tbuckley/cabot-search huggingface dataset:
Optimal systolic blood pressure target, time to intensification, and time to follow-up in treatment of hypertension: population based retrospective cohort study
Authors: W. Xu, S. I. Goldberg, M. Shubina, A. Turchin
Journal: BMJ (2015)

To investigate the optimal systolic blood pressure goal above which new antihypertensive medications should be added or doses of existing medications increased ("systolic intensification threshold") and to determine the relation between delays in medication intensification and follow-up and the risk of cardiovascular events or death.Retrospective cohort study.Primary care practices in the United Kingdom, 1986-2010.88 756 adults with hypertension from The Health Improvement Network nationwide primary care research database.Rates of acute cardiovascular events or death from any cause for patients with different hypertension treatment strategies (defined by systolic intensification threshold, time to intensification, and time to follow-up over the course of a 10 year treatment strategy assessment period) after adjustment for age, sex, smoking status, socioeconomic deprivation, history of diabetes, cardiovascular disease or chronic kidney disease, Charlson comorbidity index, body mass index, medication possession ratio, and baseline blood pressure.During a median follow-up of 37.4 months after the treatment strategy assessment period, 9985 (11.3%) participants had an acute cardiovascular event or died. No difference in risk of the outcome was seen between systolic intensification thresholds of 130-150 mm Hg, whereas systolic intensification thresholds greater than 150 mm Hg were associated with progressively greater risk (hazard ratio 1.21, 95% confidence interval 1.13 to 1.30; P<0.001 for intensification threshold of 160 mm Hg). Outcome risk increased progressively from the lowest (0-1.4 months) to the highest fifth of time to medication intensification (hazard ratio 1.12, 1.05 to 1.20; P=0.009 for intensification between 1.4 and 4.7 months after detection of elevated blood pressure). The highest fifth of time to follow-up (>2.7 months) was also associated with increased outcome risk (hazard ratio 1.18, 1.11 to 1.25; P<0.001).Systolic intensification thresholds higher than 150 mm Hg, delays of greater than 1.4 months before medication intensification after systolic blood pressure elevation, and delays of greater than 2.7 months before blood pressure follow-up after antihypertensive medication intensification were associated with increased risk of an acute cardiovascular event or death. These findings support the importance of timely medical management and follow-up in the treatment of patients with hypertension.
Complementary and Alternative Medicine for Menopausal Symptoms: A Review of Randomized, Controlled Trials
Authors: Fredi Kronenberg
Journal: Annals of Internal Medicine (2002)

Background: Women commonly use soy products, herbs, and other complementary and alternative medicine (CAM) therapies for menopausal symptoms. Randomized, controlled trials have evaluated the efficacy and short-term safety of these therapies. Purpose: To review randomized, controlled trials of CAM therapies for menopausal symptoms in order to better inform practice and guide future research. Data Sources: Searches of MEDLINE for articles published from January 1966 through March 2002, of the Alternative and Complementary Database (AMED) of the British Library for articles published from January 1985 through December 2000, and of the authors' own extensive files. Search terms were hot flash/flush, menopause, and climacteric, combined with phytoestrogens, alternative medicine, herbal medicine, traditional medicine, Traditional Chinese Medicine (TCM), Ayurveda, naturopathy, chiropractic, osteopathy, massage, yoga, relaxation therapy, homeopathy, aromatherapy, and therapeutic touch. Study Selection: 29 randomized, controlled clinical trials of CAM therapies for hot flashes and other menopausal symptoms were identified; of these, 12 dealt with soy or soy extracts, 10 with herbs, and 7 with other CAM therapies. Data Extraction: Each author extracted information from half of the studies on the number of patients, study design, outcome measures, and results; the other author then checked these results. Data Synthesis: Soy seems to have modest benefit for hot flashes, but studies are not conclusive. Isoflavone preparations seem to be less effective than soy foods. Black cohosh may be effective for menopausal symptoms, especially hot flashes, but the lack of adequate long-term safety data (mainly on estrogenic stimulation of the breast or endometrium) precludes recommending long-term use. Single clinical trials have found that dong quai, evening primrose oil, a Chinese herb mixture, vitamin E, and acupuncture do not affect hot flashes; two trials have shown that red clover has no benefit for treating hot flashes. Conclusions: Black cohosh and foods that contain phytoestrogens show promise for the treatment of menopausal symptoms. Clinical trials do not support the use of other herbs or CAM therapies. Long-term safety data on individual isoflavones or isoflavone concentrates are not available.
Determining exon connectivity in complex mRNAs by nanopore sequencing
Authors: Mohan T Bolisetty, Gopinath Rajadinakaran, Brenton R Graveley
Journal: Genome biology (2015)

Short-read high-throughput RNA sequencing, though powerful, is limited in its ability to directly measure exon connectivity in mRNAs that contain multiple alternative exons located farther apart than the maximum read length. Here, we use the Oxford Nanopore MinION sequencer to identify 7,899 'full-length' isoforms expressed from four Drosophila genes, Dscam1, MRP, Mhc, and Rdl. These results demonstrate that nanopore sequencing can be used to deconvolute individual isoforms and that it has the potential to be a powerful method for comprehensive transcriptome characterization.
The Many Faces of Diabetes in American Youth: Type 1 and Type 2 Diabetes in Five Race and Ethnic Populations: The SEARCH for Diabetes in Youth Study
Authors: Elizabeth J. Mayer-Davis, Ronny A. Bell, Dana Dabelea, Ralph D'Agostino, Giuseppina Imperatore, Jean M. Lawrence, Lenna Liu, Santica Marcovina
Journal: Diabetes Care (2009)

Diabetes, a leading cause of nephropathy, retinopathy, neuropathy, and coronary and peripheral vascular disease, is the third most prevalent severe chronic disease of childhood in the U.S. (1). People with diabetes diagnosed before the age of 20 years have a life expectancy that is 15–27 years shorter than people without diabetes (1), although prospective data show improvements in mortality for those diagnosed in more recent years (2). Until only a decade ago, diabetes diagnosed in children and adolescents was almost entirely considered to be type 1 diabetes, most often due to the autoimmune destruction of the β-cells of the pancreas leading to an absolute deficiency of insulin. Diabetes in children and adolescents is now viewed as a complex disorder with heterogeneity in its pathogenesis, clinical presentation, and clinical outcome. The occurrence of what appears clinically to be type 2 diabetes in youth, particularly overweight minority youth, has been documented in several studies.

The SEARCH for Diabetes in Youth Study, funded by the Centers for Disease Control and Prevention, Division of Diabetes Translation, with support from the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, began in 2000 with an overarching objective to describe childhood diabetes as it occurs among the five major race and ethnic groups in the U.S. These groups include non-Hispanic white, Hispanic, Asian/Pacific Islander, African American, and American Indian. Key aims of the study with a focus on race and ethnicity are the following: 

As previously published by the SEARCH study, both type 1 and type 2 diabetes occur in each of the five major race/ethnic …
Filaggrin Mutations Associated with Skin and Allergic Diseases
Authors: Alan D. Irvine, W.H. Irwin McLean, Donald Y.M. Leung
Journal: New England Journal of Medicine (2011)

Mutations in the filaggrin gene are associated with a broad range of skin and allergic diseases. The biology of this molecule and the role of mutations in its altered function offer new insights into a range of conditions not previously thought to be related to one another.
Prevalence of and risk factors for resistance to second-line drugs in people with multidrug-resistant tuberculosis in eight countries: a prospective cohort study
Authors: Tracy Dalton, Peter Cegielski, Somsak Akksilp, Luis Asencios, Janice Campos Caoili, Sang-Nae Cho, Vladislav V Erokhin, Julia Ershova, Ma Tarcela Gler, Boris Y Kazennyy, Hee Jin Kim, Kai Kliiman, Ekaterina Kurbatova, Charlotte Kvasnovsky, Vaira Leimane, Martie van der Walt, Laura E Via, Grigory V Volchenkov, Martin A Yagui, Hyungseok Kang
Journal: The Lancet (2012)
Whole genome transcriptome polymorphisms in Arabidopsis thaliana
Authors: Xu Zhang, Jake K Byrnes, Thomas S Gal, Wen-Hsiung Li, Justin O Borevitz
Journal: Genome biology (2008)

Whole genome tiling arrays are a key tool for profiling global genetic and expression variation. In this study we present our methods for detecting transcript level variation, splicing variation and allele specific expression in Arabidopsis thaliana. We also developed a generalized hidden Markov model for profiling transcribed fragment variation de novo. Our study demonstrates that whole genome tiling arrays are a powerful platform for dissecting natural transcriptome variation at multi-dimension and high resolution.
Cathepsin B as a potential prognostic and therapeutic marker for human lung squamous cell carcinoma
Authors: Fengming Gong, Xingchen Peng, Can Luo, Guobo Shen, Chengjian Zhao, Liqun Zou, Longhao Li, Yaxiong Sang, Yuwei Zhao, Xia Zhao
Journal: Molecular Cancer (2013)

The lung squamous cell carcinoma survival rate is very poor despite multimodal treatment. It is urgent to discover novel candidate biomarkers for prognostic assessment and therapeutic targets to lung squamous cell carcinoma (SCC).Herein a two-dimensional gel electrophoresis and ESI-Q-TOF MS/MS-based proteomic approach was used to identify differentially expressed proteins between lung SCC and adjacent normal tissues. 31 proteins with significant alteration were identified. These proteins were mainly involved in metabolism, calcium ion binding, signal transduction and so on. Cathepsin B (CTSB) was one of the most significantly altered proteins and was confirmed by western blotting. Immunohistochemistry showed the correlation between higher CTSB expression and lower survival rate. No statistically significant difference between CTSB-shRNA treated group and the controls was observed in tumor volume, tumor weight, proliferation and apoptosis. However, the CTSB-shRNA significantly inhibited tumor metastases and prolonged survival in LL/2 metastatic model. Moreover, CTSB, Shh and Ptch were up-regulated in patients with metastatic lung SCC, suggesting that hedgehog signaling might be activated in metastatic lung SCC which could affect the expression of CTSB that influence the invasive activity of lung SCC.These data suggested that CTSB might serve as a prognostic and therapeutic marker for lung SCC.
Can phrenic stimulation protect the diaphragm from mechanical ventilation-induced damage?
Authors: Hicham Masmoudi, Catherine Coirault, Alexandre Demoule, Julien Mayaux, Maud Beuvin, Norma Romero, Jalal Assouad, Thomas Similowski
Journal: European Respiratory Journal (2013)

To the Editor: 

Mechanical ventilation is a prominent lifesaving treatment. It is, however, associated with an array of adverse effects, which include ventilator-associated pneumonias, volume-induced lung injury and, more recently identified, ventilator-induced diaphragm dysfunction (VIDD) [1–3]. VIDD combines diaphragm weakness with muscle fibre atrophy, remodelling and injury. Its mechanisms involve decreased protein synthesis, increased proteolysis, increased oxidative stress and mitochondrial dysfunction [2, 4]. Controlled mechanical ventilation appears to be the main, if not the sole, risk factor for VIDD, which in animal models is attenuated by the maintenance of respiratory efforts (assisted ventilatory modes) [2]. Although the corresponding human evidence is still lacking, this underlies the current notion that “clinicians should encourage persistent diaphragmatic activity” in patients receiving mechanical ventilation [2]. Diaphragm pacing has been proposed as a surrogate for spontaneous respiratory activity when the latter is not compatible with the condition of the patient [2, 5], but this approach has, seemingly, not yet been tested experimentally.

Here we report a preliminary description of putative beneficial effects of diaphragm pacing in three mechanically ventilated sheep. Three female adult sheep (41, 32 and 34 kg), were anaesthetised (premedication: acepromazine 1.3 mg·kg−1 i.m. , 30 min before induction; induction: propofol 6 mg·kg−1 i.v. ; maintenance: continuous propofol 1–2 mg·kg−1·h−1, midazolam 0.3–2 mg·kg−1·h−1 and morphine 0.2–0.3 mg·kg−1·h−1; no paralysing agents), tracheotomised and mechanically ventilated with a minute ventilation ensuring normocapnia (Aisys, GE Healthcare, Datex Ohmeda, Madison, WI, USA). Additional oxygen was given to maintain transcutaneous-pulsed oxygen saturation >92%. Adequate fluid and nutritional support was provided and glycaemia controlled. Body temperature, heart rate and arterial pressure were monitored. Intradiaphragmatic phrenic nerve stimulation electrodes were inserted bilaterally in …
Asymmetric Involution of the Myocardial Field Drives Heart Tube Formation in Zebrafish
Authors: Stefan Rohr, Cécile Otten, Salim Abdelilah-Seyfried
Journal: Circulation Research (2008)

Many vertebrate organs are derived from monolayered epithelia that undergo morphogenesis to acquire their shape. Whereas asymmetric left/right gene expression within the zebrafish heart field has been well documented, little is known about the tissue movements and cellular changes underlying early cardiac morphogenesis. Here, we demonstrate that asymmetric involution of the myocardium of the right-posterior heart field generates the ventral floor, whereas the noninvoluting left heart field gives rise to the dorsal roof of the primary heart tube. During heart tube formation, asymmetric left/right gene expression within the myocardium correlates with asymmetric tissue morphogenesis. Disruption of left/right gene expression causes randomized myocardial tissue involution. Time-lapse analysis combined with genetic analyses reveals that motility of the myocardial epithelium is a tissue migration process. Our results demonstrate that asymmetric morphogenetic movements of the 2 bilateral myocardial cell populations generate different dorsoventral regions of the zebrafish heart tube. Failure to generate a heart tube does not affect the acquisition of atrial versus ventricular cardiac cell shapes. Therefore, establishment of basic cardiac cell shapes precedes cardiac function. Together, these results provide the framework for the integration of single cell behaviors during the formation of the vertebrate primary heart tube.
Predicting the development of hepatocellular cancer in hepatitis B carriers
Authors: M S De Mitri, M Bernardi
Journal: Gut (2007)

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and its incidence is rising in many countries. Like most types of cancer, hepatocarcinogenesis is a multistep process involving a number of different genetic alterations that ultimately lead to malignant transformation of the hepatocyte. Large geographic differences in the incidence of HCC suggest that environmental factors likely contribute to its development. However, the relative contribution of different factors and their molecular interactions are still poorly understood.

Epidemiological studies indicated that chronic viral infection is the most important oncogenetic agent for HCC development and hepatitis B (HBV)-associated carcinogenesis is currently construed as a multifactorial process comprising both direct and indirect mechanisms that likely act synergistically.1 In the Western world, 70–90% of HCC develop in a cirrhotic liver. Cirrhosis has been considered as a pre-neoplastic condition, as it leads to a hypermutagenic status that affects cell cycle genes and promotes deregulated proliferation.2 The strong association between cirrhosis and HCC suggests that the common pathway for hepatocarcinogenesis may be the increased liver cell turnover induced by chronic liver injury and regeneration, which induces or selects a malignant clone. However, while HBV-related HCC mostly develops in patients with underlying cirrhosis in the Caucasian population, the tumour occurs more frequently in the absence of cirrhosis in Asian patients. Thus, although it is clear that HBV-induced cirrhosis likely represents a major factor involved in liver carcinogenesis, evidence for a direct effect of HBV is rapidly growing.3

HBV-induced HCC probably results from a combination of different interacting effects; for example, the integration of HBV DNA and the transactivating activity of viral proteins, such as the enigmatic HBx and the truncated PreS2/S. Integration of HBV sequences into the host cell genome is not essential for viral replication, but it allows the viral genome to …
Response of Cortical Metabolic Deficits to Serotonergic Challenge in Familial Mood Disorders
Authors: Lawrence S. Kegeles, Kevin M. Malone, Mark Slifstein, Steven P. Ellis, Eric Xanthopoulos, John G. Keilp, Carl Campbell, Maria Oquendo, Ronald L. Van Heertum, J. John Mann
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: In subjects with mood disorders, positron emission tomography (PET) with [18F]fluorodeoxyglucose has shown prefrontal cortical metabolism deficits, including in a subgenual region in subjects with familial illness. The authors applied a dl-fenfluramine challenge method to study metabolic response in this region to serotonergic challenge in familial major depression. METHOD: The study group consisted of 19 depressed subjects with major depressive disorder or bipolar disorder, all of whom had at least one first-degree relative with history of major depression, and 10 healthy volunteers with similar age and gender distributions. PET images were acquired under placebo and challenge conditions, and volumetric MRI scans were also obtained. Group comparisons of metabolic and volumetric data were performed. Ratings of acute mood change during serotonergic challenge were compared with the imaging data. RESULTS: Within Brodmann's area 32, a glucose metabolism deficit in the depressed subjects on placebo day was observed by voxel-level analysis, but no volumetric deficit was found in the subgenual regions examined. Under challenge, both groups suppressed metabolism similarly. Within the patient group, the correlation between acute mood improvement during challenge and greater metabolic suppression approached significance. CONCLUSIONS: In familial mood disorders, a ventromedial prefrontal cortical deficit in baseline metabolism is not due to altered structural volume, and the response to serotonergic challenge appears predictive of acute mood response. The potential to predict treatment response can be tested by a combined challenge and treatment study.
Early matched sibling hematopoietic cell transplantation for adult AML in first remission using an age-adapted strategy: long-term results of a prospective GOELAMS study
Authors: Bruno Lioure, Marie C. Béné, Arnaud Pigneux, Anne Huynh, Patrice Chevallier, Nathalie Fegueux, Didier Blaise, Brigitte Witz, Martine Delain, Jérôme Cornillon, Isabelle Luquet, Odile Blanchet, Pascale Cornillet-Lefebvre, Martin Carré, Mathilde Hunault, Fabrice Larosa, Thierry Lamy, Edouard Randriamalala, Mario Ojeda-Uribe, Christian Berthou, Luc Fornecker, Jean-Luc Harousseau, Didier Bouscary, Norbert Ifrah, Jean-Yves Cahn
Journal: Blood (2012)
Analysis of Airborne Pollen in Lebanon
Authors: Z.E. Baz, M. Nader, F. Zaitoun, R. Dana, C. Irani, A. Hejjaoui, E. Kairallah, B. Abi Salloum, S. Abi Dib Antoun, S. Chreiteh, H. Maatouk, B. Andary
Journal: Journal of Allergy and Clinical Immunology (2010)
Immune reactivity to -tubulin isotype 5 and vesicular integral-membrane protein 36 in patients with autoimmune gastrointestinal disorders
Authors: K. Op De Beeck, K. Van den Bergh, S. Vermeire, S. Decock, R. Derua, E. Waelkens, P. Rutgeerts, F. Nevens, X. Bossuyt
Journal: Gut (2010)

It was with interest that we read the paper by Terjung et al 1, in a recent issue of Gut , where human myeloid cell-specific β-tubulin isotype 5 was identified as the target antigen of atypical p-ANCA in autoimmune liver disorders. The authors suggest cross-reactivity with the bacterial protein FtsZ, probably reflecting an abnormal immune response to intestinal microorganisms.1

In attempts to identify novel anti-nuclear and anti-neutrophil antibodies in autoimmune hepatitis, we performed 2D gel electrophoresis and western blotting starting from nuclear HeLa cell extracts or enriched nuclear envelope extracts from HL60 cells or neutrophils. The blots were incubated with serum samples from patients with autoimmune hepatitis and controls. Spots to which there was reactivity with serum from patients but not from controls were excised and identified by MALDI-TOF/TOF.

In experiments in which we used non-myeloid HeLa cell extracts, a prominent protein spot of 49 670.82 Da (pI 4.78) was identified as β-tubulin isotype 5 (TBB5). The immune reactivity to tubulin was confirmed by western blotting. A cohort (n=468) of patients with autoimmune liver disease, viral hepatitis, inflammatory bowel disease and vasculitis was evaluated for reactivity to tubulin by ELISA using porcine tubulin (figure 1A) and recombinant human TBB5 (figure 1B …
Inhibition of sumoylation prevents experimental fibrosis
Authors: Aisa Khodzhigorova, Alfiya Distler, Veronika Lang, Clara Dees, Holm Schneider, Christian Beyer, Kolja Gelse, Oliver Distler, Georg Schett, Jörg H W Distler
Journal: Annals of the Rheumatic Diseases (2012)

Objectives Fibrosis is a predominant cause of death in systemic sclerosis (SSc). First epigenetic modifications have recently been shown to contribute to activation of SSc fibroblasts. Here, we investigated inhibition of sumoylation as a novel antifibrotic approach. Methods Sumoylation was inhibited by siRNA-mediated knockdown of the Small Ubiquitin-like MOdifiers (SUMO) E2-conjugating enzyme Ubc9, which is essential for sumoylation. The effects of knockdown of Ubc9 were analysed in bleomycin-induced dermal fibrosis, and in the model of fibrosis induced by overexpression of a constitutively active TGF-beta receptor type I (TBR). SUMO-1 and phosphorylated Smad3 were detected by immunohistochemistry. Results Increased staining for SUMO-1 was detected in patients with SSc and in experimental fibrosis. Inhibition of sumoylation exerted potent antifibrotic effects and prevented dermal thickening, myofibroblast differentiation and accumulation of collagen induced by bleomycin, or by overexpression of constitutively active TBR. Moreover, knockdown of Ubc9 reduced the accumulation of phosphorylated Smad3 in experimental fibrosis indicating that inhibition of sumoylation may normalise canonical TGF-β signalling in vivo. Conclusions We demonstrate that inhibition of sumoylation reduces canonical TGF-β signalling and prevents experimental fibrosis in different preclinical models. These data provide first evidence that targeting of aberrant sumoylation may be a novel therapeutic approach for fibrotic diseases.