tbuckley/cabot-search huggingface dataset:
The association of respiratory symptoms and lung function with the use of gas for cooking. European Community Respiratory Health Survey
Authors: D Jarvis, S Chinn, J Sterne, C Luczynska, P Burney
Journal: European Respiratory Journal (1998)

The association of respiratory symptoms and lung function with the use of gas for cooking was examined using data collected as part of the European Community Respiratory Health Survey, an international multicentre study. Associations between gas cooking and respiratory symptoms and respiratory function were assessed by logistic and multiple regression models. Tests for interaction were used to examine whether the effect of gas cooking varied between centres and, as there was evidence for this, the average effects were estimated using standard methods for random effects meta-analysis. Data from 5,561 males and 6,029 females living in 23 centres in 11 countries were analysed. There was no significant association found between respiratory symptoms and gas cooking in males. In females the association between some respiratory symptoms and gas cooking varied between centres with an overall positive association with "wheeze in the last 12 months" (odds ratio (OR) 1.24: 95% confidence interval (95% CI) 1.00-1.54) and "wheeze with breathlessness in the last 12 months" (OR 1.33: 95% CI 1.06-1.69). There was no evidence that atopy modified this association. Cooking with gas was associated with airways obstruction in both males and females although the differences failed to reach statistical significance. In some countries the use of gas for cooking is associated with respiratory symptoms suggestive of airways obstruction in females.
MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis—clinical implementation in the diagnostic process
Authors: Àlex Rovira, Mike P. Wattjes, Mar Tintoré, Carmen Tur, Tarek A. Yousry, Maria P. Sormani, Nicola De Stefano, Massimo Filippi, Cristina Auger, Maria A. Rocca, Frederik Barkhof, Franz Fazekas, Ludwig Kappos, Chris Polman, David Miller, Xavier Montalban
Journal: Nature Reviews Neurology (2015)

The use of MRI in patients with multiple sclerosis (MS) is commonplace in clinical settings. However, the precise implementation of MRI in the diagnosis of MS is highly variable, which is problematic in the context of the substantial technical advances of the past decade. In these Evidence-based Guidelines, members of the MAGNIMS study group present a standardized approach to the use of MRI in the diagnosis of MS. The clinical use of MRI in patients with multiple sclerosis (MS) has advanced markedly over the past few years. Technical improvements and continuously emerging data from clinical trials and observational studies have contributed to the enhanced performance of this tool for achieving a prompt diagnosis in patients with MS. The aim of this article is to provide guidelines for the implementation of MRI of the brain and spinal cord in the diagnosis of patients who are suspected of having MS. These guidelines are based on an extensive review of the recent literature, as well as on the personal experience of the members of the MAGNIMS (Magnetic Resonance Imaging in MS) network. We address the indications, timing, coverage, reporting and interpretation of MRI studies in patients with suspected MS. Our recommendations are intended to help radiologists and neurologists standardize and optimize the use of MRI in clinical practice for the diagnosis of MS.
Circulating Inflammation Markers, Risk of Lung Cancer, and Utility for Risk Stratification
Authors: Meredith S. Shiels, Hormuzd A. Katki, Allan Hildesheim, Ruth M. Pfeiffer, Eric A. Engels, Marcus Williams, Troy J. Kemp, Neil E. Caporaso, Ligia A. Pinto, Anil K. Chaturvedi
Journal: JNCI Journal of the National Cancer Institute (2015)

Background:We conducted two independent nested case-control studies to identify circulating inflammation markers reproducibly associated with lung cancer risk and to investigate the utility of replicated markers for lung cancer risk stratification.
Classification of segmental vitiligo on the face: clues for prognosis
Authors: D-Y. Kim, S.H. Oh, S-K. Hann
Journal: British Journal of Dermatology (2010)

The origin of the distribution of segmental vitiligo (SV) has not yet been clearly elucidated. Segmental configurations of cutaneous disorders have been explained using two main interpretations, i.e. following either dermatomal or blaschkolinear distributions. However, facial SV does not always correspond to either of these distributions.We classified facial SV into several distinctive subtypes according to specific distributions based on long-term observations.In total, 257 patients with facial SV were included, all of whom were closely observed for more than 1 year. The distribution patterns of facial SV were classified according to morphological similarities based on clinical observations.The lesions of facial SV were categorized into six subtypes: types I-a and I-b, and types II-V. Type I-a and type IV broadly involved the mid-level face from the forehead to the lower cheek, but type IV lesions selectively appeared on the right side of the face and did not cross the midline. Type I-b lesions chiefly involved the forehead and scalp hair. Types II and III involved the lower face and, frequently, the neck area, and type V lesions were distributed mostly around the right orbital area. The most frequent type of lesion in this study was type I-a (28·8%), followed by types II (16·0%), III (14·4%), IV (10·9%), I-b (10·5%) and V (8·6%).Newly established patterns of facial SV may be valuable for certain aspects of prognosis, such as the likely degree and path of lesion spreading.
Simplification of Inhalation Therapy in Asthmatic children
Authors: S. Pedersen, G. Steffensen
Journal: Allergy (1986)

In a placebo‐controlled double blind cross‐over study of 3 × 3 weeks' duration the effectiveness of a new set of simple instructions for the use of spacer aerosols was compared with that of the rather complicated manufacturer's instructions in the daily treatment of 22 children with severe asthma. All children received inhaled budesonide and terbutaline at the lowest dose possible for satisfactory symptom control. Both the simple and complicated regimes were significantly better than placebo ( P &lt; 0.01), but there was no indication that the complicated regime was superior to the simple regime. On the contrary, the children used significantly more rescue terbutaline and experienced more day time symptoms when treated according to the complicated regime ( P &lt; 0.01). 19 of 21 children who completed the study preferred to use the simple regime ( P &lt; 0.01). It is concluded that conclusions for the use of spacer aerosols should be substantially simplified and that conclusions from laboratory studies should be tested in the day‐to‐day of asthmatics before these aerosols become widely used.
Successful Imatinib Therapy for Neuroendocrine Carcinoma With Activating<i>KIT</i>Mutation: A Case Study
Authors: James Perkins, Patrick Boland, Steven J. Cohen, Anthony J. Olszanski, Yan Zhou, Paul Engstrom, Igor Astsaturov
Journal: Journal of the National Comprehensive Cancer Network (2014)

Neuroendocrine tumors (NET) and gastrointestinal stromal tumors (GIST) are believed to originate from the cells of Cajal that are randomly dispersed along the aerodigestive tract. Despite their distinct morphologic appearance, NET and GIST may share oncogenic mechanisms. Often presenting in the metastatic setting, treatment options for patients with NET are limited. This case report presents a patient with refractory metastatic NET that did not respond conventional chemotherapy. The patient was treated with a KIF11 inhibitor in a phase I clinical trial and experienced a prolonged and clinically meaningful partial response. On progression at 20 months, the patient's tumor was sequenced to reveal a KIT exon 11 mutation. Institution of imatinib therapy achieved a rapid and sustained antitumor effect with profound clinical benefit. Despite previously reported KIT expression in NET, this is the first documented case of an activating KIT mutation in NET and of successful treatment with both a KIF11 inhibitor and imatinib, each of which was elucidated through molecular profiling of the patient's tumor. Imatinib may be a valuable therapy in NET harboring activating KIT mutations.
MicroRNA-331-3p promotes proliferation and metastasis of hepatocellular carcinoma by targeting PH domain and leucine-rich repeat protein phosphatase
Authors: Rui-Min Chang, Hao Yang, Feng Fang, Jiang-Feng Xu, Lian-Yue Yang
Journal: Hepatology (2014)

Hepatocellular carcinoma (HCC) is a highly invasive tumor with frequent intrahepatic or pulmonary metastasis, which is the main reason for high recurrence and poor survival of HCC after liver resection. However, the mechanisms for metastasis remain incompletely clear. Given that microRNAs (miRNAs) are implicated in HCC progression, we explored a potential role of miRNAs in metastasis by performing miRNA expression profiling in three subtypes of HCC with different metastatic potentials. We discovered miR-331–3p as one of most significantly overexpressed miRNAs and highly associated with metastasis of HCC. Increased expression of miR-331–3p was correlated with poor long-term survival of HCC. We provided both in vivo and in vitro evidence demonstrating that miR-331–3p promoted proliferation and metastasis of HCC cells. Using an integrated approach, we uncovered that PH domain and leucine-rich repeat protein phosphatase (PHLPP) was a novel target of miR-331–3p. Indeed, the miR-331–3p-mediated effects were antagonized by reexpression of PHLPP or mimicked by silencing of PHLPP. We further showed that miR-331–3p-mediated inhibition of PHLPP resulted in stimulation of protein kinase B (AKT) and subsequent epithelial mesenchymal transition (EMT). Finally, inhibition of miR-331–3p through a jetPEI-mediated delivery of anti-miR-331–3p vector resulted in marked inhibition of proliferation and metastasis of HCC in xenograft mice. Conclusion : miR-331–3p promotes proliferation and EMT-mediated metastasis of HCC through suppression of PHLPP-mediated dephosphorylation of AKT. Our work implicates miR-331–3p as a potential prognostic biomarker and a novel therapeutic target. (Hepatology 2014;60:1251–1263)
Regional distinctions regarding COPD prevalence in Russian Arctic: Results of national population study
Authors: Marine Gambaryan, Anna Kalinina, Alexander Deev
Journal: European Respiratory Journal (2013)

The problem of COPD in Russian Arctic where respiratory diseases have shown higher premature mortality seem to be neglected despite the economic importance of the region for Russia.  The aim of the study is to explore whether there are regional distinctions regarding the prevalence of COPD in Russian Arctic.  Methods  Data from National multi-centre population based study with randomly selected subjects aged 35-64 (N=3771; RR=81%)-selected regions - Yakutsk (Russian Arctic), Chelyabinsk (industrial) and Vologda (midland Russia) were analysed. Chi-squared tests and odds ratios (OR) were utilized; multiple logistic regression was employed to analyse the association between COPD, smoking patterns and regional distinctions.  Results  The prevalence of COPD was 21.9%: 23.1% among men, 21.1% among women and only 50.9% had a respiratory diagnose (p  Chances of COPD were significantly higher among heavy smokers– 10.5 times among men (OR 5=10.5; 95%CI 5.4-19) and 5 times among women (OR=95%CI 2.8-8.8).  The odds of COPD in Yakut people were significantly higher– 2.2 times in men (OR=2.2, 95%CI 1.6–3) (p  The status of hyperborean had the highest significant contribution to chances of COPD– comparable only with heavy smoking status.  Conclusion  Russian arctic regions have higher prevalence of COPD, with biggest contribution of smoking and environmental factors. Integrated preventive programs will need to address the regional inequalities.
Smoking during pregnancy induces early lung senescence in neonates
Authors: Melissa Baravalle, Guillaume Lezmi, Shamila Vibushan, Marie Laure Franco Montoya, Jorge Boczkowski, Christophe Delacourt
Journal: European Respiratory Journal (2013)

Background and Aim. In utero smoke exposure is associated to altered lung growth and airflow limitation in early adult life, which may predispose to chronic respiratory diseases such as COPD. As accelerated lung aging has been demonstrated as a key pathogenic mechanism of COPD, the aim of our study was to demonstrate the induction of early lung senescence by in utero exposure to cigarette smoke (CS).  Methods. Female mice were cyclically exposed to CS during their pregnancy, while control females were exposed in same conditions to air. Body growth, lung volume, and lung function were measured in pups. Lung expression of genes controlling senescence and apoptosis was analyzed in pups at birth, and at 21 days of postnatal age.  Results. When compared to control litters, in utero smoke exposure induced lower birth weight (p  Conclusion. In our mouse model, in utero smoke exposure reproduced growth alterations observed in humans. We demonstrated the induction of early lung cellular senescence, associated to permanent impairment in respiratory function. These molecular abnormalities may induce susceptibility to the development of COPD in adults.
High throughput, quantitative DNA methylation screening using a quantum dot based nanotechnology assay
Authors: Bailey Vasudev, Yi Zhang, Hariharan Easwaran, Elizabeth Griffiths, James Herman, Stephen Baylin, Hetty Carraway, Jeff Wang
Journal: Clinical Cancer Research (2008)

PL01  Background:  The impact of detecting DNA methylation is profound, as it has been demonstrated that a larger number of tumor suppressor genes become inactivated by epigenetic silencing from DNA methylation than by mutations. Current methods of DNA methylation detection include qualitative methylation specific PCR (MSP) and quantitative real time PCR. We have demonstrated a nanotechnology assay that meets the needs for high throughput and ultra-sensitive DNA methylation analyses. The new technology will be likely to have a huge impact for both cancer diagnosis as well as assessing response to therapy.  Methods:  Our technology allows for performing multiple PCRs through a droplet-in-oil microfluidic PCR platform with single sample injection. It utilizes quantum dot (QD) nanosensors for the detection and quantification of DNA methylation. QDs serve as both a FRET donor as well as a nanoconcentrator to capture fluorescently labeled target amplicons which are generated through methylation specific PCR (MSP).  Results:  With our oil-in-droplet PCR platform, we were able to demonstrate valuable downscaling in reagent and sample consumption (800nL/ reaction). Our nanoassay allowed detecting as little as 15 pg of methylated DNA in the presence of a 10,000-fold excess of unmethylated alleles. We extended the analysis to clinical samples by detecting methylation for ASC/ TMS1 in low concentrations of DNA from human sputum without using nested PCR. The nanoassay featured low intrinsic background and high sensitivity with few PCR amplification cycles. We quantified methylation reversal with high resolution in pre and post bone marrow aspirate samples obtained from Myelodysplastic Syndrome (MDS) patients who were treated with epigenetic therapy using 5-azacytidine (Vidaza) and a histone deacetylase inhibitor (MS-275).  Conclusion:  Our QD-based nanoassay is fully compatible with the widely-used MSP. The use of an oil-in-droplet PCR system offers unprecedented ease in sample handling for a cost-effective multiplexed gene analysis. By simply end-labeling existing MSP primers and using commercially available QDs, our technique allows for quantitative, high-throughput and ultrasensitive methylation detection.
Pigmentary retinal dystrophy and the syndrome of maternally inherited diabetes and deafness caused by the mitochondrial DNA 3243 tRNALeu A to G mutation11The authors have no proprietary interest in the development or marketing of any device or medications mentioned in the article or any competing device.
Authors: Paul R Smith, Stephen C Bain, Peter A Good, Andrew T Hattersley, Anthony H Barnett, Jon M Gibson, Paul M Dodson
Journal: Ophthalmology (1999)
Thromboelastography for the prediction of bleeding after transplant renal biopsy.
Authors: C L Davis, W L Chandler
Journal: Journal of the American Society of Nephrology (1995)

The ability of prebiopsy coagulation assays to predict mild postbiopsy bleeding was evaluated in renal transplant patients undergoing renal allograft biopsy (N = 120). The coagulation assays studied included the bleeding time, prothrombin time, partial thromboplastin time, platelet count, and thromboelastograph (TEG). Coagulation results were defined as abnormal if they fell outside the established normal reference range. Bleeding was defined as a drop in the hematocrit equal to or more than 4 points 6 h after the procedure or ultrasound evidence of a new perirenal hematoma. Overall, 21% of patients showed evidence of mild bleeding. Of those who bled, 78% had normal results on all coagulation tests, indicating that most mild bleeding was not associated with coagulation abnormalities. Of the assays tested, only abnormal TEG:angle (P < 0.01) and TEG:k (P < 0.04) values were associated with an increased risk of bleeding. Bleeding times were not predictive of an increased risk of postbiopsy bleeding; five patients had abnormal bleeding times ranging from 10 to 20 min of whom only one bled. All prothrombin time, partial thromboplastin time, and platelet count abnormalities were mild (e.g., no prothrombin times longer than 15 s, no platelet counts below 129,000/microL); none of these assays predicted postbiopsy bleeding. Other clinical characteristics, including patient age, sex, serum creatinine, blood pressure (if less than 160/90 mm Hg), number of biopsy passes, or renal pathology, did not appear to influence bleeding after biopsy. It was concluded that most bleeding after transplant renal biopsy was not associated with coagulation abnormalities and that the TEG was the best assay for detecting mild coagulation abnormalities associated with an increased risk of bleeding.
Sputum culture conversion among the first cohorts of MDR-TB patients managed in Nigeria at a tertiary care hospital
Authors: Olusoji Ige, Yemisi Akindele, Regina Oladokun, Oludele Adebiyi
Journal: European Respiratory Journal (2014)

The aim of this study was to evaluate sputum culture conversion as an interim indicator of final treatment outcome of MDRTB using standardized regimen of the Nigerian National TB Control Program.  A retrospective study was conducted for the period 2010-2013, at the MDR-TB treatment center of the University College Hospital Ibadan, Nigeria. This was the first treatment center established in the country with 25 beds capacity that stated treating cases since 6 th  July 20010. All the culture and drug subsceptility test (DST)) proven cases of MDR pulmonary TB were admitted for 6 months for the intensive phase, followed by 12 months of ambulatory phase. The patients were followed up at monthly interval at the outpatient department of the center. Sputum culture was done on monthly bases while chest x rays were at every 6 months during treatment.  105 patients that were managed at the facility had their statistics analysed. 67 males (63.40%) and 38 females with mean age of 32.44 ± 12.63 years were studied. At month two 81(77.0%) patients were culture negative, which became 87.0% at month three while at month four 99(94 .00%) out of the 105 patients were negative  At month five 102(97.0%) have been culture negative while 3% were still culture positive.  3 patients who had sputum conversion, subsequently had positive cultures achieved reconversion again at month 6.  Overall 3 patients had treatment failure while 97% achieved a successful treatment outcome. The treatment outcome was significantly better in patients that convert within 2 months of treatment.  The study has shown that most patients with MDRTB achieved sputum culture conversion within 12 weeks of starting treatment.
Abstract 123: Optical Mapping of Host and Human Embryonic Stem Cell-Derived Cardiomyocyte Graft Electrical Activity in Injured Hearts
Authors: Dominic Filice, Wei-Zhong Zhu, Benjamin Van Biber, Kip D Hauch, Michael A Laflamme
Journal: Circulation Research (2014)

Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) show tremendous promise for cardiac repair, but more information is required as to their electrical behavior in vivo. hESC-CMs expressing the protein calcium sensor GCaMP3 provide a graft autonomous reporter of activation, which we have used to show hESC-CM grafts can couple with host myocardium in injured hearts. When we sought to assess host-graft electrical interactions by optical voltage mapping, we found the commonly used lipophilic voltage dyes RH237 and di-4-ANEPPS label host but not graft tissue. We hypothesized the water-soluble voltage dye di-2-ANEPEQ could overcome this limitation and efficiently label both host and graft. After confirming good spectral separation of GCaMP3 and di-2-ANEPEQ signals by spectrofluorimetry and confocal spectral imaging, we transplanted 1x10^8 GCaMP3+ hESC-CMs into guinea pig hearts (n=6) at 4 weeks following cardiac injury and then imaged engrafted hearts at 2 weeks post-transplantation with a dual-channel CCD-based system. We found a differential time-course of di-2-ANEPEQ labeling between host and graft tissues, with stable optical action potentials (APs) obtained in host and graft tissue after ~4 and ~13 minutes of dye perfusion, respectively. This differential labeling kinetics, which was also observed on washout, presumably reflects sluggish graft perfusion and provides another tool for distinguishing host and graft signals. No regions of 1:1 host-graft coupling were identified, and graft tissue had spontaneous rates from 0.1-2 Hz and long optical AP durations from 500-1090 ms. Activation maps based on di-2-ANEPEQ and GCaMP3 signals indicated relatively slow conduction velocities in graft tissue, as well as patterns of propagation that commonly occurred along a vector distinct from that in host tissue. These imaging studies reveal multiple potentially pro-arrhythmic properties in hESC-CM graft tissue including slow propagation, ultralong AP duration, as well as aberrant patterns of activation that can vary from beat to beat. We conclude the electrical behavior of both graft and host myocardium can be reliably assessed by the simultaneous imaging of a graft-autonomous fluorescent reporter of activation and a water-soluble voltage dye.