tbuckley/cabot-search huggingface dataset:
Human Urine-Derived Renal Progenitors for Personalized Modeling of Genetic Kidney Disorders
Authors: Elena Lazzeri, Elisa Ronconi, Maria Lucia Angelotti, Anna Peired, Benedetta Mazzinghi, Francesca Becherucci, Sara Conti, Giulia Sansavini, Alessandro Sisti, Fiammetta Ravaglia, Duccio Lombardi, Aldesia Provenzano, Anna Manonelles, Josep M. Cruzado, Sabrina Giglio, Rosa Maria Roperto, Marco Materassi, Laura Lasagni, Paola Romagnani
Journal: Journal of the American Society of Nephrology (2015)

The critical role of genetic and epigenetic factors in the pathogenesis of kidney disorders is gradually becoming clear, and the need for disease models that recapitulate human kidney disorders in a personalized manner is paramount. In this study, we describe a method to select and amplify renal progenitor cultures from the urine of patients with kidney disorders. Urine-derived human renal progenitors exhibited phenotype and functional properties identical to those purified from kidney tissue, including the capacity to differentiate into tubular cells and podocytes, as demonstrated by confocal microscopy, Western blot analysis of podocyte-specific proteins, and scanning electron microscopy. Lineage tracing studies performed with conditional transgenic mice, in which podocytes are irreversibly tagged upon tamoxifen treatment ( NPHS2.iCreER;mT/mG ), that were subjected to doxorubicin nephropathy demonstrated that renal progenitors are the only urinary cell population that can be amplified in long-term culture. To validate the use of these cells for personalized modeling of kidney disorders, renal progenitors were obtained from ( 1 ) the urine of children with nephrotic syndrome and carrying potentially pathogenic mutations in genes encoding for podocyte proteins and ( 2 ) the urine of children without genetic alterations, as validated by next-generation sequencing. Renal progenitors obtained from patients carrying pathogenic mutations generated podocytes that exhibited an abnormal cytoskeleton structure and functional abnormalities compared with those obtained from patients with proteinuria but without genetic mutations. The results of this study demonstrate that urine-derived patient-specific renal progenitor cultures may be an innovative research tool for modeling of genetic kidney disorders.
Does the nervous system depend on kinesthetic information to control natural limb movements?
Authors: S. C. Gandevia, David Burke
Journal: Behavioral and Brain Sciences (1992)

Abstract This target article draws together two groups of experimental studies on the control of human movement through peripheral feedback and centrally generated signals of motor commands. First, during natural movement, feedback from muscle, joint, and cutaneous afferents changes; in human subjects these changes have reflex and kinesthetic consequences. Recent psychophysical and microneurographic evidence suggests that joint and even cutaneous afferents may have a proprioceptive role. Second, the role of centrally generated motor commands in the control of normal movements and movements following acute and chronic deafferentation is reviewed. There is increasing evidence that subjects can perceive their motor commands under various conditions, but that this is inadequate for normal movement; deficits in motor performance arise when the reliance on proprioceptive feedback is abolished either experimentally or because of pathology. During natural movement, the CNS appears to have access to functionally useful input from a range of peripheral receptors as well as from internally generated command signals. The unanswered questions that remain suggest a number of avenues for further research.
The Protective Effect of Late Preconditioning Against Myocardial Stunning in Conscious Rabbits Is Mediated by Nitric Oxide Synthase
Authors: Roberto Bolli, Srinivas Manchikalapudi, Xian-Liang Tang, Hitoshi Takano, Yumin Qiu, Yiru Guo, Qin Zhang, Asad K. Jadoon
Journal: Circulation Research (1997)

Seventy-four conscious rabbits undergoing a sequence of six 4-minute coronary occlusion/4-minute reperfusion cycles for 3 consecutive days (days 1, 2, and 3) were assigned to nine groups. In group I (controls, n = 8), the recovery of systolic wall thickening (WTh) after the sixth reperfusion was markedly improved on days 2 and 3 compared with day 1, indicating late preconditioning (PC) against myocardial stunning; the total deficit of WTh after the sixth reperfusion was reduced by 56% on day 2 and 50% on day 3 compared with day 1 (P < .01). Administration on day 2 of the nonselective NO synthase (NOS) inhibitor N omega-nitro-L-arginine (L-NA) (group II, n = 8) or of the selective inducible NOS inhibitors aminoguanidine (AG) (group IV, n = 8) and S-methylisothiourea sulfate (SMT) (group VI, n = 6) completely abrogated late PC against stunning on day 2. On day 3, the expected PC effect became manifest in all groups. Administration of L-NA, AG, or SMT on day 1 (groups III [n = 7], V [n = 6], and VII [n = 5], respectively) had no discernible effect on the deficit of WTh on day 1, indicating that these agents do not augment the severity of myocardial stunning in nonpreconditioned myocardium. In group VIII (n = 7), the abrogation of late PC by SMT on day 2 was completely reversed by the concomitant administration of L-arginine (595 mg/kg IV), indicating that it was not due to nonspecific NOS-unrelated actions. Administration of L-arginine alone on day 2 (group IX [n = 5]) had no effect on the deficit of WTh. Furthermore, administration of L-NA on day 1 (group III) prevented the appearance of the PC effect on day 2, whereas AG (group V) and SMT (group VI) did not, suggesting that the development of late PC on day 1 is triggered by the endothelial (type III) isoform of NOS. This study demonstrates that three structurally different NOS inhibitors (L-NA, AG, and SMT), given 24 hours after the PC ischemia, consistently abrogate late PC against myocardial stunning in conscious rabbits, indicating that this cardioprotective effect is mediated by the activity of NOS. The results obtained with AG and SMT specifically implicate the inducible (type II) isoform as the mediator of the protection on day 2. Previous studies have shown that NO triggers the development of late PC. The present results indicate that NO plays a dual role in late PC against stunning, acting initially as the trigger and subsequently as the mediator of the protection.
Structure of the Type B Human Natriuretic Peptide Receptor Gene and Association of a Novel Microsatellite Polymorphism With Essential Hypertension
Authors: Duolikun Rehemudula, Tomohiro Nakayama, Masayoshi Soma, Yukie Takahashi, Jiro Uwabo, Mikano Sato, Yoichi Izumi, Katsuo Kanmatsuse, Yukio Ozawa
Journal: Circulation Research (1999)

Abstract —The natriuretic peptide (NP) system may play a crucial role in development of essential hypertension (EH). C-type NP dilates arteries and lowers blood pressure and inhibits proliferation of vascular smooth muscle cells via the type B NP receptor (NPR-B). However, the association of the human NPR-B gene with EH has not been studied, because little is known about the genomic organization of this gene. We designed oligonucleotide primers based on the cDNA sequence of the human NPR-B gene, and long-range polymerase chain reaction (PCR) was performed. The amplified fragments were sequenced directly, and the exon/intron organization of the human NPR-B gene was determined. The gene, which spans ≈16.5 kbp, is composed of 22 exons, and the intron-exon junctions follow the GT-AG rule. Seven hundred fifty base pairs of the 5′-flanking region were sequenced using a thermal asymmetric interlaced–PCR (TAIL-PCR) method. This region contains 10 potential Sp1 binding sites and lacks a TATA box. Rapid amplification of cDNA ends (RACE) revealed the transcriptional start site at −14 bp. A CA/GT microsatellite repeat was identified with a hybridization-based method and was converted to a sequence-tagged site (STS). The GT microsatellite repeat was localized to intron 2 ≈150 bp downstream of the exon-intron junction. Two alleles, (GT)10 and (GT)11, were detected in both EH patients and age-matched normotensive (NT) controls. Multiple logistic linear regression analysis indicated that the NPR-B genotype is associated significantly with EH (odds ratio 1.55; 95% confidence interval, 1.02 to 2.35). The (GT)11 frequency was 0.316 (65/206) for the EH group and 0.218 (44/202) for the NT group and differed significantly between the EH and NT groups (χ 2 =4.97, P =0.026). The structural organization of the human NPR-B gene was determined, and a novel GT repeat polymorphism, which associated with EH, was identified. These results suggest that one cause of EH is a mutation in this gene or a closely related gene or region.
Assessing the Conservation of Mammalian Gene Expression Using High-Density Exon Arrays
Authors: Yi Xing, Zhengqing Ouyang, Karen Kapur, Matthew P. Scott, Wing Hung Wong
Journal: Molecular Biology and Evolution (2007)

Microarray data from multiple species have been used to study evolutionary constraints on gene expression. Expression measurements from conventional microarray platforms such as the 3' expression arrays are strongly affected by platform-dependent probe effects that may introduce apparent but misleading discrepancies between species. In this manuscript, we assess the conservation of mammalian gene expression in adult tissues using data from a high-density exon array platform. The exon arrays have more than 6 million probes on a single array targeting all exons in a genome. We find that, unlike 3' array data, gene expression measurements from exon arrays reveal patterns of gene expression that are highly conserved between humans and mice in multiple tissues. Our analysis provides strong evidence for widespread stabilizing selection pressure on transcript abundance during mammalian evolution.
Chemically determined mineral content of explanted porcine aortic valve bioprostheses: correlation with radiographic assessment of calcification and clinical data.
Authors: F J Schoen, J L Kujovich, C L Webb, R J Levy
Journal: Circulation (1987)

Bioprosthetic valve calcification is usually assessed pathologically by gross inspection, radiographic studies, and histologic examination. Quantitation of mineral content by chemical assay has not been reported for failed clinical valves removed from adults. In this study, calcium determination by atomic absorption spectroscopy was done on 52 removed porcine valves after routine pathologic examination, including specimen radiography done by a standard technique. Specimens included 31 valves with calcific primary tissue failure, two calcified (but not overtly dysfunctional) valves removed simultaneously with failed valves, 14 nondeteriorated valves obtained at reoperation or autopsy after long-term implantation, and five valves removed within 1 month after insertion. Chemically determined mineral content varied widely among patients and duration of function. Valves with calcific failure had 113 +/- 68 micrograms/mg calcium overall (mean +/- SD) after 36 to 156 months (mean 87) of function. Almost all dysfunctional porcine valves with radiographically demonstrated calcific deposits had greater than 34 and 67 micrograms/mg calcium for mitral and aortic valves, respectively. Nondeteriorated valves (implanted 8 to 145 months, mean 57) had 5 +/- 6 micrograms/mg calcium. Failed aortic valves had more calcium than failed mitral valves and valves with calcific stenosis more than valves with regurgitation caused by calcification with tearing. Correlation of semiquantitative radiographic grading with chemically determined valve mineral was good, indicating that radiographic assessment of calcification may be used reliably for clinical comparisons between valves.
Bioconductor: open software development for computational biology and bioinformatics
Authors: Robert C Gentleman, Vincent J Carey, Douglas M Bates, Ben Bolstad, Marcel Dettling, Sandrine Dudoit, Byron Ellis, Laurent Gautier, Yongchao Ge, Jeff Gentry, Kurt Hornik, Torsten Hothorn, Wolfgang Huber, Stefano Iacus, Rafael Irizarry, Friedrich Leisch, Cheng Li, Martin Maechler, Anthony J Rossini, Gunther Sawitzki, Colin Smith, Gordon Smyth, Luke Tierney, Jean YH Yang, Jianhua Zhang
Journal: Genome biology (2004)

Abstract The Bioconductor project is an initiative for the collaborative creation of extensible software for computational biology and bioinformatics. The goals of the project include: fostering collaborative development and widespread use of innovative software, reducing barriers to entry into interdisciplinary scientific research, and promoting the achievement of remote reproducibility of research results. We describe details of our aims and methods, identify current challenges, compare Bioconductor to other open bioinformatics projects, and provide working examples.
A novel approach to the diagnosis of pancreatic serous cystadenoma: needle-based confocal laser endomicroscopy
Authors: Bertrand Napoléon, Anne-Isabelle Lemaistre, Bertrand Pujol, Fabrice Caillol, Damien Lucidarme, Raphaël Bourdariat, Blandine Morellon-Mialhe, Fabien Fumex, Christine Lefort, Vincent Lepilliez, Laurent Palazzo, Geneviève Monges, Bernard Filoche, Marc Giovannini
Journal: Endoscopy (2014)

<b>Background and study aims:</b> The differential diagnosis of solitary pancreatic cystic lesions is frequently difficult. Needle-based confocal laser endomicroscopy (nCLE) performed during endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a new technology enabling real-time imaging of the internal structure of such cysts. The aim of this pilot study was to identify and validate new diagnostic criteria on nCLE for pancreatic cystic lesions. <b>Patients and methods:</b> A total of 31 patients with a solitary pancreatic cystic lesion of unknown diagnosis were prospectively included at three centers. EUS-FNA was combined with nCLE. The final diagnosis was based on either a stringent gold standard (surgical specimen and/or positive cytopathology) or a committee consensus. Six nonblinded investigators reviewed nCLE sequences from patients with the most stringent final diagnosis, and identified a single feature that was only present in serous cystadenoma (SCA). The findings were correlated with the pathology of archived specimens. After a training session, four blinded independent observers reviewed a separate independent video set, and the yield and interobserver agreement for the criterion were assessed. <b>Results:</b> A superficial vascular network pattern visualized on nCLE was identified as the criterion. It corresponded on pathological specimen to a dense and subepithelial capillary vascularization only seen in SCA. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of this sign for the diagnosis of SCA were 87 %, 69 %, 100 %, 100 %, and 82 %, respectively. Interobserver agreement was substantial (κ = 0.77). <b>Conclusion:</b> This new nCLE criterion seems highly specific for the diagnosis of SCA. The visualization of this criterion could have a direct impact on the management of patients by avoiding unnecessary surgery or follow-up. Clinicaltrials.gov NCT01563133.
Comparison of micro- vs. nanostructured colloidal gelatin gels for sustained delivery of osteogenic proteins: Bone morphogenetic protein-2 and alkaline phosphatase
Authors: Huanan Wang, Otto C. Boerman, Kemal Sariibrahimoglu, Yubao Li, John A. Jansen, Sander C.G. Leeuwenburgh
Journal: Biomaterials (2012)
Spinal Instability Neoplastic Score: An Analysis of Reliability and Validity From the Spine Oncology Study Group
Authors: Daryl R. Fourney, Evan M. Frangou, Timothy C. Ryken, Christian P. DiPaola, Christopher I. Shaffrey, Sigurd H. Berven, Mark H. Bilsky, James S. Harrop, Michael G. Fehlings, Stefano Boriani, Dean Chou, Meic H. Schmidt, David W. Polly, Roberto Biagini, Shane Burch, Mark B. Dekutoski, Aruna Ganju, Peter C. Gerszten, Ziya L. Gokaslan, Michael W. Groff, Norbert J. Liebsch, Ehud Mendel, Scott H. Okuno, Shreyaskumar Patel, Laurence D. Rhines, Peter S. Rose, Daniel M. Sciubba, Narayan Sundaresan, Katsuro Tomita, Peter P. Varga, Luiz R. Vialle, Frank D. Vrionis, Yoshiya Yamada, Charles G. Fisher
Journal: Journal of Clinical Oncology (2011)

Standardized indications for treatment of tumor-related spinal instability are hampered by the lack of a valid and reliable classification system. The objective of this study was to determine the interobserver reliability, intraobserver reliability, and predictive validity of the Spinal Instability Neoplastic Score (SINS).Clinical and radiographic data from 30 patients with spinal tumors were classified as stable, potentially unstable, and unstable by members of the Spine Oncology Study Group. The median category for each patient case (consensus opinion) was used as the gold standard for predictive validity testing. On two occasions at least 6 weeks apart, each rater also scored each patient using SINS. Each total score was converted into a three-category data field, with 0 to 6 as stable, 7 to 12 as potentially unstable, and 13 to 18 as unstable.The κ statistics for interobserver reliability were 0.790, 0.841, 0.244, 0.456, 0.462, and 0.492 for the fields of location, pain, bone quality, alignment, vertebral body collapse, and posterolateral involvement, respectively. The κ statistics for intraobserver reliability were 0.806, 0.859, 0.528, 0.614, 0.590, and 0.662 for the same respective fields. Intraclass correlation coefficients for inter- and intraobserver reliability of total SINS score were 0.846 (95% CI, 0.773 to 0.911) and 0.886 (95% CI, 0.868 to 0.902), respectively. The κ statistic for predictive validity was 0.712 (95% CI, 0.676 to 0.766).SINS demonstrated near-perfect inter- and intraobserver reliability in determining three clinically relevant categories of stability. The sensitivity and specificity of SINS for potentially unstable or unstable lesions were 95.7% and 79.5%, respectively.
Comparison of the diagnostic and prognostic value of biological markers in neuroblastoma
Authors: M.C. Favrot, P. Ambros, F. Schilling, D. Frappaz, V. Combaret, F. Berthold, C. Dominici, R. Erttmann, J. Esteve, A. Jenkner, R. Kerbl, J. Mann, P. Mathieu, L. Parker, J. Powell, T. Philip
Journal: Annals of Oncology (1996)

The prognosis of pediatric neuroblastoma depends both on clinical presentation and on certain cellular and molecular characteristics. Screening programs have been initiated in infants of less than one year of age, based on the hypothesis that neuroblastoma progresses from early to late clinical stages through a classical multistep process linked to an accumulation of molecular abnormalities. However, recent analyses suggest that most cases discovered by screening are low stage tumors considered as dysembryogenetic residues devoid from major abnormalities and that high-grade tumors with molecular abnormalities are unrelated diseases.To confirm one or the other hypothesis, and eventually identify biological factors possibly responsible for the initiation and progression of the disease, it is of utmost importance that all investigators agree on biological criteria for analysis when neuroblastoma tissue is available in screened and unscreened populations. This paper reviews the biological tools available for prognosis in neuroblastoma, the priority for analysis of biological markers according to both methodological reliability and feasibility, and the conditions of tissue storage for further analysis of these biological markers.The standardized biological evaluation of neuroblastoma will allow to collect sufficient data for multivariate analysis; such analysis is now fundamental if one wants to clearly define the respective impacts of biological abnormalities on neuroblastoma progression.
Adherence to asthma management guidelines by middle-aged adults with current asthma
Authors: R K Kandane-Rathnayake, M C Matheson, J A Simpson, M L K Tang, D P Johns, D Meszaros, R Wood-Baker, I Feather, S Morrison, M A Jenkins, G G Giles, J Hopper, M J Abramson, S C Dharmage, E H Walters
Journal: Thorax (2009)

<h3>Background:</h3> With the increasing burden of asthma worldwide, much effort has been given to developing and updating management guidelines. Using data from the Tasmanian Longitudinal Health Study (TAHS), the adequacy of asthma management for middle-aged adults with asthma was investigated. <h3>Methods:</h3> Information about spirometry, medication history and current asthma status was collected by the most recent TAHS when participants were in their mid 40s. Only those who reported ever having asthma were eligible for analysis. <h3>Results:</h3> Of the 702 participants who reported ever having asthma, 50% had current asthma (n = 351) of whom 71% were categorised as having persistent asthma (n = 98 mild, n = 92 moderate, n = 58 severe). The majority (85.2%) of participants with current asthma had used some form of asthma medication in the past 12 months, but the proportion of the use of minimally adequate preventer medication was low (26%). Post-bronchodilator airflow obstruction increased progressively from mild to severe persistent asthma for those inadequately managed, but not for those on adequate therapy. <h3>Conclusion:</h3> Appropriate use of asthma medication by this middle-aged group of adults with current asthma was inadequate, especially for those with adult-onset moderate or severe persistent disease and without a family history of asthma. These results suggest that proper use of preventer medication could protect against the progressive decline in lung function associated with increasing severity. This has implications not just for poor quality of life, but also for the development of fixed airflow obstruction.
Effect of Finasteride on the Sensitivity of PSA for Detecting Prostate Cancer
Authors: Ian M. Thompson, Chen Chi, Donna Pauler Ankerst, Phyllis J. Goodman, Catherine M. Tangen, Scott M. Lippman, M. Scott Lucia, Howard L. Parnes, Charles A. Coltman
Journal: JNCI Journal of the National Cancer Institute (2006)

In the Prostate Cancer Prevention Trial (PCPT), men receiving finasteride had a 24.8% lower risk of prostate cancer than men receiving placebo but a higher risk of high-grade cancer. We examined the impact of finasteride on the sensitivity and area under the receiver operating characteristic curve (AUC) of prostate-specific antigen (PSA) for detecting prostate cancer.We studied men in the placebo and finasteride groups of the PCPT who had a prostate biopsy and concurrent PSA tests during the 7-year study. We compared the placebo and finasteride groups for sensitivity and AUC of PSA for the detection of all prostate cancer, of Gleason grade 7 or higher prostate cancer, and of Gleason grade 8 or higher prostate cancer. All statistical tests were two-sided.Of 5112 men in the placebo group, prostate cancer was detected in 1111. Gleason tumor grade was available for 1100 men, of whom 240 had grade 7 or higher and 55 had grade 8 or higher. Of 4579 men in the finasteride group, 695 had prostate cancer. Gleason grade was available for 686 men, of whom 264 had grade 7 or higher and 81 had grade 8 or higher. The AUC of PSA for all outcomes was greater for the finasteride group than the placebo group. For detecting prostate cancer versus no cancer, the AUCs were 0.757 and 0.681, respectively (P < .001); for detecting Gleason grade > or = 7 versus < or = 6 or no cancer, the AUCs were 0.838 and 0.781, respectively (P = .003); and for detecting Gleason grade > or = 8 versus < or = 7 or no cancer, the AUCs were 0.886 and 0.824, respectively (P = .071). The sensitivity of PSA was higher for men in the finasteride group than in the placebo group at all PSA cutoffs matched by specificity.PSA had statistically significantly better sensitivity and AUC for detecting prostate cancer in the finasteride arm of the PCPT than in the placebo arm. This bias would be expected to contribute to greater detection of all grades of prostate cancer with finasteride.