tbuckley/cabot-search huggingface dataset:
Integrin β1 Subunit Controls Mural Cell Adhesion, Spreading, and Blood Vessel Wall Stability
Authors: Sabu Abraham, Naoko Kogata, Reinhard Fässler, Ralf H. Adams
Journal: Circulation Research (2008)

Growth, maturation, and integrity of the blood vessel network require extensive communication between the endothelial cells, which line the vascular lumen, and associated mural cells, namely vascular smooth muscle cells and pericytes. Pericytes extend long processes, make direct contact with the capillary endothelium, and promote vascular quiescence by suppressing angiogenic sprouting. Vascular smooth muscle cells are highly contractile, extracellular matrix–secreting cells that cover arteries and veins and provide them with mechanical stability and elasticity. In the damaged blood vessel wall, for example in atherosclerotic lesions, vascular smooth muscle cells lose their differentiated state and acquire a highly mitotic, so-called “synthetic” phenotype, which is thought to promote pathogenesis. Among other factors, extracellular matrix molecules and integrin family cell–matrix receptors may regulate this phenotypic transition. Here we show that the inactivation of the gene encoding the integrin β1 subunit ( Itgb1 ) with a Cre-loxP approach in mice leads to mural cell defects and postnatal lethality. Integrin β1–deficient vascular smooth muscle cells display several hallmarks of the synthetic phenotype: Cell proliferation is enhanced, whereas differentiation and their ability to support blood vessels are compromised. Similarly, mutant pericytes are poorly spread but present in larger numbers. Our analysis of this mutant model shows that integrin β1–mediated cell–matrix adhesion is a major determinant of the mural cell phenotype.
Inability to obtain deferred consent due to early death in emergency research: effect on validity of clinical trial results
Authors: Tim C. Jansen, Jan Bakker, Erwin J. O. Kompanje
Journal: Intensive Care Medicine (2010)

To illustrate the impact on the validity of trial results due to excluding patients from a randomized controlled trial for whom no deferred consent could be obtained after randomization because study procedures had already been finished.The unadjusted and adjusted primary outcome measures of a recent randomized controlled multicentre study in the field of intensive care medicine were compared, including (n = 348) or excluding (n = 289) patients with missing deferred consent.Thirty-nine patients (11%) died early, before the patient or his/her proxy could be approached and consent be obtained. In another 20 patients (6%), it was not possible to inform proxies and ask consent within the period of study procedures. A significant treatment effect (p = 0.006) in the adjusted analysis became non-significant (p = 0.35) when the patients with missing deferred consent were excluded.Exclusion of patients without obtained deferred consent can reduce statistical power, introduce selection bias, make randomization asymmetrical, decrease external validity and thereby jeopardize study results. This may have implications for emergency research in various disciplines.
Statin Use Is Associated with Prolonged Survival of Renal Transplant Recipients
Authors: Franz Wiesbauer, Georg Heinze, Christa Mitterbauer, Franz Harnoncourt, Walter H. Ho[Combining Diaeresis]rl, Rainer Oberbauer
Journal: Journal of the American Society of Nephrology (2008)

The efficacy of statins for the prevention of cardiovascular events is well established in the general population but remains unknown in renal transplant recipients. In this study, the association of statin use with patient and graft survival was investigated in a cohort of 2041 first-time recipients of renal allografts between 1990 and 2003. Multivariable Cox regression demonstrated that statin use was independently associated with lower mortality rates. Twelve-year survival rates were 73% for statin users and 64% for nonusers (P = 0.055). The adjusted hazard ratio for all-cause mortality associated with statin use was 0.64 (95% confidence interval 0.48 to 0.86). Graft survival rates during the same time period were 76% for statin users and 70% for nonusers (P = 0.055). The adjusted hazard ratio for graft survival associated with statin use was 0.76 (95% confidence interval 0.55 to 1.04). Results from marginal structural models were virtually identical. In summary, statin use was associated with prolonged patient survival, but no difference in graft survival was detected. Although these results are encouraging, a definitive causal relationship can be determined only from randomized clinical trials.
Genetic Variation Is Associated With C-Reactive Protein Levels in the Third National Health and Nutrition Examination Survey
Authors: Dana C. Crawford, Christopher L. Sanders, Xiaoting Qin, Joshua D. Smith, Cynthia Shephard, Michelle Wong, Laura Witrak, Mark J. Rieder, Deborah A. Nickerson
Journal: Circulation (2006)

Increased serum C-reactive protein (CRP) is an independent risk factor for cardiovascular disease. Previous studies have suggested that genetic variation within the CRP gene is associated with serum CRP.We genotyped CRP genetic variants in 7159 individuals from the Third National Health and Nutrition Examination Survey (NHANES III). NHANES III is American population-based sample linked to hundreds of phenotypes, including CRP; however, the CRP assay used in this survey is not a high-sensitivity CRP assay, and 65% of participants (n=4679) had CRP measurements at or below the level of detection. Despite these limitations, we identified specific CRP single-nucleotide polymorphisms (SNPs) and haplotypes associated with serum CRP levels in the general population. Two variants were associated with increased levels of serum CRP: SNP rs3093058 (in linkage disequilibrium with a CRP promoter SNP rs3093062) in the non-Hispanic black sample and the triallelic promoter SNP rs3091244 in the non-Hispanic black and Mexican American samples. Two other SNPs were associated with decreased levels of serum CRP in either the non-Hispanic black (rs1205 and rs2808630) or Mexican American (rs1205) samples. Three haplotypes inferred from 7 SNPs (ATTGCGA, TTAGCGA, and AAAGAGA) were associated (P < or = 0.01) with increased levels of serum CRP in the non-Hispanic black sample; 2 haplotypes (ATTGCGA and AAAGCGA) were associated (P < 0.05) with increased levels in the Mexican American sample; and 1 haplotype (AAAGCGA) was associated (P < 0.03) with increased levels in the non-Hispanic white sample. Post hoc analysis suggests that the AA genotype of the triallelic SNP rs3091244, after adjustment for covariates, was associated with prevalent coronary heart disease in the non-Hispanic white population sample.Genetic variation within CRP is associated with serum CRP levels in the general population and may be associated with prevalent coronary heart disease.
Presentation and analysis of radiographic data in clinical trials and observational studies
Authors: R Landewe
Journal: Annals of the Rheumatic Diseases (2005)

Despite the advent of sophisticated imaging systems, plain radiography continues to be a valuable outcome variable in clinical trials of inflammatory disorders for a number of reasons. This paper discusses the pros and cons of the different ways in which radiographic data in trials is presented; the minimum time needed to demonstrate radiographic progression in the context of a clinical trial; and the best ways to statistically analyse radiographic data.
Traffic-related air pollution and respiratory health during the first 2 yrs of life
Authors: U. Gehring, J. Cyrys, G. Sedlmeir, B. Brunekreef, T. Bellander, P. Fischer, C.P. Bauer, D. Reinhardt, H.E. Wichmann, J. Heinrich
Journal: European Respiratory Journal (2002)

As part of an international collaborative study on the impact of Traffic-Related Air Pollution on Childhood Asthma (TRAPCA), the health effects associated with long-term exposure to particles with a 50% cut-off aerodynamic diameter of 2.5 µm (PM 2.5 ), PM 2.5 absorbance, and nitrogen dioxide (NO 2 ) were analysed. The German part of the TRAPCA study used data from subpopulations of two ongoing birth cohort studies (German Infant Nutrition Intervention Programme (GINI) and Influences of Lifestyle Related Factors on the Human Immune System and Development of Allergies in Children (LISA)) based in the city of Munich. Geographic information systems (GIS)-based exposure modelling was used to estimate traffic-related air pollutants at the birth addresses of 1,756 infants. Logistic regression was used to analyse possible health effects and potential confounding factors were adjusted for. The ranges in estimated exposures to PM 2.5 , PM 2.5 absorbance, and NO 2 were 11.9–21.9 µg·m −3 , 1.38–4.39×10 −5 m −1 , and 19.5–66.9 µg·m 3 , respectively. Significant associations between these pollutants and cough without infection (odds ratio (OR) (95% confidence interval (CI)): 1.34 (1.11–1.61), 1.32 (1.10–1.59), and 1.40 (1.12–1.75), respectively) and dry cough at night (OR (95% CI): 1.31 (1.07–1.60), 1.27 (1.04–1.55), and 1.36 (1.07–1.74), respectively) in the first year of life were found. In the second year of life, these effects were attenuated. There was some indication of an association between traffic-related air pollution and symptoms of cough. Due to the very young age of the infants, it was too early to draw definitive conclusions from this for the development of asthma.
Further Evidence for the Role of Genes on Chromosome 2 and Chromosome 5 in the Inheritance of Pulmonary Function
Authors: Alka Malhotra, Andy P. Peiffer, Darin T. Ryujin, Tami Elsner, Richard E. Kanner, Mark F. Leppert, Sandra J. Hasstedt
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

The spirometric measurements FEV1, FVC, and the ratio FEV1/FVC are used in the diagnosis of lung function disorders. Therefore, understanding the genetics underlying these spirometric measurements will increase our knowledge of the genetics of pulmonary function. FEV1 and FVC were measured on 264 members of 26 Utah Genetic Reference pedigrees, originally collected for the Centre d'Etude du Polymorphisme Humain genetic mapping project. Using segregation analysis, we inferred major locus inheritance of the FEV1/FVC ratio, although we could not distinguish between a dominant or recessive mode of inheritance. No evidence of major locus inheritance was found for either FEV1 or FVC. Suggestive evidence of linkage for the ratio FEV1/FVC was found on chromosome 2 (heterogeneity lod = 2.36, dominant model) and chromosome 5 (heterogeneity lod = 2.23, recessive model), replicating linkages from other studies. In addition, nonparametric variance component linkage analysis showed linkage of FEV1/FVC in both of these regions, providing further support to the results. No nonparametric lod scores over 1.5 were obtained for either FEV1 or FVC.
Comprehensive Training in Forensic Psychiatry
Authors: ROBERT L. SADOFF
Journal: American Journal of Psychiatry (1974)

The University of Pennsylvania's program of training in legal psychiatry is presented as a model of an integrated program of training, research, and service. With the establishment of similar programs at various university centers around the country and with the growth and development of the American Academy of Psychiatry and the Law, the subspecialty of forensic or legal psychiatry has taken on a broader role and responsibility. The author stresses the need for formal training in this subspecialty instead of relying, as in the past, on self-training or preceptorships.
Targeting a Common Collaborator in Cancer Development
Authors: Andrea P. Myers, Lewis C. Cantley
Journal: Science Translational Medicine (2010)

In this issue of Science Translational Medicine, Wallin et al. have identified a subset of breast and ovarian cancer cell lines that show synergistic response to the combination of doxorubicin and GDC-0941, a class IA phosphatidylinositol 3-kinase (PI3K) inhibitor. Here, we discuss the potential implications of these data on the clinical development of PI3K pathway inhibitors as cancer therapeutics.
Monoclonal antibody-associated progressive multifocal leucoencephalopathy in patients treated with rituximab, natalizumab, and efalizumab: a Review from the Research on Adverse Drug Events and Reports (RADAR) Project
Authors: Kenneth R Carson, Daniele Focosi, Eugene O Major, Mario Petrini, Elizabeth A Richey, Dennis P West, Charles L Bennett
Journal: The Lancet Oncology (2009)
Antibodies inhibit the protease-mediated processing of a malaria merozoite surface protein.
Authors: M J Blackman, T J Scott-Finnigan, S Shai, A A Holder
Journal: The Journal of Experimental Medicine (1994)

When merozoites of the malaria parasite Plasmodium falciparum are released from infected erythrocytes and invade new red cells, a component of a protein complex derived from the merozoite surface protein 1 (MSP-1) precursor undergoes a single proteolytic cleavage known as secondary processing. This releases the complex from the parasite surface, except for a small membrane-bound fragment consisting of two epidermal growth factor (EGF)-like domains, which is the only part of MSP-1 to be carried into invaded erythrocytes. We report that, a group of monoclonal antibodies specific for epitopes within the EGF-like domains, some interfere with secondary processing whereas others do not. Those that most effectively inhibit processing have previously been shown to prevent invasion. Other antibodies, some of which can block this inhibition, not only do not prevent invasion but are carried into the host cell bound to the merozoite surface. These observations unequivocally demonstrate that the binding of antibody to the COOH-terminal region of MSP-1 on the merozoite surface may not be sufficient to prevent erythrocyte invasion, and show that the interaction of different antibodies with adjacent epitopes within the EGF-like domains of MSP-1 can have distinct biochemical effects on the molecule. Inhibition of MSP-1 processing on merozoites may be a mechanism by which protective antibodies interrupt the asexual cycle of the malaria parasite.
On the Physical Death of Jesus Christ
Authors: Dennis E. Smith
Journal: JAMA (1986)

<h3>To the Editor.—</h3> The article, "On the Physical Death of Jesus Christ,"<sup>1</sup>is a disgrace to your credibility as a journal of scientific inquiry. The intention throughout the article is to present an apology for the Christian faith, yet it masquerades as a scientific study, which you legitimate by printing it. The apologetic intentions are especially transparent in the concluding paragraph: "Accordingly, interpretations based on the assumption that Jesus did not die on the cross appear to be at odds with modern medical knowledge." This is a non sequitur. Medical data can only lend credibility to what is essentially a historical hypothesis. The hypothesis itself must stand or fall on the basis of the validity of the historical analysis that lies behind it. Yet, the depiction of the death of Jesus that is presented represents an uncritical, literal reading of the biblical text that would not be followed by
Nasal Asthma: Its Causes and Treatment
Authors: G. H. Mackenzie
Journal: BMJ (1885)

Bangladesh is in the rising phase of the ongoing pandemic of the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The scientific literature on clinical manifestations of COVID-19 patients from Bangladesh is scarce. This study aimed to report the sociodemographic and clinical characteristics of patients with COVID-19 in Bangladesh. We conducted a cross-sectional study at three dedicated COVID-19 hospitals. The severity of the COVID-19 cases was assessed based on the WHO interim guidance. Data were collected only from non-critical COVID-19 patients as critical patients required immediate intensive care admission making them unable to respond to the questions. A total of 103 RT-PCR confirmed non-critical COVID-19 patients were enrolled. Most of the patients (71.8%) were male. Mild, moderate and severe illness were assessed in 74.76%, 9.71% and 15.53% of patients respectively. Nearly 52.4% of patients had a co-morbidity, with hypertension being the most common (34%), followed by diabetes mellitus (21.4%) and ischemic heart disease (9.7%). Fever (78.6%), weakness (68%) and cough (44.7%) were the most common clinical manifestations. Other common symptoms included loss of appetite (37.9%), difficulty in breathing (37.9%), altered sensation of taste or smell (35.0%), headache (32%) and body ache (32%). The median time from onset of symptom to attending hospitals was 7 days (IQR 4-10). This study will help both the clinicians and epidemiologists to understand the magnitude and clinical spectrum of COVID-19 patients in Bangladesh.
Acquired resistance to the Hedgehog pathway inhibitor vismodegib due to smoothened mutations in treatment of locally advanced basal cell carcinoma
Authors: Tjinta Brinkhuizen, Marie G. Reinders, Michel van Geel, Annelot J.L. Hendriksen, Aimée D.C. Paulussen, Véronique J. Winnepenninckx, Kristien B. Keymeulen, Patricia M.M.B. Soetekouw, Maurice A.M. van Steensel, Klara Mosterd
Journal: Journal of the American Academy of Dermatology (2014)
Serum Concentration of Cystatin C and Risk of End-Stage Renal Disease in Diabetes
Authors: Andrzej S. Krolewski, James H. Warram, Carol Forsblom, Adam M. Smiles, Lena Thorn, Jan Skupien, Valma Harjutsalo, Robert Stanton, John H. Eckfeldt, Lesley A. Inker, Per-Henrik Groop
Journal: Diabetes Care (2012)

Patients with diabetes have a high risk of end-stage renal disease (ESRD). We examined whether prediction of this outcome, according to chronic kidney disease (CKD) staging by creatinine-based estimates of the glomerular filtration rate (eGFRcreat), is improved by further staging with serum cystatin C-based estimates (eGFRcyst).Patients with diabetes in CKD stages 1-3 were selected from three cohorts: two from Joslin Diabetes Center, one with type 1 diabetes (N = 364) and one with type 2 diabetes (N = 402), and the third from the Finnish Diabetic Nephropathy (FinnDiane) Study of type 1 (N = 399). Baseline serum concentrations of creatinine and cystatin C were measured in all patients. Follow-up averaged 8-10 years and onsets of ESRD (n = 246) and death unrelated to ESRD (n = 159) were ascertained.Although CKD staging by eGFRcyst was concordant with that by eGFRcreat for 62% of Joslin patients and 73% of FinnDiane patients, those given a higher stage by eGFRcyst than eGFRcreat had a significantly higher risk of ESRD than those with concordant staging in all three cohorts (hazard ratio 2.3 [95% CI 1.8-3.1]). Similarly, patients at a lower stage by eGFRcyst than by eGFRcreat had a lower risk than those with concordant staging (0.30 [0.13-0.68]). Deaths unrelated to ESRD followed the same pattern, but differences were not as large.In patients with diabetes, CKD staging based on eGFRcyst significantly improves ESRD risk stratification based on eGFRcreat. This conclusion can be generalized to patients with type 1 and type 2 diabetes and to diabetic patients in the U.S. and Finland.
Blunted nocturnal fall in blood pressure in hypertensive women with future cardiovascular morbid events.
Authors: P Verdecchia, G Schillaci, C Gatteschi, I Zampi, M Battistelli, C Bartoccini, C Porcellati
Journal: Circulation (1993)

In essential hypertension, a blunted or absent nocturnal fall in blood pressure (BP) may be associated with increased target organ damage. In this case-control study, we tested the hypothesis that an association exists between a blunted or absent nocturnal fall in BP and future cardiovascular morbid events in patients with essential hypertension.Case subjects were 32 hypertensive patients with a first fatal or nonfatal major cardiovascular event who had off-therapy ambulatory BP monitoring 1 to 5 years earlier in the context of a registry of morbidity and mortality in hypertensive patients. Control subjects were 49 hypertensive patients free from cardiovascular events. The groups were matched with regard to date of baseline ambulatory BP monitoring, age, sex, clinic systolic and diastolic BP, and daytime ambulatory systolic and diastolic BP. At their baseline evaluation, cases and controls did not differ, in either sex, with respect to clinic BP (men, 164/100 vs 162/99 mmHg; women, 178/96 vs 180/93 mmHg), mean daytime ambulatory BP (men, 151/94 vs 147/95 mm Hg; women, 156/90 vs 158/89 mm Hg), age (men, 55 vs 56 years; women, 69 vs 68 years), sex, body weight, serum cholesterol, known duration and family history of hypertension, smoking habits, renal function, or prevalence of diabetes. Echocardiographic left ventricular mass, determined in a subset of patients, was greater in cases than in controls in men (145 vs 115 g/m2, P = .038) and women (137 vs 102 g/m2, P = .032). The time interval between baseline ambulatory BP monitoring and subsequent cardiovascular event (cases: mean, 2.1 years) or last contact with our center (controls: mean, 2.5 years) did not differ between the groups. In the baseline ambulatory BP profile, the nocturnal reductions of systolic and diastolic BP in men were 9% and 11%, respectively, in cases vs 9% and 12% in controls (all P = NS), whereas in women they were 3% and 8% in cases vs 11% and 16% in controls (P = .002/.004).This retrospective case-control study suggests an association between the reduction or absence of the usual nocturnal fall in BP and future cardiovascular morbid events in white women with essential hypertension.
Modulation of Oncogenic Phenotype in Human Glioma Cells by Cytomegalovirus IE1–Mediated Mitogenicity
Authors: Charles S. Cobbs, Liliana Soroceanu, Scott Denham, Wenyue Zhang, Matthias H. Kraus
Journal: Cancer Research (2008)

Recent evidence indicates that human cytomegalovirus (HCMV) infection occurs in a high percentage of human malignant gliomas in vivo, as the HCMV immediate early-1 (IE1) protein is detected in >90% of these tumors. The HCMV IE1 protein is essential for viral infection and has potent trans-activating and oncomodulatory properties. To investigate a potential role of HCMV in glioma biology, we stably expressed the HCMV IE1 gene product in immortalized and malignant human glial cells. Here we show that stable IE1 expression can differentially affect the growth of human glioblastoma cells, resulting in either growth proliferation or arrest. IE1 expression led to dysregulation of phosphatidylinositol 3-kinase/AKT activity, Rb phosphorylation, and expression of the p53 family of proteins. In U87 and U118 glioblastoma cells, IE1 induced cellular proliferation paralleled by reduction in steady-state expression level of Rb and p53 family proteins (including p53, p63, or p73) and simultaneous induction of the phosphatidylinositol 3-kinase/AKT signaling pathway. In contrast, IE1 expression in LN229 and U251 glioblastoma cells and immortalized human astrocytes was associated with increased expression of p53 family proteins, accompanied by growth arrest or lack of enhanced proliferation. Moreover, IE1 promoted cell cycle entry and DNA synthesis of human glioma cells on both stable expression in tumor-derived cell lines as well as transient expression in primary glioblastoma cells. These findings indicate that HCMV IE1 can significantly affect important oncogenic signaling pathways in glioblastoma cells.