tbuckley/cabot-search huggingface dataset:
Impaired duodenal mucosal integrity and low-grade inflammation in functional dyspepsia
Authors: Hanne Vanheel, Maria Vicario, Tim Vanuytsel, Lukas Van Oudenhove, Cristina Martinez, Åsa V Keita, Nicolas Pardon, Javier Santos, Johan D Söderholm, Jan Tack, Ricard Farré
Journal: Gut (2013)

<h3>Objective</h3> Functional dyspepsia (FD) is an extremely common functional gastrointestinal disorder, the pathophysiology of which is poorly understood. We hypothesised that impaired intestinal barrier function is involved in the onset and persistence of this disorder by inducing low-grade inflammation. Therefore, our aim was to evaluate duodenal mucosal integrity and low-grade inflammation in patients with FD. <h3>Design</h3> Duodenal biopsy specimens were obtained from 15 patients with FD fulfilling the Rome III criteria and 15 age- and gender-matched healthy volunteers. Transepithelial electrical resistance (TEER) and paracellular permeability were measured in Ussing chambers. Expression of cell-to-cell adhesion proteins was evaluated by real-time PCR, western blot and/or immunofluorescence. Numbers of mast cells, eosinophils and intraepithelial lymphocytes were assessed by immunohistochemistry. <h3>Results</h3> Patients with FD displayed lower TEER and increased paracellular passage compared with healthy controls, which is indicative of impaired mucosal integrity. In addition, abnormal expression of cell-to-cell adhesion proteins at the level of tight junctions, adherens junctions and desmosomes was shown. Furthermore, patients were characterised by the presence of low-grade inflammation, as demonstrated by increased infiltration of mucosal mast cells and eosinophils. A significant association between the expression level of several cell-to-cell adhesion proteins, the extent of increased permeability and the severity of low-grade inflammation was found. <h3>Conclusions</h3> These findings challenge the classical paradigm that patients with FD show no structural changes in the gastrointestinal tract. We suggest that impaired intestinal barrier function is a pathophysiological mechanism in FD. Thus, restoration of intestinal barrier integrity may be a potential therapeutic target for treating patients with FD.
How should renal hemodynamic data be indexed in obesity?
Authors: R E Schmieder, A H Beil, H Weihprecht, F H Messerli
Journal: Journal of the American Society of Nephrology (1995)

Clearance data are customarily indexed to body surface area of 1.73 m2. This study examined whether this standard procedure gives correct values for renal perfusion in obese subjects. In 215 subjects who varied in age, gender, height, weight, obesity, and mean arterial blood pressure, RPF was determined by measuring the clearance of (131I)para-aminohippuric acid. Multiple regression analysis of the whole study group revealed that age (beta = -0.44, P < 0.001), height (beta = +0.25, P < 0.01), and arterial blood pressure (beta = -0.19, P < 0.01) were independent predictors of RPF, but that weight or body mass index was not. When related to body surface area, RPF appeared to decline with increasing obesity as follows: normal weight, 609 +/- 153 mL/min per 1.73 m2; overweight, 572 +/- 149 mL/min per 1.73 m2; severely overweight, 530 +/- 145 mL/min per 1.73 m2 (P < 0.012). In contrast, RPF related to height reflected a pattern concordant with the multiple regression analysis: normal weight, 3.76 +/- 0.9 mL/min per meter; overweight, 3.86 +/- 1.0 mL/min per meter; and severely overweight, 3.86 +/- 1.0 mL/min per meter (not significant). A separate repetition of the whole analysis for both normotensive (N = 55) and hypertensive subjects (N = 160) revealed a result similar to that found for the whole group. Thus, our results show that obesity was not a determinant of RPF, and when related to body surface area, inappropriately low values of RPF were calculated for obese patients. It was concluded that RPF values correlate with height and not with surface area in obese subjects.
Treatment of refractory antibody mediated autoimmune disorders with an anti-CD20 monoclonal antibody (rituximab)
Authors: K Arzoo
Journal: Annals of the Rheumatic Diseases (2002)

<b>Background:</b> Rituximab, a chimeric monoclonal anti-CD20 antibody, has recently been used for the treatment of refractory antibody mediated autoimmune diseases such as immune mediated thrombocytopenia and haemolytic anaemia. <b>Patients:</b> Because of its novel mechanism of action, rituximab was used to treat three patients with refractory systemic antibody mediated autoimmune disorders. The first patient, a 71 year old woman with idiopathic type II mixed essential cryoglobulinaemia, had both dermatological and neurological manifestations with marked renal disease attributed to her cryoglobulinaemia. Patient 2, a 73 year old woman with Goodpasture9s syndrome, was refractory to conventional treatment (cyclophosphamide, prednisone, plasmapheresis). She had persistent haemoptysis and haematuria and positive antiglomerular basement membrane antibodies. The third patient, a 75 year old man with primary biliary cirrhosis, myelodysplasia, and systemic immune complex vasculitis, had progressive renal insufficiency, a macular erythematous rash, and severe thrombocytopenia. <b>Results:</b> Treatment with rituximab resolved all clinical and laboratory manifestations in the three patients. <b>Conclusions:</b> Rituximab may be an important therapeutic agent for the treatment of patients refractory or intolerant to corticosteroid or cytotoxic treatment, or both.
Effects of Proton-Pump Inhibitors on Functional Dyspepsia: A Meta-analysis of Randomized Placebo-Controlled Trials
Authors: Wei Hong Wang, Jia Qing Huang, Ge Fan Zheng, Harry H X Xia, Wai Man Wong, Xin Guang Liu, Johan Karlberg, Benjamin C Y Wong
Journal: Clinical Gastroenterology and Hepatology (2006)
PFOS and PFOA in Humans: New Study Links Prenatal Exposure to Lower Birth Weight
Authors: Kellyn Betts
Journal: Environmental Health Perspectives (2007)

About 15% of the U.S. population get their drinking and household water from a largely unmonitored source: private residential wells.About 400,000 new wells are drilled every year.A new USGS study suggests that the water in a small percentage of domestic wells could contain unsafe levels of volatile organic compounds (VOCs) [EHP 115:1539-1546; Rowe et al.].VOCs come from a wide variety of sources, including gasoline, plastics, paints, dyes, solvents, adhesives, insecticides, and spot removers, and have wide-ranging health effects.The chemical and physical properties of VOCs allow the compounds to move between the atmosphere, soil, surface water, and groundwater.Once in the environment, some VOCs degrade quickly whereas others persist for decades.The USGS collected data on 55 VOCs primarily between 1991 and 2002.The team analyzed water samples before homeowners treated or filtered the water, which could help reduce VOCs.Many-possibly half of all well users-don't filter their water.The wells ranged in depth from 6 to 1,500 feet, with a median depth of about 140 feet.Of the 2,401 wells studied, 65% had detectable levels of VOCs, and 1% had levels above the EPA maximum contaminant level for the compound(s) observed.The most common compounds found were chloroform, toluene, 1,2,4-trimethylbenzene, and perchloroethene.Factors associated with the presence of VOCs were dissolved oxygen content, precipitation, the presence of a hazardous waste site within 1 km of the well, aquifer type, and water temperature.The authors note that identifying factors associated with VOC occurrence may aid in understanding the sources, transport, and fate of these compounds in groundwater.-
PWE-249 Body mass index in the aetiology of inflammatory bowel disease—data from a European cohort study (EPIC)
Authors: S Chan
Journal: Gut (2012)

<h3>Introduction</h3> There are plausible biological mechanisms for how obesity may be involved in the development of inflammatory bowel disease (IBD) due to the pro-inflammatory cytokines synthesised by adipose tissue including TNF-α. The aim of this work was to conduct the first prospective cohort study of obesity in the aetiology of IBD. <h3>Methods</h3> The cohort consisted of 366 351 healthy men and women aged 30–74 years from centres in Europe (EPIC—European Prospective Investigation into Cancer) recruited between the years 1991 and 1998. At recruitment participants9 weight, height and energy intake were measured and physical activity from questionnaires and their body mass index (BMI) calculated. The cohort was monitored to 2004 to identify those who developed Crohn9s disease (CD) or ulcerative colitis (UC). Each diagnosis was medically confirmed via review of the medical notes. Each case was matched with four controls, for gender, age at recruitment and centre. BMI was divided into five categories. Conditional logistic regression was used to calculate OR and 95% CI adjusted for smoking. <h3>Results</h3> In the cohort, 102 participants developed incident CD (73% female, mean age of 55.9 years, SD=11.0 years) and 213 participants developed incident UC (61% female, mean age of 57.5 years, SD=10.8 years). There were no associations between the four higher categories of BMI and the development of CD (Trend=1.00, 95% CI 0.79 to 1.27, p=0.91) or UC (Trend=1.03, 95% CI 0.83 to 1.29, p 0.76). Dividing BMI in two categories. <h3>Conclusion</h3> No associations were found between BMI and either CD or UC. Further studies are required to confirm these results. If confirmed then BMI does not need to be measured in future epidemiological studies of IBD. <h3>Competing interests</h3> None declared.
Upregulation of miR-196a and<i>HOTAIR</i>Drive Malignant Character in Gastrointestinal Stromal Tumors
Authors: Takeshi Niinuma, Hiromu Suzuki, Masanori Nojima, Katsuhiko Nosho, Hiroyuki Yamamoto, Hiroyuki Takamaru, Eiichiro Yamamoto, Reo Maruyama, Takayuki Nobuoka, Yasuaki Miyazaki, Toshirou Nishida, Takeo Bamba, Tatsuo Kanda, Yoichi Ajioka, Takahiro Taguchi, Satoshi Okahara, Hiroaki Takahashi, Yasunori Nishida, Masao Hosokawa, Tadashi Hasegawa, Takashi Tokino, Koichi Hirata, Kohzoh Imai, Minoru Toyota, Yasuhisa Shinomura
Journal: Cancer Research (2012)

Abstract Large intergenic noncoding RNAs (lincRNA) have been less studied than miRNAs in cancer, although both offer considerable theranostic potential. In this study, we identified frequent upregulation of miR-196a and lincRNA HOTAIR in high-risk gastrointestinal stromal tumors (GIST). Overexpression of miR-196a was associated with high-risk grade, metastasis and poor survival among GIST specimens. miR-196a genes are located within the HOX gene clusters and microarray expression analysis revealed that the HOXC and HOTAIR gene were also coordinately upregulated in GISTs which overexpress miR-196a. In like manner, overexpression of HOTAIR was also strongly associated with high-risk grade and metastasis among GIST specimens. RNA interference–mediated knockdown of HOTAIR altered the expression of reported HOTAIR target genes and suppressed GIST cell invasiveness. These findings reveal concurrent overexpression of HOX genes with noncoding RNAs in human cancer in this setting, revealing miR-196a and HOTAIR as potentially useful biomarkers and therapeutic targets in malignant GISTs. Cancer Res; 72(5); 1126–36. ©2012 AACR.
Clinical features of ageing skin
Authors: J. J. LEYDEN
Journal: British Journal of Dermatology (1990)

Ageing of the skin involves the intrinsic process of senescence and extrinsic damage induced by chronic exposure to UV radiation. A recent consensus forum of the American Academy of Dermatology concluded that the majority of undesirable clinical features associated with 'skin ageing' are the result of damage to skin due to UV radiation (photoageing). Clinically photoageing is characterized by coarseness, wrinkling, mottled pigmentation, laxity, telangiectasia, and premalignant and malignant neoplasms. The role of genetics, hormones and diet needs to be clarified. Appropriate lifelong use of sunscreens may minimize many of the changes associated with photoageing.
Immune activation set point during early HIV infection predicts subsequent CD4+ T-cell changes independent of viral load
Authors: Steven G. Deeks, Christina M. R. Kitchen, Lea Liu, Hua Guo, Ron Gascon, Amy B. Narváez, Peter Hunt, Jeffrey N. Martin, James O. Kahn, Jay Levy, Michael S. McGrath, Frederick M. Hecht
Journal: Blood (2004)
Influence of hypoxia and neoangiogenesis on the growth of pancreatic cancer.
Authors: John P Duffy, Guido Eibl, Howard A Reber, Oscar J Hines
Journal: Molecular Cancer (2003)

As with other solid tumors, the growth and metastasis of pancreatic cancer is critically dependent on tumor angiogenesis. A major stimulus for a tumor's recruitment of additional blood vessels is cellular hypoxia, a condition which is especially pronounced in this neoplasm. Hypoxia induces transcriptional activation of genes that alter cellular metabolism and promote neoangiogenesis. Pancreatic cancer cells have demonstrated activation of such adaptive pathways even in the absence of hypoxia. A highly-angiogenic response in this neoplasm correlates with increased tumor growth, increased metastasis, and decreased survival. Pancreatic cancers expressing high levels of vascular endothelial growth factor, a potent pro-angiogenic cytokine, also have a higher incidence of metastasis and poorer prognosis. Pancreatic cancer cells uniquely express receptors for vascular endothelial growth factor, indicating a role for an autocrine loop in tumor proliferation and invasion. Multiple experimental anti-angiogenic strategies, many of which target vascular endothelial growth factor, reduce pancreatic cancer growth, spread, and angiogenesis. Anti-angiogenic treatments for pancreatic cancer will likely be most effective when used as an integral part of a combination chemotherapeutic regimen.
Chronic Myeloid Leukemia: An Update of Concepts and Management Recommendations of European LeukemiaNet
Authors: Michele Baccarani, Jorge Cortes, Fabrizio Pane, Dietger Niederwieser, Giuseppe Saglio, Jane Apperley, Francisco Cervantes, Michael Deininger, Alois Gratwohl, François Guilhot, Andreas Hochhaus, Mary Horowitz, Timothy Hughes, Hagop Kantarjian, Richard Larson, Jerald Radich, Bengt Simonsson, Richard T. Silver, John Goldman, Rudiger Hehlmann
Journal: Journal of Clinical Oncology (2009)

To review and update the European LeukemiaNet (ELN) recommendations for the management of chronic myeloid leukemia with imatinib and second-generation tyrosine kinase inhibitors (TKIs), including monitoring, response definition, and first- and second-line therapy.These recommendations are based on a critical and comprehensive review of the relevant papers up to February 2009 and the results of four consensus conferences held by the panel of experts appointed by ELN in 2008.Cytogenetic monitoring was required at 3, 6, 12, and 18 months. Molecular monitoring was required every 3 months. On the basis of the degree and the timing of hematologic, cytogenetic, and molecular results, the response to first-line imatinib was defined as optimal, suboptimal, or failure, and the response to second-generation TKIs was defined as suboptimal or failure.Initial treatment was confirmed as imatinib 400 mg daily. Imatinib should be continued indefinitely in optimal responders. Suboptimal responders may continue on imatinb, at the same or higher dose, or may be eligible for investigational therapy with second-generation TKIs. In instances of imatinib failure, second-generation TKIs are recommended, followed by allogeneic hematopoietic stem-cell transplantation only in instances of failure and, sometimes, suboptimal response, depending on transplantation risk.
Mitochondrial pathology in cardiac failure
Authors: J Marin-Garcia
Journal: Cardiovascular Research (2001)

Time for primary review 34 days. 

The heart is highly dependent for its function on oxidative energy generated in mitochondria, primarily by fatty acid β-oxidation, respiratory electron chain and oxidative phosphorylation (OXPHOS). In this review, we survey the available evidence that mitochondrial dysfunction may play a pivotal role in cardiac failure. We also discuss how mitochondrial dysfunction may be related to other critical cellular and molecular changes found in cardiac hypertrophy and failure, including dysfunctional structural and cytoskeletal proteins, apoptosis, calcium flux and handling, and signalling pathways. The review also focuses on the biochemical and molecular changes in severe heart failure secondary to primary cardiomyopathy (dilated/hypertrophic) in humans as well as findings in animal models of heart failure related to volume and/or pressure overload.

Mitochondria are abundant in energy-demanding cardiac tissue constituting 20–40% of cellular volume (greater proportion than in skeletal muscle). Mitochondrial energy production depends on genetic factors which modulate normal mitochondrial function including enzyme activity and cofactor availability and on environmental factors including the availability of fuels (e.g. sugars, fats and proteins) and oxygen. Fatty acids are the primary energy substrate for heart muscle ATP generation by OXPHOS and the mitochondrial respiratory chain, the most important supply of cardiac energy. The supply of ATP from other sources, e.g. glycolytic metabolism is limited in normal cardiac tissue. Fatty acid β-oxidation and the oxidation of carbohydrates through the TCA cycle generate the majority of intramitochondrial NADH and FADH which are the direct source of electrons for the electron transport chain (and produce as well a small proportion of the ATP supply) (Fig. 1) [1]. The heart also maintains stored high-energy phosphates (e.g. ATP and phosphocreatine pools).



Fig. 1 
Mitochondrial bioenergetic pathways in cardiac failure. Mitochondrial inner-membrane localized respiratory complexes I–V (hatched circles) with associated electron-transfer components, CoQ and Cyt c, are … 



* Corresponding author. Tel.: +1-732-220-1719; fax: +1-732-220-2992 tmci{at}worldnet.att.net
Assisted assembly: how to improve a de novo genome assembly by using related species
Authors: Sante Gnerre, Eric S Lander, Kerstin Lindblad-Toh, David B Jaffe
Journal: Genome biology (2009)

We describe a new assembly algorithm, where a genome assembly with low sequence coverage, either throughout the genome or locally, due to cloning bias, is considerably improved through an assisting process via a related genome. We show that the information provided by aligning the whole-genome shotgun reads of the target against a reference genome can be used to substantially improve the quality of the resulting assembly.
Activation of mTORC1/mTORC2 signaling in pediatric low-grade glioma and pilocytic astrocytoma reveals mTOR as a therapeutic target
Authors: Marianne Hütt-Cabezas, Matthias A. Karajannis, David Zagzag, Smit Shah, Iren Horkayne-Szakaly, Elisabeth J. Rushing, J. Douglas Cameron, Deepali Jain, Charles G. Eberhart, Eric H. Raabe, Fausto J. Rodriguez
Journal: Neuro-Oncology (2013)

Previous studies support a role for mitogen-activated protein kinase pathway signaling, and more recently Akt/mammalian target of rapamycin (mTOR), in pediatric low-grade glioma (PLGG), including pilocytic astrocytoma (PA). Here we further evaluate the role of the mTORC1/mTORC2 pathway in order to better direct pharmacologic blockade in these common childhood tumors.We studied 177 PLGGs and PAs using immunohistochemistry and tested the effect of mTOR blockade on 2 PLGG cell lines (Res186 and Res259) in vitro.Moderate (2+) to strong (3+) immunostaining was observed for pS6 in 107/177 (59%) PAs and other PLGGs, while p4EBP1 was observed in 35/115 (30%), pElF4G in 66/112 (59%), mTOR (total) in 53/113 (47%), RAPTOR (mTORC1 component) in 64/102 (63%), RICTOR (mTORC2 component) in 48/101 (48%), and pAkt (S473) in 63/103 (61%). Complete phosphatase and tensin homolog protein loss was identified in only 7/101 (7%) of cases. In PA of the optic pathways, compared with other anatomic sites, there was increased immunoreactivity for pS6, pElF4G, mTOR (total), RICTOR, and pAkt (P < .05). We also observed increased pS6 (P = .01), p4EBP1 (P = .029), and RICTOR (P = .05) in neurofibromatosis type 1 compared with sporadic tumors. Treatment of the PLGG cell lines Res186 (PA derived) and Res259 (diffuse astrocytoma derived) with the rapalog MK8669 (ridaforolimus) led to decreased mTOR pathway activation and growth.These findings suggest that the mTOR pathway is active in PLGG but varies by clinicopathologic subtype. Additionally, our data suggest that mTORC2 is differentially active in optic pathway and neurofibromatosis type 1-associated gliomas. MTOR represents a potential therapeutic target in PLGG that merits further investigation.
Cardiometabolic Risk in Impaired Fasting Glucose and Impaired Glucose Tolerance
Authors: James S. Pankow, David K. Kwan, Bruce B. Duncan, Maria I. Schmidt, David J. Couper, Sherita Golden, Christie M. Ballantyne
Journal: Diabetes Care (2007)

We compared and contrasted cardiovascular disease (CVD) risk factors, subclinical manifestations of CVD, incident coronary heart disease (CHD), and all-cause mortality by categories of impaired glucose regulation in nondiabetic individuals.
Prisoners' and Their Health
Authors: J. C. Brown
Journal: BMJ (1975)

It is our ontention that, though there is some evidence that venous thrombosis after operation and impaired fibrinolysis are re- lated, the link is still only tenuous and un- likely to be of major importance.This would explain on the one hand why prophylactic regimens sudh as phenformin and ethyl- oestrenol (which increase fibrinolytic activity) have not been effective in preventing postoperative venous thuombosis7 and on the other hand why a powerful fibrinolytic in- hibitor E-amnnoaproic acid, admiiinistered during the perioperative period was not associated with an increased incidence of deep vein xirombosis.8-We are, etc.,
Management of HER2-positive breast cancer in Asia: consensus statement from the Asian Oncology Summit 2009
Authors: Nan Soon Wong, Benjamin O Anderson, Kei Siong Khoo, Peng Tiam Ang, Cheng Har Yip, Yen-Shen Lu, Narind Voravud, Zhi-Ming Shao, Kathleen I Pritchard
Journal: The Lancet Oncology (2009)
Cerebrovascular reactivity assessed by transcranial Doppler ultrasound in sport-related concussion: a systematic review
Authors: Andrew J Gardner, Can Ozan Tan, Philip N Ainslie, Paul van Donkelaar, Peter Stanwell, Christopher R Levi, Grant L Iverson
Journal: British Journal of Sports Medicine (2014)

Background Traumatic brain injury influences regulation of cerebral blood flow in animal models and in human studies. We reviewed the use of transcranial Doppler ultrasound (US) to monitor cerebrovascular reactivity following sport-related concussion. Review method A narrative and systematic review of articles published in the English language, from December 1982 to October 2013. Data sources Articles were retrieved via numerous databases using relevant key terms. Observational, cohort, correlational, cross-sectional and longitudinal studies were included. Results Three publications met the criteria for inclusion; these provided data from 42 athletes and 33 controls. All three studies reported reductions in cerebrovascular reactivity via transcranial Doppler US. Conclusions These initial results support the use of cerebrovascular reactivity as a research tool for identifying altered neurophysiology and monitoring recovery in adult athletes. Larger cross-sectional, prospective and longitudinal studies are required to understand the sensitivity and prognostic value of cerebrovascular reactivity in sport-related concussion.