tbuckley/cabot-search huggingface dataset:
Molecular evolution of the 5'-flanking regions of the duplicated Amy genes in Drosophila melanogaster species subgroup
Authors: E. Okuyama, H. Shibata, H. Tachida, T. Yamazaki
Journal: Molecular Biology and Evolution (1996)

The nucleotide sequences of the 5'-flanking regions of the duplicated Amy genes in eight sibling species belonging to the melanogaster species subgroup are analyzed. In Drosophila melanogaster, a region of about 450 bp immediately upstream of the translation initiation site of the two paralogous genes (the proximal and distal genes) has sequence similarities. However, we could not detect any significant sequence similarity in the region more upstream than -450. This result indicates that the coding regions of the ancestral Amy gene were duplicated together with 450 bp of the 5'-flanking region as one unit. Multiple alignment of these 450-bp sequences in the proximal and distal genes of all eight species revealed a mosaic pattern of highly conserved and divergent regions. The conserved regions included almost all the putative regulatory elements identified in previous analyses of the sequences. A phylogenetic analysis of the aligned sequences shows that these 450-bp sequences are clustered into the proximal and the distal groups. As a whole, the divergence between groups in this region is very large in contrast to that in the coding regions. Based on the divergence between groups, the 450-bp region is divided into two subregions. We found that the ratios of the divergence between groups to that within groups differ in the two subregions. From these observations, we discuss a possibility of positive selection acting on the subregion immediately upstream of the Amy coding region to cause divergence of regulatory elements of the paralogous genes.
Paracrine Network: Another Step in the Complexity of Resistance to EGFR Blockade?
Authors: Ramon Salazar, Gabriel Capellà, Josep Tabernero
Journal: Clinical Cancer Research (2014)

Abstract Increased secretion of EGFR ligands amphiregulin and TGFα by limited KRAS-mutant clones is suggested as a paracrine resistance mechanism to anti-EGFR antibodies in colorectal cancer models. These findings are biologically sound but need to be replicated, including in the clinical setting, to foresee whether they are clinically relevant and therapeutically exploitable. Clin Cancer Res; 20(24); 6227–9. ©2014 AACR.
Whither the foreskin? A consideration of routine neonatal circumcision
Authors: E. N. Preston
Journal: JAMA (1970)

Routine neonatal circumcision has been advocated as a means of preventing genitourinary diseases and genital cancers. However, the procedure has been found to be of questionable benefit and to be associated with both immediate and delayed risks and complications. These in turn may produce undesirable psychologic, sexual, and medico-legal difficulties. Circumcision is considered with respect to carcinoma of the cervix, penis, and prostate; there is little evidence that circumcision of the newborn affords protection against subsequent development of these cancers in individuals who practice good personal hygiene.
Neoadjuvant Vaccination Provides Superior Protection against Tumor Relapse following Surgery Compared with Adjuvant Vaccination
Authors: Natalie Grinshtein, Byram Bridle, Yonghong Wan, Jonathan L. Bramson
Journal: Cancer Research (2009)

Tumors that recur following surgical resection of melanoma are typically metastatic and associated with poor prognosis. Using the murine B16F10 melanoma and a robust antimelanoma vaccine, we evaluated immunization as a tool to improve tumor-free survival following surgery. We investigated the utility of vaccination in both neoadjuvant and adjuvant settings. Surprisingly, neoadjuvant vaccination was far superior and provided approximately 100% protection against tumor relapse. Neoadjuvant vaccination was associated with enhanced frequencies of tumor-specific T cells within the tumor and the tumor-draining lymph nodes following resection. We also observed increased infiltration of antigen-specific T cells into the area of surgery. This method should be amenable to any vaccine platform and can be readily extended to the clinic.
Are British hospitals ready for the next major incident? Analysis of hospital major incident plans
Authors: S. Carley, K. Mackway-Jones
Journal: BMJ (1996)

Although major incidents are uncommon, they require careful planning and preparation if they are to be managed well.1 2 In 1990 guidelines were issued for health service arrangements for major incidents.2 These required regional health authorities to ensure that comprehensive plans were in place for all health service responses to an incident. We examined hospital major incident plans to assess the level of compliance with these guidelines.

The major incident plan was requested from all 224 British hospitals with an emergency department receiving more than 30 000 patients a year. Altogether 142 (63%) were received and analysed. The number of plans complying with different aspects of current guidance are shown in table 1.

View this table:

Table 1 
Number of …
Marine versus terrestrial variability in relation to social learning
Authors: Rebecca Thomas
Journal: Behavioral and Brain Sciences (2001)

Rendell and Whitehead state that marine ecosystems are more variable than terrestrial ecosystems over time scales of months or longer. The marine environment is actually less variable than the terrestrial at these shorter time scales, and probably equally variable over centuries. This issue is important when considering claims that environmental variability affects benefits of social learning versus individual learning and genetics.
Equipment for the Disabled: Home Management
Authors: M. A. Chamberlain
Journal: Annals of the Rheumatic Diseases (1982)

This soft-backed section of Home Management is remarkably good value for £3-00.The layout remains the same as in previous editions, and both the pictures and the text are clear and well laid out.The only illustration I found difficult was that of international textile care labelling, which was so small that those with poor eyesight would have difficulty in reading it.This series of booklets should be in every rheumatology department.Physicians would not be wasting their time if they read the general introduction to each section when looking up a particular problem.The series is a mine of practical and useful information.
Advances in Adjuvant Hormonal Therapy for Postmenopausal Women
Authors: Kathrin Strasser-Weippl, Paul E. Goss
Journal: Journal of Clinical Oncology (2005)

INTRODUCTION Since George Beatson and A. Schinzinger produced remissions of advanced breast cancer by performing bilateral oophorectomy in premenopausal patients more than 100 years ago, the effect of antihormonal therapy on breast cancer has been known. Initial endocrine therapy included oophorectomy, hypophysectomy, and adrenalectomy. The latter two were abandoned when tamoxifen citrate was approved by the US Food and Drug Administration for use in advanced breast cancer in 1978. Selective estrogen receptormodulators (SERMs), such as tamoxifen, antagonize estrogen receptor (ER) function by binding competitively to it. Since 1978, more than 40,000 breast cancer patients, most of them postmenopausal, have been treated with tamoxifen, either in the context of clinical research studies or in clinical practice.
Complement Factors C3a and C5a Are Increased in Bronchoalveolar Lavage Fluid after Segmental Allergen Provocation in Subjects with Asthma
Authors: NORBERT KRUG, THOMAS TSCHERNIG, VEIT J. ERPENBECK, JENS M. HOHLFELD, JÖRG KÖHL
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Allergic asthma is thought to be the result of an inappropriate specific immune response against common environmental antigens. However, studies of animal asthma models have also linked the innate immune system, in particular complement factors C3a and C5, to murine airway hyperresponsiveness. Because the possible role of these anaphylatoxins in patients with asthma is not understood, we tested the hypothesis that C3a and C5a will increase in the bronchoalveolar lavage (BAL) fluid of patients with asthma after segmental allergen provocation. In a group of 15 subjects with mild asthma we found a significant upregulation of C3a and C5a 24 h after allergen challenge compared with baseline values (p < 0.01). In a control group of healthy volunteers the concentrations remained basically unchanged. Furthermore, we found a strong correlation between both anaphylatoxins and the number of eosinophils (p < 0.01) and, to a lesser degree, with the number of neutrophils (p < 0.05) in BAL fluid. These data suggest a contribution of anaphylatoxins C3a and C5a to the pathogenesis in asthma. However, the pathogenic role of these substances in relation to asthma remains to be elucidated, for example, by using anaphylatoxin receptor blockers as a possible new therapeutic principle.
High rate of obstructive pulmonary function tests in adults below 40 Years of age in Germany
Authors: Rainer Wiewrodt, Bianca Hoepfner, Lars Henning Schmist, Karlheinz Blackert, Felix J.F. Herth
Journal: European Respiratory Journal (2013)

Background:

Current studies (i.e. BOLD-project) show a high prevalence of chronic obstructive lung disease (COPD) in Germany, with more than 10% of all people over 40 years being affected. In contrast, the prevalence of obstructive pulmonary diseases in adults below 40 years of age is not well documented.

Aim:

The LuFuMobile is a mobile lung function laboratory with two test sites (Fa. Geraterm), and was inaugurated at the 52th German Thoracic Society Meeting in April 2011. Until August 2012, measurements were performed at 25 locations throughout Germany. The protocol includes a standardized questionnaire and a spirometry according to ERS/ATS-criteria, and was conducted by experienced lung function staff. The primary aim is to determine the national prevalence of obstructive pulmonary function tests (FEV1/FVC < 0.7 and/or FEV1 < 80% predicted).

Results:

Until now 2800 subjects took part (age (median) 61 yrs, range 18-91; 46.5% female). Of 462 individuals (16.5%) with known lung diseases, obstructions were present in 54.5% of them. In people unfamiliar of having lung diseases (n=2338, median 60 yrs), obstructive pulmonary function tests were observed in 20.1% (18.0% in never smokers vs. 22.1% ever smokers, p<0.02). Regarding young adults below 40 years of age (n=406, 17.4%), 10.6% showed obstructions. If they reported “occasional or frequent wheezing”, the prevalence rate increased to 18.5%, and peaked at 25% in case of additional smoking.

Conclusion:

One out of ten young adults below 40 years of age that do not know about having any kind of lung disease displays an obstructive pulmonary function test. Smoking seems to be a risk factor for obstructions in young adults, too.
Prescribing at the hospital-general practice interface
Authors: S E Josse
Journal: BMJ (1992)

SIR,-Clinical chemists have led the way m Royal Infirmary, Glasgow G4OSF developing analytical quality control, to the extent SIR,-The second of the two papers on prescribing that the public can now have considerable confi- at the hospital-general practice interface ends with dence in the correctness of the results obtained a sentence urging that patients' views be sought.'2from properly staffed laboratories.But are we g a e OSpital-Roger Jones and Michael D Rawlins's editorial resting on our laurels in respect of our service general practice interface on the subject agrees that the profession has a provision?Experience indicates that the quality of responsibility to resolve some of the current analyses, which looms large in our eyes, is now SIR,-Roger Jones and Michael D Rawlins plead difficulties.3I would like to present the views of authority.I would hope that the consultant would from the introduction of population screening for 1 Lauder I. Auditing necropsies.BMJ 1991;303:1214-5. (16 escape involvement in any civil action that a patient the risk of Down's syndrome.2November.)2Department of Health.Report on confidential enquiri'es 'nto maternal might bring against the hospital (and possibly the deaths in the United Kingdom 1985-7.
Risedronate in children with osteogenesis imperfecta: a randomised, double-blind, placebo-controlled trial
Authors: Nick Bishop, Silvano Adami, S Faisal Ahmed, Jordi Antón, Paul Arundel, Christine P Burren, Jean-Pierre Devogelaer, Thomas Hangartner, Eva Hosszú, Joseph M Lane, Roman Lorenc, Outi Mäkitie, Craig F Munns, Ana Paredes, Helene Pavlov, Horacio Plotkin, Cathleen L Raggio, Maria Loreto Reyes, Eckhard Schoenau, Oliver Semler, David O Sillence, Robert D Steiner
Journal: The Lancet (2013)
Trastuzumab Administration Can Effectively Target Chemotherapy-Resistant Cytokeratin-19 Messenger RNA–Positive Tumor Cells in the Peripheral Blood and Bone Marrow of Patients With Breast Cancer
Authors: Vassiliki Bozionellou, Dimitris Mavroudis, Maria Perraki, Savvas Papadopoulos, Stella Apostolaki, Efstathios Stathopoulos, Aliki Stathopoulou, Evi Lianidou, Vassilis Georgoulias
Journal: Clinical Cancer Research (2004)

The detection of disseminated occult breast cancer cells in peripheral blood and bone marrow is associated with poor prognosis. Since a high proportion of these cells express the HER-2 receptor, we evaluated the effectiveness of the anti-HER-2 antibody trastuzumab (Herceptin) administration to eliminate them.Thirty patients with prior chemotherapy exposure were recruited to the study on the basis of having detectable cytokeratin-19 (CK-19) mRNA transcripts by nested reverse transcription (RT)-PCR in the peripheral blood and/or bone marrow. There were 13 patients with stage I, II, or III breast cancer and 17 with stage IV disease. They were treated in two cohorts with either 4 to 8 weekly infusions of trastuzumab at 2 mg/kg (4 mg/kg loading dose; 20 patients) or 2 to 3 infusions every 3 weeks at 6 mg/kg (8 mg/kg loading dose; 10 patients). All of the patients' samples were also analyzed for HER-2 by nested RT-PCR, but detectable HER-2 messenger RNA (mRNA) was not required for inclusion in the study. After trastuzumab infusions, patients were closely monitored by nested RT-PCR and real-time RT-PCR for the detection of CK-19 mRNA-positive cells.Before trastuzumab infusions, CK-19 mRNA-positive cells were detected in the peripheral blood (n = 10), bone marrow (n = 14), or both (n = 6). In 25 of 30 patients (83%), HER-2 mRNA expression was detected by nested RT-PCR in the pretrastuzumab CK-19-positive sample. After trastuzumab infusions, overall, 28 of 30 (93%) patients became CK-19 mRNA negative by nested RT-PCR and 20 of 30 (67%) by real-time RT-PCR. After a median follow-up of 6 months (range 2 to 22+), the median duration of CK-19 mRNA negativity by nested RT-PCR was 9, 12, and 6 months for stage I/II, III, and IV disease, respectively.Therapy-resistant CK-19 mRNA-positive cells in the peripheral blood and bone marrow can be effectively targeted by trastuzumab administration. Further studies are needed to evaluate the prognostic significance of the disappearance of these cells.
The Effect of Medicare Part D on Drug and Medical Spending
Authors: Yuting Zhang, Julie M. Donohue, Judith R. Lave, Gerald O'Donnell, Joseph P. Newhouse
Journal: New England Journal of Medicine (2009)

It is not known what effect the increased use of prescription drugs by enrollees in Medicare Part D has had on spending for other medical care.We compared spending for prescription drugs and other medical care 2 years before the implementation of Part D in January 2006 with such expenditures 2 years after the program's implementation in four groups of elderly beneficiaries: Medicare Advantage enrollees with stable, uncapped, employer-based drug coverage throughout the study period (no-cap group), those who had no previous drug coverage, and those who had previous limited benefits (with either a $150 or a $350 quarterly cap) before they were covered by Part D in 2006.Between December 2005 and December 2007, as compared with the increase in the no-cap group, the increase in total monthly drug spending was $41 higher (95% confidence interval [CI], $33 to $50) (74%) among enrollees with no previous drug coverage, $27 higher (95% CI, $20 to $34) (27%) among those with a previous $150 quarterly cap, and $13 higher (95% CI, $8 to $18) (11%) among those with a previous $350 cap. The use of both lipid-lowering and antidiabetic medications rose in the groups with no or minimal previous drug coverage. As compared with expenditures in the no-cap group, monthly medical expenditures (excluding drugs) were $33 lower (95% CI, $29 to $37) in the group with no previous coverage and $46 lower (95% CI, $29 to $63) in the group with a previous $150 quarterly cap, whereas medical spending was $30 higher (95% CI, $25 to $36) in the group with a previous $350 cap.Enrollment in Medicare Part D was associated with increased spending on prescription drugs. Groups that had no or minimal drug coverage before the implementation of Part D had reductions in other medical spending that approximately offset the increased spending on drugs, but medical spending increased in the group that had more generous previous coverage.
Engineering Simulation of the Viscous Behavior of Whole Blood Using Suspensions of Flexible Particles
Authors: E. Glenn Tickner, Alvin H. Sacks
Journal: Circulation Research (1969)

Highly flexible model red cells were molded of acrylamide gel and suspended in a mixture of castor oil and diiodomethane to produce a neutrally buoyant fluid suspension in which the particles behaved mechanically very much like living erythrocytes. The various suspensions were permitted to flow down long cylindrical tubes while measurements of flow rate and pressure drop were made for various concentrations. The fluid suspensions were found to exhibit non-Newtonian viscous behavior which agrees very well with that of whole blood under comparable conditions. The fluid suspensions also exhibited a yield stress below which particle motion ceases. The yield stress was found to depend strongly on particle concentration, as is the case for whole blood.
Randomized Phase III Study of Exatecan and Gemcitabine Compared With Gemcitabine Alone in Untreated Advanced Pancreatic Cancer
Authors: Ghassan K. Abou-Alfa, Richard Letourneau, Graydon Harker, Manuel Modiano, Herbert Hurwitz, Nerses Simon Tchekmedyian, Kevie Feit, Judie Ackerman, Robert L. De Jager, S. Gail Eckhardt, Eileen M. O'Reilly
Journal: Journal of Clinical Oncology (2006)

Exatecan mesylate is a hexacyclic, water-soluble, topoisomerase-1 inhibitor. Exatecan has single-agent and combination activity with gemcitabine in advanced pancreatic cancer. A multicenter, randomized, phase III trial comparing exatecan plus gemcitabine versus gemcitabine alone in advanced pancreatic cancer was conducted.Eligibility criteria included Karnofsky performance status > or = 60%, locally advanced or metastatic pancreatic adenocarcinoma, and no prior chemotherapy. Radiation alone for locally advanced disease was permitted. Patients were randomly assigned on a 1:1 basis. For the exatecan plus gemcitabine arm, exatecan 2.0 mg/m2 and gemcitabine 1,000 mg/m2 were administered on days 1 and 8, every 3 weeks. Gemcitabine alone was dosed at 1,000 mg/m2 up to 7 weeks in the first cycle, then once a week for the first 3 weeks of a 4-week cycle. Tumor assessment was performed every 6 weeks. The primary end point was overall survival. An intent-to-treat analysis was used.From August 2001 to January 2003, 349 patients were randomly assigned, 175 to exatecan plus gemcitabine and 174 to gemcitabine alone. Twenty-four patients (6.9%) were not treated. The median survival time was 6.7 months for exatecan plus gemcitabine and 6.2 months for gemcitabine alone (P = .52). One complete response (CR; < 1%) and 11 partial responses (PRs; 6.3%) were observed in the exatecan plus gemcitabine treatment group, and one CR (< 1%) and eight PRs (4.6%) were observed in the gemcitabine-alone group. Grade 3 and 4 toxicities were higher for the exatecan plus gemcitabine arm versus the gemcitabine alone arm; neutropenia (30% v 15%) and thrombocytopenia (15% v 4%).Exatecan plus gemcitabine was not superior to gemcitabine alone with respect to overall survival in the first-line treatment of advanced pancreatic cancer.
In silico gene expression analysis – an overview
Authors: David Murray, Peter Doran, Padraic MacMathuna, Alan C Moss
Journal: Molecular Cancer (2007)

Abstract Efforts aimed at deciphering the molecular basis of complex disease are underpinned by the availability of high throughput strategies for the identification of biomolecules that drive the disease process. The completion of the human genome-sequencing project, coupled to major technological developments, has afforded investigators myriad opportunities for multidimensional analysis of biological systems. Nowhere has this research explosion been more evident than in the field of transcriptomics. Affordable access and availability to the technology that supports such investigations has led to a significant increase in the amount of data generated. As most biological distinctions are now observed at a genomic level, a large amount of expression information is now openly available via public databases. Furthermore, numerous computational based methods have been developed to harness the power of these data. In this review we provide a brief overview of in silico methodologies for the analysis of differential gene expression such as Serial Analysis of Gene Expression and Digital Differential Display. The performance of these strategies, at both an operational and result/output level is assessed and compared. The key considerations that must be made when completing an in silico expression analysis are also presented as a roadmap to facilitate biologists. Furthermore, to highlight the importance of these in silico methodologies in contemporary biomedical research, examples of current studies using these approaches are discussed. The overriding goal of this review is to present the scientific community with a critical overview of these strategies, so that they can be effectively added to the tool box of biomedical researchers focused on identifying the molecular mechanisms of disease.