tbuckley/cabot-search huggingface dataset:
Integrative Microarray Analysis of Pathways Dysregulated in Metastatic Prostate Cancer
Authors: Sunita R. Setlur, Thomas E. Royce, Andrea Sboner, Juan-Miguel Mosquera, Francesca Demichelis, Matthias D. Hofer, Kirsten D. Mertz, Mark Gerstein, Mark A. Rubin
Journal: Cancer Research (2007)

Abstract Microarrays have been used to identify genes involved in cancer progression. We have now developed an algorithm that identifies dysregulated pathways from multiple expression array data sets without a priori definition of gene expression thresholds. Integrative microarray analysis of pathways (IMAP) was done using existing expression array data from localized and metastatic prostate cancer. Comparison of metastatic cancer and localized disease in multiple expression array profiling studies using the IMAP approach yielded a list of about 100 pathways that were significantly dysregulated (P &amp;lt; 0.05) in prostate cancer metastasis. The pathway that showed the most significant dysregulation, HIV-I NEF, was validated at both the transcript level and the protein level by quantitative PCR and immunohistochemical analysis, respectively. Validation by unsupervised analysis on an independent data set using the gene expression signature from the HIV-I NEF pathway verified the accuracy of our method. Our results indicate that this pathway is especially dysregulated in hormone-refractory prostate cancer. [Cancer Res 2007;67(21):10296–303]
Iron status of beta thalassemia carriers
Authors: B. C. Mehta, B. G. Pandya
Journal: American Journal of Hematology (1987)

Abstract One hundred twenty‐four relatives (aged 17‐52 years) of 35 children with severe transfusion‐dependent beta thalassemia major were investigated for their beta thalassemia carrier status (determined by Hb‐A 2 level) and iron status (determined by serum ferritin level). Forty‐eight males had beta thalassemia trait (BTT) and 18 males did not have BTT (control); 41 females had BTT and 17 females did not have BTT (control). Serum ferritin levels (mean ± SEM) of male BTT, male control, female BTT, and female control groups were 151.0 ± 27.4, 59.6 ± 16.3, 120.6 ± 36.6, and 17.2 ± 6.1 meg/liter respectively; the differences between the two male and the two female groups were statistically significant ( p = 0.05 and p &lt; 0.001). Iron deficiency (serum ferritin below 10.0 meg/liter) was present in 6.3%, 38.9%, 24.4%, and 58.8% of male BTT, male control Female BTT, and female control groups, respectively; the differences between the two male and two female groups were statistically significant ( p &lt; 0.01 and p &lt; 0.01). Serum ferritin was over 1,000 meg/liter in four individuals with BTT (2 male and 2 female). Thus, the BTT group had better iron nutrition. This may suggest that the BTT group has an advantage in maintaining iron balance.
Anticoagulant treatment for acute pulmonary embolism: a pathophysiology-based clinical approach
Authors: Giancarlo Agnelli, Cecilia Becattini
Journal: European Respiratory Journal (2015)

The management of patients with acute pulmonary embolism is made challenging by its wide spectrum of clinical presentation and outcome, which is mainly related to patient haemodynamic status and right ventricular overload. Mechanical embolic obstruction and neurohumorally mediated pulmonary vasoconstriction are responsible for right ventricular overload. The pathophysiology of acute pulmonary embolism is the basis for risk stratification of patients as being at high, intermediate and low risk of adverse outcomes. This risk stratification has been advocated to tailor clinical management according to the severity of pulmonary embolism. Anticoagulation is the mainstay of the treatment of acute pulmonary embolism. New direct oral anticoagulants, which are easier to use than conventional anticoagulants, have been compared with conventional anticoagulation in five randomised clinical trials including &gt;11 000 patients with pulmonary embolism. Patients at high risk of pulmonary embolism (those with haemodynamic compromise) were excluded from these studies. Direct oral anticoagulants have been shown to be as effective and at least as safe as conventional anticoagulation in patients with pulmonary embolism without haemodynamic compromise, who are the majority of patients with this disease. Whether these agents are appropriate for the acute-phase treatment of patients at intermediate–high risk pulmonary embolism (those with both right ventricle dysfunction and injury) regardless of any risk stratification remains undefined.
Epithelial Cell Hyperproliferation Induced in the Exocrine Pancreas of Mice by a Western-Style Diet
Authors: L. Xue, K. Yang, H. Newmark, D. Leung, M. Lipkin
Journal: JNCI Journal of the National Cancer Institute (1996)

Background : Pancreatic cancer is a common cause of mortality in the United States, with an estimated 27 800 people dying of the disease in this country in 1996. Epidemiologic studies have suggested that Western diets containing high fat, high protein, and low calcium contents are associated with increased incidence of pancreatic cancer. Purpose : We investigated whether a Western-style diet containing increased fat content and decreased calcium and vitamin D contents would induce epithelial cell hyperproliferation (excess cell duplication) or hyperplasia (excess cell accumulation) in the pancreas, as was previously demonstrated in the colon and mammary gland. Methods : C57BL/6J mice at 4 weeks of age were randomly assigned to one of two groups of 14 mice each. One group received the control diet ad libitum, and the other group was given the Western-style diet ad libitum. After 6, 9, and 15 weeks on the diet, four or five mice per group were infused with 5-bromo-2'-deoxyuridine (BrdU) for 72 hours by use of subcutaneously implanted Alzet osmotic pumps. The mice were then killed, and the pancreas of each mouse was removed. In the exocrine pancreas with ductal secretion, the duct system (including interlobular and intralobular ducts and centroacinar [i.e., centroductular] cells) and acini were measured both histopathologically and immunohistochemically (BrdU) and were analyzed without knowledge of the source of the specimens. Two-way analysis of variance was carried out. All P values were generated from two-sided tests for statistical significance. Results : The number of pancreatic ducts (inter-lobular, intralobular, and centroacinar—cancer-prone regions in certain rodent models and in humans) and acini per mouse in the Western-style diet group was similar to that in the control diet group during the entire feeding period ( P =.76, .32, .93, and.42, respectively). Statistically significant higher BrdU-labeling indices of the ductal interlobular and intralobular epithelial cells were seen in mice fed the Western-style diet than in mice fed the control diet during the entire observation period ( P =.014 and .016, respectively). There was no statistically significant difference ( P =.098) between both diet groups in the BrdU-labeling indices of the centroacinar epithelial cells. Conclusions : A Western-style diet induced pancreatic epithelial cell hyperproliferation in mice, further suggesting that increased fat content and decreased calcium and vitamin D contribute to the development of pancreatic neoplasms. [J Natl Cancer Inst 1996; 88:1586-90]
An Improved Implementation of Effective Number of Codons (Nc)
Authors: X. Sun, Q. Yang, X. Xia
Journal: Molecular Biology and Evolution (2012)

The effective number of codons (Nc) is a widely used index for characterizing codon usage bias because it does not require a set of reference genes as does codon adaptation index (CAI) and because of the freely available computational tools such as CodonW. However, Nc, as originally formulated has many problems. For example, it can have values far greater than the number of sense codons; it treats a 6-fold compound codon family as a single-codon family although it is made of a 2-fold and a 4-fold codon family that can be under dramatically different selection for codon usage bias; the existing implementations do not handle all different genetic codes; it is often biased by codon families with a small number of codons. We developed a new Nc that has a number of advantages over the original Nc. Its maximum value equals the number of sense codons when all synonymous codons are used equally, and its minimum value equals the number of codon families when exactly one codon is used in each synonymous codon family. It handles all known genetic codes. It breaks the compound codon families (e.g., those involving amino acids coded by six synonymous codons) into 2-fold and 4-fold codon families. It reduces the effect of codon families with few codons by introducing pseudocount and weighted averages. The new Nc has significantly improved correlation with CAI than the original Nc from CodonW based on protein-coding genes from Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, Escherichia coli, Bacillus subtilis, Micrococcus luteus, and Mycoplasma genitalium. It also correlates better with protein abundance data from the yeast than the original Nc.
ABC of Clinical haematology: Iron deficiency anaemia
Authors: R. Frewin, A. Henson, D. Provan
Journal: BMJ (1997)

<h3>Background</h3> Vitamin D supplementation lowers exacerbation frequency in severe vitamin D-deficient patients with COPD. Data regarding the effect of vitamin D on elastin degradation are lacking. Based on the vitamin9s anti-inflammatory properties, we hypothesised that vitamin D supplementation reduces elastin degradation, particularly in vitamin D-deficient COPD patients. We assessed the effect of vitamin D status and supplementation on elastin degradation by measuring plasma desmosine, a biomarker of elastin degradation. <h3>Methods</h3> Desmosine was measured every 4 months in plasma of 142 vitamin D-naïve COPD patients from the Leuven vitamin D intervention trial (100 000 IU vitamin D3 supplementation every 4 weeks for 1 year). <h3>Results</h3> No significant association was found between baseline 25-hydroxyvitamin D (25(OH)D) and desmosine levels. No significant difference in desmosine change over time was found between the placebo and intervention group during the course of the trial. In the intervention arm, an unexpected inverse association was found between desmosine change and baseline 25(OH)D levels (p=0.005). <h3>Conclusions</h3> Vitamin D supplementation did not have a significant overall effect on elastin degradation compared to placebo. Contrary to our hypothesis, the intervention decelerated elastin degradation in vitamin D-sufficient COPD patients and not in vitamin D-deficient subjects.
SINGLE-LUNG TRANSPLANTATION IN EMPHYSEMA
Authors: F.J. Veith, S.K. Koerner, L.A. Attai, P. Bardfeld, S.J. Boley, A. Bloomberg, M. Everhard, J. Anderson, B. Pollara, R. Steckler, H. Nagashima, S. Siegelman, P. Lalezari, M.L. Gliedman
Journal: The Lancet (1972)
SIGNIFICANCE OF CRYOPROFIBRIN IN FIBRINOGEN-FIBRIN CONVERSION
Authors: John R. Shainoff, Irvine H. Page
Journal: The Journal of Experimental Medicine (1962)

Fibrinogen altered by thrombin-catalyzed liberation of fibrinopeptide A was found to combine with native fibrinogen to form a cold-precipitable complex we have called "cryoprofibrin." The altered fibrinogen lacking fibrino-peptide A polymerized into fibrin, but not until conditions for equilibrium between its incorporation into both cryoprofibrin and fibrin were satisfied. At equilibrium, the concentration of cryoprofibrin was maintained at a threshold proportional to the concentration of fibrinogen. When the concentration of cryoprofibrin was below threshold, fibrin could be depolymerized and solubilized by fibrinogen with resultant formation of cryoprofibrin. Since threshold concentrations of cryoprofibrin appear necessary for precipitation of fibrin, the concentration of cryoprofibrin in plasma provides a basis for determining intravascular deposition of fibrin. Intravascular deposition of fibrin does not appear to occur normally in rabbits, because the concentration of cryoprofibrin in plasma from normal rabbits is far below the threshold for precipitation of fibrin. The applicability of cryoprofibrin as an indicator of fibrin deposition is demonstrated by the occurrence of levels of cryoprofibrin approaching the threshold for precipitation of fibrin in plasma from endotoxin-treated rabbits. The current concept that the fibrinogen molecule can dissociate into subunits can be used to explain the conversion of fibrinogen to cryoprofibrin. As one possibility, the two residues of fibrinopeptide A contained in fibrinogen may be located on two separate subunits of the molecule; cryoprofibrin is produced when one of these subunits is replaced by a subunit altered by loss of fibrinopeptide A. Recombination of native subunits with subunits altered by loss of A would counter dissociation of cryoprofibrin and inhibit polymerization of subunits lacking fibrinopeptide A. As an alternate mechanism, two residues of A may be liberated concurrently from a single subunit. Cryoprofibrin would then correspond to a fibrinogen molecule, containing a subunit with two residues of A, in combination with an altered molecule containing a subunit lacking two residues of A. Liberation of fibrinopeptide B did not contribute measurably to production of fibrin resulting from limited action of thrombin on rabbit fibrinogen. Both fibrin containing B but not A, and fibrin containing neither B nor A, as is produced by extensive action of thrombin, could be solubilized by fibrinogen. Thrombin, or another enzyme utilizing tosyl-L-arginine methyl ester as substrate, appeared reversibly to inhibit polymerization of fibrin containing fibrinopeptide B. This enzyme and fibrinogen were the only proteins appearing to inhibit polymerization in plasma from normal rabbits.
Phase II Study of Cisplatin and Vinorelbine in Squamous Cell Carcinoma of the Cervix: A Gynecologic Oncology Group Study
Authors: Mitchell Morris, John A. Blessing, Bradley J. Monk, Ramon McGehee, David H. Moore
Journal: Journal of Clinical Oncology (2004)

Purpose To evaluate the efficacy and toxicity of intravenous cisplatin and vinorelbine as combination chemotherapy in patients with advanced or recurrent squamous cell carcinoma of the cervix. Patients and Methods Between August 1997 and January 2001, 73 patients with advanced or recurrent squamous cell carcinoma of the cervix were entered onto this study. Eligible patients had received no prior therapeutic chemotherapy, except when administered concurrent with primary radiation therapy. The initial doses administered were cisplatin 75 mg/m 2 every 4 weeks and vinorelbine 30 mg/m 2 weekly. Subsequent doses were unchanged, reduced, escalated, or omitted according to observed toxicity and protocol guidelines. Patients were evaluated for response and toxicity using standard Gynecologic Oncology Group criteria. Results Of 73 patients, 67 were eligible and assessable. The overall response rate was 30% (five complete and 15 partial responses). The overall median response duration was 5.5+ months. The major toxicity was neutropenia, with 16% grade 3 and 67% grade 4 reported. Gastrointestinal and neurotoxicity were infrequent and mild. Conclusion The combination of cisplatin and vinorelbine has moderate activity in advanced or recurrent squamous cell carcinoma of the cervix. Additional study of this regimen in a phase III setting is justified in this patient population.
Carboxyl-Terminal Modulator Protein Positively Regulates Akt Phosphorylation and Acts as an Oncogenic Driver in Breast Cancer
Authors: Yu-Peng Liu, Wen-Chi Liao, Luo-Ping Ger, Jiun-Chin Chen, Tai-I Hsu, Yu-Cheng Lee, Hong-Tai Chang, Yu-Chia Chen, Yi-Hua Jan, Kuen-Haur Lee, Yu-Hao Zeng, Michael Hsiao, Pei-Jung Lu
Journal: Cancer Research (2013)

Akt activation has been implicated broadly in tumorigenesis, but the basis for its dysregulation in cancer cells is incompletely understood. In this study, we sought to clarify a regulatory role for the Akt-binding carboxy-terminal modulator protein (CTMP), which has been controversial. In evaluating CTMP expression in paired normal-tumor specimens of 198 patients with breast cancer, we found that CTMP was upregulated in breast tumors, where it was associated with poor patient survival. Notably, CTMP expression also correlated positively with Akt phosphorylation in breast cancer clinical specimens and cell lines. Furthermore, ectopic expression of CTMP promoted cell proliferation and enhanced the tumorigenic properties of estrogen-dependent breast cancer cells. This effect was correlated with increased sensitivity to insulin-induced Akt phosphorylation, which is mediated primarily by the phosphoinositide 3-kinase-Akt pathway. In contrast, short hairpin RNA-mediated silencing of endogenous CTMP decreased the proliferation of estrogen-dependent or estrogen-independent breast cancer cells. Mechanistic investigations defined the N-terminal domain of CTMP at amino acids 1 to 64 as responsible for Akt binding. Taken together, our results firmly corroborate the concept that CTMP promotes Akt phosphorylation and functions as an oncogenic molecule in breast cancer.
Endothelial Wnt/β-catenin signaling inhibits glioma angiogenesis and normalizes tumor blood vessels by inducing PDGF-B expression
Authors: Marco Reis, Cathrin J. Czupalla, Nicole Ziegler, Kavi Devraj, Jenny Zinke, Sascha Seidel, Rosario Heck, Sonja Thom, Jadranka Macas, Ernesto Bockamp, Marcus Fruttiger, Makoto M. Taketo, Stefanie Dimmeler, Karl H. Plate, Stefan Liebner
Journal: The Journal of Experimental Medicine (2012)

Endothelial Wnt/β-catenin signaling is necessary for angiogenesis of the central nervous system and blood-brain barrier (BBB) differentiation, but its relevance for glioma vascularization is unknown. In this study, we show that doxycycline-dependent Wnt1 expression in subcutaneous and intracranial mouse glioma models induced endothelial Wnt/β-catenin signaling and led to diminished tumor growth, reduced vascular density, and normalized vessels with increased mural cell attachment. These findings were corroborated in GL261 glioma cells intracranially transplanted in mice expressing dominant-active β-catenin specifically in the endothelium. Enforced endothelial β-catenin signaling restored BBB characteristics, whereas inhibition by Dkk1 (Dickkopf-1) had opposing effects. By overactivating the Wnt pathway, we induced the Wnt/β-catenin-Dll4/Notch signaling cascade in tumor endothelia, blocking an angiogenic and favoring a quiescent vascular phenotype, indicated by induction of stalk cell genes. We show that β-catenin transcriptional activity directly regulated endothelial expression of platelet-derived growth factor B (PDGF-B), leading to mural cell recruitment thereby contributing to vascular quiescence and barrier function. We propose that reinforced Wnt/β-catenin signaling leads to inhibition of angiogenesis with normalized and less permeable vessels, which might prove to be a valuable therapeutic target for antiangiogenic and edema glioma therapy.
Five-Year Data and Prognostic Factor Analysis of Oxaliplatin and Irinotecan Combinations for Advanced Colorectal Cancer: N9741
Authors: Hanna K. Sanoff, Daniel J. Sargent, Megan E. Campbell, Roscoe F. Morton, Charles S. Fuchs, Ramesh K. Ramanathan, Stephen K. Williamson, Brian P. Findlay, Henry C. Pitot, Richard M. Goldberg
Journal: Journal of Clinical Oncology (2008)

In this report, we update survival (OS) and time-to-progression (TTP) data for the Intergroup trial N9741 after a median 5 years of follow-up by using risk-stratified and prognostic factor analyses to determine if treatment outcomes differ in specific patient subgroups.
5-fluorouracil in the treatment of scleroderma: a randomised, double blind, placebo controlled international collaborative study.
Authors: J A Casas, P A Saway, I Villarreal, C Nolte, B L Menajovsky, E E Escudero, W D Blackburn, G S Alarcon, C P Subauste
Journal: Annals of the Rheumatic Diseases (1990)

A six month controlled study of 5-fluorouracil in the treatment of scleroderma showed a modest benefit in skin scores, Raynaud9s phenomenon, and patients9 global assessment. Visceral organ and hand function were unaffected. Mild to moderate toxicity was common in the 5-fluorouracil treated patients but usually responded to dose reduction. Two patients receiving 5-fluorouracil died from causes seemingly unrelated to treatment. Significant clinical improvement in scleroderma was not noted in the first six months of treatment with 5-fluorouracil.
PyCogent: a toolkit for making sense from sequence
Authors: Rob Knight, Peter Maxwell, Amanda Birmingham, Jason Carnes, J Gregory Caporaso, Brett C Easton, Michael Eaton, Micah Hamady, Helen Lindsay, Zongzhi Liu, Catherine Lozupone, Daniel McDonald, Michael Robeson, Raymond Sammut, Sandra Smit, Matthew J Wakefield, Jeremy Widmann, Shandy Wikman, Stephanie Wilson, Hua Ying, Gavin A Huttley
Journal: Genome biology (2007)

Abstract We have implemented in Python the COmparative GENomic Toolkit, a fully integrated and thoroughly tested framework for novel probabilistic analyses of biological sequences, devising workflows, and generating publication quality graphics. PyCogent includes connectors to remote databases, built-in generalized probabilistic techniques for working with biological sequences, and controllers for third-party applications. The toolkit takes advantage of parallel architectures and runs on a range of hardware and operating systems, and is available under the general public license from http://sourceforge.net/projects/pycogent .
Prevalence of Diabetes in U.S. Youth in 2009: The SEARCH for Diabetes in Youth Study
Authors: David J. Pettitt, Jennifer Talton, Dana Dabelea, Jasmin Divers, Giuseppina Imperatore, Jean M. Lawrence, Angela D. Liese, Barbara Linder, Elizabeth J. Mayer-Davis, Catherine Pihoker, Sharon H. Saydah, Debra A. Standiford, Richard F. Hamman
Journal: Diabetes Care (2013)

To estimate the prevalence of diabetes in U.S. youth aged <20 years in 2009 and to estimate the total number of youth with diabetes in the U.S. by age, race/ethnicity, and diabetes type.
Alcohol abuse: prevalence and detection in a general hospital
Authors: R. Hearne, A. Connolly, J. Sheehan
Journal: Journal of the Royal Society of Medicine (2002)

Despite a high prevalence of alcohol-related disabilities and the availability of cost-effective interventions, alcohol abuse and dependence commonly go undetected in hospital inpatients. In a university teaching hospital we compared three well validated screening methods for sensitivity and specificity—the Alcohol Use Disorders Identification Test (AUDIT, with various cut-off scores), CAGE (a four-question screening tool), and a 10-question version of the Michigan Alcoholism Screening Test (BMAST). A subset of patients also completed the DSM IV structured clinical interview for diagnosis. 1133 adult patients were randomly selected from all hospital admissions, with exclusion of day cases and patients too ill to be interviewed. Two-thirds of the patients were interviewed, most of the remainder being unavailable at the time. 30% of the men and 8% of the women met the DSM IV criteria for alcohol abuse or dependence. Sensitivities and specificities of the screening tools were as follows: AUDIT (with cut-off score > 8) 89% and 91%; CAGE 77% and 99%; BMAST 37% and 100%. 255 case records of patients scoring above the cut-off on one or more questionnaires were subsequently reviewed. The admitting team recognized an alcohol problem in only 46, of whom 17 were referred for appropriate follow up. As in previous hospital surveys, alcohol abuse and dependence was not receiving proper attention. The most efficient screening tool was the CAGE questionnaire.