tbuckley/cabot-search huggingface dataset:
Pivotal role of the CCL5/CCR5 interaction for recruitment of endothelial progenitor cells in mouse wound healing
Authors: Yuko Ishida, Akihiko Kimura, Yumi Kuninaka, Masanori Inui, Kouji Matsushima, Naofumi Mukaida, Toshikazu Kondo
Journal: Journal of Clinical Investigation (2012)

BM-derived endothelial progenitor cells (EPCs) are critical and essential for neovascularization in tissue repair and tumorigenesis. EPCs migrate from BM to tissues via the bloodstream, but specific chemotactic cues have not been identified. Here we show in mice that the absence of CCR5 reduced vascular EPC accumulation and neovascularization, but not macrophage recruitment, and eventually delayed healing in wounded skin. When transferred into Ccr5-/- mice, Ccr5+/+ BM cells, but not Ccr5-/- cells, accumulated in the wound site, were incorporated into the vasculature, and restored normal neovascularization. Consistent with these observations, CCL5 induced in vitro EPC migration in a CCR5-dependent manner. Moreover, expression of VEGF and TGF-β was substantially diminished at wound sites in Ccr5-/- mice, which suggests that EPCs are important not only as the progenitors of endothelial cells, but also as the source of growth factors during tissue repair. Taken together, these data identify the CCL5/CCR5 interaction as what we believe to be a novel molecular target for modulation of neovascularization and eventual tissue repair.
Articular scanning and external counting in experimental synovitis in the guinea-pig.
Authors: A G Mowat, T F Disney, J H Vaughan
Journal: Annals of the Rheumatic Diseases (1971)

<h3>Abstract</h3> Segmental duplications (SDs) are a class of long, repetitive DNA elements whose paralogs share a high level of sequence similarity with each other. SDs mediate chromosomal rearrangements that lead to structural variation in the general population as well as genomic disorders associated with multiple congenital anomalies, including the 7q11.23 (Williams-Beuren Syndrome, WBS), 15q13.3, and 16p12.2 microdeletion syndromes. These three genomic regions, and the SDs within them, have been previously analyzed in a small number of individuals. However, population-level studies have been lacking because most techniques used for analyzing these complex regions are both labor- and cost-intensive. In this study, we present a high-throughput technique to genotype complex structural variation using a single molecule, long-range optical mapping approach. We identified novel structural variants (SVs) at 7q11.23, 15q13.3 and 16p12.2 using optical mapping data from 154 phenotypically normal individuals from 26 populations comprising 5 super-populations. We detected several novel SVs for each locus, some of which had significantly different prevalence between populations. Additionally, we refined the microdeletion breakpoints located within complex SDs in two patients with WBS, one patient with 15q13.3, and one patient with 16p12.2 microdeletion syndromes. The population-level data presented here highlights the extreme diversity of large and complex SVs within SD-containing regions. The approach we outline will greatly facilitate the investigation of the role of inter-SD structural variation as a driver of chromosomal rearrangements and genomic disorders.
Inhaled corticosteroids in COPD: quantifying risks and benefits
Authors: Chris Cates
Journal: Thorax (2012)

It is by no means straightforward to analyse the change in the rate of chronic obstructive pulmonary disease (COPD) exacerbations in clinical trials. Exacerbation rates do not follow a normal distribution, nor do they occur at random. High exacerbation rates in a few patients can make average rates difficult to calculate and interpret. So, surely, transforming exacerbation rates into numbers needed to treat (NNT) should help. Not necessarily so—this is the message from Professor Suissa's paper.1 He points out that the simplistic transformation from annual exacerbation rates to NNT in some published papers is misleading. He then goes on to present an alternative way of calculating NNT from survival curves showing time to first exacerbation, and a model to estimate such curves even if they are not presented.

I have used the exponential model suggested by Suissa, with the data from two of the arms of the Towards a Revolution in Chronic obstructive pulmonary disease Health (TORCH) trial2 to show how this works in practice. I chose the arms in TORCH, that compared combination fluticasone/salmeterol therapy with salmeterol alone, as this seems to me to be a fair way to estimate the impact of additional inhaled corticosteroids. Figure 1 shows pairs of modelled survival curves for pneumonia (in the upper part), and for COPD exacerbation (in the lower part). …
Traveling Waves in Visual Cortex
Authors: Tatsuo K. Sato, Ian Nauhaus, Matteo Carandini
Journal: Neuron (2012)

Electrode recordings and imaging studies have revealed that localized visual stimuli elicit waves of activity that travel across primary visual cortex. Traveling waves are present also during spontaneous activity, but they can be greatly reduced by widespread and intensive visual stimulation. In this Review, we summarize the evidence in favor of these traveling waves. We suggest that their substrate may lie in long-range horizontal connections and that their functional role may involve the integration of information over large regions of space. Electrode recordings and imaging studies have revealed that localized visual stimuli elicit waves of activity that travel across primary visual cortex. Traveling waves are present also during spontaneous activity, but they can be greatly reduced by widespread and intensive visual stimulation. In this Review, we summarize the evidence in favor of these traveling waves. We suggest that their substrate may lie in long-range horizontal connections and that their functional role may involve the integration of information over large regions of space.
Expression of<i>Interleukin-10</i>Splicing Variants Is a Positive Prognostic Feature in Relapsed Childhood Acute Lymphoblastic Leukemia
Authors: Shuling Wu, Reinhard Geβner, Tillmann Taube, Arend von Stackelberg, Günter Henze, Karl Seeger
Journal: Journal of Clinical Oncology (2005)

Biologic features of hematologic malignancies have prognostic implications and are essential elements in the design of current therapeutic trials. This study aimed to determine the expression of a splicing-derived variant of interleukin (IL) -10 in leukemic cells and its clinical relevance in children with acute lymphoblastic leukemia (ALL) at first relapse.Between January 1997 and December 2001, bone marrow (BM) samples were collected from 98 children with first relapse of ALL at diagnosis. These patients were enrolled in the relapse trial ALL-REZ BFM (ALL-Relapse Berlin-Frankfurt-Munster) 95 and 96. The detection of IL-10 isoforms in leukemic cells of BM samples were performed by conventional reverse transcriptase polymerase chain reaction and by immunoblotting.IL-10 was detected in 93.9% BM samples. In addition to expressing full-length IL-10, a new splicing-derived IL-10 variant (termed IL-10delta3) that lacked the entire exon 3 was identified in leukemic cells. The IL-10delta3 variant was found in 80.4% of BM samples. Most importantly, expression of IL-10delta3 was associated with a significantly better response to chemotherapy (P = .001) and probability of event-free survival (P = .01) at 5 years.These results indicate that splicing-derived IL-10 isoforms may modulate IL-10-mediated biologic effects and therapeutic efficacy in lymphatic disease, and expression of IL-10delta3 is a positive prognostic feature in relapsed childhood ALL.
Phase 1 first-in-human study of the enhancer of zeste-homolog 2 (EZH2) histone methyl transferase inhibitor E7438
Authors: V. Ribrag, J.-C. Soria, L. Reyderman, R. Chen, P. Salazar, N. Kumar, G. Kuznetsov, H. Keilhack, L.H. Ottesen, A. Italiano
Journal: Annals of Oncology (2015)
Echocardiographic insights into the mechanisms of relief of left ventricular outflow tract obstruction after nonsurgical septal reduction therapy in patients with hypertrophic obstructive cardiomyopathy
Authors: Ramiro Flores-Ramirez, Nasser M Lakkis, Katherine J Middleton, Donna Killip, William H Spencer, Sherif F Nagueh
Journal: Journal of the American College of Cardiology (2001)
New Paradigms for HIV/AIDS Vaccine Development
Authors: Louis J. Picker, Scott G. Hansen, Jeffrey D. Lifson
Journal: Annual Review of Medicine (2011)

HIV-1 and its simian counterpart SIV have been exquisitely tailored by evolution to evade host immunity. By virtue of specific adaptations that thwart individual innate or adaptive immune mechanisms, and an overall replication strategy that provides for rapid establishment of a large, systemic viral population, capable of dynamic adaptation to almost all immune selection pressures, these viruses, once established, almost invariably stay one step ahead of the host's immune system, and in the vast majority of infected individuals, replicate indefinitely. Although many vaccine approaches tested to date have been able to enhance the magnitude of the immune responses to HIV/SIV infection, most of these responses, whether cellular or humoral, have largely failed to be both effectively antiviral and targeted to prevent the emergence of fully functional escape variants. Recent advances, however, have provided strong evidence that the initial stages of infection following mucosal transmission of these viruses are more vulnerable to immune intervention, and have led to the development of vaccine strategies that elicit responses able to effectively intervene in these early stages of infection, either preventing acquisition of infection or establishing early, stringent, and durable control. Here, we place HIV/AIDS vaccine development in the context of the basic immunobiology of HIV and SIV, review the evidence for their vulnerability to immune responses immediately after mucosal transmission, and discuss how this newly recognized vulnerability might be exploited for the development of an effective HIV/AIDS vaccine.
European evidence based consensus on the diagnosis and management of Crohn's disease: current management
Authors: S P L Travis
Journal: Gut (2006)

This second section of the European Crohn's and Colitis Organisation (ECCO) Consensus on the management of Crohn's disease concerns treatment of active disease, maintenance of medically induced remission, and surgery. The first section on definitions and diagnosis includes the aims and methods of the consensus, as well as sections on diagnosis, pathology, and classification of Crohn's disease. The third section on special situations in Crohn's disease includes postoperative recurrence, fistulating disease, paediatrics, pregnancy, psychosomatics, extraintestinal manifestations, and alternative therapy for Crohn's disease.
Chronic hepatitis B reactivation: a word of caution regarding the use of systemic glucocorticosteroid therapy
Authors: C-H. Yang, T-S. Wu, C-T. Chiu
Journal: British Journal of Dermatology (2007)

Background The potentially fatal complications associated with viral hepatitis B (HBV) reactivation have not been characterized in bullous/connective tissue disease patients receiving prolonged systemic glucocorticosteroids (GCs). Objectives This study reports HBV reactivation following GC therapy for a case series of pemphigus vulgaris and dermatomyositis. Methods The retrospective study cohort comprised 98 patients who received at least 6 months of systemic GC therapy. Results Four cases of HBV carriers with viral hepatitis flare were identified. Two patients suffered fulminant hepatitis and died, while the remaining two patients experienced recurrent hepatitis flare following antiviral medication. The mean time from the start of GCs to the time of HBV reactivation was 10.5 months. Conclusions HBV infection is an important global public health problem. Fatal HBV reactivation may occur following long-term systemic GC therapy. Given the risk of mortality, all bullous/connective tissue disease patients should be screened for serum hepatitis B markers before commencing systemic GC therapy.
Skin disinfection with octenidine dihydrochloride for central venous catheter site care: a double-blind, randomized, controlled trial
Authors: M. Dettenkofer, C. Wilson, A. Gratwohl, C. Schmoor, H. Bertz, R. Frei, D. Heim, D. Luft, S. Schulz, A.F. Widmer
Journal: Clinical Microbiology and Infection (2009)
Tumor Antigen-Specific Immunization of Bone Marrow Transplantation Donors as Adoptive Therapy Against Established Tumor
Authors: R. L. Hornung, O. C. Bowersox, D. L. Longo, L. W. Kwak
Journal: JNCI Journal of the National Cancer Institute (1995)

Background: Persistence of the underlying malignancy remains the main obstacle to the successful treatment of human malignancies with high-dose chemoradiotherapy and bone marrow transplantation. Purpose: The aim of this study was to determine whether antigen-specific antitumor immune responses, elicited in normal donor mice by immunization with the soluble form of a surrogate tumor antigen (i.e., ovalbumin [OVA]), can be transferred via bone marrow transplantation into lethally irradiated, syngeneic recipient mice. An additional goal was to evaluate the ability of these adoptively transferred bone marrow cells to eradicate established recombinant OVA-expressing lymphomas that recurred after lethal-dose total-body irradiation (TBI). Methods: Female C57BL/6 donor mice were immunized twice with OVA emulsified in a muramyli-dipeptide-containing adjuvant. Syngeneic mice bearing a day-10 or day-11, approximately 1-cm subcutaneous E.G7-OVA tumor (E.G7-OVA tumor cells were derived from transfection of EL-4 thymoma tumor cells using the coding sequence of chicken OVA gene complementary DNA) were treated with TBI and reconstituted with bone marrow from nonimmune or OVA-immunized mice. In subsequent experiments, tumor-bearing mice, treated with TBI and OVA-immune bone marrow, were given additional therapy either with a single OVA immunization or by the adoptive transfer of 1 * 10 7 in vitro activated spleen cells derived from OVA-immune donor mice and cultured 5 days with irradiated E.G7-OVA cells before transfer.Z Results: E.G7-OVA tumor-bearing mice given TBI and OVA-immune bone marrow showed a significantly increased cure rate when compared with that among controls reconstituted with nonimmune bone marrow after TBI (logrank, P<.01). The antitumor effect of immune bone marrow was abrogated by T-cell depletion of the marrow graft (P<.O16). The antitumor effect of immune marrow was enhanced by the addition of OVA immunization of tumor-bearing recipients (P<.015). OVA-specific cytotoxic T-lymphocyte (CTL) activity was recovered from tumor-bearing recipients of immune marrow 14 days after bone marrow transplantation. The antitumor effect observed following the adoptive transfer of immune marrow was further augmented by the addition of 1 x 10 7 splenic E.G7-OVA-specific in vitro activated CTLs derived from OVA-immune mice (P<.03). Conclusion: These studies establish the principle that antigen-specific T-cell immunity against a defined tumor-specific antigen can be transferred with bone marrow from an immune donor. Implications: Active immunization of normal human bone marrow or T-cell donors with a refined, safe tumor antigen and transfer of immunity to the patient may represent a novel strategy for circumventing the obstacle of host immune suppression associated with the tumor-bearing state. [J Natl Cancer Inst 1995; 87: 1289–96]
Epidemiological evidence of effects of coarse airborne particles on health
Authors: B. Brunekreef, B. Forsberg
Journal: European Respiratory Journal (2005)

Studies on health effects of airborne particulate matter (PM) have traditionally focused on particles <10 microm in diameter (PM10) or particles <2.5 microm in diameter (PM2.5). The coarse fraction of PM10, particles >2.5 microm, has only been studied recently. These particles have different sources and composition compared with PM2.5. This paper is based on a systematic review of studies that have analysed fine and coarse PM jointly and examines the epidemiological evidence for effects of coarse particles on health. Time series studies relating ambient PM to mortality have in some places provided evidence of an independent effect of coarse PM on daily mortality, but in most urban areas, the evidence is stronger for fine particles. The few long-term studies of effects of coarse PM on survival do not provide any evidence of association. In studies of chronic obstructive pulmonary disease, asthma and respiratory admissions, coarse PM has a stronger or as strong short-term effect as fine PM, suggesting that coarse PM may lead to adverse responses in the lungs triggering processes leading to hospital admissions. There is also support for an association between coarse PM and cardiovascular admissions. It is concluded that special consideration should be given to studying and regulating coarse particles separately from fine particles.
Localization patterns of plasma apolipoproteins in human atherosclerotic lesions.
Authors: H F Hoff, C L Heideman, R L Jackson, R J Bayardo, H S Kim, A M Gotto
Journal: Circulation Research (1975)

The localization patterns of human plasma lipoproteins and their respective apoproteins and of neutral lipid were determined in normal and atherosclerotic arteries. Specific antisera were prepared against plasma low-density lipoproteins(LDL) and their apoproteins (apoB), high-density lipoproteins(HDL) and one of their major apoproteins (apoA-I1, and apoC-III, which is a major apoprotein of very low-density lipoproteins (VLDL). Using immunofluorescence techniques, the various antigens were localized in arterial samples obtained at surgery or autopsy. The three apoproteins and neutral lipid were localized to the same tissue areas, namely, lipid core regions and certain connective tissue of atherosclerotic lesions, in 61% of the fibrous plaques and 48% of the fatty streaks examined. In marked contrast, none of the uninvolved arterial regions showed the presence of all four factors together. As controls, the localization of other serum proteins was also determined in these arteries using immunofluorescence techniques. Fibrinogen was associated with regions of maximum complementary localization of factors in 37% of the fibrous plaques and 64% of the fatty streaks. However, albumin was found in only 4-5% of these same regions. The present results suggest that not only LDL but also HDL and VLDL or their respective apoproteins as well as fibrinogen are specifically retained by certain tissue components of the atherosclerotic lesion.
Machine Learning for Detection and Diagnosis of Disease
Authors: Paul Sajda
Journal: Annual Review of Biomedical Engineering (2006)

Machine learning offers a principled approach for developing sophisticated, automatic, and objective algorithms for analysis of high-dimensional and multimodal biomedical data. This review focuses on several advances in the state of the art that have shown promise in improving detection, diagnosis, and therapeutic monitoring of disease. Key in the advancement has been the development of a more in-depth understanding and theoretical analysis of critical issues related to algorithmic construction and learning theory. These include trade-offs for maximizing generalization performance, use of physically realistic constraints, and incorporation of prior knowledge and uncertainty. The review describes recent developments in machine learning, focusing on supervised and unsupervised linear methods and Bayesian inference, which have made significant impacts in the detection and diagnosis of disease in biomedicine. We describe the different methodologies and, for each, provide examples of their application to specific domains in biomedical diagnostics.
Temozolomide in Combination With Interferon-Alfa Versus Temozolomide Alone in Patients With Advanced Metastatic Melanoma: A Randomized, Phase III, Multicenter Study from the Dermatologic Cooperative Oncology Group
Authors: Roland Kaufmann, Konstanze Spieth, Ulrike Leiter, Cornelia Mauch, Peter von den Driesch, Thomas Vogt, Ruthild Linse, Wolfgang Tilgen, Dirk Schadendorf, Jürgen C. Becker, Günther Sebastian, Sven Krengel, Lutz Kretschmer, Claus Garbe, Reinhard Dummer
Journal: Journal of Clinical Oncology (2005)

Temozolomide (TMZ) has shown efficacy in metastatic melanoma equal to that of dacarbazine (DTIC), the standard chemotherapeutic agent for melanoma. As the combination with interferon-alfa (IFN-alpha) appears superior to single-agent DTIC regarding response rates, the purpose of this study was to compare TMZ alone and TMZ plus IFN-alpha in terms of objective response (OR), overall survival, and safety in a prospective, randomized, multicenter trial.Two hundred ninety-four patients with untreated stage IV metastatic melanoma (American Joint Committee on Cancer staging system) were randomly assigned to receive either oral TMZ alone (200 mg/m2/day; days 1 through 5 every 28 days) or in combination with subcutaneous IFN-alpha (5 MU/m2; days 1, 3, and 5 every week).Two hundred eighty-two patients were eligible for an intent-to-treat analysis, 271 patients were treated per protocol. In the TMZ + IFN-alpha arm, 33 (24.1%) of 137 patients responded to therapy (partial or complete remission) whereas in the monotherapy arm, in 18 (13.4%) of 134 patients, a response was evident. Thus, the response rate was significantly higher in the combination arm (P = .036). Median survival time was 8.4 months for patients treated with TMZ (95% CI, 7.07 to 9.27) and 9.7 months for those treated with the combination (95% CI, 8.26 to 11.18; P = .16). Dose modifications and interval prolongations due to hematologic toxicity were significantly more frequent in the TMZ + IFN-alpha arm (P < .001).In metastatic melanoma treatment with TMZ + IFN-alpha leads to a significantly superior OR rate compared to treatment with TMZ alone, which did not translate into prolonged survival in our study population.
Rainbow: Global, Phase 3, Randomized, Double-Blind Study of Ramucirumab Plus Paclitaxel vs Placebo Plus Paclitaxel Patients with Previously Treated Gastric or Gastroesophageal Junction Adenocarcinoma – Patient-Reported Outcomes and Performance Status
Authors: S.E. Al-Batran, E. Van Cutsem, C. Oh Sang, G. Bodoky, Y. Shimada, S. Hironaka, N. Sugimoto, O. Lipatov, T.Y. Kim, D. Cunningham, P. Rougier, K. Muro, A. Liepa, S. Ballal, M. Emig, A. Ohtsu, H. Wilke
Journal: Annals of Oncology (2014)
Differences in the polarization of the inflammatory response of patients with chronic obstructive pulmonary disease (COPD) secondary to smoking and to biomass smoke exposure
Authors: María Inés Vargas-Rojas, Helena Solleiro-Villavicencio, Alejandra Ramírez-Venegas, Mónica Velázquez-Uncal, Roger Quintana, Raúl Sansores-Martínez
Journal: European Respiratory Journal (2013)

Introduction.  Smoking and exposure to biomass smoke cause the release of pro-inflammatory mediators, as well as the activation of T helper (Th) cells. This inflammatory response can lead to the development of COPD; however, there are different clinical features between patients with COPD secondary to smoking (sCOPD) and to exposure to biomass smoke (bsCOPD), and these may be due to the kind of predominant Th response.   Aim.  Quantify the TCD4 +  cells subpopulations and the cytokines in peripheral blood of patients with sCOPD, bsCOPD and healthy controls (HC).   Methods . 41 patients were recruited, 24 sCOPD and 17 bsCOPD; we included 25 HC. Through flow cytometry the proportion of TCD4 +  cells subpopulations was defined. The serum cytokines were quantified through Luminex system. The differences between groups were evaluated with a Kruskal-Wallis test, and a post-hoc analysis was performed through a U of Mann Whitney test.   Results.  A prevalence of Th17 cells was observed in the sCOPD group (10.3±3.4%), when compared with bsCOPD (3.5±0.9%) and HC (0.9±0.4%) p   Conclusions.  Our data show a polarization of Th17 cells in sCOPD, and of Th2 cells in bsCOPD. There are differences in the wsCOPD and the sCOPD cytokine profiles, which may explain some of the clinical features observed in the COPD phenotypes.