instances, strongly impacted on the prognostic effect of both diagnostic and predictive biomarkers. Our data draw a comprehensive picture of the prevalence and interplay of established histological and molecular ADC characteristics. These data will help to develop time- and cost-effective diagnostic and treatment algorithms for ADC.
Differentiation of T Regulatory Cells by Immature Dendritic Cells
Authors: Maria-Grazia Roncarolo, Megan K. Levings, Catia Traversari
Journal: The Journal of Experimental Medicine (2001)

The induction of antigen-specific tolerance is critical for the prevention of autoimmunity and maintenance of immune homeostasis. The immune system's ability to distinguish between self and non-self and between innocuous and harmful foreign antigens is controlled by mechanisms of central and
Cavitary pulmonary metastases
Authors: M. R. Chaudhuri
Journal: Thorax (1970)

<h3>Abstract</h3> <h3>Background</h3> The role of copy number variants (CNVs) in susceptibility to asthma is not well understood. This is, in part, due to the difficulty of accurately measuring CNVs in large enough sample sizes to detect associations. The recent availability of whole-exome sequencing (WES) in large biobank studies provides an unprecedented opportunity to study the role of CNVs in asthma. <h3>Methods</h3> We called common CNVs in 49,953 individuals in the first release of UK Biobank WES using ClinCNV software. CNVs were tested for association with asthma in a stage 1 analysis comprising 7,098 asthma cases and 36,578 controls from the first release of sequencing data. Nominally-associated CNVs were then meta-analysed in stage 2 with an additional 17,280 asthma cases and 115,562 controls from the second release of UK Biobank exome sequencing, followed by validation and fine-mapping. <h3>Results</h3> Five of 189 CNVs were associated with asthma in stage 2, including a deletion overlapping the <i>HLA-DQA1</i> and <i>HLA-DQB1</i> genes, a duplication of <i>CHROMR/PRKRA</i>, deletions within <i>MUC22</i> and <i>TAP2</i>, and a duplication in <i>FBRSL1</i>. The <i>HLA-DQA1, HLA-DQB1, MUC22</i> and <i>TAP2</i> genes all reside within the human leukocyte antigen (HLA) region on chromosome 6. <i>In silico</i> analyses demonstrated that the deletion overlapping <i>HLA-DQA1</i> and <i>HLA-DQB1</i> is likely to be an artefact arising from under-mapping of reads from non-reference HLA haplotypes, and that the <i>CHROMR/PRKRA</i> and <i>FBRSL1</i> duplications represent presence/absence of pseudogenes within the HLA region. Bayesian fine-mapping of the HLA region suggested that there are two independent asthma association signals. The variants with the largest posterior inclusion probability in the two credible sets were an amino acid change in <i>HLA-DQB1</i> (glutamine to histidine at residue 253) and a multi-allelic amino acid change in <i>HLA-DRB1</i> (presence/absence of serine, glycine or leucine at residue 11). <h3>Conclusions</h3> At least two independent loci characterised by amino acid changes in the <i>HLA-DQA1, HLA-DQB1</i> and <i>HLA-DRB1</i> genes are likely to account for association of SNPs and CNVs in this region with asthma. The high divergence of haplotypes in the HLA can give rise to spurious CNVs, providing an important, cautionary tale for future large-scale analyses of sequencing data.
Prevention of Recurrent Bacteriuria with Continuous Chemotherapy
Authors: RICHARD B. FREEMAN
Journal: Annals of Internal Medicine (1968)

Preliminary results were obtained from a cooperative study designed to determine the efficacy of continuous therapy with urine-sterilizing agents in the treatment of chronic urinary tract infections. The primary objectives of the study are as follows: [1] to determine the efficacy of continuous therapy with sulfamethizole, nitrofurantoin, methenamine mandelate, and placebo in controlling bacteriuria after specific broad-spectrum antibiotic therapy; and [2] to determine if control of bacteriuria has a favorable effect on renal function. The results of the control of bacteriuria with the various treatment programs are described in detail. Initial broad-spectrum antibiotic therapy was successful in eradicating bacteriuria in 88% of the first 122 patients entered in the study. Methenamine mandelate prevented recurrence of infection in 78% of these cases over a 13-month follow-up period. Nitrofurantoin and sulfamethizole prevented recurrence in one half of the individuals treated compared with only 14% who received placebo therapy. The greater number of courses of antibiotics given for incidental infections and minor variations in the distribution of patients with adverse host factors in the methenamine mandelate group may have contributed to the better response rate with this drug. Unless initial therapy eradicated or severely suppressed bacteriuria, active continuous therapy was ineffective in inducing a bacteriologic response. The patients who received multiple previous courses of therapy for urinary tract infection had a significantly lower response rate to the therapy given in the study. The patients on active continuous therapy required fewer short courses of broad-spectrum antibiotic treatment for clinical exacerbations of urinary tract infection compared with the placebo group during the follow-up period. There was no correlation between symptomatology and bacteriuria, but the urine sediment and stained smear provided a reasonably accurate index in predicting a positive culture. No conclusions can presently be drawn from the renal function studies as to whether or not control of bacteriuria has a favorable effect on renal function.
Experimental Antitumor Activity of Pyrazomycin
Authors: Martin J. Sweeney, Fred A. Davis, Gerald E. Gutowski, Robert L. Hamill, David H. Hoffman, Gerald A. Poore
Journal: Cancer Research (1973)

Summary  Pyrazomycin (PM) completely inhibited the growth of Walker carcinosarcoma 256. Mammary carcinoma 755, Gardner lymphosarcoma, and X5563 plasma cell myeloma were inhibited more than 50% by PM. Tumors that showed more than a minimum response of 30% were the C3H and 115 mammary carcinomas, Mecca lymphosarcoma, Taper liver tumor, and Ridgeway osteogenic sarcoma. The S91 melanoma, Sarcoma 180 ascites tumors, and Ehrlich ascites solid tumor showed no significant biological responses. PM also caused several well-established dimethyl-benzanthracene-induced mammary carcinomas to regress completely. The majority of the dimethylbenzanthracene-induced tumors in the treated rats regressed to some degree while most of the control tumors increased in size. The murine leukemias L1210, C1498, P1534, AKR, P388, or B82 showed no response to PM. Although PM did not inhibit the Ehrlich or Sarcoma 180 ascites tumors in mice, PM did cause up to 90% prolongation of life in rats with the Walker carcinosarcoma 256 ascites, and 9 of the 30 rats survived more than 45 days.  PM showed comparable activity against either Walker carcinosarcoma 256 or Gardner lymphosarcoma when given p.o., i.p., i.v., or i.m. It also showed comparable activity against Walker carcinosarcoma 256 when given once every 2, 3, 4, or 5 days. Plasma levels of PM-like activity were detected 3 days after a single p.o. dose of PM at 10 mg/kg in rats.
THE PROPOSED YOUTH CORRECTION AUTHORITY ACT
Authors: HARVIE DEJ. COGHILL
Journal: American Journal of Psychiatry (1943)

The Youth Correction Authority Act was created by a committee of the American Law Institute. It is a model law which attempts to prevent repeated crime in the 16 to 21 group of youthful offenders through a coordinated effort to provide suitable treatment. The status of this model act is the subject of a nation wide survey or inquiry made by the Youth Correction Act Committee of the Section on Forensic Psychiatry of the American Psychiatric Association. The situation as it now appears on a basis of incomplete information is as follows: Bills incorporating the essential features of the Youth Correction Authority Act have been introduced in six states with these results: California, introduced and passed in 1941. Introduced but failed of passage in Illinois, 1941; Michigan, , 1940; New York, 1941; Pennsylvania, 1941; Wisconsin, 1941; Kansas, 1942. No legislative efforts were made in 28 states. No report has been received yet from 13 other states. Some interests shown in 31 states and requests for more information have been received from 23 states. A committee is active with Congress in establishing a uniform youth correction act dealing with Federal regulations. In view of the foregoing, it is recommended that your Committee be empowered (1) to continue its inquiry into the status of, and facilities for carrying out the provisions of the Youth Correction Act throughout the United States, and (2) continue to cooperate with the American Law Institute and local committees in the states in their educational efforts.
Uninformed Compliance or Informed Choice? A Needed Shift in Our Approach to Cancer Screening
Authors: M. Edward Stefanek
Journal: JNCI Journal of the National Cancer Institute (2011)

It has been more than 30 years since the first consensus development meeting was held to deal with guidelines of mammography screening. Although the National Cancer Institute has wisely focused on the science of screening and of screening benefits vs harm, many professional organizations, advocacy groups, and the media have maintained a focus on establishing who should be screened and promoting recommendations for which age groups should be screened. Guidelines have been developed not only for mammography but also for screening at virtually all major cancer sites, especially for prostate cancer, and most recently, with the preliminary results of the National Lung Screening Trial, for lung cancer. It seems clear that we have done an inadequate job of educating screening candidates about the harms and benefits of cancer screening, including the extent to which screening can reduce cancer mortality. We must also question whether our practice of summoning women to have mammograms, while providing men informed choice for prostate cancer screening, is consistent with a scientific analysis of the relative harms and benefits. We have spent a staggering amount of time and energy over the past several decades developing, discussing, and debating guidelines. Professional and advocacy groups have spent much time aggressively advocating the adoption of guidelines supported by their respective groups. It seems that it would be much more productive to devote such energy to educating screening candidates about the harms and benefits of screening and to engaging in shared decision making.
Enhancing performance and sport injury prevention in disability sport: moving forwards in the field of football
Authors: Osman Hassan Ahmed, Ayser W Hussain, Ian Beasley, Jiri Dvorak, Richard Weiler
Journal: British Journal of Sports Medicine (2014)

According to the WHO, approximately 15.6% of the world population live with some form of disability, including 70 million children world-wide aged between 15 and 18 years.1 The benefits of exercise for individuals living with disability have been highlighted in the literature,2 and participation in team sports, such as football, provides additional benefits (such as facilitating social inclusion, creating peer group networks and challenging perceived social stereotypes). While prevention of injury is an important issue for all athletes, the impact of a sporting injury to an individual with a disability may severely affect their ability to function independently on a daily basis. For example, an athlete with a lower limb amputation who sustains a major injury such as an ACL and osteochondral injury could suffer long-term health consequences. In addition, gaining access to healthcare services and rehabilitation may be more challenging for individuals with a disability.3 Given the many health and social benefits of sporting participation in the disabled population and the …