tbuckley/cabot-search huggingface dataset:
Adjuvant Hormonal Therapy Use Among Insured, Low-Income Women With Breast Cancer
Authors: Gretchen Kimmick, Roger Anderson, Fabian Camacho, Monali Bhosle, Wenke Hwang, Rajesh Balkrishnan
Journal: Journal of Clinical Oncology (2009)

PURPOSE Use of adjuvant hormonal therapy, which significantly decreases breast cancer mortality, has not been well described among poor women, who are at higher risk of cancer-related death. Here we explore use of adjuvant hormonal therapy in an insured, low-income population. METHODS A North Carolina Cancer Registry-Medicaid linked data set was used. Women with hormone receptor-positive or unknown, nonmetastatic breast cancer, diagnosed between 1998 and 2002, were included. Main outcomes were (1) prescription fill within 1 year of diagnosis, (2) adherence (medication possession ratio), and (3) persistence (absence of a 90-day gap in prescription fills over 12 months). Results The population consisted of 1,491 women (mean age, 67 years). Sixty-four percent filled prescriptions. Predictors of prescription fill included the following: older age (odds ratio [OR], 1.01; P = .017), greater number of prescription medications (OR, 1.06; P < .001), nonmarried status (OR, 1.82; P = .001), higher stage (OR, 1.83; P < .001), positive hormone receptor status (positive v unknown, OR, 1.98; P < .001), not receiving adjuvant chemotherapy (OR, 1.74; P = .001), receipt of adjuvant radiation (OR, 1.55; P = .004), and treatment in a small hospital (OR, 1.49; P = .024). Adherence and persistence rates were 60% and 80%, respectively. Nonmarried status predicted greater adherence (OR, 1.90; P = .006) and persistence (OR, 1.75; P = .031). CONCLUSION Prescription fill, adherence, and persistence to adjuvant hormonal therapy among socioeconomically disadvantaged women are low. Improving use of adjuvant hormonal therapy may lead to lower breast cancer-specific mortality in this population.
Selling Products Out of the Office
Authors: G J Povar, L Snyder
Journal: Annals of Internal Medicine (1999)

The sale of products from the physician's office raises several ethical issues and may affect the trust necessary to sustain the patient–physician relationship. When deciding whether to sell products out of the office and, if so, which ones, physicians should carefully consider such criteria as the urgency of the patient's need, the clinical relevance to the patient's condition, the adequacy of evidence to support use of the product, and geographic and time constraints for the patient in otherwise obtaining the product. Physicians should make full disclosure about their financial interests in selling the product and inform patients about alternatives for purchasing the product. Charges for products sold through the office should be limited to the reasonable costs incurred in making them available.
Use of Technetium-99m–labeled Eosinophils to Detect Active Eosinophilic Inflammation in Humans
Authors: Neda Farahi, Chrystalla Loutsios, Adrien M. Peters, Alison M. Condliffe, Edwin R. Chilvers
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

However, the additional flush after EVLP is expected to clear the medication from the vasculature.Furthermore, the accumulation of the drug in the extravascular space has been shown to be minimal and would have been rapidly dissipated once in vivo status had been reestablished (10).In our case there were no signs of fibrinolytic complication such as bleeding.With the success obtained in the Human Ex vivo Lung Perfusion trial and evidence from research studies demonstrating stable pulmonary function over prolonged normothermic perfusions over 12 hours, we believe that advanced lung preservation techniques should involve EVLP as a platform for accurate diagnosis and directed therapy ( 16).As opposed to our ongoing preclinical research using advanced molecular therapeutics such as adenoviral IL-10 gene therapy (17), in this case we used readily available clinical diagnostic techniques and a clinically proven, readily available medication to treat donor lungs in an almost guideline-based fashion, but in the ex vivo setting.Thus, this case exemplifies how the concept of personalized medicine for the donor organ can be applied in the field of lung transplantation.
Influence of smoking on disease severity and antimalarial therapy in cutaneous lupus erythematosus: analysis of 1002 patients from the <scp>EUSCLE</scp> database
Authors: A. Kuhn, J. Sigges, C. Biazar, V. Ruland, N. Patsinakidis, A. Landmann, S. Amler, G. Bonsmann, M. Haust, F. Nyberg, Z. Bata, L. Mihályi, R. Olteanu, R.M. Pujol, J.M. Sánchez‐Schmidt, L. Medenica, D. Skiljevic, A. Reich, J.C. Szepietowski, C. Dalle Vedove, G. Girolomoni, T. Hawro, A. Zalewska‐Janowska, R. Glaeser, R. Huegel, H. Jedličková, A. Bygum, R. Laurinaviciene, S. Benoit, E. Broecker, F.A. Bahmer, E. Aberer, N. Wutte, J. Lipozencic, B. Marinovic, M. Sárdy, V. Bekou, T. Ruzicka, C. Frances, B. Soutou, H. Lee, M. Worm, A. Gruschke, N. Hunzelmann, K. Steinbrink, R. Romiti, M. Sticherling, C. Erfurt‐Berge, G. Avgerinou, D. Papafragkaki, E. Antiga, M. Caproni, B. Mayer, B. Volc‐Platzer, A. Kreuter, C. Tigges, P.M. Heil, G. Stingl
Journal: British Journal of Dermatology (2014)

In recent years it has been controversially discussed in the literature if smoking is associated with the activity of cutaneous lupus erythematosus (CLE) and the efficacy of antimalarial agents.To investigate the influence of smoking on disease severity and antimalarial treatment in patients with CLE using the Core Set Questionnaire of the European Society of Cutaneous Lupus Erythematosus (EUSCLE).A total of 1002 patients (768 female, 234 male) with different CLE subtypes were included in this cross-sectional study, which was performed in 14 different countries. Smoking behaviour was assessed by the EUSCLE Core Set Questionnaire in 838 patients and statistically analysed using an SPSS database. The results were correlated with the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and the efficacy of antimalarial treatment.A high percentage (87·2%) of the 499 patients with CLE, who have ever smoked, had already smoked at the date of their first diagnosis. Patients with intermittent CLE have ever smoked significantly more often than patients with subacute CLE (P < 0·05) and chronic CLE (P < 0·05). The total CLASI activity and damage score of patients with CLE was 6·6 ± 7·1 and 2·6 ± 4·3, respectively, and was higher in patients who have ever smoked than in nonsmokers. Antimalarial treatment was successful in 84·3% of cases, with a significantly higher efficacy in nonsmokers than in patients with CLE who have ever smoked (P < 0·05).This analysis of a multicentre study population of 838 patients with CLE assessed by the EUSCLE Core Set Questionnaire confirms that smoking negatively influences CLE disease severity and the efficacy of antimalarial treatment.
Blocking and Randomization to Improve Molecular Biomarker Discovery
Authors: Li-Xuan Qin, Qin Zhou, Faina Bogomolniy, Liliana Villafania, Narciso Olvera, Magali Cavatore, Jaya M. Satagopan, Colin B. Begg, Douglas A. Levine
Journal: Clinical Cancer Research (2014)

Randomization and blocking have the potential to prevent the negative impacts of nonbiologic effects on molecular biomarker discovery. Their use in practice, however, has been scarce. To demonstrate the logistic feasibility and scientific benefits of randomization and blocking, we conducted a microRNA study of endometrial tumors (n = 96) and ovarian tumors (n = 96) using a blocked randomization design to control for nonbiologic effects; we profiled the same set of tumors for a second time using no blocking or randomization. We assessed empirical evidence of differential expression in the two studies. We performed simulations through virtual rehybridizations to further evaluate the effects of blocking and randomization. There was moderate and asymmetric differential expression (351/3,523, 10%) between endometrial and ovarian tumors in the randomized dataset. Nonbiologic effects were observed in the nonrandomized dataset, and 1,934 markers (55%) were called differentially expressed. Among them, 185 were deemed differentially expressed (185/351, 53%) and 1,749 not differentially expressed (1,749/3,172, 55%) in the randomized dataset. In simulations, when randomization was applied to all samples at once or within batches of samples balanced in tumor groups, blocking improved the true-positive rate from 0.95 to 0.97 and the false-positive rate from 0.02 to 0.002; when sample batches were unbalanced, randomization was associated with the true-positive rate (0.92) and the false-positive rate (0.10) regardless of blocking. Normalization improved the detection of true-positive markers but still retained sizeable false-positive markers. Randomization and blocking should be used in practice to more fully reap the benefits of genomics technologies.
To Screen or Not To Screen for Lynch Syndrome
Authors: J. Peres
Journal: JNCI Journal of the National Cancer Institute (2010)

rosatellite instability (MSI) test. Patients with an abnormal screen can then have a diagnostic DNA test for mismatch repair mutations to confi rm or rule out Lynch syndrome. Family history is the basis for two different sets of criteria to determine which patients should be considered at risk for Lynch syndrome: the Amsterdam criteria and the Bethesda guidelines. But family history isn’t always available, and many patients are thus missed, along with the opportunity to identify their at-risk relatives. That’s why the federal Centers for Disease Control and Prevention (CDC) convened its independent panel — the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group — to consider a broader screening strategy. The working group released its fi ndings in January 2009. According to the CDC website, the group “found good scientifi c evidence to recommend that all individuals with a new diagnosis of colorectal cancer (regardless of age or family history) be offered genetic testing for Lynch syndrome, in order to help prevent cancer in their close relatives.” It did not fi nd enough evidence to recommend any specifi c preliminary screening strategy, e.g., MSI versus IHC.
Evaluation of non-tuberculous mycobacteria effect in the tuberculosis infection diagnosis: Interim analysis of a TBNET study
Authors: Jose Dominguez, Irene Latorre, Maria Tsolia, Virginia Amanatidou, Nuria Diez, Irene Mialdea, Neus Altet, Mar Serra, Jessica Diaz, Alicia Lacoma, Malu De Souza, Juan Ruiz-Manzano, Empar Giner, Cristina Prat, Amparo Escribano, Vicente Ausina
Journal: European Respiratory Journal (2012)

The aim was to determine the role of previous non-tuberculous mycobacteria (NTM) sensitization in children as a factor of discordant results between tuberculin skin test (TST) and T-SPOT.TB assay (Oxford Immunotec). We studied the presence of M.avium sensitized T cells in 87 non BCG vaccinated paediatric patients with discordant results: TST positive and T-SPOT.TB negative. We also included as controls 11 individuals with a negative TST and a negative T-SPOT.TB, and 8 patients with microbiologicaly confirmed NTM infection. Peripheral blood mononuclear cells were stimulated with M.avium sensitin. The presence of reactive T cells were determined by means of ELISPOT.  From the 87 children, in 31 cases (35.6%) we obtained a positive ELISPOT result after stimulation with M. avium sensitin, in 50 cases the result was negative (57.5%), and in the remaining 6 cases the test failure. The number of responder T cells after M.avium sensitin stimulation was significantly higher that the number of responder T cells after specific M.tuberculosis antigens stimulation. In all children included as controls were obtained negative ELISPOT results after stimulation with M.avium sensitin. The differences of the number of responder T cells to M.avium sensitin between the study and the control group were significant. In 4 cases a positive result was obtained between patients with confirmed NTM infection. Our results suggest that previous NTM sensitization in children induces false positive results in TST for diagnosing latent tuberculosis infection. The use of IFN-γ tests provide a more specific diagnostic of TB infection in childhood.
The impact of nanoparticles on the mucosal translocation and transport of GLP-1 across the intestinal epithelium
Authors: Francisca Araújo, Neha Shrestha, Mohammed-Ali Shahbazi, Pedro Fonte, Ermei M. Mäkilä, Jarno J. Salonen, Jouni T. Hirvonen, Pedro L. Granja, Hélder A. Santos, Bruno Sarmento
Journal: Biomaterials (2014)
Tumor necrosis factor-α–dependent expression of phosphodiesterase 2: role in endothelial hyperpermeability
Authors: Joachim Seybold, Dirk Thomas, Martin Witzenrath, Şengül Boral, Andreas C. Hocke, Alexander Bürger, Armin Hatzelmann, Hermann Tenor, Christian Schudt, Matthias Krüll, Hartwig Schütte, Stefan Hippenstiel, Norbert Suttorp
Journal: Blood (2005)

The pleiotropic cytokine tumor necrosis factor-alpha (TNF-alpha) and thrombin lead to increased endothelial permeability in sepsis. Numerous studies demonstrated the significance of intracellular cyclic nucleotides for the maintenance of endothelial barrier function. Actions of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) are terminated by distinct cyclic nucleotide phosphodiesterases (PDEs). We hypothesized that TNF-alpha could regulate PDE activity in endothelial cells, thereby impairing endothelial barrier function. In cultured human umbilical vein endothelial cells (HUVECs), we found a dramatic increase of PDE2 activity following TNF-alpha stimulation, while PDE3 and PDE4 activities remained unchanged. Significant PDE activities other than PDE2, PDE3, and PDE4 were not detected. TNF-alpha increased PDE2 expression in a p38 mitogen-activated protein kinase (MAPK)-dependent manner. Endothelial barrier function was investigated in HUVECs and in isolated mice lungs. Selective PDE2 up-regulation sensitized HUVECs toward the permeability-increasing agent thrombin. In isolated mice lungs, we demonstrated that PDE2 inhibition was effective in preventing thrombin-induced lung edema, as shown with a reduction in both lung wet-to-dry ratio and albumin flux from the vascular to bronchoalveolar compartment. Our findings suggest that TNF-alpha-mediated up-regulation of PDE2 may destabilize endothelial barrier function in sepsis. Inhibition of PDE2 is therefore of potential therapeutic interest in sepsis and acute respiratory distress syndrome (ARDS).
Molecular Changes After Left Ventricular Assist Device Support for Heart Failure
Authors: Emma J. Birks
Journal: Circulation Research (2013)

Heart failure is associated with remodeling that consists of adverse cellular, structural, and functional changes in the myocardium. Until recently, this was thought to be unidirectional, progressive, and irreversible. However, irreversibility has been shown to be incorrect because complete or partial reversal can occur that can be marked after myocardial unloading with a left ventricular assist device (LVAD). Patients with chronic advanced heart failure can show near-normalization of nearly all structural abnormalities of the myocardium or reverse remodeling after LVAD support. However, reverse remodeling does not always equate with clinical recovery. The molecular changes occurring after LVAD support are reviewed, both those demonstrated with LVAD unloading alone in patients bridged to transplantation and those occurring in the myocardium of patients who have recovered enough myocardial function to have the device removed. Reverse remodeling may be attributable to a reversal of the pathological mechanisms that occur in remodeling or the generation of new pathways. A reduction in cell size occurs after LVAD unloading, which does not necessarily correlate with improved cardiac function. However, some of the changes in both the cardiac myocyte and the matrix after LVAD support are specific to myocardial recovery. In the myocyte, increases in the cytoskeletal proteins and improvements in the Ca²⁺ handling pathway seem to be specifically associated with myocardial recovery. Changes in the matrix are complex, but excessive scarring appears to limit the ability for recovery, and the degree of fibrosis in the myocardium at the time of implantation may predict the ability to recover.
The role of chemokine receptors in acute lung allograft rejection
Authors: S. Geleff, D. Draganovici, P. Jaksch, S. Segerer
Journal: European Respiratory Journal (2009)

Recruitment of inflammatory cells to vascularised allografts is a hallmark of rejection, and paves the way for chronic allograft injury. Chemokines play pivotal roles in the directed movement of leukocytes. Herein, we define the distribution of chemokine receptors for the most common cell types during human lung allograft rejection as a prerequisite for therapeutic interventions. Immunohistochemistry was performed on lung allograft biopsies from 54 patients for the chemokine receptors CCR5, CXCR3 and CXCR1 and the Duffy antigen/receptor for chemokines (DARC). Perivascular infiltrates in acute lung rejection are composed of subsets of mononuclear cells expressing the chemokine receptors CXCR1, CXCR3 and CCR5. DARC-positive small vessels and capillary vessels were associated with sites of inflammation and their number was increased during episodes of acute lung rejection. DARC expression correlated with an increase in interstitial CCR5-positive T-cells and CXCR1-positive leukocytes. Leucokytic infiltrates in bronchial/bronchiolar rejection express CXCR1 and CXCR3. This is the first study that demonstrates an induction of the chemokine binding protein DARC at sites of acute human lung allograft rejection. Co-localisation with the chemokine receptors CXCR1 and CCR5 may indicate a role for DARC expression during leukocyte adhesion and interstitial infiltration.
Abstract 1062: Hypermethylation of BARHL2 gene is useful as a molecular marker in early stage of gastric cancer
Authors: Yoshiyuki Watanabe, Ritsuko Oikawa, Hiroyuki Yamamoto, Fumio Itoh
Journal: Cancer Research (2015)

Abstract Aim: Although minimal invasive treatment is accepted for gastric cancer, we still do not have any appropriate risk markers to detect residual neoplasia and recurrence. We previously reported that aberrant DNA methylation is an early and frequent process in gastric carcinogenesis and could be useful for detection of neoplasia. Our goal is to find some candidate genes as a treatment marker using genome wide DNA methylation analysis for early gastric cancer (EGC). Methods and Results: We studied Methylated CpG Island Amplification Microarray (MCAM) analysis using 12 gastric washes (each 6 before (Pre) and after (Post) endoscopic treatment in same patients). One of them is BARHL2. We examined the DNA methylation status of BARHL2 in a validation set consisting of 128 washes samples (Pre, 64: Post, 64) at EGC. We next identified functional studies about BARHL2 as a putative tumor suppressor gene. Treating GCa cells that lacked BARHL2 expression with a methyltransferase inhibitor, 5-aza-2′-deoxycytidine, restored the gene's expression. Introduction of exogenous BARHL2 into silenced cells suppressed colony formation. Moreover, BARHL2 showed significantly differential methylation between before and after treatment in EGC patient (BARHL2, p&amp;lt;0.0001). Discussion: Our data suggest that silencing of BARHL2 occurs frequently in EGC and may play a key role in development and progression of the disease. Citation Format: Yoshiyuki Watanabe, Ritsuko Oikawa, Hiroyuki Yamamoto, Fumio Itoh. Hypermethylation of BARHL2 gene is useful as a molecular marker in early stage of gastric cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1062. doi:10.1158/1538-7445.AM2015-1062
Genomics and outbreak investigation: from sequence to consequence
Authors: Esther R Robinson, Timothy M Walker, Mark J Pallen
Journal: Genome Medicine (2013)

Outbreaks of infection can be devastating for individuals and societies. In this review, we examine the applications of new high-throughput sequencing approaches to the identification and characterization of outbreaks, focusing on the application of whole-genome sequencing (WGS) to outbreaks of bacterial infection. We describe traditional epidemiological analysis and show how WGS can be informative at multiple steps in outbreak investigation, as evidenced by many recent studies. We conclude that high-throughput sequencing approaches can make a significant contribution to the investigation of outbreaks of bacterial infection and that the integration of WGS with epidemiological investigation, diagnostic assays and antimicrobial susceptibility testing will precipitate radical changes in clinical microbiology and infectious disease epidemiology in the near future. However, several challenges remain before WGS can be routinely used in outbreak investigation and clinical practice.
Tumor targeting using magnetic nanoparticle Hsp70 conjugate in a model of C6 glioma
Authors: Maxim A. Shevtsov, Ludmila Y. Yakovleva, Boris P. Nikolaev, Yaroslav Y. Marchenko, Anatolii V. Dobrodumov, Kirill V. Onokhin, Yana S. Onokhina, Sergey A. Selkov, Anastasiia L. Mikhrina, Irina V. Guzhova, Marina G. Martynova, Olga A. Bystrova, Alexander M. Ischenko, Boris A. Margulis
Journal: Neuro-Oncology (2013)

Superparamagnetic iron oxide nanoparticles (SPIONs), due to their unique magnetic properties, have the ability to function both as magnetic resonance (MR) contrast agents, and can be used for thermotherapy. SPIONs conjugated to the heat shock protein Hsp70 that selectively binds to the CD40 receptor present on glioma cells, could be used for MR contrast enhancement of experimental C6 glioma. The magnetic properties of the Hsp70-SPIONs were measured by NMR relaxometry method. The uptake of nanoparticles was assessed on the C6 glioma cells by confocal and electron microscopes. The tumor selectivity of Hsp70-SPIONs being intravenously administered was analyzed in the experimental model of C6 glioma in the MRI scanner. Hsp70-SPIONs relaxivity corresponded to the properties of negative contrast agents with a hypointensive change of resonance signal in MR imaging. A significant accumulation of the Hsp70-SPIONs but not the non-conjugated nanoparticles was observed by confocal microscopy within C6 cells. Negative contrast tumor enhancement in the T2-weighted MR images was higher in the case of Hsp70-SPIONs in comparison to non-modified SPIONs. Histological analysis of the brain sections confirmed the retention of the Hsp70-SPIONs in the glioma tumor but not in the adjacent normal brain tissues. The study demonstrated that Hsp70-SPION conjugate intravenously administered in C6 glioma model accumulated in the tumors and enhanced the contrast of their MR images.
Affect as a Social Process
Authors: RICHARD RABKIN
Journal: American Journal of Psychiatry (1968)

The author discusses the similarities between the concepts of the "imponderables"—a group of weightless substances including heat, electricity, and love—of the 19th century—and the psychodynamic factors of the 20th century. He espouses a new concept of affect in which it is viewed not as a substance or as inner states of one person but as part of a process in which the tensions and emotions of the family and other natural groups are determined by the configuration and motion of their systems.