tbuckley/cabot-search huggingface dataset:
Sphingomyelinase-Like Phosphodiesterase 3b Expression Levels Determine Podocyte Injury Phenotypes in Glomerular Disease
Authors: Tae-Hyun Yoo, Christopher E. Pedigo, Johanna Guzman, Mayrin Correa-Medina, Changli Wei, Rodrigo Villarreal, Alla Mitrofanova, Farah Leclercq, Christian Faul, Jing Li, Matthias Kretzler, Robert G. Nelson, Markku Lehto, Carol Forsblom, Per-Henrik Groop, Jochen Reiser, George William Burke, Alessia Fornoni, Sandra Merscher
Journal: Journal of the American Society of Nephrology (2014)

Diabetic kidney disease (DKD) is the most common cause of ESRD in the United States. Podocyte injury is an important feature of DKD that is likely to be caused by circulating factors other than glucose. Soluble urokinase plasminogen activator receptor (suPAR) is a circulating factor found to be elevated in the serum of patients with FSGS and causes podocyte αVβ3 integrin-dependent migration in vitro. Furthermore, αVβ3 integrin activation occurs in association with decreased podocyte-specific expression of acid sphingomyelinase-like phosphodiesterase 3b (SMPDL3b) in kidney biopsy specimens from patients with FSGS. However, whether suPAR-dependent αVβ3 integrin activation occurs in diseases other than FSGS and whether there is a direct link between circulating suPAR levels and SMPDL3b expression in podocytes remain to be established. Our data indicate that serum suPAR levels are also elevated in patients with DKD. However, unlike in FSGS, SMPDL3b expression was increased in glomeruli from patients with DKD and DKD sera-treated human podocytes, where it prevented αVβ3 integrin activation by its interaction with suPAR and led to increased RhoA activity, rendering podocytes more susceptible to apoptosis. In vivo, inhibition of acid sphingomyelinase reduced proteinuria in experimental DKD but not FSGS, indicating that SMPDL3b expression levels determined the podocyte injury phenotype. These observations suggest that SMPDL3b may be an important modulator of podocyte function by shifting suPAR-mediated podocyte injury from a migratory phenotype to an apoptotic phenotype and that it represents a novel therapeutic glomerular disease target.
Prosthesis-Patient Mismatch Affects Survival After Aortic Valve Replacement
Authors: V. Rao, W. R. E. Jamieson, J. Ivanov, S. Armstrong, T. E. David
Journal: Circulation (2000)

Surgeons traditionally avoid the use of "small" aortic prostheses because of the potential for residual left ventricular outflow tract obstruction and persistent transvalvular gradients. This study examines the ratio between prosthetic valve size and the body surface area (BSA) of patients undergoing aortic valve replacement (AVR). We sought to determine the effect of potential "prosthesis-patient" mismatch on long-term survival.Follow-up was conducted on 2981 patients who underwent AVR with stented bioprostheses between 1976 and 1996. To account for differences between manufacturers' labeled valve sizes, we calculated the ratio between the prosthetic valve effective orifice area (EOA) and the patient's BSA (recorded for 2154 patients). The lowest decile in this cohort had a calculated EOA/BSA of <0.75 cm(2)/m(2) (Small group, n=227) compared with the control group (n=1927), in whom the EOA/BSA ratio was >0.75 cm(2)/m(2). Operative mortality was higher in the Small group (8% versus 5%, P:=0.03). Actuarial survival at 12 years was 50+/-5% in the Small group compared with 49+/-2% in the control group (P:=0.27). However, freedom from valve-related mortality was significantly lower in the Small group (75+/-5% versus 84+/-2%, P:=0.004). Cox regression analysis determined age and NYHA functional class to be the multivariate predictors of overall mortality, whereas advanced age and EOA/BSA <0.75 cm(2)/m(2) were found to be the predictors of valve-related mortality.Prosthesis-patient mismatch results in significantly higher early and late mortality after bioprosthetic AVR. We recommend careful selection of stented bioprostheses to ensure an adequate ratio of EOA to BSA. An EOA/BSA ratio of >0.75 cm(2)/m(2) may avoid residual left ventricular outflow tract obstruction and persistent transvalvular gradients. Careful prosthesis-patient matching will improve both early and late survival after AVR.
Ultrasound-Mediated Gene Delivery with Cationic Versus Neutral Microbubbles: Effect of DNA and Microbubble Dose on <i>In Vivo</i> Transfection Efficiency
Authors: Cedric M. Panje, David S. Wang, Marybeth A. Pysz, Ramasamy Paulmurugan, Ying Ren, Francois Tranquart, Lu Tian, Jürgen K. Willmann
Journal: Theranostics (2012)

Objective: To assess the effect of varying microbubble (MB) and DNA doses on the overall and comparative efficiencies of ultrasound (US)-mediated gene delivery (UMGD) to murine hindlimb skeletal muscle using cationic versus neutral MBs.Materials and Methods: Cationic and control neutral MBs were characterized for size, charge, plasmid DNA binding, and ability to protect DNA against endonuclease degradation.UMGD of a codon optimized firefly luciferase (Fluc) reporter plasmid to endothelial cells (1 MHz, 1 W/cm², 20% duty cycle, 1 min) was performed in cell culture using cationic, neutral, or no MBs.In vivo UMGD to mouse hindlimb muscle was performed by insonation (1 MHz, 2 W/cm², 50% duty cycle, 5 min) after intravenous administration of Fluc combined with cationic, neutral, or no MBs.Gene delivery efficiency was assessed by serial in vivo bioluminescence imaging.Efficiency of in vivo UMGD with cationic versus neutral MBs was systematically evaluated by varying plasmid DNA dose (10, 17.5, 25, 37.5, and 50 µg) while maintaining a constant MB dose of 1x10 8 MBs and by changing MB dose (1x10 7 , 5x10 7 , 1x10 8 , or 5x10 8 MBs) while keeping a constant DNA dose of 50 µg.Results: Cationic and size-matched control neutral MBs differed significantly in zeta potential with cationic MBs being able to bind plasmid DNA (binding capacity of 0.03 pg/MB) and partially protect DNA from nuclease degradation while neutral MBs could not.Cationic MBs enhanced UMGD compared to neutral MBs as well as no MB and no US controls both in cell culture (P < 0.001) and in vivo (P < 0.05).Regardless of MB type, in vivo UMGD efficiency increased dose-dependently with DNA dose and showed overall maximum transfection with 50 µg DNA.However, there was an inverse correlation (ρ = -0.90;P = 0.02) between DNA dose and the degree of enhanced UMGD efficiency observed with using cationic MBs instead of neutral MBs.The delivery efficiency advantage associated with cationic MBs was most prominent at the lowest investigated DNA dose (7.5-fold increase with cationic versus neutral MBs at a DNA dose of 10 µg; P = 0.02) compared to only a 1.4-fold increase at a DNA dose of 50 µg (P < 0.01).With increasing MB dose, overall in vivo UMGD efficiency increased dose-dependently with a maximum reached at a dose of 1x10 8 MBs with no further significant increase with 5x10 8 MBs (P = 0.97).However, compared to neutral MBs, cationic MBs enhanced UMGD efficiency the most at low MB doses.Relative enhancement of UMGD effi-Ivyspring International
The Neural Substrates of Impaired Prosodic Detection in Schizophrenia and Its Sensorial Antecedents
Authors: David I. Leitman, Matthew J. Hoptman, John J. Foxe, Erica Saccente, Glenn R. Wylie, Jay Nierenberg, Maria Jalbrzikowski, Kelvin O. Lim, Daniel C. Javitt
Journal: American Journal of Psychiatry (2007)

Objective: Individuals with schizophrenia show severe deficits in their ability to decode emotions based upon vocal inflection (affective prosody). This study examined neural substrates of prosodic dysfunction in schizophrenia with voxelwise analysis of diffusion tensor magnetic resonance imaging (MRI). Method: Affective prosodic performance was assessed in 19 patients with schizophrenia and 19 comparison subjects with the Voice Emotion Identification Task (VOICEID), along with measures of basic pitch perception and executive processing (Wisconsin Card Sorting Test). Diffusion tensor MRI fractional anisotropy valves were used for voxelwise correlation analyses. In a follow-up experiment, performance on a nonaffective prosodic perception task was assessed in an additional cohort of 24 patients and 17 comparison subjects. Results: Patients showed significant deficits in VOICEID and Distorted Tunes Task performance. Impaired VOICEID performance correlated significantly with lower fractional anisotropy values within primary and secondary auditory pathways, orbitofrontal cortex, corpus callosum, and peri-amygdala white matter. Impaired Distorted Tunes Task performance also correlated with lower fractional anisotropy in auditory and amygdalar pathways but not prefrontal cortex. Wisconsin Card Sorting Test performance in schizophrenia correlated primarily with prefrontal fractional anisotropy. In the follow-up study, significant deficits were observed as well in nonaffective prosodic performance, along with significant intercorrelations among sensory, affective prosodic, and nonaffective measures. Conclusions: Schizophrenia is associated with both structural and functional disturbances at the level of primary auditory cortex. Such deficits contribute significantly to patients’ inability to decode both emotional and semantic aspects of speech, highlighting the importance of sensorial abnormalities in social communicatory dysfunction in schizophrenia.
Transcriptome analysis of the acoelomate human parasite Schistosoma mansoni
Authors: Sergio Verjovski-Almeida, Ricardo DeMarco, Elizabeth A L Martins, Pedro E M Guimarães, Elida P B Ojopi, Apuã C M Paquola, João P Piazza, Milton Y Nishiyama, João P Kitajima, Rachel E Adamson, Peter D Ashton, Maria F Bonaldo, Patricia S Coulson, Gary P Dillon, Leonardo P Farias, Sheila P Gregorio, Paulo L Ho, Ricardo A Leite, L Cosme C Malaquias, Regina C P Marques, Patricia A Miyasato, Ana L T O Nascimento, Fernanda P Ohlweiler, Eduardo M Reis, Marcela A Ribeiro, Renata G Sá, Gaëlle C Stukart, M Bento Soares, Cybele Gargioni, Toshie Kawano, Vanderlei Rodrigues, Alda M B N Madeira, R Alan Wilson, Carlos F M Menck, João C Setubal, Luciana C C Leite, Emmanuel Dias-Neto
Journal: Nature Genetics (2003)
Evolution of Proteins and Gene Expression Levels are Coupled in Drosophila and are Independently Associated with mRNA Abundance, Protein Length, and Number of Protein-Protein Interactions
Authors: B. Lemos
Journal: Molecular Biology and Evolution (2005)

Organismic evolution requires that variation at distinct hierarchical levels and attributes be coherently integrated, often in the face of disparate environmental and genetic pressures. A central part of the evolutionary analysis of biological systems remains to decipher the causal connections between organism-wide (or genome-wide) attributes (e.g., mRNA abundance, protein length, codon bias, recombination rate, genomic position, mutation rate, etc) as well as their role—together with mutation, selection, and genetic drift—in shaping patterns of evolutionary variation in any of the attributes themselves. Here we combine genome-wide evolutionary analysis of protein and gene expression data to highlight fundamental relationships among genomic attributes and their associations with the evolution of both protein sequences and gene expression levels. Our results show that protein divergence is positively coupled with both gene expression polymorphism and divergence. We show moreover that although the number of protein-protein interactions in Drosophila is negatively associated with protein divergence as well as gene expression polymorphism and divergence, protein-protein interactions cannot account for the observed coupling between regulatory and structural evolution. Furthermore, we show that proteins with higher rates of amino acid substitutions tend to have larger sizes and tend to be expressed at lower mRNA abundances, whereas genes with higher levels of gene expression divergence and polymorphism tend to have shorter sizes and tend to be expressed at higher mRNA abundances. Finally, we show that protein length is negatively associated with both number of protein-protein interactions and mRNA abundance and that interacting proteins in Drosophila show similar amounts of divergence. We suggest that protein sequences and gene expression are subjected to similar evolutionary dynamics, possibly because of similarity in the fitness effect (i.e., strength of stabilizing selection) of disruptions in a gene's protein sequence or its mRNA expression. We conclude that, as more and better data accumulate, understanding the causal connections among biological traits and how they are integrated over time to constrain or promote structural and regulatory evolution may finally become possible.
Old ideas, new mistakes: All learning is relational
Authors: Stellan Ohlsson
Journal: Behavioral and Brain Sciences (1997)

Learning is the acquisition of knowledge, not of input/output mappings. The distinction between statistical and relational learning, as Clark &amp; Thornton define those terms, is not useful because all human learning is relational. However, prior knowledge does influence later learning and the sequence in which learning tasks are encountered is indeed crucial. Simulations of sequence effects would be interesting.
A REPORT OF NINE CASES IN WHICH HAAB'S MAGNET WAS USED FOR THE EXTRACTION OF FOREIGN BODIES FROM THE EYE
Authors: W. T. H. Spicer, A. F. Maccallan
Journal: BMJ (1902)

mo I3' far as I know the " dot " in this case was permanent.The patient asserted that in looking at a line he observed the portion looked at to be thicker (metamorphopsia).This phenomenon has beon observed in a few of the recorded eases.It was absent in the case I now relate.Many years ago a case came under my notice of a girl3 who suffered from retinitis in consequence of receiving the sun, on a hot summer's day, full on her eye from a reflector which a boy passing her was using.The eye recovered well.The instance related here is of interest as both eyes were affected, and the patient, an unusually intelligent man and an excellent observer, has been able to give a good account of his case.Here the ophthalmoscopic signs were practically nil; in some of the cases recorded fine changes have been noted at the macula, whilst in others similar indefinite alterations to those referred to in my present case have been observed; in others again no abnormal appearances have been mentioned.The prognosis appears to be favourable in these cases, vision, for practical purposes, being restored, but in many a scotoma, more or less distinct, has been left permanently.The cases illustrate thse utter uselessnessof the "glasses" toofrequently used in observing eclipses.
Osteopontin expression and relation to disease severity in human asthma
Authors: K. Samitas, E. Zervas, S. Vittorakis, M. Semitekolou, T. Alissafi, A. Bossios, H. Gogos, E. Economidou, J. Lötvall, G. Xanthou, V. Panoutsakopoulou, M. Gaga
Journal: European Respiratory Journal (2010)

Recent studies have associated osteopontin (OPN) with allergic inflammation; however, its role in human asthma remains unclear. The aim of this study was to measure OPN levels in the serum, bronchoalveolar lavage fluid (BALF) and bronchial tissue of healthy controls and asthmatics, identify cellular sources of OPN and examine possible correlations between OPN expression, disease severity and airway remodelling. Serum samples were obtained from 35 mild-to-moderate asthmatics, 19 severe asthmatics and 17 healthy controls in the steady state and in cases of exacerbation. Of these subjects, 29 asthmatics and nine controls underwent bronchoscopy with endobronchial biopsy and BALF collection. OPN expression was determined by ELISA and immunohistochemistry/immunofluorescence. Reticular basement membrane thickness and goblet cell hyperplasia were also determined. Serum and BALF OPN levels were significantly increased in all asthmatics in the steady state, whereas serum levels decreased during exacerbations. OPN was upregulated in the bronchial tissue of all patients, and expressed by epithelial, airway and vascular smooth muscle cells, myofibroblasts, T-lymphocytes and mast cells. OPN expression correlated with reticular basement membrane thickness and was more prominent in subepithelial inflammatory cells in severe compared to mild-to-moderate asthma. OPN expression is upregulated in human asthma and associated with remodelling changes, and its subepithelial expression correlates with disease severity.
Intestinal renin–angiotensin system is stimulated after deletion of Lkb1
Authors: Boris Y Shorning, Thierry Jardé, Afshan McCarthy, Alan Ashworth, Wendy W J de Leng, George Johan A Offerhaus, Nicoletta Resta, Trevor Dale, Alan R Clarke
Journal: Gut (2011)

<h3>Background and aims</h3> LKB1 is a serine-threonine kinase, mutation of which can lead to the development of multiple benign intestinal hamartomas (Peutz–Jeghers syndrome). In this study, the authors investigate the mechanisms underlying this phenotype by exploring the transcriptional changes associated with Lkb1 deletion in intestinal epithelium. <h3>Methods</h3> The authors used mice with Lkb1 deleted in the intestinal epithelium using a Cyp1a1-specific inducible Cre recombinase and used Affymetrix (Santa Clara, California, USA) microarray analysis to examine the transcriptional changes occurring immediately after Lkb1 loss. The authors also generated crypt–villus organoid culture to analyse Lkb1 role in intestinal responses to exogenous stimuli. <h3>Results</h3> Affymetrix analysis identified the most significant change to be in <i>Ren1</i> expression, a gene encoding a protease involved in angiotensinogen processing. Lkb1 deletion also enhanced ACE expression and subsequently angiotensin II (AngII) production in the mouse intestine. Intestinal apoptosis induced by Lkb1 deficiency was suppressed by ACE inhibitor captopril. Lkb1-deficient intestinal epithelium showed dynamic changes in AngII receptor type 1, suggesting a possible compensatory response to elevated AngII levels. A similar reduction in epithelial AngII receptor type 1 was also observed in human Peutz–Jeghers syndrome tumours contrasting with high expression of the receptor in the tumour stroma. Mechanistically, the authors showed two pieces of data that position Lkb1 in renin expression regulation, and they implied the importance of Lkb1 in linking cell responses with nutrient levels. First, the authors showed that Lkb1 deletion in isolated epithelial organoid culture resulted in renin upregulation only when the organoids were challenged with external cues such as AngII; second, that renin upregulation was dependent upon the MEK/ERK pathway in a circadian fashion and corresponded to active feeding time when nutrient levels were high. <h3>Conclusions</h3> Taken together, these data reveal a novel role for Lkb1 in regulation of the gastrointestinal renin–angiotensin system.
Association Between Influenza Vaccination and Cardiovascular Outcomes in High-Risk Patients
Authors: Jacob A. Udell, Rami Zawi, Deepak L. Bhatt, Maryam Keshtkar-Jahromi, Fiona Gaughran, Arintaya Phrommintikul, Andrzej Ciszewski, Hossein Vakili, Elaine B. Hoffman, Michael E. Farkouh, Christopher P. Cannon
Journal: JAMA (2013)

Among nontraditional cardiovascular risk factors, recent influenzalike infection is associated with fatal and nonfatal atherothrombotic events.To determine if influenza vaccination is associated with prevention of cardiovascular events.A systematic review and meta-analysis of MEDLINE (1946-August 2013), EMBASE (1947-August 2013), and the Cochrane Library Central Register of Controlled Trials (inception-August 2013) for randomized clinical trials (RCTs) comparing influenza vaccine vs placebo or control in patients at high risk of cardiovascular disease, reporting cardiovascular outcomes either as efficacy or safety events.Two investigators extracted data independently on trial design, baseline characteristics, outcomes, and safety events from published manuscripts and unpublished supplemental data. High-quality studies were considered those that described an appropriate method of randomization, allocation concealment, blinding, and completeness of follow-up.Random-effects Mantel-Haenszel risk ratios (RRs) and 95% CIs were derived for composite cardiovascular events, cardiovascular mortality, all-cause mortality, and individual cardiovascular events. Analyses were stratified by subgroups of patients with and without a history of acute coronary syndrome (ACS) within 1 year of randomization.Five published and 1 unpublished randomized clinical trials of 6735 patients (mean age, 67 years; 51.3% women; 36.2% with a cardiac history; mean follow-up time, 7.9 months) were included. Influenza vaccine was associated with a lower risk of composite cardiovascular events (2.9% vs 4.7%; RR, 0.64 [95% CI, 0.48-0.86], P = .003) in published trials. A treatment interaction was detected between patients with (RR, 0.45 [95% CI, 0.32-0.63]) and without (RR, 0.94 [95% CI, 0.55-1.61]) recent ACS (P for interaction = .02). Results were similar with the addition of unpublished data.In a meta-analysis of RCTs, the use of influenza vaccine was associated with a lower risk of major adverse cardiovascular events. The greatest treatment effect was seen among the highest-risk patients with more active coronary disease. A large, adequately powered, multicenter trial is warranted to address these findings and assess individual cardiovascular end points.
Effects of IL28B rs12979860 CC Genotype on Metabolic Profile and Sustained Virologic Response in Patients With Genotype 1 Chronic Hepatitis C
Authors: Salvatore Petta, Chiara Rosso, Reynold Leung, Maria Lorena Abate, David Booth, Federico Salomone, Roberto Gambino, Mario Rizzetto, Paolo Caviglia, Antonina Smedile, Stefania Grimaudo, Calogero Cammà, Antonio Craxì, Jacob George, Elisabetta Bugianesi
Journal: Clinical Gastroenterology and Hepatology (2012)
Budesonide treatment of collagenous colitis: a randomised, double blind, placebo controlled trial with morphometric analysis
Authors: O K Bonderup
Journal: Gut (2003)

<b>Background:</b> Collagenous colitis is characterised by diarrhoea, lymphocytic inflammation, and a thickened subepithelial collagen layer in the colorectal mucosa. No standard treatment of the disease is established. <b>Aims:</b> To investigate the clinical and histological effect of oral budesonide (Entocort, AstraZeneca) in the treatment of collagenous colitis. <b>Patients:</b> Twenty patients with collagenous colitis (collagen layer &gt;10 μm) and diarrhoea (&gt;4 stools/day and/or stool weight &gt;200 g/day). <b>Methods:</b> A randomised, double blind, placebo controlled trial of budesonide treatment. Patients were randomised to placebo or budesonide for eight weeks. Stool frequency and stool weight were registered before and after treatment. Sigmoidoscopy was performed before and after treatment, and biopsies at fixed locations were obtained for morphometric analysis. <b>Results:</b> Ten patients were randomised to budesonide and 10 to placebo. All 10 patients receiving budesonide had a clinical response compared with two in the placebo group (p&lt;0.001). In the budesonide group, stool weight was reduced from 574 g/day to 200 g/day and stool frequency was reduced from 6.2/day to 1.9/day (p&lt;0.01). The histological inflammation grade in the sigmoid mucosa and the thickness of the collagen layer were significantly reduced. A correlation between the grade of inflammation as well as collagen layer thickness and stool weight was found. No side effects were reported. Eight of 10 patients had relapse of symptoms within eight weeks after stopping treatment. <b>Conclusions:</b> Budesonide is a highly effective and well tolerated treatment of collagenous colitis. There is a high risk of relapse after stopping eight weeks of treatment.
Prophylactic platelet transfusions from healthy apheresis platelet donors undergoing treatment with thrombopoietin
Authors: Lawrence T. Goodnough, David J. Kuter, Jeffrey McCullough, Sherrill J. Slichter, John DiPersio, John Romo, Randolph Peterson, Kenneth J. Smith, Thomas Raife, Dianne Tomita, Susan Armstrong
Journal: Blood (2001)