tbuckley/cabot-search huggingface dataset:
Differential Gene Expression Patterns and Interaction Networks in <i>BCR-ABL</i>–Positive and –Negative Adult Acute Lymphoblastic Leukemias
Authors: Dejan Juric, Norman J. Lacayo, Meghan C. Ramsey, Janis Racevskis, Peter H. Wiernik, Jacob M. Rowe, Anthony H. Goldstone, Peter J. O'Dwyer, Elisabeth Paietta, Branimir I. Sikic
Journal: Journal of Clinical Oncology (2007)

Purpose To identify gene expression patterns and interaction networks related to BCR-ABL status and clinical outcome in adults with acute lymphoblastic leukemia (ALL). Patients and Methods DNA microarrays were used to profile a set of 54 adult ALL specimens from the Medical Research Council UKALL XII/Eastern Cooperative Oncology Group E2993 trial (21 p185 BCR-ABL –positive, 16 p210 BCR-ABL –positive and 17 BCR-ABL–negative specimens). Results Using supervised and unsupervised analysis tools, we detected significant transcriptomic changes in BCR-ABL–positive versus –negative specimens, and assessed their validity in an independent cohort of 128 adult ALL specimens. This set of 271 differentially expressed genes (including GAB1, CIITA, XBP1, CD83, SERPINB9, PTP4A3, NOV, LOX, CTNND1, BAALC, and RAB21) is enriched for genes involved in cell death, cellular growth and proliferation, and hematologic system development and function. Network analysis demonstrated complex interaction patterns of these genes, and identified FYN and IL15 as the hubs of the top-scoring network. Within the BCR-ABL–positive subgroups, we identified genes overexpressed (PILRB, STS-1, SPRY1) or underexpressed (TSPAN16, ADAMTSL4) in p185 BCR-ABL –positive ALL relative to p210 BCR-ABL –positive ALL. Finally, we constructed a gene expression- and interaction-based outcome predictor consisting of 27 genes (including GRB2, GAB1, GLI1, IRS1, RUNX2, and SPP1), which correlated with overall survival in BCR-ABL–positive adult ALL (P = .0001), independent of age (P = .25) and WBC count at presentation (P = .003). Conclusion We identified prominent molecular features of BCR-ABL–positive adult ALL, which may be useful for developing novel therapeutic targets and prognostic markers in this disease.
Do mutations in <i>BRCA1</i> /<i>BRCA2</i> confer a higher risk of skin cancer?
Authors: S. Wu
Journal: British Journal of Dermatology (2015)

Journal Article Do mutations in BRCA1/BRCA2 confer a higher risk of skin cancer? Get access S. Wu S. Wu Department of Dermatology Brigham and Women's Hospital Harvard Medical School Boston MA U.S.ADepartment of Dermatology Warren Alpert Medical School Brown University Providence RI U.S.A https://orcid.org/0000-0002-8786-4375 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 172, Issue 6, 1 June 2015, Page 1473, https://doi.org/10.1111/bjd.13767 Published: 01 June 2015
Protocol Core Needle Biopsy and Histologic Chronic Allograft Damage Index (CADI) as Surrogate End Point for Long-Term Graft Survival in Multicenter Studies
Authors: Serdar Yilmaz, Steven Tomlanovich, Timothy Mathew, Eero Taskinen, Timo Paavonen, Merci Navarro, Eleanor Ramos, Leon Hooftman, Pekka Ha[Combining Diaeresis]yry
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. This study is an investigation of whether a protocol biopsy may be used as surrogate to late graft survival in multicenter renal transplantation trials. During two mycophenolate mofetil trials, 621 representative protocol biopsies were obtained at baseline, 1 yr, and 3 yr. The samples were coded and evaluated blindly by two pathologists, and Chronic Allograft Damage Index (CADI) score was constructed. At 1 yr, only 20% of patients had elevated (&gt;l.5 mg/100 ml) serum creatinine, whereas 60% of the biopsies demonstrated an elevated (&gt;2.0) CADI score. The mean CADI score at baseline, 1.3 ± 1.1, increased to 3.3 ± 1.8 at 1 yr and to 4.1 ± 2.2 at 3 yr. The patients at 1 yr were divided into three groups, those with CADI &lt;2, between 2 and 3.9, and &gt;4.0, the first two groups having normal (1.4 ± 0.3 and 1.5 ± 0.6 mg/dl) and the third group pathologic (1.9 ± 0.8 mg/dl) serum creatinine. At 3 yr, there were no lost grafts in the low CADI group, six lost grafts (4.6%) in the in the elevated CADI group, and 17 lost grafts (16.7%) in the high CADI group (<i>P</i> &lt; 0.001). One-year histologic CADI score predicts graft survival even when the graft function is still normal. This observation makes it possible to use CADI as a surrogate end point in prevention trials and to identify the patients at risk for intervention trials. E-mail: pekka.hayry@helsinki.fi
Bisphosphonate risedronate prevents bone loss in women with artificial menopause due to chemotherapy of breast cancer: a double-blind, placebo-controlled study.
Authors: P D Delmas, R Balena, E Confravreux, C Hardouin, P Hardy, A Bremond
Journal: Journal of Clinical Oncology (1997)

PURPOSE To determine the effectiveness and safety of the bisphosphonate risedronate in preventing bone loss in young women with breast cancer and early menopause induced by chemotherapy who are at major risk for the development of postmenopausal osteoporosis. PATIENTS AND METHODS Fifty-three white women, aged 36 to 55 years, with breast cancer and artificially induced menopause were stratified according to prior tamoxifen use. Thirty-six patients received tamoxifen (20 mg/d). Within each stratum, patients were randomly assigned to receive risedronate (n = 27) or placebo (n = 26). Treatment consisted of eight cycles oral risedronate 30 mg/d or placebo daily for 2 weeks followed by 10 weeks of no drug (12 weeks per cycle). Patients were monitored for a third year without treatment. RESULTS Main outcomes of the study were changes in lumbar spine and proximal femur (femoral neck, trochanter, and Ward's triangle) bone mineral density (BMD), and biochemical markers of bone turnover. In contrast to a significant decrease of BMD at the lumbar spine and hip in the placebo group, there was an increase in BMD in the risedronate group. On treatment withdrawal, bone loss ensued, which suggests that treatment needs to be continuous to maintain a protective effect on bone mass. At 2 years, the mean difference (+/- SEM) between groups was 2.5% +/- 1.2%, (95% confidence interval [CI], 0.2 to 4.9) at the lumbar spine (P = .041) and 2.6% +/- 1.1%, (95% CI, 0.3 to 4.8) at the femoral neck (P = .029). Similar results were observed at the hip trochanter. Results by stratum indicate a beneficial, although partial, effect of tamoxifen in reducing bone loss. Risedronate was well tolerated and showed a good safety profile, with no evidence of laboratory abnormalities. CONCLUSION Risedronate appears to be a safe treatment that prevents both trabecular and cortical bone loss in women with menopause induced by chemotherapy for breast cancer.
Cognition in the Vegetative State
Authors: Martin M. Monti
Journal: Annual Review of Clinical Psychology (2012)

Awake but not aware: This puzzling dissociation of the two central elements of consciousness defines the vegetative state. Traditionally, this condition has been believed to imply a brain with preserved hypothalamic and brainstem autonomic functions but with no capacity for cortical cognitive processes. As is discussed in this review, over a 20-year span neuroimaging techniques have clearly demonstrated that this characterization of patients in a vegetative state is incorrect. Contrary to the initial belief, the "vegetative" brain can retain several high-level aspects of cognitive functions, across sensory modalities, including language processing and learning dynamics. Nonetheless, the residual cognitive functions observed in vegetative patients might reflect intact but functionally disconnected cortical modules that do not give rise to the subjective feeling of phenomenological awareness.
Patient Data Management Systems in Critical Care
Authors: REINHOLD FRETSCHNER, WOLFGANG BLEICHER, ALEXANDRA HEININGER, KLAUS UNERTL
Journal: Journal of the American Society of Nephrology (2001)

Electronic patient data management systems (PDMS) were clinically used for the first time in the 1970s. Their purpose was to automatically document vital parameters sampled by monitors and to replace handwritten medical files. Because of the continuous development of computer technology, however, demands on PDMS have increased immensely. PDMS are currently expected to assist clinicians at every level of intensive care, i.e., at the strategic level of physicians' orders and prescriptions, at the operational level, and at the administrative level. In 1994, a PDMS (CareVue; Agilent Technologies) was installed and further developed in the anesthesiologic intensive care unit of the university hospital in Tübingen. The goals of this article were to describe the current demands on PDMS, to communicate our experiences in implementing a PDMS, to list the costs of purchasing and maintaining the system, and to report on the acceptance among physicians and nursing personnel. This article may assist new users in planning for, purchasing, and implementing a PDMS.
Who Should Receive Life Support During a Public Health Emergency? Using Ethical Principles to Improve Allocation Decisions
Authors: Douglas B. White
Journal: Annals of Internal Medicine (2009)

A public health emergency, such as an influenza pandemic, will lead to shortages of mechanical ventilators, critical care beds, and other potentially life-saving treatments. Difficult decisions about who will and will not receive these scarce resources will have to be made. Existing recommendations reflect a narrow utilitarian perspective, in which allocation decisions are based primarily on patients' chances of survival to hospital discharge. Certain patient groups, such as the elderly and those with functional impairment, are denied access to potentially life-saving treatments on the basis of additional allocation criteria. We analyze the ethical principles that could guide allocation and propose an allocation strategy that incorporates and balances multiple morally relevant considerations, including saving the most lives, maximizing the number of “life-years” saved, and prioritizing patients who have had the least chance to live through life's stages. We also argue that these principles are relevant to all patients and therefore should be applied to all patients, rather than selectively to the elderly, those with functional impairment, and those with certain chronic conditions. We discuss strategies to engage the public in setting the priorities that will guide allocation of scarce life-sustaining treatments during a public health emergency.
Immunoglobulin Responses at the Mucosal Interface
Authors: Andrea Cerutti, Kang Chen, Alejo Chorny
Journal: Annual Review of Immunology (2011)

Mucosal surfaces are colonized by large communities of commensal bacteria and represent the primary site of entry for pathogenic agents. To prevent microbial intrusion, mucosal B cells release large amounts of immunoglobulin (Ig) molecules through multiple follicular and extrafollicular pathways. IgA is the most abundant antibody isotype in mucosal secretions and owes its success in frontline immunity to its ability to undergo transcytosis across epithelial cells. In addition to translocating IgA onto the mucosal surface, epithelial cells educate the mucosal immune system as to the composition of the local microbiota and instruct B cells to initiate IgA responses that generate immune protection while preserving immune homeostasis. Here we review recent advances in our understanding of the cellular interactions and signaling pathways governing IgA production at mucosal surfaces and discuss new findings on the regulation and function of mucosal IgD, the most enigmatic isotype of our mucosal antibody repertoire.
Airway Inflammation in Young Marijuana and Tobacco Smokers
Authors: MICHAEL D. ROTH, ASHIM ARORA, SANFORD H. BARSKY, ERIC C. KLEERUP, MICHAEL SIMMONS, DONALD P. TASHKIN
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Forty healthy young subjects, ages 20 to 49 yr, underwent videobronchoscopy, mucosal biopsy, and bronchial lavage to evaluate the airway inflammation produced by habitual smoking of marijuana and/or tobacco. Videotapes were graded in a blinded manner for central airway erythema, edema, and airway secretions using a modified visual bronchitis index. The bronchitis index scores were significantly higher in marijuana smokers (MS), tobacco smokers (TS), and in combined marijuana/tobacco smokers (MTS), than in nonsmokers (NS). As a pathologic correlate, mucosal biopsies were evaluated for the presence of vascular hyperplasia, submucosal edema, inflammatory cell infiltrates, and goblet cell hyperplasia. Biopsies were positive for two of these criteria in 97% of all smokers and for three criteria in 72%. By contrast, none of the biopsies from NS exhibited greater than one positive finding. Finally, as a measure of distal airway inflammation, neutrophil counts and interleukin-8 (IL-8) concentrations were determined in bronchial lavage fluid. The percentage of neutrophils correlated with IL-8 levels and exceeded 20% in 0 of 10 NS, 1 of 9 MS, 2 of 9 TS, and 5 of 10 MTS. We conclude that regular smoking of marijuana by young adults is associated with significant airway inflammation that is similar in frequency, type, and magnitude to that observed in the lungs of tobacco smokers.
Comparison of optic nerve head assessment with a digital stereoscopic camera (discam), scanning laser ophthalmoscopy, and stereophotography11The authors have no propietary interest in the products or devices mentioned herein.The first two authors had equal part in preparation of the manuscript.
Authors: Anthony J Correnti, Gadi Wollstein, Lori Lyn Price, Joel S Schuman
Journal: Ophthalmology (2003)
Hyperthyroidism Associated With Philadelphia-Chromosome–Positive Acute Lymphoblastic Leukemia
Authors: Satoko Oka, Taiji Yokote, Tetuya Hiraiwa, Toshikazu Akioka, Satoshi Hara, Kichinosuke Kobayashi, Yuji Hirata, Takeshi Yamano, Keiji Tanimoto, Motomu Tsuji, Toshiaki Hanafusa
Journal: Journal of Clinical Oncology (2006)
Ets2 Determines the Inflammatory State of Endothelial Cells in Advanced Atherosclerotic Lesions
Authors: Caroline Cheng, Dennie Tempel, Wijnand K. Den Dekker, Remco Haasdijk, Ihsan Chrifi, Frank L. Bos, Kim Wagtmans, Esther H. van de Kamp, Lau Blonden, Erik A.L. Biessen, Frans Moll, Gerard Pasterkamp, Patrick W. Serruys, Stefan Schulte-Merker, Henricus J. Duckers
Journal: Circulation Research (2011)

Neovascularization is required for embryonic development and plays a central role in diseases in adults. In atherosclerosis, the role of neovascularization remains to be elucidated. In a genome-wide microarray-screen of Flk1+ angioblasts during murine embryogenesis, the v-ets erythroblastosis virus E26 oncogene homolog 2 (Ets2) transcription factor was identified as a potential angiogenic factor.We assessed the role of Ets2 in endothelial cells during atherosclerotic lesion progression toward plaque instability.In 91 patients treated for carotid artery disease, Ets2 levels showed modest correlations with capillary growth, thrombogenicity, and rising levels of tumor necrosis factor-α (TNFα), monocyte chemoattractant protein 1, and interleukin-6 in the atherosclerotic lesions. Experiments in ApoE(-/-) mice, using a vulnerable plaque model, showed that Ets2 expression was increased under atherogenic conditions and was augmented specifically in the vulnerable versus stable lesions. In endothelial cell cultures, Ets2 expression and activation was responsive to the atherogenic cytokine TNFα. In the murine vulnerable plaque model, overexpression of Ets2 promoted lesion growth with neovessel formation, hemorrhaging, and plaque destabilization. In contrast, Ets2 silencing, using a lentiviral shRNA construct, promoted lesion stabilization. In vitro studies showed that Ets2 was crucial for TNFα-induced expression of monocyte chemoattractant protein 1, interleukin-6, and vascular cell adhesion molecule 1 in endothelial cells. In addition, Ets2 promoted tube formation and amplified TNFα-induced loss of vascular endothelial integrity. Evaluation in a murine retina model further validated the role of Ets2 in regulating vessel inflammation and endothelial leakage.We provide the first evidence for the plaque-destabilizing role of Ets2 in atherosclerosis development by induction of an intraplaque proinflammatory phenotype in endothelial cells.
Sex Differences in Mortality Following Acute Coronary Syndromes
Authors: Jeffrey S. Berger
Journal: JAMA (2009)

Conflicting information exists about whether sex differences modulate short-term mortality following acute coronary syndromes (ACS).To investigate the relationship between sex and 30-day mortality in ACS, and to determine whether this relationship was modified by clinical syndrome or coronary anatomy using a large database across the spectrum of ACS and adjusting for potentially confounding clinical covariates.A convenience sample of patients pooled from 11 independent, international, randomized ACS clinical trials between 1993 and 2006 whose databases are maintained at the Duke Clinical Research Institute, Durham, North Carolina. Of 136 247 patients, 38 048 (28%) were women; 102 004 (26% women) with ST-segment elevation myocardial infarction (STEMI), 14 466 (29% women) with non-STEMI (NSTEMI), and 19 777 (40% women) with unstable angina.Thirty-day mortality following ACS.Thirty-day mortality was 9.6% in women and 5.3% in men (odds ratio [OR], 1.91; 95% confidence interval [CI], 1.83-2.00). After multivariable adjustment, mortality was not significantly different between women and men (adjusted OR, 1.06; 95% CI, 0.99-1.15). A significant sex by type of ACS interaction was demonstrated (P < .001). In STEMI, 30-day mortality was higher among women (adjusted OR, 1.15; 95% CI, 1.06-1.24), whereas in NSTEMI (adjusted OR, 0.77; 95% CI, 0.63-0.95) and unstable angina, mortality was lower among women (adjusted OR, 0.55; 95% CI, 0.43-0.70). In a cohort of 35 128 patients with angiographic data, women more often had nonobstructive (15% vs 8%) and less often had 2-vessel (25% vs 28%) and 3-vessel (23% vs 26%) coronary disease, regardless of ACS type. After additional adjustment for angiographic disease severity, 30-day mortality among women was not significantly different than men, regardless of ACS type. The relationship between sex and 30-day mortality was similar across the levels of angiographic disease severity (P for interaction = .70).Sex-based differences existed in 30-day mortality among patients with ACS and vary depending on clinical presentation. However, these differences appear to be largely explained by clinical differences at presentation and severity of angiographically documented disease.
Enhanced Tumor Uptake and Penetration of Virotherapy Using Polymer Stealthing and Focused Ultrasound
Authors: Robert Carlisle, James Choi, Miriam Bazan-Peregrino, Richard Laga, Vladimir Subr, Libor Kostka, Karel Ulbrich, Constantin-C. Coussios, Leonard W. Seymour
Journal: JNCI Journal of the National Cancer Institute (2013)

BackgroundOncolytic viruses are among the most powerful and selective cancer therapeutics under development and are showing robust activity in clinical trials, particularly when administered directly into tumor nodules. However, their intravenous administration to treat metastatic disease has been stymied by unfavorable pharmacokinetics and inefficient accumulation in and penetration through tumors.
Validation of the Consensus-Definition for Cancer Cachexia and evaluation of a classification model—a study based on data from an international multicentre project (EPCRC-CSA)
Authors: D. Blum, G.B. Stene, T.S. Solheim, P. Fayers, M.J. Hjermstad, V.E. Baracos, K. Fearon, F. Strasser, S. Kaasa, Van den Block Lieve, Meeussen Koen, Brearley Sarah, Caraceni Augusto, Cohen Joachim, Costantini Massimo, Francke Anneke, Harding Richard, J. Higginson Irene, Kaasa Stein, Linden Karen, Miccinesi Guido, Onwuteaka-Philipsen Bregje, Pardon Koen, Pasman Roeline, Pautex Sophie, Payne Sheila, Deliens Luc
Journal: Annals of Oncology (2014)
S133 Eosinophilic airway inflammation is associated with FEV1 decline in severe asthma
Authors: J. Agbetile, D. Desai, B. Hargadon, P. Bradding, A. J. Wardlaw, I. D. Pavord, R. H. Green, C. E. Brightling, S. Siddiqui
Journal: Thorax (2010)

<h3>Background</h3> Severe asthma is a multidimensional disease, with recent evidence supporting the notion that eosinophilic airway inflammation (EAI) is an important driver for exacerbations. In addition EAI has been shown to be associated with airflow limitation in cross sectional studies. However, it remains to be established whether EAI may drive FEV<sub>1</sub> decline. <h3>Methods</h3> The severe asthma registry at Glenfield hospital, Leicester, was screened for patients with a physician diagnosis of asthma and at least 5 years of longitudinal data recording sputum eosinophils, pre- and post-bronchodilator spirometry, inhaled corticosteroid usage as well as standard demographic indices during stable scheduled follow-up visits. Linear mixed effects models were used to investigate the effect of log sputum eosinophils as a time varying covariate on decline of post bronchodilator FEV<sub>1</sub>. Models were iteratively compared and refined using standard information criteria. Other fixed effects in the final model were, time and the interaction terms for time * log sputum eosinophils and time *daily dose of inhaled corticosteroids and pack years smoked. Individual variations in the slopes and intercepts of time and time*log sputum eosinophils were considered by adding them iteratively as random effects. A first-order autoregressive correlation structure was used to model covariance of random effects. <h3>Results</h3> 92 patients, 46% male with severe asthma were identified from a registry cohort of 686 between 2000 and 2009. The mean (sem) age was 54(12.9) years and age of onset 23 (2.1) years. The mean (range) duration of follow-up and number of visits were 6 years (4.6–10.5), 2.7/year. We found a significant interaction between sputum eosinophils, time and post bronchodilator FEV<sub>1</sub>. Indicating a net decline (95% CI) of −16.8 mls(25.8–7.8 mls) /annum/log unit increase in sputum eosinophils (F(1, 43.4); p&lt;0.0001). In contrast there was a net decline 95%CI of −0.015 mls (0.029 to 0.0014 mls)/annum/mcg of inhaled beclamethasonediproprionate daily (F(1,726); p=0.031). <h3>Conclusion</h3> Eosinophilic airway inflammation is associated with a significant decline in FEV<sub>1</sub> in severe asthma.