tbuckley/cabot-search huggingface dataset:
Prolonged continuous intravenous infusion interleukin-2 and lymphokine-activated killer-cell therapy for metastatic renal cell carcinoma.
Authors: J A Thompson, K L Shulman, M C Benyunes, C G Lindgren, C Collins, P H Lange, W H Bush, L A Benz, A Fefer
Journal: Journal of Clinical Oncology (1992)

PURPOSE Two consecutive protocols of continuous intravenous (CIV) infusion interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells were carried out in patients with metastatic renal cell carcinoma (RCC) to determine the response rate and toxicity. PATIENTS AND METHODS In both protocols, patients received induction IL-2 at 6 x 10(6) U/m2/d on days 1 to 5, and underwent leukapheresis on days 7 to 9 at the peak of rebound lymphocytosis. LAK cells were generated by a 5-day incubation with IL-2 at 1,000 U/mL, and were infused on days 12 to 14. For the first 20 patients (protocol A), maintenance IL-2 was administered at 6 x 10(6) U/m2/d on days 12 to 16. On the assumption that less IL-2 might be required to maintain rather than to induce LAK activity, and that a longer duration of maintenance IL-2 might enhance LAK survival and function in vivo, the protocol for the subsequent 22 patients (protocol B) was altered so that the maintenance phase consisted of a lower dose of IL-2 (2 x 10(6) U/m2/d) administered for a longer period of time (days 10 to 20). RESULTS In protocol A, there were two complete responses (CRs) and three partial responses (PRs), for a total response rate of 25%. One PR was surgically converted into a CR. The durations of the CRs are 36+, 18+, and 18+ months. Hypotension and capillary leak were most severe during maintenance, which limited the median duration of maintenance IL-2 to 4 days. In protocol B, no patient experienced severe hypotension, and the median duration of maintenance IL-2 was 9 days. Two patients exhibited a CR and seven a PR, for a total response rate of 41%. Two PRs were surgically converted to CRs. The durations of CR are 14+, 9+, 6+, and 5+ months. In both protocols, the CIV induction regimen resulted in marked rebound lymphocytosis (mean, 11,097/microL) and LAK-cell yield (mean, 18.1 x 10(10)). The cumulative response rate was 14 of 42 patients, or 33% (95% confidence interval, 19% to 47%). CONCLUSION These results demonstrate that both protocols of CIV IL-2 plus LAK cells have substantial antitumor activity, and that a longer maintenance phase of IL-2 at a lower dose is associated with significantly less toxicity without a loss of therapeutic efficacy.
Adolescent bullying linked to depression in early adulthood
Authors: M. M. Ttofi
Journal: BMJ (2015)

Evidence supports early intervention that involves parents, teachers, and young people

Throughout the school years, probably the one thing beyond schoolwork that young people have in common is the need to fit in with their peer group. When young people do not fit in, things may turn ugly.1 We have all heard stories of young people being the target of racist, homophobic, or other forms of bullying. Bullying can hamper the psychosocial development of young people.2 Notably, scientific interest in the topic emerged after the well publicised suicides of three Norwegian students in 1982, resulting in a nationwide campaign against bullying and victimisation.3

In a linked paper (doi:10.1136/bmj.h2469) Bowes and colleagues4 investigated the long term adverse effect of bullying by peers on the mental health of victims, with a focus on depression in early adulthood. The authors used sophisticated longitudinal analyses from the Avon Longitudinal Study of Parents and Children (ALSPAC) study, a UK community based birth cohort, to investigate the predictive efficacy of victimisation by peers at age 13 years on depression five years later. The study, based on data from over 2600 adolescents, …
Laryngoscopy but not resting spirometry is diagnostic for exercise induced laryngeal obstruction
Authors: Astrid Sandnes, Magnus Hilland, Hege Havstad Clemm, John-Helge Heimdal, Thomas Halvorsen, Ola Drange Røksund
Journal: European Respiratory Journal (2013)

Background:  Studies have suggested that abnormal (truncated) resting maximal inspiratory flow volume loops (FVL) and increased FEF50/FIF50 ratios are features characterizing vocal cord dysfunction (VCD), and hence may be used to diagnose patients with exercise induced laryngeal obstruction (EILO). The evidence supporting these assumptions is weak.   Objectives : To study relationships between maximal resting flow volume loops and corresponding laryngeal response patterns, aiming to address if and how baseline maximal spirometry may serve as a diagnostic tool in patients with EILO.   Methods:  Ten patients (15.6 years) with EILO diagnosed objectively with continuous laryngoscopy exercise (CLE) test performed spirometry with simultaneous and real-time video recorded transnasal laryngoscopy. Spirometry was performed with Vmax 22 â spirometer according to guidelines, while corresponding laryngeal response patterns were video-taped and scored by an experienced otolaryngologist according to Maat et al.   Results:  In 9/10 subjects laryngeal structures (supraglottic or glottic) adducted during the inspiratory part of the spirometric maneuver, to a varying extent obstructing the laryngeal inlet. However, this observed adduction was not clearly associated with a truncated or otherwise abnormal inspiratory flow volume loop. In 4/10 subjects the FEF50/FIF50 ratio did not exceed 1.0 despite observed laryngoscopic abnormalities.   Conclusion : Laryngoscopy but not spirometry during a resting maximal respiratory maneuver may serve as a diagnostic tool in VCD or EILO. The sensitivity of truncated maximal FVLs and increased FEF50/FIF50 ratios was low. Larger studies should explore these issues.
Abstract MP71: Aggressive Blood Pressure Control increased Cardiovascular Heart disease Risk in the Diabetic Patients among Louisiana
Authors: Wenhui Zhao, Peter T Katzmarzyk, Ronald Horswell, Yujie Wang, Wei Li, Jolene Johnson, Steven B Heymsfield, Donna H Ryan, Gang Hu
Journal: Circulation (2013)

Background: Blood pressure control can reduce the risk of coronary heart disease (CHD) among diabetic patents, however, it is not known if the lowest risk of CHD is among diabetic patients with the...
Development of general considerations for clinical research and assessment index for cancer clinical trials on traditional Korean medicine
Authors: Ju Hyun Baek, Mi Hyune Oh, Ko Eun Kim, Jong Pill Lee, Chang Hee Cho, Won Im Do, Jae Hyung Ahn, Jung Hee Cho
Journal: Clinical Cancer Research (2007)

C78   With the tremendous expansion in the use of Traditional Korean Medicine(TKM) worldwide, safety and efficacy as well as quality control have become important issues. Researchers and pharmaceutical manufacturers were increasingly requesting KFDA to provide standards and information on these concerns. This guidelines were carefully developed through the various experts9 opinions, guidelines of KFDA, WHO, EMEA, FDA, NCI, TGA and ICH related to clinical study. The contents of the      General considerations for clinical research on   are definition, general concerns, methodologies for research and evaluation of TKM products. The methodologies are composed of basic principles, sample size, study design, selection of patients, control groups, randomization and blind assessment, study outcome measure and safety and efficacy assessment, interaction between drugs, evaluation of quality of life, traditional medicinal diagnosis and other issues related to clinical trials. The  Assessment index for cancer clinical trials on   suggest that syndrome improvement is mainly evaluated by Zubrod and Karnofsky(%) methods. Questionnaire on physical, emotional, cognitive, social and role subjects availability, three more syndromes (Fatigue, Pain and Nausea/Vomit), quality of life(QOL) will be evaluated by GLM statistics. The assessment endpoints for efficacy to reduce side effects induced by chemotherapy and radiotherapy, the data of image scanning and hemato-urinalysis can be usefully applied on immune response, weight loss, indigestion, hematopoietic damage and injury of liver and kidney. However, it is still necessary to determine the ratio between scientific analytical method and traditional medicine differentiation method as well as confirm the traditional medicine assessment endpoints by clinical trial. These guidelines could be contributed to improving of the quality and value of clinical research in TKM and developing of TKM.
Strength and power in sport, 2nd edn
Authors: J Keogh
Journal: British Journal of Sports Medicine (2004)

Edited by P V Komi. London: Blackwell Publishing, 2003, £75.00, pp 523, hardcover. ISBN 0632059117

Enhancing strength and power is now acknowledged as an integral part of the training process for many sports, as well as being beneficial for members of the general public. However, a number of myths and misconceptions about strength and power training still exist. By encapsulating our current knowledge in this area, Strength and power in sports may help to dispel some of these myths and lead to better practice in the field. The range of topics covered in this book is vast, spanning most of the issues that influence the development of strength and power. These issues are examined in detail within the five sections of the book, which are: definitions; the biological basis for strength and power; mechanisms for adaptation in strength and power training; special problems in strength and power training; strength …
Abstract 11147: NF-{kappa}B P50 and Oct 3/4 Determine the Facilitation of C-Kit+ Cardiac Stem Cells Into Cardiac Commitments by Hdac Inhibition
Authors: Ting Zhao, Xin Qin, Yu Zhao
Journal: Circulation (2011)

Background: We have demonstrated that inhibition of histone deacetylates promotes self-renewal and cardiogenesis in mouse embryonic stem cells. However, the molecular mechanism by which HDAC inhibi...
Small airway function and peripheral airway disease in healthy subjects and smokers
Authors: Sofia-Antiopi Gennimata, Evangelia Daniil, Georgios Kaltsakas, Anastasios Palamidas, Antonia Koutsoukou, John Jordanoglou, Nickolaos G. Koulouris
Journal: European Respiratory Journal (2013)

Functional changes pertinent to the peripheral airways of smokers can be detected even when these smokers present with “normal” spirometry (GOLD 2013), indicating that early structural changes in the small airways develop before the diagnosis of overt COPD is established. The slope of phase III, FEF25-75% (Chest 1984; 86: 100-5), and effective time (Thorax 1980; 35: 375-378) and its variations are advocated for early detection of small airways disease. These tests discriminate between never smokers and smokers with “normal” spirometry. However, it is not clear which of these aforementioned tests is the “most” appropriate to detect early small airways disease.

We studied 64 (36 men) Caucasian subjects (24 never smokers, 27 smokers with normal spirometry, and 13 COPDers of GOLD I). All subjects were free from any co-morbidities and had (mean±SD): age=45±14 y, FVC, %pred=110±12, FEV1, %pred=100±14, FEV1/FVC, %=76±9, TLC, %pred=103±11, FRC, %pred=97±18, and DLCO, %pred=88±15. Simple spirometry, the slope of phase III (ΔN2/L), and the effective time at the 60-70% part of the forced vital capacity of the lung (TEFFp7) were measured.

In the group of subjects with “normal” spirometry: The FEF25-75%, %pred (83±23) was abnormal in 15/51 subjects. The ΔN2/L, %pred (117±63) was abnormal in 14/51 subjects. TEFFp7, %pred (116±43) was abnormal in 20/51. Multiple linear regression analysis showed that TEFFp7, %pred is the “most appropriate”, amongst the tests performed, to discriminate smokers with “normal” spirometry from never smokers (p=0.036).

In conclusion, TEFFp7 appears to be a sensitive test for the early detection of small airway disease.
Parents practise triage for paediatric attendances
Authors: T. Bradley, B. Mccann, J. Glasgow, C. Patterson
Journal: BMJ (1995)

with splenomegaly but, unexpectedly, bone marrow fibrosis and hypocholesterolaemia (total cholesterol concentration 2-4 mmol/l, low density lipoprotein cholesterol concentration 1-5 mmol/l).It seems to us that the common denominator in low proliferating disorders with hypocholesterolaemia -that is, hairy cell leukaemia, myelofibrosis, and Gaucher's disease-is splenomegaly with an expanded reticuloendothelial system.Acute myeloid leukaemia, in contrast, is a disease of rapidly proliferating tumour cells, in which hypocholesterolaemia is associated with tumour cell burden and increased degradation by tumour cells mediated by low density lipoprotein receptors.
Induction of DNA Degradation In Vivo by Adriamycin 2
Authors: Young C. Lee, John E. Byfield
Journal: JNCI Journal of the National Cancer Institute (1976)

The anthracycline antibiotic adriamycin (Ad) induced degradation (single-strand breaks) of cell DNA in vivo in murine L1210 leukemia cells. Measurement was made by alkaline sucrose gradient methods. Exposure of isolated DNA to Ad had little effect; the in vivo DNA strand breaks were probably due to the action of nucleases on DNA distorted by bound Ad. Toxicity of Ad to postmitotic cells such as cardiac cells could be mediated by this mechanism, since it could be demonstrated in periods substantially shorter than the cell generation time and thus could be responsible for interphase death.
Indirect Macrophage Migration Inhibition Response to 3-&lt;italic&gt;M&lt;/italic&gt; KCI Extract of Gastric Carcinoma
Authors: T Akiyoshi, F Koba, M Kawaguchi, S Miyazaki, H Tsuji
Journal: JNCI Journal of the National Cancer Institute (1982)

With the use of indirect macrophage migration inhibition (MMI) test, the MMI response to 3-M KCl extract from gastric carcinoma or adjacent normal tissue was studied in patients with gastric carcinoma, in patients with other types of carcinoma, and in normal controls. The migration index (MI) of less than 75, which was 2 SD below the mean MI of normal controls, was considered positive. Twelve (23%) of 52 patients with gastric carcinoma showed positive response to autologous tumor extract, whereas only 2 (6%) of 35 patients responded to autologous normal tissue extract (P less than 0.03). Positive response to allogeneic gastric carcinoma extract occurred in 4 (9%) of 47 patients with gastric carcinoma and in none of 25 patients with other types of carcinoma. None of 39 patients with gastric carcinoma and 19 patients with nongastric carcinoma responded to allogeneic normal tissue extract. These results appeared to show a lower degree of sensitivity but a relatively higher degree of specificity in the indirect MMI test, as compared to those in the direct leukocyte migration inhibition test, for detection of the cell-mediated immune response to tumor-associated antigens in patients with gastric carcinoma.
Does emphysema influence the application of du Bois score in idiopathic pulmonary fibrosis
Authors: Aline Bodlet, Luc Delaunois, Caroline Dahlqvist, Jacques Jamart, GisÃ¨le Maury
Journal: European Respiratory Journal (2012)

Idiopathic pulmonary fibrosis (IPF) is the most frequent interstitial pulmonary fibrosis. Development in CT scan technology improved accuracy in lung study. Emphysema can be associated to IPF, the most common form is the «Combined pulmonary fibrosis and emphysema» syndrome (CPFE).

The aim of this retrospective cohort study was to assess the impact of emphysema associated to IPF on functional parameters (Forced Vital Capacity FVC and Total Lung Capacity TLC) at baseline (t0) and on the loss of FVC after 6 months (t6) which is used in the du Bois prognostic score.

Data from 73 patients suffering from IPF were collected between 1982 and 2011 in an University Hospital with access to pharmacological studies and lung transplantation. Fifty six patients (M/F: 44/12; age: 65.5±10.8) were considered for analysis. Diagnosis of emphysema was based on CT scan criteria used by Schmidt et al [1].

View this table:



Emphysema seemed to influence significantly TLC and FVC at t0. Du Bois score was not statistically different between the two groups although they corresponded to different subclasses of 1-year mortality risk. According to the du Bois score, patients with emphysema were at lower risk of mortality than the others.

[1] Schmidt SL, Nambiar AM, Tayob N, et al. Pulmonary function measures predict mortality differently in IPF versus combined pulmonary fibrosis and emphysema. Eur Respir J 2011; 38: 176–183.
Anopheles gambiae genome reannotation through synthesis of ab initio and comparative gene prediction algorithms.
Authors: Jun Li, Michelle M Riehle, Yan Zhang, Jiannong Xu, Frederick Oduol, Shawn M Gomez, Karin Eiglmeier, Beatrix M Ueberheide, Jeffrey Shabanowitz, Donald F Hunt, José MC Ribeiro, Kenneth D Vernick
Journal: Genome biology (2006)

Abstract Background Complete genome annotation is a necessary tool as Anopheles gambiae researchers probe the biology of this potent malaria vector. Results We reannotate the A. gambiae genome by synthesizing comparative and ab initio sets of predicted coding sequences (CDSs) into a single set using an exon-gene-union algorithm followed by an open-reading-frame-selection algorithm. The reannotation predicts 20,970 CDSs supported by at least two lines of evidence, and it lowers the proportion of CDSs lacking start and/or stop codons to only approximately 4%. The reannotated CDS set includes a set of 4,681 novel CDSs not represented in the Ensembl annotation but with EST support, and another set of 4,031 Ensembl-supported genes that undergo major structural and, therefore, probably functional changes in the reannotated set. The quality and accuracy of the reannotation was assessed by comparison with end sequences from 20,249 full-length cDNA clones, and evaluation of mass spectrometry peptide hit rates from an A. gambiae shotgun proteomic dataset confirms that the reannotated CDSs offer a high quality protein database for proteomics. We provide a functional proteomics annotation, ReAnoXcel, obtained by analysis of the new CDSs through the AnoXcel pipeline, which allows functional comparisons of the CDS sets within the same bioinformatic platform. CDS data are available for download. Conclusion Comprehensive A. gambiae genome reannotation is achieved through a combination of comparative and ab initio gene prediction algorithms.
Gut Virome Associated With Malnutrition in Children
Authors: M. J. Friedrich
Journal: JAMA (2015)

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Inflammation, Endoleaks, and Aortic Remodeling—The Chicken or the Egg
Authors: Michael Sobel, Gale L. Tang
Journal: JAMA Surgery (2015)

Shalaby and colleagues1have taken a fresh look at inflammationandaortic aneurysmsbyexamining thecontinued remodeling of the residual aneurysmal sac after endovascular repair of infrarenal aortic aneurysms (endovascular aneurysm repair [EVAR]). Two long-term pitfalls for EVAR areendoleaksandcontinuedexpansionof the residual sac.The rate of type II endoleaks may be as low as 15%2 or as high as 27%.3Type II endoleaksusually involve continued flowwithin the aneurysm sac. Approximately 60% resolve within 6 months, but persistence of a type II endoleak after the first 6 months is associatedwith higher rates (55%) of aneurysm sac enlargement.2 The search for risk factors for type II endoleaks and sac expansion have primarily focused on anatomical factors (after all, it is a plumbingproblem): thenumber of patent lumbars, the sizeof the inferiormesenteric artery, theburden of laminated thrombus in the aneurysm, or the technical complexities of the endovascular procedure. Inflammation in the arterialwall has long been suspected as a causative factor for thedevelopment and expansionof an infrarenal aortic aneurysm, which is the most common type of sporadic, nonsyndromic aneurysm. An abundance of inflammatory cells can be found in the aneurysm wall, as well as increases in proteolytic activity and matrix protein degradation.4 This article1 suggests that increased systemic inflammationmay play a role in the failure of sac shrinkage and the development of endoleaks. In a retrospective group of 79 patients undergoingEVAR, 65%had some type of inflammatory condition (eg, allergic rhinitis, osteoarthritis, gout, or rheumatoid arthritis). The “inflammatory” group showed comparable long-termsurvival, experiencedmorepostoperativecomplications (no surprise), and had a significantly higher rate of type II endoleaks, as well as less sac shrinkage in the longterm. Their observations support the intuitive idea that excessive systemic inflammation leads to a failure of aorticwall fibrosis and contraction, resulting in retarded sac shrinkage. Why should this cause more endoleaks, primarily an anatomic problem? Instead of the conventional wisdom that endoleaks cause a failure of sac shrinkage, perhaps the reverse is true: does failure of sac shrinkage foster endoleaks? Themain caveat to their conclusions is that their classification of systemic inflammatory diseasewas based on a diagnosis proffered by others and lacked independent confirmation or, even better, some objective measurements of inflammation.Without confirmatorydata, itwouldbehard to understandhowallergic rhinitisandrheumatoidarthritismight confer a similar derangement of the systemic inflammatory state. This points to a key therapeutic question: what aspect(s) of systemic inflammationmightbeassociatedwith failure of aortic remodeling and which pathways are involved? Some directions for further study may be found in disorders in transforminggrowth factor–βsignalingandtheSMADgenes, bothofwhich share clinical associationswith aneurysmal diseases and osteoarthritis.4,5
Polo‐like kinase and its inhibitors: Ready for the match to start?
Authors: Neil D. Palmisiano, Margaret T. Kasner
Journal: American Journal of Hematology (2015)

Polo-like kinases (Plks) plays a central role in the normal cell cycle and their upregulation has been shown to play a role in the pathogenesis of multiple human cancers. Preclinical work demonstrates that targeting Plk has a significant impact on the treatment of both solid and hematologic malignancies in vitro and in vivo. We review here the basic science and clinical work to date with the Plks as well as future directions with this novel class of mitotic inhibitors.