tbuckley/cabot-search huggingface dataset:
Reduced Prevalence of Diabetic Ketoacidosis at Diagnosis of Type 1 Diabetes in Young Children Participating in Longitudinal Follow-Up
Authors: Helena Elding Larsson, Kendra Vehik, Ronny Bell, Dana Dabelea, Lawrence Dolan, Catherine Pihoker, Mikael Knip, Riitta Veijola, Bengt Lindblad, Ulf Samuelsson, Reinhard Holl, Michael J. Haller
Journal: Diabetes Care (2011)

Young children have an unacceptably high prevalence of diabetic ketoacidosis (DKA) at the clinical diagnosis of type 1 diabetes. The aim of this study was to determine whether knowledge of genetic risk and close follow-up for development of islet autoantibodies through participation in The Environmental Determinants of Diabetes in the Young (TEDDY) study results in lower prevalence of DKA at diabetes onset in children aged <2 and <5 years compared with population-based incidence studies and registries.
Monitoring Kidney Function in Type 2 Diabetic Patients With Incipient and Overt Diabetic Nephropathy
Authors: P. Rossing
Journal: Diabetes Care (2006)

The purpose of this study was to assess agreement between glomerular filtration rate (GFR) and the decline in GFR estimated with the Modification of Diet in Renal Disease (MDRD) Study Group equation or the Cockcroft-Gault formula and measured by the plasma clearance of 51Cr-EDTA.We followed a cohort of 156 microalbuminuric type 2 diabetic patients for 8 years with four measurements of GFR and another cohort of 227 type 2 diabetic patients with overt diabetic nephropathy for 6.5 (range 3-17) years with seven (3-22) measurements of GFR.For patients with microalbuminuria, mean +/- SD baseline GFR was 117 +/- 24 measured, 92 +/- 20 estimated (MDRD equation), or 103 +/- 24 ml x min(-1) per 1.73 m2 estimated (Cockcroft-Gault formula) (both P < 0.001); 95% limits of agreement were -66.1 to 20.3 (MDRD equation) and -58.7 to 30.7 (Cockcroft-Gault formula). The rate of decline in GFR was 4.1 +/- 4.2 measured, 2.9 +/- 2.8 estimated (MDRD equation), or 3.4 +/- 3.2 ml x min(-1) per 1.73 m2 estimated (Cockcroft-Gault formula) (both P < 0.001). For patients with overt nephropathy, baseline GFR was 84 +/- 30 measured, 73 +/- 24 estimated (MDRD equation), or 81 +/- 28 ml x min(-1) per 1.73 m2 estimated (Cockcroft-Gault formula) (both P < 0.001) with 95% limits of agreement -47 to 25 (MDRD equation) and -39 to 33 (Cockcroft-Gault formula). The rate of decline in GFR was 5.2 +/- 4.1 measured, 4.2 +/- 3.8 estimated (MDRD equation), and 4.6 +/- 4.1 ml x min(-1) per 1.73 m2 estimated (Cockcroft-Gault formula) (both P < 0.001).Particularly in microalbuminuric (hyperfiltering) patients, GFR is significantly underestimated with wide limits of agreement by the MDRD equation as well as by the Cockcroft-Gault formula. The rate of decline in GFR is also significantly underestimated with both equations. This makes GFR estimations based upon these equations unacceptable for monitoring kidney function in type 2 diabetic patients with incipient and overt diabetic nephropathy.
Peroxisome Proliferator–Activated Receptor-δ Agonist Enhances Vasculogenesis by Regulating Endothelial Progenitor Cells Through Genomic and Nongenomic Activations of the Phosphatidylinositol 3-Kinase/Akt Pathway
Authors: Jung-Kyu Han, Hyun-Sook Lee, Han-Mo Yang, Jin Hur, Soo-In Jun, Ju-Young Kim, Chung-Hyun Cho, Gou-Young Koh, Jeffrey M. Peters, Kyung-Woo Park, Hyun-Jai Cho, Hae-Young Lee, Hyun-Jae Kang, Byung-Hee Oh, Young-Bae Park, Hyo-Soo Kim
Journal: Circulation (2008)

Despite the therapeutic potential of endothelial progenitor cells (EPCs) in ischemic vascular diseases, their insufficient numbers limit clinical applications. Peroxisome proliferator-activated receptor (PPAR)-delta belongs to the nuclear hormone receptor superfamily, and its functions in various tissues and cells are almost unexplored, especially with respect to vascular biology.PPAR-delta activation in EPCs phosphorylated Akt, and this phosphorylation was mediated not only by genomic but also by nongenomic pathways through interaction with the regulatory subunit of phosphatidylinositol 3-kinase. PPAR-delta activation with agonist (GW501516 or L-165041) increased the proliferation of human EPCs and protected them from hypoxia-induced apoptosis. In addition, PPAR-delta activation enhanced EPC functions, such as transendothelial migration, and tube formation. These actions by PPAR-delta activation in EPCs were dependent on the phosphatidylinositol 3-kinase/Akt pathway. In ischemic hindlimb of mice models, transplantation of PPAR-delta agonist-treated human or mouse EPCs enhanced blood flow recovery to ischemic limbs compared with vehicle-treated EPCs. In EPCs from PPAR-delta-knockout mice, however, treatment with PPAR-delta agonist did not enhance in vivo vasculogenic potential. Systemic administration of PPAR-delta agonist increased hematopoietic stem cells in bone marrow and EPCs in peripheral blood, leading to improved vasculogenesis with incorporation of bone marrow-derived cells to new vessels in a corneal neovascularization model and limb salvage with better blood flow in an ischemic hindlimb model.The results of our study suggest that PPAR-delta agonist has therapeutic vasculogenic potential for the treatment of ischemic cardiovascular diseases.
Targeting cytomegalovirus (CMV) antigens for GBM immunotherapy
Authors: Smita K Nair, Gabriel De Leon, David Boczkowski, Robert Schmittling, Weihua Xie, Gerald Archer, John H Sampson, Duane A Mitchell
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts Despite aggressive and incapacitating conventional therapy, glioblastoma multiforme (GBM) remains uniformly lethal. Immunotherapy in which the immune system (particularly cellular effectors such as T cells) is harnessed to specifically attack malignant cells offers a treatment
Mechanics in Neuronal Development and Repair
Authors: Kristian Franze, Paul A. Janmey, Jochen Guck
Journal: Annual Review of Biomedical Engineering (2013)

Biological cells are well known to respond to a multitude of chemical signals. In the nervous system, chemical signaling has been shown to be crucially involved in development, normal functioning, and disorders of neurons and glial cells. However, there are an increasing number of studies showing that these cells also respond to mechanical cues. Here, we summarize current knowledge about the mechanical properties of nervous tissue and its building blocks, review recent progress in methodology and understanding of cellular mechanosensitivity in the nervous system, and provide an outlook on the implications of neuromechanics for future developments in biomedical engineering to aid overcoming some of the most devastating and currently incurable CNS pathologies such as spinal cord injuries and multiple sclerosis.
Rapid activation of the type B versus type A natriuretic factor gene by aortocaval shunt induced cardiac volume overload
Authors: W. Lear, P. H Boer
Journal: Cardiovascular Research (1995)

The aim was to compare activities of the type A and type B natriuretic factor genes during development of cardiac hypertrophy by use of a non-radioactive method designed for assessment of stable atrial and brain natriuretic factor (ANF, BNF) transcript levels in biopsy sized tissue samples.At 1 and 7 days after aortocaval shunt or sham surgery in rats, quantitative reverse transcriptase mediated polymerase chain reaction (Q-RT-PCR) was used to determine mRNA levels in cardiac tissues. Phosphoglycerate kinase-1 (PGK-1) mRNA levels served as an external standard for Q-RT-CR.The shunt increased left ventricular end diastolic pressure at days 1 and 7, and cardiac weight was increased by day 7. By day 1, left ventricular BNF mRNA levels were twice those of controls, whereas ANF mRNA levels were not changed. By day 7, left ventricular BNF mRNA levels were increased 15-fold, and those for ANF were increased fivefold; the BNF mRNAs were also increased in right atria and right ventricle, about fivefold in both cases.Both natriuretic factor genes were activated by cardiac volume overload, and the increase in the level of left ventricular BNF transcripts-observed for the first time-was in fact more rapid and exceeded that of ANF. The Q-RT-PCR assay will be of value to investigate the response to increased work load of cardiac muscle in vivo.
S27 Should routine screening for vitamin d deficiency be incorporated into current guidelines for treatment of paediatric TB patients?
Authors: A. Ting, M. Jiki, C. Bell, C. Murray, Z. Mughal, F. Child
Journal: Thorax (2010)

<h3>Introduction and Objectives</h3> The association between low vitamin D levels and increased severity/susceptibility to TB infection due to suppression of innate immunity is well known. In the United Kingdom, low levels of background ultraviolet B radiation limit the photoconversion of 7 dehydrocholestrol in skin to cholecalciferol (vitamin D3). In addition the majority of paediatric TB cases in the UK occur in non-Caucasian patients who by nature of their skin colour are less able to absorb the UV radiation. Current guidelines do not suggest routine checking of serum 25-dihydroxyvitamin D (25(OH)D); a reliable measure of body stores of vitamin D, in paediatric TB cases and providing Vitamin D supplementation as required. We hypothesised that all paediatric TB patients require screening for Vitamin D deficiency and that many would benefit from supplementation. <h3>Methods</h3> This is a prospective cohort study. Between January 2009 and June 2010, all paediatric TB cases were prospectively recorded into a hospital database. Data collected include age, sex, serum concentrations of 25(OH)D, calcium (Ca), phosphate (P), alkaline phosphatase (ALP) and parathyroid hormone (PTH). <h3>Results</h3> 45 patients (18 males) were diagnosed with TB over the 18 month period. The mean age was 7.5 years (range 5 months to 17 years). The results for Vitamin D were not available in 5 patients (3 in progress, 2 not performed). Of the 40 patients with results available, 39 (97.5%) were found to have low levels of 25 (OH)D and were commenced on supplementation. Of these, 29/40 (72.5%) had profound Vitamin D deficiency (25(OH)D levels &lt;10 ng/ml). Of these 29 patients, 15 had high PTH levels, 2 had low Ca (no data for one patient), 4 had low P levels and 5 had elevated ALP levels. One patient had radiologically confirmed rickets. <h3>Conclusions</h3> Our study supports the incorporation of routine Vitamin D screening into the current guidelines for the management of TB, especially as TB itself can worsen pre-existing vitamin D deficiency.
Gut feelings: a psychologist's 20-year journey with paediatric surgeons
Authors: L. Ludman
Journal: Journal of the Royal Society of Medicine (2003)

My journey with the paediatric surgeons at Great Ormond Street Hospital for Children (GOSH) started many years ago, and led to a question posed by the editor of Archives of Diseases in Childhood in his editorial comments on one of my recent publications1: ‘should we be surprised that a psychologist's questions might probe more deeply than the surgeons fingers?’2.

First, I must go back to the beginning of my association with the paediatric surgeons, way back in 1982 when I began developing a research study which formed the basis of my doctorate, and which was my introduction to the issues of psychology in paediatric surgery. The research on which this thesis was based, and which was initiated by Professor Lewis Spitz (Nuffield Professor of Paediatric Surgery) and Dr Richard Lansdown (then head of the Department of Psychological Medicine), was concerned with newborn babies who had a mixture of life-threatening surgically correctable congenital anomalies. Subsequent research studies moved in a bottom-up direction, along the gut, from anorectal malformations, through Hirschsprung's disease, to oesophageal atresia.
In vivo T cell tumor therapy with monoclonal antibody directed to the V beta chain of T cell antigen receptor.
Authors: O Kanagawa
Journal: The Journal of Experimental Medicine (1989)

To test whether antibodies directed to TCR affect T cell tumor growth in vivo, mice were inoculated intravenously with C6VL tumor cells expressing V beta 6 TCR and then treated intraperitoneally with mAb specific for V beta 6 TCR. Administration of anti-V beta 6 antibody prolonged survival of mice bearing V beta 6-expressing tumor cells and it led to the induction of host immunity to the tumor cells in surviving animals. This treatment eliminated not only tumor cells bearing V beta 6 TCR but also normal host T cells expressing V beta 6 T cells receptors. However, the lack of V beta 6-expressing T cells in such treated mice did not result in generalized immune disfunction. These data demonstrate the utility of anti-TCR V segment antibody in the treatment of T cell tumors. Most importantly, since the number of V genes for the T cell antigen receptor is limited, both in man and in mouse, it should be possible to establish a panel of mAbs directed to each V gene product and use such antibodies in the treatment of T cell neoplasms.
Profiling of moisture status in venous leg ulcers
Authors: Joshua Burke, Mustafa Khanbhai, Charles McCollum, Patricia Connolly, Eileen Temple
Journal: International Journal of Surgery (2013)

The most important factors in the management of venous leg ulcers (VLUs) are leg elevation and compression. However, moisture content and its role in VLU healing is not known. The aim of this study was to assess wound moisture levels and to evaluate correlation with ulcer healing.
Impact of Micropapillary Histologic Subtype in Selecting Limited Resection vs Lobectomy for Lung Adenocarcinoma of 2cm or Smaller
Authors: Jun-ichi Nitadori, Adam J. Bograd, Kyuichi Kadota, Camelia S. Sima, Nabil P. Rizk, Eduardo A. Morales, Valerie W. Rusch, William D. Travis, Prasad S. Adusumilli
Journal: JNCI Journal of the National Cancer Institute (2013)

We sought to analyze the prognostic significance of the new International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS) lung adenocarcinoma (ADC) classification for patients undergoing resection for small (≤2cm) lung ADC and to investigate whether histologic subtyping can predict recurrence after limited resection (LR) vs lobectomy (LO).
Activation Patterns of Purkinje Fibers During Long-Duration Ventricular Fibrillation in an Isolated Canine Heart Model
Authors: Paul B. Tabereaux, Greg P. Walcott, Jack M. Rogers, Jong Kim, Derek J. Dosdall, Peter G. Robertson, Cheryl R. Killingsworth, William M. Smith, Raymond E. Ideker
Journal: Circulation (2007)

Background— The roles of Purkinje fibers (PFs) and focal wave fronts, if any, in the maintenance of ventricular fibrillation (VF) are unknown. If PFs are involved in VF maintenance, it should be possible to map wave fronts propagating from PFs into the working ventricular myocardium during VF. If wave fronts ever arise focally during VF, it should be possible to map them appearing de novo. Methods and Results— Six canine hearts were isolated, and the left main coronary artery was cannulated and perfused. The left ventricular cavity was exposed, which allowed direct endocardial mapping of the anterior papillary muscle insertion. Nonperfused VF was induced, and 6 segments of data, each 5 seconds long, were analyzed during 10 minutes of VF. During 36 segments of data that were analyzed, 1018 PF or focal wave fronts of activation were identified. In 534 wave fronts, activation was mapped propagating from working ventricular myocardium to PF. In 142 wave fronts, activation was mapped propagating from PF to working ventricular myocardium. In 342 wave fronts, activation was mapped arising focally. More than 1 of these 3 patterns could occur in the same wave front. Conclusions— PFs are highly active throughout the first 10 minutes of VF. In addition to retrograde propagation from the working ventricular myocardium to PFs, antegrade propagation occurs from PFs to working ventricular myocardium, which suggests PFs are important in VF maintenance. Prior plunge needle recordings in dogs indicate activation propagates from the endocardium toward the epicardium after 1 minute of VF, which suggests that focal sites on the endocardium may represent foci and not breakthrough. If so, in addition to reentry, abnormal automaticity or triggered activity may also occur during VF.
Inferring the History of Speciation from Multilocus DNA Sequence Data: The Case of Drosophila pseudoobscura and Close Relatives
Authors: Carlos A. Machado, Richard M. Kliman, Jeffrey A. Markert, Jody Hey
Journal: Molecular Biology and Evolution (2002)

The divergence of Drosophila pseudoobscura from its close relatives, D. persimilis and D. pseudoobscura bogotana, was examined using the pattern of DNA sequence variation in a common set of 50 inbred lines at 11 loci from diverse locations in the genome. Drosophila pseudoobscura and D. persimilis show a marked excess of low-frequency variation across loci, consistent with a model of recent population expansion in both species. The different loci vary considerably, both in polymorphism levels and in the levels of polymorphisms that are shared by different species pairs. A major question we address is whether these patterns of shared variation are best explained by gene flow or by persistence since common ancestry. A new test of gene flow, based on patterns of linkage disequilibrium, is developed. The results from these, and other tests, support a model in which D. pseudoobscura and D. persimilis have exchanged genes at some loci. However, the pattern of variation suggests that most gene flow, although occurring after speciation began, was not recent. There is less evidence of gene flow between D. pseudoobscura and D. p. bogotana. The results are compared with recent work on the genomic locations of genes that contribute to reproductive isolation between D. pseudoobscura and D. persimilis. We show that there is a good correspondence between the genomic regions associated with reproductive isolation and the regions that show little or no evidence of gene flow.
Sports-related concussion: ongoing debate
Authors: Semyon Slobounov, Jeff Bazarian, Erin Bigler, Robert Cantu, Mark Hallett, Robert Harbaugh, David Hovda, Andrew R Mayer, Marc R Nuwer, Zhifeng Kou, Giuseppe Lazzarino, Linda Papa, Roberto Vagnozzi
Journal: British Journal of Sports Medicine (2013)

Research in mild traumatic brain injury (mTBI), also known as concussion, has increased significantly within the past decade parallel to the increased attention being given from injured athletes on high school, collegiate and professional sports teams. These patients have focused the research community's efforts into further understanding the pathophysiological underpinnings of the injury as well as its both short-term and long-term effects.1 Widespread media coverage and several high-profile cases have raised the issue of possible severe and devastating long-term consequences of repetitive sports-related brain trauma that may involve the acquisition of a proteinopathy2 as well as an increased risk for developing neurodegenerative diseases associated with repetitive concussive and subconcussive blows.3

Following a concussive episode there is a destructive pathophysiological and biochemical response that initiates a chain of neurometabolic and neurochemical reactions that include activation of inflammatory response, imbalances of ion concentrations, increase in the presence of excitatory amino acids, dysregulation of neurotransmitter synthesis and release, imbalance in mitochondrial functions and energy metabolism, and production of free radicals.4 Most of these molecular changes resolve spontaneously but, since cells are highly vulnerable, a second concussive event during this period of altered cell functions may have catastrophic …
Comparative Effects of Therapy With Captopril and Digoxin in Patients With Mild to Moderate Heart Failure
Authors: Jay Cohn
Journal: JAMA (1988)

This multicenter, double-blind, placebo-controlled study compares the effects of captopril treatment with those of digoxin treatment during maintenance diuretic therapy in patients with mild to moderate heart failure. Compared with placebo, captopril therapy resulted in significantly improved exercise time (mean increase, 82 s vs 35 s) and improved New York Heart Association class (41% vs 22%), but digoxin therapy did not. Digoxin treatment increased ejection fraction (4.4% increase) compared with captopril therapy (1.8% increase) and placebo (0.9% increase). The number of ventricular premature beats decreased 45% in the captopril group and increased 4% in the digoxin group in patients with more than ten ventricular premature beats per hour. Treatment failures, increased requirements for diuretic therapy, and hospitalizations were significantly more frequent in patients receiving placebo compared with those receiving either active drug. Transitory hypotension occurred more frequently with administration of captopril. Captopril treatment is significantly more effective than placebo and is an alternative to digoxin therapy in patients with mild to moderate heart failure who are receiving diuretic maintenance therapy. (<i>JAMA</i>1988;259:539-544)
Phase II study of concurrent chemotherapy and radiotherapy for unresectable stage III non-small-cell lung cancer: Long-term follow-up results. Japan Clinical Oncology Group Protocol 8902
Authors: K. Kubota, T. Tamura, M. Fukuoka, K. Furuse, H. Ikegami, Y. Ariyoshi, Y. Kurita, N. Saijo
Journal: Annals of Oncology (2000)
Rare (pulmonary) disease day: “feeding the breath, energy for life!”
Authors: Sergio Harari, Edmund M.T. Lau, Yuichi Tamura, Vincent Cottin, Gérald Simonneau, Marc Humbert
Journal: European Respiratory Journal (2015)

Broadly speaking, a rare disease is any disease that affects a small percentage of people in a population. Although there is no more specific, widely accepted definition of a rare disease, the European Commission on Public Health defines rare diseases as "life-threatening or chronically debilitating diseases, which are of such low prevalence that special combined efforts are needed to address them" [1]. The term "low prevalence" is defined as generally meaning fewer than one in 2000 people [1, 2]. With a conservative estimate that primary or secondary lung involvement occurs in ∼5% of rare diseases (>6000 types), approximately 1–2 million people in the European Union are likely to be affected by rare pulmonary diseases. Therefore, cumulatively, rare pulmonary diseases represent a significant burden of disease, with many of these being severe conditions that result in premature death or major morbidity. Feeding the breath, energy for life! <http://ow.ly/FypVm>
<i>SF3B1</i> Mutations Are Associated with Alternative Splicing in Uveal Melanoma
Authors: Simon J. Furney, Malin Pedersen, David Gentien, Amaury G. Dumont, Audrey Rapinat, Laurence Desjardins, Samra Turajlic, Sophie Piperno-Neumann, Pierre de la Grange, Sergio Roman-Roman, Marc-Henri Stern, Richard Marais
Journal: Cancer Discovery (2013)

Uveal melanoma, the most common eye malignancy, causes severe visual morbidity and is fatal in approximately 50% of patients. Primary uveal melanoma can be cured by surgery or radiotherapy, but the metastatic disease is treatment refractory. To understand comprehensively uveal melanoma genetics, we conducted single-nucleotide polymorphism arrays and whole-genome sequencing on 12 primary uveal melanomas. We observed only approximately 2,000 predicted somatic single-nucleotide variants per tumor and low levels of aneuploidy. We did not observe an ultraviolet radiation DNA damage signature, but identified SF3B1 mutations in three samples and a further 15 mutations in an extension cohort of 105 samples. SF3B1 mutations were associated with good prognosis and were rarely coincident with BAP1 mutations. SF3B1 encodes a component of the spliceosome, and RNA sequencing revealed that SF3B1 mutations were associated with differential alternative splicing of protein coding genes, including ABCC5 and UQCC, and of the long noncoding RNA CRNDE.