tbuckley/cabot-search huggingface dataset:
Text mining for biology - the way forward: opinions from leading scientists
Authors: Russ B Altman, Casey M Bergman, Judith Blake, Christian Blaschke, Aaron Cohen, Frank Gannon, Les Grivell, Udo Hahn, William Hersh, Lynette Hirschman, Lars Juhl Jensen, Martin Krallinger, Barend Mons, Seán I O'Donoghue, Manuel C Peitsch, Dietrich Rebholz-Schuhmann, Hagit Shatkay, Alfonso Valencia
Journal: Genome biology (2008)

Abstract This article collects opinions from leading scientists about how text mining can provide better access to the biological literature, how the scientific community can help with this process, what the next steps are, and what role future BioCreative evaluations can play. The responses identify several broad themes, including the possibility of fusing literature and biological databases through text mining; the need for user interfaces tailored to different classes of users and supporting community-based annotation; the importance of scaling text mining technology and inserting it into larger workflows; and suggestions for additional challenge evaluations, new applications, and additional resources needed to make progress.
William Osler and Bartholomaeus Anglicus' De proprietatibus rerum
Authors: R. Palmer Howard
Journal: JAMA (1969)

William Osler (1849-1919) was the beloved physician of his age. He inspired his associates, students, patients, and friends wherever he encountered them. The bonds were lasting through his lifetime and those of his acquaintances too. His influence on members of the medical profession and many allied fields was indeed a "potent ferment" and burned deeply into the hearts of those who knew him<sup>1</sup>(the author's grandfather used the phrase "potent ferment" in a letter to Osler in 1884). Through their spoken tributes and his own deeds and writings, Osler's name is engraved with honor on the minds of untold numbers in the succeeding generations of men and women. Osler's fame today may be ascribed to many things, among which are his writings and his love of books.<i>The Principles and Practice of Medicine</i>in 1892 established his preeminence as a talented medical writer.<sup>2</sup>It rapidly became the standard
Very-Low-Calorie Diet Increases Myocardial Triglyceride Content and Decreases Diastolic Left Ventricular Function in Type 2 Diabetes With Cardiac Complications
Authors: Jacqueline T. Jonker, Roxana Djaberi, Linda D. van Schinkel, Sebastiaan Hammer, Mieke T.J. Bus, Gijs Kerpershoek, Aan V. Kharagjitsingh, Johannes A. Romijn, Jeroen J. Bax, J. Wouter Jukema, Albert de Roos, Johannes W.A. Smit, Hildo J. Lamb
Journal: Diabetes Care (2013)

In healthy subjects and patients with uncomplicated type 2 diabetes, short-term very-low-calorie diet (VLCD) increases myocardial triglyceride (TG) content and decreases diastolic cardiac function (1). We hypothesized that in diabetic patients with cardiac complications, the adaptive capacity of the heart to adjust myocardial TG content, depending on the metabolic context, is diminished or lost. We aimed to assess the effects of a short-term VLCD in type 2 diabetic patients with cardiac complications on myocardial TG content and cardiac function.

Therefore, 14 type 2 diabetic patients were included in this study (7 men, mean age 57 ± 3 years, 10 insulin users). Cardiac complications were defined as 1 ) obstructive coronary artery disease on multislice computed tomography angiography (≥50% luminal narrowing) and/or 2 ) myocardial perfusion defect on single photon emission computed tomography (summed stress score ≥3) (2). Exclusion criteria were age <18 years, thiazolidinedione use, congenital cardiac disease, or contraindications for magnetic resonance imaging. Written informed consent was obtained from all patients. This study was …
FCGR2A and FCGR3A Polymorphisms Associated With Clinical Outcome of Epidermal Growth Factor Receptor–Expressing Metastatic Colorectal Cancer Patients Treated With Single-Agent Cetuximab
Authors: Wu Zhang, Michael Gordon, Anne M. Schultheis, Dong Yun Yang, Fumio Nagashima, Mizutomo Azuma, Heung-Moon Chang, Eva Borucka, Georg Lurje, Andy E. Sherrod, Syma Iqbal, Susan Groshen, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2007)

Purpose Cetuximab, a chimeric immunoglobulin G 1 (IgG1) anti–epidermal growth factor receptor (EGFR) monoclonal antibody (mAb), has shown efficacy in 10% of patients with metastatic colorectal cancer (CRC). Recent studies demonstrate antibody-dependent cell-mediated cytotoxicity (ADCC) is one of the modes of action for rituximab and trastuzumab. Fragment c (Fc) portion of IgG1 mAb has shown to induce ADCC. Fragment c gamma receptors (FcγR) play an important role in initiating ADCC. Studies have shown that two IgG FcγR polymorphisms (FCGR2A-H131R and FCGR3A-V158F) independently predict response to rituximab in patients with follicular lymphoma. We tested the hypothesis of whether these two polymorphisms are associated with clinical outcome in metastatic CRC patients treated with single-agent cetuximab. Patients and Methods Thirty-nine metastatic CRC patients were enrolled onto the ImClone0144 trial. Using an allele-specific polymerase chain reaction (PCR) –based method, gene polymorphisms of FCGA2A-H131R and FCGA3A-V158F were assessed from genomic DNA extracted from peripheral blood samples. Results FCGR2A-H131R and FCGR3A-V158F polymorphisms were independently associated with progression-free survival (PFS; P = .037 and .055, respectively; log-rank test). Combined analysis of these two polymorphisms showed that patients with the favorable genotypes (FCGR2A, any histidine allele, and FCGR3A, any phenylalanine allele) showed a median PFS of 3.7 months (95% CI, 2.4 to 4.4 months), whereas patients with any two unfavorable genotypes (FCGR2A arginine/arginine or valine/valine) had a PFS of 1.1 months (95% CI, 1.0 to 1.4 months; P = .004; log-rank test). Conclusion Our preliminary data suggest that these two polymorphisms may be useful molecular markers to predict clinical outcome in metastatic CRC patients treated with cetuximab and that they may indicate a role of ADCC of cetuximab.
Summary of the Informal Discussion of Cancers of the Pancreas and Stomach and Miscellaneous Dietary Factors
Authors: Guy R. Newell
Journal: Cancer Research (1975)

considered. He also thought that it is very important to recognize that some of these theories cannot be dealt with in small laboratory animals and that, therefore, it is quite important that some of the ideas that derive from epidemi ology are developed into experimental approaches as rap idly as possible. Dr. Fraumenisuggested that perhapstask forcesshould be set up in the area of pancreatic cancer and that the sooner the leads from epidemiology are followed up the sooner preventive measures can be proposed. Dr. Hirayama commented that the epidemiology of pancreatic cancer is based on ongoing prospective studies and that unexpectedly he found that the risk is enormously high in whiskey drinkers, much higher than with other factors.
A Double-Blind, Randomized, Dose-Response Study Investigating the Pharmacodynamic and Pharmacokinetic Properties of the Long-Acting Insulin Analog Detemir
Authors: Johannes Plank, Manfred Bodenlenz, Frank Sinner, Christoph Magnes, Evelyn Görzer, Werner Regittnig, Lars A. Endahl, Eberhard Draeger, Milan Zdravkovic, Thomas R. Pieber
Journal: Diabetes Care (2005)

OBJECTIVE—To investigate the pharmacodynamic profile and duration of action for five subcutaneous doses of insulin detemir (0.1, 0.2, 0.4, 0.8, and 1.6 units/kg; 1 unit = 24 nmol) and one subcutaneous dose of NPH insulin (0.3 IU/kg; 1 IU = 6 nmol). RESEARCH DESIGN AND METHODS—This single-center, randomized, double-blind, six-period, crossover study was carried out as a 24-h isoglycemic clamp (7.2 mmol/l) in 12 type 1 diabetic patients. RESULTS—Duration of action for insulin detemir was dose dependent and varied from 5.7, to 12.1, to 19.9, to 22.7, to 23.2 h for 0.1, 0.2, 0.4, 0.8, and 1.6 units/kg, respectively. Interpolation of the dose-response relationships for AUCGIR (area under the glucose infusion rate curve) revealed that a detemir dose of 0.29 units/kg would provide the same effect as 0.3 IU/kg NPH but has a longer duration of action (16.9 vs. 12.7 h, respectively). Lower between-subject variability was observed for insulin detemir on duration of action (0.4 units/kg insulin detemir vs. 0.3 IU/kg NPH, P &amp;lt; 0.05) and GIRmax (maximal glucose infusion rate) (0.2 and 0.4 units/kg insulin detemir vs. 0.3 IU/kg NPH, both P &amp;lt; 0.05). Assessment of endogenous glucose production (EGP) and peripheral glucose uptake (PGU) resulted in an AOCEGP (area over the EGP curve) of 636 mg/kg (95% CI 279–879) vs. 584 (323–846) and an AUCPGU (area under the PGU curve) of 173 (47–316) vs. 328 (39–617) for 0.29 units/kg detemir vs. 0.3 IU/kg NPH, respectively. CONCLUSIONS—This study shows that insulin detemir provides a flat and protracted pharmacodynamic profile.
Association of Colonoscopy and Death From Colorectal Cancer
Authors: Nancy N. Baxter
Journal: Annals of Internal Medicine (2009)

Background: Colonoscopy is advocated for screening and prevention of colorectal cancer (CRC), but randomized trials supporting the benefit of this practice are not available. Objective: To evaluate the association between colonoscopy and CRC deaths. Design: Population-based, case–control study. Setting: Ontario, Canada. Patients: Persons age 52 to 90 years who received a CRC diagnosis from January 1996 to December 2001 and died of CRC by December 2003. Five controls matched by age, sex, geographic location, and socioeconomic status were randomly selected for each case patient. Measurements: Administrative claims data were used to detect exposure to any colonoscopy and complete colonoscopy (to the cecum) from January 1992 to an index date 6 months before diagnosis in each case patient and the same assigned date in matched controls. Exposures in case patients and controls were compared by using conditional logistic regression to control for comorbid conditions. Secondary analyses were done to see whether associations differed by site of primary CRC, age, or sex. Results: 10 292 case patients and 51 460 controls were identified; 719 case patients (7.0%) and 5031 controls (9.8%) had undergone colonoscopy. Compared with controls, case patients were less likely to have undergone any attempted colonoscopy (adjusted conditional odds ratio [OR], 0.69 [95% CI, 0.63 to 0.74; P < 0.001]) or complete colonoscopy (adjusted conditional OR, 0.63 [CI, 0.57 to 0.69; P < 0.001]). Complete colonoscopy was strongly associated with fewer deaths from left-sided CRC (adjusted conditional OR, 0.33 [CI, 0.28 to 0.39]) but not from right-sided CRC (adjusted conditional OR, 0.99 [CI, 0.86 to 1.14]). Limitation: Screening could not be differentiated from diagnostic procedures. Conclusion: In usual practice, colonoscopy is associated with fewer deaths from CRC. This association is primarily limited to deaths from cancer developing in the left side of the colon. Funding: Canadian Institutes of Health Research and American Society of Clinical Oncology.
A Dirichlet Process Prior for Estimating Lineage-Specific Substitution Rates
Authors: T. A. Heath, M. T. Holder, J. P. Huelsenbeck
Journal: Molecular Biology and Evolution (2011)

We introduce a new model for relaxing the assumption of a strict molecular clock for use as a prior in Bayesian methods for divergence time estimation. Lineage-specific rates of substitution are modeled using a Dirichlet process prior (DPP), a type of stochastic process that assumes lineages of a phylogenetic tree are distributed into distinct rate classes. Under the Dirichlet process, the number of rate classes, assignment of branches to rate classes, and the rate value associated with each class are treated as random variables. The performance of this model was evaluated by conducting analyses on data sets simulated under a range of different models. We compared the Dirichlet process model with two alternative models for rate variation: the strict molecular clock and the independent rates model. Our results show that divergence time estimation under the DPP provides robust estimates of node ages and branch rates without significantly reducing power. Further analyses were conducted on a biological data set, and we provide examples of ways to summarize Markov chain Monte Carlo samples under this model.
Immune Evasion by Chimeric Trachea
Authors: Megan Sykes
Journal: New England Journal of Medicine (2010)

The types of allogeneic organs and tissues that can be transplanted have expanded considerably in the past three decades. In addition to organs such as liver, heart, lungs, and pancreas, the list of allografts now includes islets of Langerhans and composite tissues such as hands and face. In this issue of the Journal, Delaere and colleagues report the successful transplantation of a tracheal cartilaginous allograft in which the mucosa was first replaced and revascularization established in a heterotopic location in the recipient; the graft was then implanted orthotopically and accepted without immunosuppressive therapy.1 Allografts typically require nonspecific immunosuppressive therapy to . . .
Structure of a monoclonal kappa chain of the V kappa IV subgroup in the kidney and plasma cells in light chain deposition disease.
Authors: M Cogné, J L Preud'homme, M Bauwens, G Touchard, P Aucouturier
Journal: Journal of Clinical Investigation (1991)

That structural abnormalities may be responsible for nonamyloid immunoglobulin (Ig) light chain deposition disease (LCDD) is suggested by previous results of Ig biosynthesis studies, but this hypothesis was not documented at the molecular level. We report on the first complete primary sequence deduced from cDNA analysis of a kappa light chain responsible for LCDD associated with an apparently nonsecretory myeloma. Bone marrow myeloma cells contained intracellular kappa chains and no heavy chains by immunofluorescence. Kidney biopsy showed typical nonamyloid PAS-positive kappa chain deposits. SDS-PAGE analysis of material extracted from a kidney biopsy specimen and of Ig produced by the myeloma cells revealed kappa chains of abnormally high apparent molecular mass (30,000). Comparison of the NH2-terminal aminoacid sequence of the kappa chain deposited in the kidney and of the complete sequence of several identical kappa cDNA clones from bone marrow cells showed the identity of the tissue deposited and plasma cell kappa chain. The kappa mRNA had an overall normal structure and corresponded to the V kappa IV gene rearranged to J kappa 1 and followed by a normal constant exon of the Km(3) allotype. The variable sequence differed from the V kappa IV germline gene by nine point mutations, including an Asp----Asn substitution at position +70 resulting in a potential N-glycosylation site. In vitro biosynthesis experiments and treatment with N-glycosidase provided evidence for the intracellular glycosylation of the monoclonal kappa chain. The peculiar sequence and the glycosylation of a kappa chain of the rare V kappa IV subgroup might be responsible for structural abnormalities leading to tissue deposition.
UK has more guidance on dealing with abandoned cars than abandoned babies, study finds
Authors: R. Dobson
Journal: BMJ (2009)

Researchers have called for national guidelines in the United Kingdom on how to handle abandoned babies, after they found that only three of 170 NHS organisations have any relevant policies in place.

The authors of the study, from the Royal Free and University College Medical School, London, wrote: “There are currently greater provisions in terms of policies for abandoned vehicles than for babies—a sad state of affairs . . . Overall, there is a vast lack of standardised guidelines for dealing with an abandoned baby …
Phase II Feasibility and Pharmacokinetic Study of Concurrent Administration of Trastuzumab and High-Dose Chemotherapy in Advanced HER2+ Breast Cancer
Authors: Yago Nieto, James J. Vredenburgh, Elizabeth J. Shpall, Scott I. Bearman, Peter A. McSweeney, Nelson Chao, David Rizzieri, Christina Gasparetto, Steve Matthes, Anna E. Barón, Roy B. Jones
Journal: Clinical Cancer Research (2004)

Abstract Purpose: To evaluate the safety of concurrent treatment with trastuzumab and high-dose chemotherapy (HDC), using cyclophosphamide, cisplatin, and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), with autologous hematopoietic progenitor cells support, in patients with HER2+ advanced breast cancer. Experimental Design: Patients with HER2-overexpressing high-risk primary breast cancer (HRPBC; defined as ≥4 involved nodes or inflammatory disease), or metastatic breast cancer (MBC) were eligible. Treatment consisted of a loading dose of trastuzumab at 4 mg/kg (day −5), HDC (days −5 to −2), autologous hematopoietic progenitor cells infusion on day 0, and weekly maintenance trastuzumab (2 mg/kg) from day +1 (minimum of 9 doses). Cardiac monitoring included serial left ventricular ejection fraction measurements before treatment and on days +20 and +65. Results: Thirty-three patients were prospectively enrolled (13 HRPBC, 20 MBC). Toxicity seemed similar to that expected with this HDC regimen alone. Neutrophils and platelets engrafted promptly. There were no cases of grade 4 or 5 toxicity. One patient experienced symptomatic grade 3 acute cardiac failure on day −4, responsive to treatment. Trastuzumab did not alter the pharmacokinetics of HDC. Eleven of twelve MBC patients with measurable disease (nine of them refractory to previous chemotherapy) experienced an objective response (9 complete and 2 partial responses). At median follow-up of 34 (13–58) months, all HRPBC patients remain alive and free of disease; the MBC group has event-free survival and overall survival rates of 45 and 70%, respectively. Conclusions: Incorporation of trastuzumab into HDC (cyclophosphamide, cisplatin, and BCNU) is feasible, with no apparent increased toxicity or pharmacokinetic interactions.
The role of indigenous phlebotomine sandflies and mammals in the spreading of leishmaniasis agents in the Mediterranean region
Authors: M Antoniou, M Gramiccia, R Molina, V Dvorak, P Volf
Journal: Eurosurveillance (2013)

An updated view of the establishment and spread of the leishmaniases in Europe is presented, mostly with respect to newly emerging and re-emerging foci and the incrimination of neglected as well as new reservoir hosts. At the same time, a concept of specific versus permissive vectors reassesses the potential role of various sandfly species in Leishmania transmission and considers the risk of introduction of exotic Leishmania species in Europe. The leishmaniases are dynamic diseases and the circumstances of transmission are continually changing in relation to environmental, demographic and human behavioural factors. Changes in the habitat of the natural hosts and vectors, immunosuppressive conditions (like infection with human immunodeficiency virus (HIV) or organ transplantation-associated therapies in humans) and the consequences of war, all contribute to the transformation of the epidemiology of leishmaniasis. Such changes should be considered when studying the spread of the disease throughout Europe for targeted control measures to safeguard public health.
Risk-Reduction Mastectomy: Clinical Issues and Research Needs
Authors: M. Stefanek, L. Hartmann, W. Nelson
Journal: JNCI Journal of the National Cancer Institute (2001)

Risk-reduction mastectomy (RRM), also known as bilateral prophylactic mastectomy, is a controversial clinical option for women who are at increased risk of breast cancer. High-risk women, including women with a strong family history of breast cancer and BRCA1/2 mutation carriers, have several clinical options: risk-reduction surgery (bilateral mastectomy and bilateral oophorectomy), surveillance (mammography, clinical breast examination, and breast self-examination), and chemoprevention (tamoxifen). We review research in a number of areas central to our understanding of RRM, including recent data on 1) the effectiveness of RRM in reducing breast cancer risk, 2) the perception of RRM among women at increased risk and health-care providers, 3) the decision-making process for follow-up care of women at high risk, and 4) satisfaction and psychological status after surgery. We suggest areas of future research to better guide high-risk women and their health-care providers in the decision-making process.
VEGF Blockade Inhibits Lymphocyte Recruitment and Ameliorates Immune-Mediated Vascular Remodeling
Authors: Jiasheng Zhang, Teresa Silva, Timur Yarovinsky, Thomas D. Manes, Sina Tavakoli, Lei Nie, George Tellides, Jordan S. Pober, Jeffrey R. Bender, Mehran M. Sadeghi
Journal: Circulation Research (2010)

There are conflicting data on the effects of vascular endothelial growth factor (VEGF) in vascular remodeling. Furthermore, there are species-specific differences in leukocyte and vascular cell biology and little is known about the role of VEGF in remodeling of human arteries.We sought to address the role of VEGF blockade on remodeling of human arteries in vivo.We used an anti-VEGF antibody, bevacizumab, to study the effect of VEGF blockade on remodeling of human coronary artery transplants in severe combined immunodeficient mice. Bevacizumab ameliorated peripheral blood mononuclear cell-induced but not interferon-gamma-induced neointimal formation. This inhibitory effect was associated with a reduction in graft T-cell accumulation without affecting T-cell activation. VEGF enhanced T-cell capture by activated endothelium under flow conditions. The VEGF effect could be recapitulated when a combination of recombinant intercellular adhesion molecule 1 and vascular cell adhesion molecule-1 rather than endothelial cells was used to capture T cells. A subpopulation of CD3+ T cells expressed VEGF receptor (VEGFR)-1 by immunostaining and FACS analysis. VEGFR-1 mRNA was also detectable in purified CD4+ T cells and Jurkat and HSB-2 T-cell lines. Stimulation of HSB-2 and T cells with VEGF triggered downstream ERK phosphorylation, demonstrating the functionality of VEGFR-1 in human T cells.VEGF contributes to vascular remodeling in human arteries through a direct effect on human T cells that enhances their recruitment to the vessel. These findings raise the possibility of novel therapeutic approaches to vascular remodeling based on inhibition of VEGF signaling.
ATM and p21 Cooperate to Suppress Aneuploidy and Subsequent Tumor Development
Authors: Kate C. Shen, Henry Heng, Yaolin Wang, Shu Lu, Guo Liu, Chu-Xia Deng, S.C. Brooks, Y. Alan Wang
Journal: Cancer Research (2005)

Abstract The DNA damage checkpoint protein kinase mutated in ataxia telangiectasia (ATM) is involved in sensing and transducing DNA damage signals by phosphorylating and activating downstream target proteins that are implicated in the regulation of cell cycle progression and DNA repair. Atm−/− cells are defective in cellular proliferation mediated by the Arf/p53/p21 pathway. In this report, we show that increased expression of p21 (also known as Waf1 or CDKN1a) in Atm−/− cells serves as a cellular defense mechanism to suppress further chromosomal instability (CIN) and tumor development because Atm−/−p21−/− mice are predisposed to carcinomas and sarcomas with intratumoral heterogeneity. It was found that Atm-deficient cells are defective in metaphase-anaphase transition leading to abnormal karyokinesis. Moreover, Atm−/−p21−/− primary embryonic fibroblasts exhibit increased CIN compared with either Atm−/− or p21−/− cells. The increased CIN is manifested at the cellular level by increased chromatid breaks and elevated aneuploid genome in Atm−/−p21−/− cells. Finally, we showed that the role of p21 in a CIN background induced by loss of Atm is to suppress numerical CIN but not structural CIN. Our data suggest that the development of aneuploidy precedes tumor formation and implicates p21 as a major tumor suppressor in a genome instability background.