tbuckley/cabot-search huggingface dataset:
The SUPPORT Prognostic Model: Objective Estimates of Survival for Seriously Ill Hospitalized Adults
Authors: William A. Knaus
Journal: Annals of Internal Medicine (1995)

Objective: To develop and validate a prognostic model that estimates survival over a 180-day period for seriously ill hospitalized adults (phase I of SUPPORT [Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments]) and to compare this model's predictions with those of an existing prognostic system and with physicians' independent estimates (SUPPORT phase II). Design: Prospective cohort study. Setting: 5 tertiary care academic centers in the United States. Participants: 4301 hospitalized adults were selected for phase I according to diagnosis and severity of illness; 4028 patients were evaluated from phase II. Measurements: A survival model was developed using the following predictor variables: diagnosis, age, number of days in the hospital before study entry, presence of cancer, neurologic function, and 11 physiologic measures recorded on day 3 after study entry. Physicians were interviewed on day 3. Patients were followed for survival for 180 days after study entry. Results: The area under the receiver-operating characteristics (ROC) curve for prediction of surviving 180 days was 0.79 in phase I, 0.78 in the phase II independent validation, and 0.78 when the acute physiology score from the APACHE (Acute Physiology, Age, Chronic Health Evaluation) III prognostic scoring system was substituted for the SUPPORT physiology score. For phase II patients, the SUPPORT model had equal discrimination and slightly improved calibration compared with physicians' estimates. Combining the SUPPORT model with physicians' estimates improved both predictive accuracy (ROC curve area = 0.82) and the ability to identify patients with high probabilities of survival or death. Conclusions: A limited amount of readily available clinical information can provide a foundation for long-term survival estimates that are as accurate as physicians' estimates. The best survival estimates combine an objective prognosis with a physician's clinical estimate.
Lifetime Cancer Risks of <i>PTEN</i> Mutation Carriers—Response
Authors: Min-Han Tan, Jessica Mester, Charis Eng
Journal: Clinical Cancer Research (2012)

We thank Daniels and colleagues for their comments on our report ([1][1]). Given that the Cleveland Clinic is the main referral center of patients with germline PTEN mutations in the United States, it is certainly possible that ascertainment bias may exist, an issue we acknowledged in our report.
The Bayesian "Star Paradox" Persists for Long Finite Sequences
Authors: M. Steel, F. A. Matsen
Journal: Molecular Biology and Evolution (2007)

The “star paradox” in phylogenetics is the tendency for a particular resolved tree to be sometimes strongly supported even when the data is generated by an unresolved (“star”) tree. There have been contrary claims as to whether this phenomenon persists when very long sequences are considered. This note settles one aspect of this debate by proving mathematically that the chance that a resolved tree could be strongly supported stays above some strictly positive number, even as the length of the sequences becomes very large.
Comparison of outcome measures for patients with chronic obstructive pulmonary disease (COPD) in an outpatient setting.
Authors: R Harper, J E Brazier, J C Waterhouse, S J Walters, N M Jones, P Howard
Journal: Thorax (1997)

BACKGROUND: To assist clinicians and researchers in choosing outcome measures for patients with chronic obstructive pulmonary disease attending routine outpatient clinics, a comparative assessment was undertaken of four questionnaires designed to reflect the patients9 perception of their physical and emotional health in terms of their feasibility, validity, reliability, and responsiveness to health change. METHODS: Two condition specific questionnaires, the St George9s Respiratory Questionnaire (SGRQ) and Guyatt9s Chronic Respiratory Questionnaire (CRQ), and two generic questionnaires, the Short Form-36 Health Survey (SF-36) and Euroqol (EQ), were compared for their discriminative and evaluative properties. Spirometric tests and a walking test were also performed. One hundred and fifty six adults who were clinically judged to have COPD and who attended an outpatient chest clinic were assessed at recruitment and six and 12 months later. Patients were also asked whether their health had changed since their last assessment. RESULTS: Completion rates and consistency between items for dimensions of the SGRQ were lower than for dimensions of the other questionnaires. The distributions of responses were skewed for certain dimensions in all questionnaires except the CRQ. Validity was supported for all instruments insofar as patients9 scores were associated with differences in disease severity. The generic questionnaires better reflected other health problems. All instruments were reliable over time. The condition specific questionnaires were more responsive between baseline and first follow up visit but this difference did not persist. While certain dimensions of the SF-36 were responsive to patient perceived changes, this did not apply to the derived single index of the EQ. The rating scale of the EQ, however, provided a quick and easy indicator of change. CONCLUSIONS: Evidence from this study supports the CRQ and the SF-36 as comprehensive outcome measures for patients with longstanding COPD.
NADPH Oxidase Inhibits the Pathogenesis of Systemic Lupus Erythematosus
Authors: Allison M. Campbell, Michael Kashgarian, Mark J. Shlomchik
Journal: Science Translational Medicine (2012)

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by loss of tolerance to self nucleic acids. The source of autoantigen that drives disease onset and progression is unclear. A candidate source of autoantigen is the neutrophil extracellular trap (NET), which releases nucleic acids into the extracellular environment, generating a structure composed of DNA coated with antimicrobial proteins. On the basis of in vitro and patient correlative studies, several groups have suggested that NETs may provide lupus autoantigens. The observation that NET release (NETosis) relies on activity of the phagocyte NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase (Nox2) in neutrophils of both humans and mice provided a genetic strategy to test this hypothesis in vivo. Therefore, we crossed an X-linked nox2 null allele onto the lupus-prone MRL.Fas(lpr) genetic background and assessed immune activation, autoantibody generation, and SLE pathology. Counter to the prevailing hypothesis, Nox2-deficient lupus-prone mice had markedly exacerbated lupus, including increased spleen weight, increased renal disease, and elevated and altered autoantibody profiles. Moreover, heterozygous female mice, which have Nox2 deficiency in 50% of neutrophils, also had exacerbated lupus and altered autoantibody patterns, suggesting that failure to undergo normal Nox2-dependent cell death may result in release of immunogenic self-constituents that stimulate lupus. Our results indicate that NETosis does not contribute to SLE in vivo; instead, Nox2 acts to inhibit disease pathogenesis, making this enzyme an important target for further study and a candidate for therapeutic intervention.
Biosensors for Cell Analysis
Authors: Qing Zhou, Kyungjin Son, Ying Liu, Alexander Revzin
Journal: Annual Review of Biomedical Engineering (2015)

Biosensors first appeared several decades ago to address the need for monitoring physiological parameters such as oxygen or glucose in biological fluids such as blood. More recently, a new wave of biosensors has emerged in order to provide more nuanced and granular information about the composition and function of living cells. Such biosensors exist at the confluence of technology and medicine and often strive to connect cell phenotype or function to physiological or pathophysiological processes. Our review aims to describe some of the key technological aspects of biosensors being developed for cell analysis. The technological aspects covered in our review include biorecognition elements used for biosensor construction, methods for integrating cells with biosensors, approaches to single-cell analysis, and the use of nanostructured biosensors for cell analysis. Our hope is that the spectrum of possibilities for cell analysis described in this review may pique the interest of biomedical scientists and engineers and may spur new collaborations in the area of using biosensors for cell analysis.
The effects of rest and treatment following sport-related concussion: a systematic review of the literature
Authors: Kathryn J Schneider, Grant L Iverson, Carolyn A Emery, Paul McCrory, Stanley A Herring, Willem H Meeuwisse
Journal: British Journal of Sports Medicine (2013)

To evaluate the evidence for rest, treatment, and rehabilitation following sport-related concussion (SRC).PubMed, CINAHL, PsychInfo, Cochrane Controlled Trials Registers, Health STAR, Sport Discus, EMBASE, Web of Science, and ProQuest.Articles were included if they met the following criteria: original research, reported SRC as a source of injury, and evaluated the effect of rest or treatment.Study design, participants, treatment, outcome measures, and key findings.Three studies met the inclusion criteria for evaluating the effects of rest and twelve for treatment. Low-intensity aerobic exercise may be of benefit.The current evidence evaluating the effect of rest and treatment following SRC is sparse. An initial period of rest may be of benefit. Low-level exercise and multimodal physiotherapy may be of benefit for those who are slow to recover. There is a strong need for high level studies evaluating the effects of rest and treatment following SRC.
Inferring Population Mutation Rate and Sequencing Error Rate Using the SNP Frequency Spectrum in a Sample of DNA Sequences
Authors: X. Liu, T. J. Maxwell, E. Boerwinkle, Y.-X. Fu
Journal: Molecular Biology and Evolution (2009)

One challenge of analyzing samples of DNA sequences is to account for the nonnegligible polymorphisms produced by error when the sequencing error rate is high or the sample size is large. Specifically, those artificial sequence variations will bias the observed single nucleotide polymorphism (SNP) frequency spectrum, which in turn may further bias the estimators of the population mutation rate θ=4Nμ for diploids. In this paper, we propose a new approach based on the generalized least squares (GLS) method to estimate θ, given a SNP frequency spectrum in a random sample of DNA sequences from a population. With this approach, error rate ε can be either known or unknown. In the latter case, ε can be estimated given an estimation of θ. Using coalescent simulation, we compared our estimators with other estimators of θ. The results showed that the GLS estimators are more efficient than other θ estimators with error, and the estimation of ε is usable in practice when the θ per bp is small. We demonstrate the application of the estimators with 10-kb noncoding region sequence sampled from a human population and provide suggestions for choosing θ estimators with error.
Ambient air pollution triggers wheezing symptoms in infants
Authors: Z J Andersen, S Loft, M Ketzel, M Stage, T Scheike, M N Hermansen, H Bisgaard
Journal: Thorax (2008)

There is limited evidence for the role of air pollution in the development and triggering of wheezing symptoms in young children. A study was undertaken to examine the effect of exposure to air pollution on wheezing symptoms in children under the age of 3 years with genetic susceptibility to asthma.Daily recordings of symptoms were obtained for 205 children participating in the birth cohort study Copenhagen Prospective Study on Asthma in Children and living in Copenhagen for the first 3 years of life. Daily air pollution levels for particulate matter <10 microm in diameter (PM(10)) and the concentrations of ultrafine particles, nitrogen dioxide (NO(2)), nitrogen oxide (NO(x)) and carbon monoxide (CO) were available from a central background monitoring station in Copenhagen. The association between incident wheezing symptoms and air pollution on the concurrent and previous 4 days was estimated by a logistic regression model (generalised estimating equation) controlling for temperature, season, gender, age, exposure to smoking and paternal history of asthma.Significant positive associations were found between concentrations of PM(10), NO(2), NO(x), CO and wheezing symptoms in infants (aged 0-1 year) with a delay of 3-4 days. Only the traffic-related gases (NO(2), NO(x)) showed significant effects throughout the 3 years of life, albeit attenuating after the age of 1 year.Air pollution related to traffic is significantly associated with triggering of wheezing symptoms in the first 3 years of life.
Genetic Polymorphisms in Antioxidant Enzymes Modulate Hepatic Iron Accumulation and Hepatocellular Carcinoma Development in Patients with Alcohol-Induced Cirrhosis
Authors: Angela Sutton, Pierre Nahon, Dominique Pessayre, Pierre Rufat, Aurélie Poiré, Marianne Ziol, Dominique Vidaud, Nathalie Barget, Nathalie Ganne-Carrié, Nathalie Charnaux, Jean-Claude Trinchet, Liliane Gattegno, Michel Beaugrand
Journal: Cancer Research (2006)

Abstract Manganese superoxide dismutase (MnSOD) converts the superoxide anion into H2O2, which, unless it is detoxified by glutathione peroxidase 1 (GPx1), can increase hepatic iron and can react with iron to form genotoxic compounds. We investigated the role of Ala/Val-MnSOD and Pro/Leu-GPx1 polymorphisms on hepatic iron accumulation and hepatocellular carcinoma development in patients with alcoholic cirrhosis. Genotypes were determined in 162 alcoholic patients with cirrhosis but without hepatocellular carcinoma initially, who were prospectively followed up for hepatocellular carcinoma development. We found that patients with two Val-MnSOD alleles (slow H2O2 production) and two Pro-GPx1 alleles (presumably quick H2O2 detoxification) had a lower risk of hepatocellular carcinoma development than other patients (χ2 trend test, P = 0.001; log-rank, P = 0.0009). Indeed, hepatocellular carcinoma percentage was 0% in subjects with this “2Val-MnSOD/2Pro-GPx1” genotype versus 16%, 27%, and 32% in “2Val-MnSOD/1or2Leu-GPx1,” “1or2Ala-MnSOD/2Pro-GPx1,” and “1or2Ala-MnSOD/1or2Leu-GPx1” patients, respectively. The percentage of patients with stainable hepatic iron increased progressively with these genotypic associations: 22%, 28%, 50%, and 53%, respectively (χ2 trend test, P = 0.005). Stainable iron was a risk factor for hepatocellular carcinoma (log-rank, P = 0.0002; relative risk, 3.40). In conclusion, polymorphisms in antioxidant enzymes modulate hepatic iron accumulation and hepatocellular carcinoma development in French alcoholic patients with cirrhosis. (Cancer Res 2006; 66(5): 2844-52)
Genetic Approaches to Unraveling Reproductive Disorders: Examples of Bedside to Bench Research in the Genomic Era
Authors: Stephanie B. Seminara, William F. Crowley
Journal: Endocrine Reviews (2002)

Despite the rapid advances in medical genetics, many clinicians and investigators remain unaware of the general approaches that can be used to map genes. Although there are specific challenges to using genetic approaches in reproductive medicine, the following report summarizes mapping efforts for three diseases: adrenal hypoplasia congenita, hypergonadotropic ovarian failure, and polycystic ovary syndrome. The themes of rare and novel phenotypes, genetically homogenous populations, and genotype/phenotype correlations are emphasized.
Radiotherapy plus chemotherapy with or without surgical resection for stage III non-small-cell lung cancer: a phase III randomised controlled trial
Authors: Kathy S Albain, R Suzanne Swann, Valerie W Rusch, Andrew T Turrisi, Frances A Shepherd, Colum Smith, Yuhchyau Chen, Robert B Livingston, Richard H Feins, David R Gandara, Willard A Fry, Gail Darling, David H Johnson, Mark R Green, Robert C Miller, Joanne Ley, Willliam T Sause, James D Cox
Journal: The Lancet (2009)
Unplanned respiratory crises requiring ventilation in Duchenne muscular dystrophy (DMD) patients can be reduced by timely respiratory review and care co-ordination at the age of transition
Authors: Emily Ballard, Natalie Grey, Heinz Jungbluth, Elizabeth Wraige, Stam Kapetanakis, Craig Davidson, Nicholas Hart
Journal: European Respiratory Journal (2012)

The introduction of home mechanical ventilation (HMV) in DMD is associated with increased life expectancy. In 2009, we introduced a transitional care coordinator role with the hypothesis that we would reduce the number of unplanned respiratory crises with early intervention. We have prospectively gathered data for all 75 patients with DMD under review in 2009.  Analysis of these data was focused on the primary respiratory crisis admission requiring ventilatory support. Within 3 years we identified 19 patients who required initiation of HMV, all known to the respiratory team prior to initiation and only 3 (15.8%) were as a result of an emergency admission. Out of the 19 patients initiated on HMV, 16 were elective with a mean length of stay of 4.7 days (2-9) days. 1 patient was admitted directly from clinic as an emergency, requiring invasive ventilation but without tracheostomy formation. Of the two patients who required tracheostomy formation, one did not require NIV post discharge from hospital. The data supports that with timely intervention and coordination you can reduce the need for emergency inititiation of ventilation through respiratory crisis.
Detection of Tissue Eosinophils and Evidence of Extensive Degranulation in Archived Clinical Biopsies Using a Novel Anti-Eosinophil Peroxidase Monoclonal Antibody
Authors: C. Protheroe, J.C. Lewis, T.N. Lunsford, G. DePetris, M.P. McGarry, N.A. Lee, J.J. Lee
Journal: Journal of Allergy and Clinical Immunology (2007)
Increased Inflammatory Gene Expression in ABC Transporter–Deficient Macrophages
Authors: Laurent Yvan-Charvet, Carrie Welch, Tamara A. Pagler, Mollie Ranalletta, Mohamed Lamkanfi, Seongah Han, Minako Ishibashi, Rong Li, Nan Wang, Alan R. Tall
Journal: Circulation (2008)

Background— Two macrophage ABC transporters, ABCA1 and ABCG1, have a major role in promoting cholesterol efflux from macrophages. Peritoneal macrophages deficient in ABCA1, ABCG1, or both show enhanced expression of inflammatory and chemokine genes. This study was undertaken to elucidate the mechanisms and consequences of enhanced inflammatory gene expression in ABC transporter–deficient macrophages. Methods and Results— Basal and lipopolysaccharide-stimulated thioglycollate-elicited peritoneal macrophages showed increased inflammatory gene expression in the order Abca1 −/− Abcg1 −/− &gt; Abcg1 −/− &gt; Abca1 −/− &gt;wild-type. The increased inflammatory gene expression was abolished in macrophages deficient in Toll-like receptor 4 (TLR4) or MyD88/TRIF. TLR4 cell surface concentration was increased in Abca1 −/− Abcg1 −/− &gt; Abcg1 −/− &gt; Abca1 −/− &gt; wild-type macrophages. Treatment of transporter-deficient cells with cyclodextrin reduced and cholesterol-cyclodextrin loading increased inflammatory gene expression. Abca1 −/− Abcg1 − bone marrow–derived macrophages showed enhanced inflammatory gene responses to TLR2, TLR3, and TLR4 ligands. To assess in vivo relevance, we injected intraperitoneally thioglycollate in Abcg1 −/− bone marrow–transplanted, Western diet–fed, Ldlr -deficient mice. This resulted in a profound inflammatory infiltrate in the adventitia and necrotic core region of atherosclerotic lesions, consisting primarily of neutrophils. Conclusions— The results suggest that high-density lipoprotein and apolipoprotein A-1 exert anti-inflammatory effects by promoting cholesterol efflux via ABCG1 and ABCA1 with consequent attenuation of signaling via Toll-like receptors. In response to a peripheral inflammatory stimulus, atherosclerotic lesions containing Abcg1 −/− macrophages experience an inflammatory “echo,” suggesting a possible mechanism of plaque destabilization in subjects with low high-density lipoprotein levels.
Reduction in Connective Tissue Growth Factor by Antisense Treatment Ameliorates Renal Tubulointerstitial Fibrosis
Authors: Hideki Yokoi, Masashi Mukoyama, Tetsuya Nagae, Kiyoshi Mori, Takayoshi Suganami, Kazutomo Sawai, Tetsuro Yoshioka, Masao Koshikawa, Takashi Nishida, Masaharu Takigawa, Akira Sugawara, Kazuwa Nakao
Journal: Journal of the American Society of Nephrology (2004)

Connective tissue growth factor (CTGF/CCN2) is one of the candidate factors mediating fibrogenic activity of TGF-β. It was shown previously that the blockade of CTGF by antisense oligonucleotide (ODN) inhibits TGF-β–induced production of fibronectin and type I collagen in cultured renal fibroblasts. The in vivo contribution of CTGF in renal interstitial fibrosis, however, remains to be clarified. With the use of a hydrodynamics-based gene transfer technique, the effects of CTGF antisense ODN are investigated in rat kidneys with unilateral ureteral obstruction (UUO). FITC-labeled ODN injection via the renal vein showed that the ODN was specifically introduced into the interstitium. At day 7 after UUO, the gene expression of CTGF, fibronectin, fibronectin ED-A, and α1(I) collagen in untreated or control ODN-treated obstructed kidneys was prominently upregulated. CTGF antisense ODN treatment, by contrast, markedly attenuated the induction of CTGF, fibronectin, fibronectin ED-A, and α1(I) collagen genes, whereas TGF-β gene upregulation was not affected. The antisense treatment also reduced interstitial deposition of CTGF, fibronectin ED-A, and type I collagen and the interstitial fibrotic areas. The number of myofibroblasts determined by the expression of α-smooth muscle actin was significantly decreased as well. Proliferation of tubular and interstitial cells was not altered with the treatment. These findings indicate that CTGF expression in the interstitium plays a crucial role in the progression of interstitial fibrosis but not in the proliferation of tubular and interstitial cells during UUO. CTGF may become a potential therapeutic target against tubulointerstitial fibrosis.
Systematic profiling of cellular phenotypes with spotted cell microarrays reveals mating-pheromone response genes.
Authors: Rammohan Narayanaswamy, Wei Niu, AlexanderD Scouras, G Traver Hart, Jonathan Davies, AndrewD Ellington, VishwanathR Iyer, EdwardM Marcotte
Journal: Genome biology (2006)

We have developed spotted cell microarrays for measuring cellular phenotypes on a large scale. Collections of cells are printed, stained for subcellular features, then imaged via automated, high-throughput microscopy, allowing systematic phenotypic characterization. We used this technology to identify genes involved in the response of yeast to mating pheromone. Besides morphology assays, cell microarrays should be valuable for high-throughput in situ hybridization and immunoassays, enabling new classes of genetic assays based on cell imaging.