tbuckley/cabot-search huggingface dataset:
Predicting mortality from HIV-associated Pneumocystis pneumonia at illness presentation: an observational cohort study
Authors: M W Fei, E J Kim, C A Sant, L G Jarlsberg, J L Davis, A Swartzman, L Huang
Journal: Thorax (2009)

Although the use of antiretroviral therapy has led to dramatic declines in AIDS-associated mortality, Pneumocystis pneumonia (PCP) remains a leading cause of death in HIV-infected patients.To measure mortality, identify predictors of mortality at time of illness presentation and derive a PCP mortality prediction rule that stratifies patients by risk for mortality.An observational cohort study with case note review of all HIV-infected persons with a laboratory diagnosis of PCP at San Francisco General Hospital from 1997 to 2006.451 patients were diagnosed with PCP on 524 occasions. In-hospital mortality was 10.3%. Multivariate analysis identified five significant predictors of mortality: age (adjusted odds ratio (AOR) per 10-year increase, 1.69; 95% CI 1.08 to 2.65; p = 0.02); recent injection drug use (AOR 2.86; 95% CI 1.28 to 6.42; p = 0.01); total bilirubin >0.6 mg/dl (AOR 2.59; 95% CI 1.19 to 5.62; p = 0.02); serum albumin <3 g/dl (AOR 3.63; 95% CI 1.72-7.66; p = 0.001); and alveolar-arterial oxygen gradient >or=50 mm Hg (AOR 3.02; 95% CI 1.41 to 6.47; p = 0.004). Using these five predictors, a six-point PCP mortality prediction rule was derived that stratifies patients according to increasing risk of mortality: score 0-1, 4%; score 2-3, 12%; score 4-5, 48%.The PCP mortality prediction rule stratifies patients by mortality risk at the time of illness presentation and should be validated as a clinical tool.
Effects of massage on physiological restoration, perceived recovery, and repeated sports performance
Authors: Brian Hemmings, Marcus Smith, Jan Graydon, Rosemary Dyson
Journal: British Journal of Sports Medicine (2000)

Despite massage being widely used by athletes, little scientific evidence exists to confirm the efficacy of massage for promoting both physiological and psychological recovery after exercise and massage effects on performance.To investigate the effect of massage on perceived recovery and blood lactate removal, and also to examine massage effects on repeated boxing performance.Eight amateur boxers completed two performances on a boxing ergometer on two occasions in a counterbalanced design. Boxers initially completed performance 1, after which they received a massage or passive rest intervention. Each boxer then gave perceived recovery ratings before completing a second performance, which was a repeated simulation of the first. Heart rates and blood lactate and glucose levels were also assessed before, during, and after all performances.A repeated measures analysis of variance showed no significant group differences for either performance, although a main effect was found showing a decrement in punching force from performance 1 to performance 2 (p<0.05). A Wilcoxon matched pairs test showed that the massage intervention significantly increased perceptions of recovery (p<0.01) compared with the passive rest intervention. A doubly multivariate multiple analysis of variance showed no differences in blood lactate or glucose following massage or passive rest interventions, although the blood lactate concentration after the second performance was significantly higher following massage (p<0.05).These findings provide some support for the psychological benefits of massage, but raise questions about the benefit of massage for physiological restoration and repeated sports performance.
Induction of a Regulatory T Cell Type 1 Response Reduces the Development of Atherosclerosis in Apolipoprotein E–Knockout Mice
Authors: Ziad Mallat, Andrea Gojova, Valérie Brun, Bruno Esposito, Nathalie Fournier, Françoise Cottrez, Alain Tedgui, Hervé Groux
Journal: Circulation (2003)

T helper type 1 (Th1) response plays a permissive role in atherosclerosis. We hypothesized that adoptive transfer of a novel subtype of T lymphocytes called regulatory T cells type 1 (Tr1) would inhibit Th1 responses by inducing a bystander immune suppression and therefore limit the development of atherosclerosis.Clones of ovalbumin (OVA)-specific Tr1 cells expanded in vitro were administered intraperitoneally (106 cells per mouse) with their cognate antigen (50 microg of OVA subcutaneously in complete Freund's adjuvant [CFA]) to female apolipoprotein E-knockout mice. A group of mice received only (OVA/CFA) immunization without Tr1 cells. Two other control groups received no immunization and were injected with either Tr1 cells or saline. After 9 weeks of treatment, mice injected with (OVA/CFA)+OVA-specific Tr1 cells showed a significant decrease in Th1 responses, as revealed by a decrease in OVA-specific IgG2a serum levels (P<0.0001), a decrease in the production of interferon-gamma (P<0.001), and an increase in interleukin-10 production (P<0.001) by cultured spleen and lymph T cells compared with controls. In addition, cytokine production by concanavalin A-stimulated spleen cells showed a clear switch to a regulatory immune response in mice treated with (OVA/CFA)+Tr1. This was associated with a significant reduction in atherosclerotic lesion size in both the thoracic aorta and aortic sinus of mice treated with (OVA/CFA)+Tr1 compared with controls (P=0.002 to P<0.0001). Plaques of mice injected with (OVA/CFA)+Tr1 showed significantly lower accumulation of macrophages and T cells than plaques of control mice.Tr1-type regulatory immune response reduces the development of experimental atherosclerosis.
Childhood Cancer and Traffic-Related Air Pollution Exposure in Pregnancy and Early Life
Authors: Julia E. Heck, Jun Wu, Christina Lombardi, Jiaheng Qiu, Travis J. Meyers, Michelle Wilhelm, Myles Cockburn, Beate Ritz
Journal: Environmental Health Perspectives (2013)

Background: The literature on traffic-related air pollution and childhood cancers is inconclusive, and little is known on rarer cancer types.Objectives: We sought to examine associations between childhood cancers and traffic-related pollution exposure.Methods: The present study included children < 6 years of age identified in the California Cancer Registry (born 1998–2007) who could be linked to a California birth certificate (n = 3,590). Controls were selected at random from California birthrolls (n = 80,224). CAlifornia LINE Source Dispersion Modeling, version 4 (CALINE4) was used to generate estimates of local traffic exposures for each trimester of pregnancy and in the first year of life at the address indicated on the birth certificate. We checked our findings by additionally examining associations with particulate matter (≤ 2.5 μm in aerodynamic diameter; PM2.5) pollution measured by community-based air pollution monitors, and with a simple measure of traffic density.Results: With unconditional logistic regression, a per interquartile range increase in exposure to traffic-related pollution during the first trimester (0.0538 ppm carbon monoxide, estimated using CALINE4) was associated with acute lymphoblastic leukemia [ALL; first trimester odds ratio (OR) = 1.05; 95% CI: 1.01, 1.10]; germ cell tumors (OR = 1.16; 95% CI: 1.04, 1.29), particularly teratomas (OR = 1.26; 95% CI: 1.12, 1.41); and retinoblastoma (OR = 1.11; 95% CI: 1.01, 1.21), particularly bilateral retinoblastoma (OR = 1.16; 95% CI: 1.02, 1.33). Retinoblastoma was also associated with average PM2.5 concentrations during pregnancy, and ALL and teratomas were associated with traffic density near the child's residence at birth.Conclusions: We estimated weak associations between early exposure to traffic pollution and several childhood cancers. Because this is the first study to report on traffic pollution in relation to retinoblastoma or germ cell tumors, and both cancers are rare, these findings require replication in other studies.Citation: Heck JE, Wu J, Lombardi C, Qiu J, Meyers TJ, Wilhelm M, Cockburn M, Ritz B. 2013. Childhood cancer and traffic-related air pollution exposure in pregnancy and early life. Environ Health Perspect 121:1385–1391; http://dx.doi.org/10.1289/ehp.1306761
Prevalence of movement disorders in men and women aged 50–89 years (Bruneck Study cohort): a population-based study
Authors: Gregor K Wenning, Stefan Kiechl, Klaus Seppi, Joerg Müller, Birgit Högl, Michael Saletu, Gregor Rungger, Arno Gasperi, Johann Willeit, Werner Poewe
Journal: The Lancet Neurology (2005)
Plasmatic Tumor Dna Assessments Predict Clinical Outcome in Egfr-Mutated Non-Small Cell Lung Cancer Patients Treated By Egfr Inhibitors
Authors: N. Pecuchet, A. Didelot, E. Zonta, C. Lours, L. Gibault, N. Rice, P. Laurent-Puig, E. Fabre, V. Taly, H. Blons
Journal: Annals of Oncology (2014)
Newer Immunosuppressive Drugs
Authors: JAN F. GUMMERT, TUIJA IKONEN, RANDALL E. MORRIS
Journal: Journal of the American Society of Nephrology (1999)

Abstract. In recent years, many new immunosuppressive drugs have been discovered and developed for clinical use in transplantation. This review focuses on those drugs (leflunomide, mycophenolate mofetil, sirolimus, tacrolimus) that have been shown to have immunosuppressive activity in patients. Different anti-interleukin-2 receptor antibodies are also reviewed as an example of a resurgence of development in the area of monoclonal antibodies. The price for reducing the incidence of allograft rejection by improved immunosuppression was thought to be a proportional increase in the incidence of infection and malignancy. Data from Phase III clinical trials of new immunosuppressants, however, show a statistically significant reduction in the incidence of acute rejection produced by these new drugs, which has not been accompanied by increases in infection and malignancy rates. The wide array of new drugs offers the opportunity to use combinations that block different pathways of immune activation while at the same time selecting drug combinations with nonoverlapping toxicity profiles so that doses of each single drug can be reduced below toxicity levels. The immunosuppressive therapy for patients can be tailored according to their individual needs.
A memorable patient: One got away, and one was lost
Authors: A. C. Gibson
Journal: BMJ (2002)

<h3>Abstract</h3> Despite accumulating evidence supporting a role for glycosylation in cancer progression and prognosis, the complexity of the human glycome and glycoproteome poses many challenges to understanding glycosylation-related events in cancer. In this study, a multifaceted genomics approach was applied to analyze the impact of differential expression of glycosyltransferases (GTs) in 16 cancers. An enzyme list was compiled and curated from numerous resources to create a consensus set of GTs. Resulting enzymes were analyzed for differential expression in cancer, and findings were integrated with experimental evidence from other analyses, including: similarity of healthy expression patterns across orthologous genes, miRNA expression, automatically-mined literature, curation of known cancer biomarkers, N-glycosylation impact, and survival analysis. The resulting list of GTs comprises 222 human enzymes based on annotations from five databases, 84 of which were differentially expressed in more than five cancers, and 14 of which were observed with the same direction of expression change across all implicated cancers. 25 high-value GT candidates were identified by cross-referencing multimodal analysis results, including <i>PYGM</i>, <i>FUT6</i> and additional fucosyltransferases, several UDP-glucuronosyltransferases, and others, and are suggested for prioritization in future cancer biomarker studies. Relevant findings are available through OncoMX at https://data.oncomx.org, and the overarching pipeline can be used as a framework for similarly analysis across diverse evidence types in cancer. This work is expected to improve the understanding of glycosylation in cancer by transparently defining the space of glycosyltransferase enzymes and harmonizing variable experimental data to enable improved generation of data-driven cancer biomarker hypotheses.
Analysis of striatal transcriptome in mice overexpressing human wild-type alpha-synuclein supports synaptic dysfunction and suggests mechanisms of neuroprotection for striatal neurons
Authors: Yofre Cabeza-Arvelaiz, Sheila M Fleming, Franziska Richter, Eliezer Masliah, Marie-Francoise Chesselet, Robert H Schiestl
Journal: Molecular Neurodegeneration (2011)

Alpha synuclein (SNCA) has been linked to neurodegenerative diseases (synucleinopathies) that include Parkinson's disease (PD). Although the primary neurodegeneration in PD involves nigrostriatal dopaminergic neurons, more extensive yet regionally selective neurodegeneration is observed in other synucleinopathies. Furthermore, SNCA is ubiquitously expressed in neurons and numerous neuronal systems are dysfunctional in PD. Therefore it is of interest to understand how overexpression of SNCA affects neuronal function in regions not directly targeted for neurodegeneration in PD. The present study investigated the consequences of SNCA overexpression on cellular processes and functions in the striatum of mice overexpressing wild-type, human SNCA under the Thy1 promoter (Thy1-aSyn mice) by transcriptome analysis. The analysis revealed alterations in multiple biological processes in the striatum of Thy1-aSyn mice, including synaptic plasticity, signaling, transcription, apoptosis, and neurogenesis. The results support a key role for SNCA in synaptic function and revealed an apoptotic signature in Thy1-aSyn mice, which together with specific alterations of neuroprotective genes suggest the activation of adaptive compensatory mechanisms that may protect striatal neurons in conditions of neuronal overexpression of SNCA.
A Phase II Study of the Efficacy and Safety of the Combination Therapy of the MEK Inhibitor Refametinib (BAY 86-9766) Plus Sorafenib for Asian Patients with Unresectable Hepatocellular Carcinoma
Authors: Ho Yeong Lim, Jeong Heo, Hye Jin Choi, Cheng-Yao Lin, Jung-Hwan Yoon, Chiun Hsu, Kun-Ming Rau, Ronnie T.P. Poon, Winnie Yeo, Joong-Won Park, Miah Hiang Tay, Wen-Son Hsieh, Christian Kappeler, Prabhu Rajagopalan, Heiko Krissel, Michael Jeffers, Chia-Jui Yen, Won Young Tak
Journal: Clinical Cancer Research (2014)

There is an unmet need for treatment options in hepatocellular carcinoma (HCC). Sorafenib is currently the only approved systemic treatment for HCC. Refametinib, an oral, allosteric MEK inhibitor, has demonstrated antitumor activity in combination with sorafenib in vitro and in vivo. A phase II study evaluated efficacy and safety of refametinib plus sorafenib in Asian patients with HCC (NCT01204177).Eligible patients received twice-daily refametinib 50 mg plus twice-daily sorafenib 200 mg (morning)/400 mg (evening), with dose escalation to sorafenib 400 mg twice daily from cycle 2 if no grade ≥ 2 hand-foot skin reaction, fatigue, or gastrointestinal toxicity occurred. Primary efficacy endpoint: disease control rate. Secondary endpoints: time to progression, overall survival, pharmacokinetic assessment, biomarker analysis, safety, and tolerability.Of 95 enrolled patients, 70 received study treatment. Most patients had liver cirrhosis (82.9%) and hepatitis B viral infection (75.7%). Disease control rate was 44.8% (primary efficacy analysis; n = 58). Median time to progression was 122 days, median overall survival was 290 days (n = 70). Best clinical responders had RAS mutations; majority of poor responders had wild-type RAS. Most frequent drug-related adverse events were diarrhea, rash, aspartate aminotransferase elevation, vomiting, and nausea. Dose modifications due to adverse events were necessary in almost all patients.Refametinib plus sorafenib showed antitumor activity in patients with HCC and was tolerated at reduced doses by most patients. Frequent dose modifications due to grade 3 adverse events may have contributed to limited treatment effect. Patients with RAS mutations appear to benefit from refametinib/sorafenib combination.
Visual outcomes in children with neurofibromatosis type 1-associated optic pathway glioma following chemotherapy: a multicenter retrospective analysis
Authors: M. J. Fisher, M. Loguidice, D. H. Gutmann, R. Listernick, R. E. Ferner, N. J. Ullrich, R. J. Packer, U. Tabori, R. O. Hoffman, S. L. Ardern-Holmes, T. R. Hummel, D. R. Hargrave, E. Bouffet, J. Charrow, L. T. Bilaniuk, L. J. Balcer, G. T. Liu
Journal: Neuro-Oncology (2012)

Optic pathway gliomas (OPGs) occur in 15%–20% of children with neurofibromatosis type 1 (NF1); up to half become symptomatic. There is little information regarding ophthalmologic outcomes after chemotherapy. A retrospective multicenter study was undertaken to evaluate visual outcomes following chemotherapy for NF1-associated OPG, to identify risks for visual loss, and to ascertain indications for treatment. Subjects included children undergoing initial treatment for OPGs with chemotherapy between January 1997 and December 2007. Of 115 subjects, visual acuity (VA) decline and tumor progression were the primary reasons to initiate treatment, although there were significant differences in the pattern of indications cited among the institutions. Eighty-eight subjects and 168 eyes were evaluable for VA outcome. At completion of chemotherapy, VA improved (32% of subjects), remained stable (40%), or declined (28%). Tumor location was the most consistent prognostic factor for poor VA outcome. There was poor correlation between radiographic and VA outcomes. Although visual outcomes for NF1-associated OPG are not optimal, approximately one-third of children regain some vision with treatment. Since radiographic outcomes do not predict visual outcomes, their use as the primary measure of treatment success is in question. The lack of consensus regarding the indications for treatment underlines the need for better standardization of care. Future clinical trials for OPG require standardized visual assessment methods and clear definitions of visual outcomes.
A unique pulmonary vascular pattern: bilateral anomalous single pulmonary veins
Authors: Arthur Soares Souza, Luciana Soares de Souza, Gláucia Zanetti, Edson Marchiori
Journal: Thorax (2013)

A 56-year-old woman underwent chest x-ray for evaluation of a pelvic tumour. The x-ray showed a unique pattern of bilateral, anomalous, curvilinear vessels (figure 1A). CT with volume-rendered reconstruction (figure 1B), coronal (figure 1C) and axial …
Critical Role of AT <sub>1</sub> Receptor Expression After Ischemia/Reperfusion in Isolated Rat Hearts
Authors: B. C. Yang, M. I. Phillips, Y. C. Zhang, B. Kimura, L. P. Shen, P. Mehta, J. L. Mehta
Journal: Circulation Research (1998)

Abstract —To examine the relevance of angiotensin II type 1 receptor (AT 1 R) expression in the determination of myocardial function after ischemia/reperfusion, Sprague-Dawley rats were treated intravenously with antisense oligodeoxynucleotides (AS-ODNs) directed at AT 1 R mRNA (100 μg/rat, n=9) or scrambled antisense oligodeoxynucleotides (Scr-ODNs, 100 μg/rat, n=6). Both AS-ODNs and Scr-ODNs were given along with 300 μg/rat of liposome DOTAP/DOPE, a positive electron carrier (wt:wt=1:1). The hearts from AS-ODN– or Scr-ODN–treated rats were excised 24 hours later, perfused in vitro, and subjected to 25 minutes of global ischemia followed by 30 minutes of reperfusion. Parallel groups of rats were given the specific AT 1 R antagonist losartan (10 mg/kg IV, n=6) or saline (n=7) 4 to 6 hours before excising the hearts. Ischemia/reperfusion resulted in a significant increase in myocardial AT 1 R expression (autoradiography and binding assay) and myocardial dysfunction, indicated by increases in coronary perfusion pressure and left ventricular end-diastolic pressure and a decrease in developed left ventricular pressure (all P &lt;0.01 versus baseline) in the saline-treated group. AT 1 R protein and mRNA levels also increased in ischemic/reperfused myocardial tissues. Administration of AS-ODNs or losartan, but not Scr-ODNs, preserved myocardial function and blocked the increased AT 1 R binding after ischemia/reperfusion (both P &lt;0.01). Myocardial AT 1 R mRNA levels were not affected by either AS-ODNs or losartan, and the AT 1 R protein levels were significantly reduced by AS-ODN, but not losartan, treatment. Plasma angiotensin II levels increased after administration of losartan but not after administration of AS-ODNs. These observations imply a critical role of AT 1 R upregulation in determining myocardial function immediately after ischemia/reperfusion. AS-ODNs to AT 1 R mRNA may be more beneficial than losartan, because losartan does not affect the plasma angiotensin II level. The sustained increase in AT 1 R mRNA, but diminished protein expression, in rat hearts treated with AS-ODNs suggests that AS-ODNs block AT 1 R at the translational level.
Phase II Study of First-Line Chemotherapy With Temozolomide in Recurrent Oligodendroglial Tumors: The European Organization for Research and Treatment of Cancer Brain Tumor Group Study 26971
Authors: M.J. van den Bent, M.J.B. Taphoorn, A.A. Brandes, J. Menten, R. Stupp, M. Frenay, O. Chinot, J.M. Kros, C.C.D. van der Rijt, Ch.J. Vecht, A. Allgeier, T. Gorlia
Journal: Journal of Clinical Oncology (2003)

Purpose: Oligodendroglial tumors are chemotherapy-sensitive tumors, with two thirds of patients responding to combination chemotherapy with procarbazine, lomustine, and vincristine (PCV). Temozolomide (TMZ), a new alkylating and methylating agent, has demonstrated high response rates in patients with recurrent anaplastic astrocytoma. We investigated TMZ as first-line chemotherapy in recurrent oligodendroglial tumors (OD) and mixed oligoastrocytomas (OA) after surgery and radiation therapy. Patients and Methods: In a prospective, nonrandomized, multicenter, phase II trial, patients were treated with 200 mg/m 2 of TMZ on days 1 through 5 in 28-day cycles for 12 cycles. Patients with a recurrence after prior surgery and radiotherapy, and with measurable and enhancing disease on magnetic resonance imaging (MRI) were eligible for this study. Patients with large lesions and mass effect or with new clinical deficits were not eligible. Pathology and the MRI scans of all responding patients were centrally reviewed. Results: Thirty-eight eligible patients were included. In three patients, pathology review did not confirm the presence of an OD or OA. TMZ was generally well tolerated. The most frequent side effects were hematologic; only one patient discontinued treatment for toxicity. In 20 (52.6%) of 38 patients (95% exact confidence interval, 35.8% to 69.0%), a complete (n = 10) or partial response to TMZ was observed. The median time to progression was 10.4 months for all patients and 13.2 months for responding patients. At 12 months from the start of treatment, 40% of patients were still free from progression. Conclusion: TMZ provides an excellent response rate with good tolerability in chemotherapy-naive patients with recurrent OD. A randomized phase III study comparing PCV with TMZ is warranted.