tbuckley/cabot-search huggingface dataset:
Population values of lung volumes and flows in children: effect of sex, body mass and respiratory conditions
Authors: R Pistelli, G Brancato, F Forastiere, P Michelozzi, GM Corbo, N Agabiti, G Ciappi, CA Perucci
Journal: European Respiratory Journal (1992)

The functional relationship of gender, anthropometric measures and respiratory condition in predicting respiratory function in children was explored, using data collected in a random sample survey in Central Italy (2,176 subjects). Regression equations for the logarithmic transformation of the functional data were obtained, using sex, ln(height), ln(body mass index) (BMI) and ln(age) as predicting variables. The fit of the model was better for forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF) (R2 = 0.655, 0.603 and 0.312, respectively) than for maximal expiratory flows. Variables indicating the presence of respiratory conditions (recent respiratory infections, asthma, cough and/or phlegm) were forced in the models; only a marginal change in the predictions was observed. Data analysis while controlling for FVC, as a proxy for total lung capacity, revealed no substantial sex difference in airways; furthermore, airways size relative to lung size falls with increasing FVC in both sexes. In overweight subjects (BMI greater than 90th percentile) the relationship between height and lung volume was modified by sex, the coefficient for ln(height) being higher in girls and lower in boys. A comparison between equations from the present study and available reference data revealed that our population differs from standards derived from laboratory data and is more similar to those derived from population studies.
Suppression of canonical Wnt/ -catenin signaling by nuclear plakoglobin recapitulates phenotype of arrhythmogenic right ventricular cardiomyopathy
Authors: E. Garcia-Gras
Journal: Journal of Clinical Investigation (2006)

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is a genetic disease caused by mutations in desmosomal proteins. The phenotypic hallmark of ARVC is fibroadipocytic replacement of cardiac myocytes, which is a unique phenotype with a yet-to-be-defined molecular mechanism. We established atrial myocyte cell lines expressing siRNA against desmoplakin (DP), responsible for human ARVC. We show suppression of DP expression leads to nuclear localization of the desmosomal protein plakoglobin and a 2-fold reduction in canonical Wnt/β-catenin signaling through Tcf/Lef1 transcription factors. The ensuing phenotype is increased expression of adipogenic and fibrogenic genes and accumulation of fat droplets. We further show that cardiac-restricted deletion of Dsp, encoding DP, impairs cardiac morphogenesis and leads to high embryonic lethality in the homozygous state. Heterozygous DP-deficient mice exhibited excess adipocytes and fibrosis in the myocardium, increased myocyte apoptosis, cardiac dysfunction, and ventricular arrhythmias, thus recapitulating the phenotype of human ARVC. We believe our results provide for a novel molecular mechanism for the pathogenesis of ARVC and establish cardiac-restricted DP-deficient mice as a model for human ARVC. These findings could provide for the opportunity to identify new diagnostic markers and therapeutic targets in patients with ARVC.
Myocardial Function, Energy Provision, and Carnitine Deficiency in Experimental Uremia
Authors: Veena Reddy, Sunil Bhandari, Anne-Marie L. Seymour
Journal: Journal of the American Society of Nephrology (2006)

Cardiac complications are the leading cause of mortality in patients with chronic renal failure. Secondary carnitine deficiency, which is frequently observed in hemodialysis patients, has been associated with cardiac hypertrophy and heart failure and may impair myocardial fatty acid oxidation. In chronic kidney disease, impaired carnitine homeostasis also may affect myocardial metabolism. In this study, myocardial function and substrate oxidation in conjunction with carnitine deficiency were investigated in experimental renal failure. Uremia was induced in male Sprague-Dawley rats via a two-stage five-sixths nephrectomy. Cardiac function and substrate oxidation were assessed in vitro by means of isovolumic perfusion using 13C nuclear magnetic resonance at 3 and 6 wk of uremia. Renal impairment as assessed by serum creatinine was more severe initially and was associated with a significant deficiency in serum free carnitine (43%; P < 0.001) and elevated acyl carnitine/free carnitine ratio. Myocardial tissue carnitine concentrations, however, were unaffected. A moderate degree of cardiac hypertrophy (10 to 14%; P < 0.05) was observed in uremia without evidence of dysfunction or changes in myocardial substrate utilization. It is concluded that renal dysfunction is associated with cardiac hypertrophy in the presence of normal myocardial carnitine levels, despite a significant depletion in serum carnitine. This may be a factor in maintaining normal cardiac function and metabolism.
A unusual cause of anaemia
Authors: G Neumayr
Journal: Gut (2005)

individuals and provide them with a suitable environment in which to work.Links should be forged with biomedical engineering as a new iteration of the old relationship between craftsman and physician that was so productive throughout the history of endoscopy.Lastly, we must forge new relationships with industry that emphasise innovation.The great American baseball player and every man's philosopher, Yogi Berra, master of the malapropism, once observed that ''the future ain't what is used to be.''For the future, the only certainty is that endoscopic innovation is no longer assured.
TNFα signalling primes chromatin for NF-κB binding and induces rapid and widespread nucleosome repositioning
Authors: Sarah Diermeier, Petros Kolovos, Leonhard Heizinger, Uwe Schwartz, Theodore Georgomanolis, Anne Zirkel, Gero Wedemann, Frank Grosveld, Tobias A Knoch, Rainer Merkl, Peter R Cook, Gernot Längst, Argyris Papantonis
Journal: Genome biology (2014)

The rearrangement of nucleosomes along the DNA fiber profoundly affects gene expression, but little is known about how signalling reshapes the chromatin landscape, in three-dimensional space and over time, to allow establishment of new transcriptional programs.
Changing the Mindset in Life Sciences Toward Translation: A Consensus
Authors: Georg N. Duda, David W. Grainger, Megan L. Frisk, Leena Bruckner-Tuderman, Andrew Carr, Ulrich Dirnagl, Karl Max Einhäupl, Stephen Gottschalk, Elliott Gruskin, Christoph Huber, Carl H. June, David J. Mooney, Ernst Th. Rietschel, Georg Schütte, Werner Seeger, Molly M. Stevens, Robert Urban, Alex Veldman, Günther Wess, Hans-Dieter Volk
Journal: Science Translational Medicine (2014)

Participants at the recent Translate! 2014 meeting in Berlin, Germany, reached a consensus on the rate-limiting factor for advancing translational medicine.
Oral amoxicillin versus injectable penicillin for severe pneumonia in children aged 3 to 59 months: a randomised multicentre equivalency study
Authors: Emmanuel Addo-Yobo, Noel Chisaka, Mumtaz Hassan, Patricia Hibberd, Juan M Lozano, Prakash Jeena, William B MacLeod, Irene Maulen, Archana Patel, Shamim Qazi, Donald M Thea
Journal: The Lancet (2004)
Cancer Models and Real-world Data: Better Together: Table 1.
Authors: Jane J. Kim, Anna NA Tosteson, Ann G. Zauber, Brian L. Sprague, Natasha K. Stout, Oguzhan Alagoz, Amy Trentham-Dietz, Katrina Armstrong, Sandi L. Pruitt, Carolyn M. Rutter
Journal: JNCI Journal of the National Cancer Institute (2015)

Decision-analytic models are increasingly used to inform health policy decisions. These models synthesize available data on disease burden and intervention effectiveness to project estimates of the long-term consequences of care, which are often absent when clinical or policy decisions must be made. While models have been influential in informing US cancer screening guidelines under ideal conditions, incorporating detailed data on real-world screening practice has been limited given the complexity of screening processes and behaviors throughout diverse health delivery systems in the United States. We describe the synergies that exist between decision-analytic models and health care utilization data that are increasingly accessible through research networks that assemble data from the growing number of electronic medical record systems. In particular, we present opportunities to enrich cancer screening models by grounding analyses in real-world data with the goals of projecting the harms and benefits of current screening practices, evaluating the value of existing and new technologies, and identifying the weakest links in the cancer screening process where efforts for improvement may be most productively focused. We highlight the example of the National Cancer Institute–funded consortium Population-based Research Optimizing Screening through Personalized Regimens (PROSPR), a collaboration to harmonize and analyze screening process and outcomes data on breast, colorectal, and cervical cancers across seven research centers. The pairing of models with such data can create more robust models to not only better inform policy but also inform health care systems about best approaches to improve the provision of cancer screening in the United States.
Metabolic Response to Pegylated Arginine Deiminase in Mesothelioma With Promoter Methylation of Argininosuccinate Synthetase
Authors: Peter W. Szlosarek, Phuong Luong, Melissa M. Phillips, Marina Baccarini, Stephen Ellis, Teresa Szyszko, Michael T. Sheaff, Norbert Avril
Journal: Journal of Clinical Oncology (2013)
Role of Cationic Channel TRPV2 in Promoting Prostate Cancer Migration and Progression to Androgen Resistance
Authors: Michaël Monet, V'yacheslav Lehen'kyi, Florian Gackiere, Virginie Firlej, Matthieu Vandenberghe, Morad Roudbaraki, Dimitra Gkika, Albin Pourtier, Gabriel Bidaux, Christian Slomianny, Philippe Delcourt, François Rassendren, Jean-Pierre Bergerat, Jocelyn Ceraline, Florence Cabon, Sandrine Humez, Natalia Prevarskaya
Journal: Cancer Research (2010)

Castration resistance in prostate cancer (PCa) constitutes an advanced, aggressive disease with poor prognosis, associated with uncontrolled cell proliferation, resistance to apoptosis, and enhanced invasive potential. The molecular mechanisms involved in the transition of PCa to castration resistance are obscure. Here, we report that the nonselective cationic channel transient receptor potential vanilloid 2 (TRPV2) is a distinctive feature of castration-resistant PCa. TRPV2 transcript levels were higher in patients with metastatic cancer (stage M1) compared with primary solid tumors (stages T2a and T2b). Previous studies of the TRPV2 channel indicated that it is primarily involved in cancer cell migration and not in cell growth. Introducing TRPV2 into androgen-dependent LNCaP cells enhanced cell migration along with expression of invasion markers matrix metalloproteinase (MMP) 9 and cathepsin B. Consistent with the likelihood that TRPV2 may affect cancer cell aggressiveness by influencing basal intracellular calcium levels, small interfering RNA-mediated silencing of TRPV2 reduced the growth and invasive properties of PC3 prostate tumors established in nude mice xenografts, and diminished expression of invasive enzymes MMP2, MMP9, and cathepsin B. Our findings establish a role for TRPV2 in PCa progression to the aggressive castration-resistant stage, prompting evaluation of TRPV2 as a potential prognostic marker and therapeutic target in the setting of advanced PCa.
Common Cancer Stem Cell Gene Variants Predict Colon Cancer Recurrence
Authors: Armin Gerger, Wu Zhang, Dongyun Yang, Pierre Bohanes, Yan Ning, Thomas Winder, Melissa J. LaBonte, Peter M. Wilson, Leonor Benhaim, David Paez, Rita El-Khoueiry, Anthony El-Khoueiry, Michael Kahn, Heinz-Josef Lenz
Journal: Clinical Cancer Research (2011)

Recent evidence suggests that cancer stem cells (CSC) are responsible for key elements of colon cancer progression and recurrence. Germline variants in CSC genes may result in altered gene function and/or activity, thereby causing interindividual differences in a patient's tumor recurrence capacity and chemoresistance. We investigated germline polymorphisms in a comprehensive panel of CSC genes to predict time to tumor recurrence (TTR) in patients with stage III and high-risk stage II colon cancer.A total of 234 patients treated with 5-fluorouracil-based chemotherapy at the University of Southern California were included in this study. Whole blood samples were analyzed for germline polymorphisms in genes that have been previously associated with colon CSC (CD44, Prominin-1, DPP4, EpCAM, ALCAM, Msi-1, ITGB1, CD24, LGR5, and ALDH1A1) by PCR-RFLP or direct DNA-sequencing.The minor alleles of CD44 rs8193 C>T, ALCAM rs1157 G>A, and LGR5 rs17109924 T>C were significantly associated with increased TTR (9.4 vs. 5.4 years; HR, 0.51; 95% CI: 0.35-0.93; P = 0.022; 11.3 vs. 5.7 years; HR, 0.56; 95% CI: 0.33-0.94; P = 0.024, and 10.7 vs. 5.7 years; HR, 0.33; 95% CI: 0.12-0.90; P = 0.023, respectively) and remained significant in the multivariate analysis stratified by ethnicity. In recursive partitioning, a specific gene variant profile including LGR5 rs17109924, CD44 rs8193, and ALDH1A1 rs1342024 represented a high-risk subgroup with a median TTR of 1.7 years (HR, 6.71, 95% CI: 2.71-16.63, P < 0.001).This is the first study identifying common germline variants in colon CSC genes as independent prognostic markers for stage III and high-risk stage II colon cancer patients.
On the Combined Use of Thomas's and Furneaux Jordan's Laminated Splints
Authors: E. S. Bishop
Journal: BMJ (1883)

Where great inflammation or shrinking exists, extraction is out of the question, for sympathetic ophthalmia is thereby favoured, with- out any compensatory improvement of vision.iEnucleation only remains for such cases.A few items of a statistical nature may be added.Cysticercus in the eyeball is rarer in England than on the Continent, and especially few are the cases from English sources where the deeper parts of the eye were conicerned.On the other hand, where the anterior parts were the seat, the number is relatively large.In North Ger- many, in von Griife's time, the proportion was 1 per 1,000; but, in the last few years, a decline has been observed by Hirschberg, wlho met witlh only three cases in 8,000 new eye-patients during fourteen months-1882-83.This is probably the result of the compulsory examination of flesh-meats, both in respect of trichina and of cysticereus, which obtains in Germany.The occurrence of the parasite is much rarer in southern Germany, Austria, Italy, etc.In Vienna, for example, Taenia mediocanellata is the rule, T. solium the excep- tion.As Cysticercus mediocanellata infests oxen, and cannot thrive in the human subject, it is never met with in the human eye.The only scolex found in the human eye is C. cellulos,, and hitherto only one entozoon has been found in a given eye, thouglh Becker (Mauthner's Op)hthatrn.) says he has seenl two in the same eye.The greatest size and age on record in the hiuman eye arc 15 millimetres and two years respectively.The number of cases reported where an anatomical examination of the eye took place is about twenty, and of these, ten were sub- retinal, ten in the vitreous body.Von Griife thought that the original seat of the parasite was twice as often beneath the retina as in the vitreous body, the enitozoon in a nuamber of cases subsequently breaking through into the latter.
Low-Molecular-Weight Heparin in the Treatment of Patients with Venous Thromboembolism
Authors: The Columbus Investigators
Journal: New England Journal of Medicine (1997)

Low-molecular-weight heparin is known to be safe and effective for the initial treatment of patients with proximal deep-vein thrombosis. However, its application to patients with pulmonary embolism or previous episodes of thromboembolism has not been studied.
The Nose after Laryngectomy
Authors: Victoria Moore-Gillon
Journal: Journal of the Royal Society of Medicine (1985)

Previous studies of nasal function after laryngectomy have suggested that patients must accept complete and irreversible anosmia as an inevitable consequence of the operation, and that this is due to interruption of a poorly defined neuronal interaction between larynx and nose. In this study nasal function was investigated in 23 laryngectomees and 10 patients about to undergo laryngectomy. Scanning electron microscopy showed a more densely ciliated nasal epithelium in the laryngectomees compared with the preoperative controls, and nasal mucociliary transport, measured by saccharine clearance, was significantly faster (P less than 0.01) in laryngectomees. Olfactory acuity, as determined by the threshold for detection of insufflated pyridine vapour, was normal in laryngectomees. Some laryngectomees did have a relatively normal sense of smell; these were shown to be those who had discovered a technique of sniffing using buccopharyngeal rather than respiratory musculature. These findings have obvious implications for the rehabilitation of laryngectomees, many of whom may otherwise have to contend with distressing anosmia as well as the other physical and psychological consequences of the operation.
APOL1 Variants Associate with Increased Risk of CKD among African Americans
Authors: Meredith C. Foster, Josef Coresh, Myriam Fornage, Brad C. Astor, Morgan Grams, Nora Franceschini, Eric Boerwinkle, Rulan S. Parekh, W.H. Linda Kao
Journal: Journal of the American Society of Nephrology (2013)

Although case-control studies suggest that African Americans with common coding variants in the APOL1 gene are 5–29 times more likely than those individuals without such variants to have focal segmental glomerulosclerosis, HIV-associated nephropathy, or ESRD, prospective studies have not yet evaluated the impact of these variants on CKD in a community-based sample of African Americans. Here, we studied whether the APOL1 G1 and G2 risk alleles associate with the development of CKD and progression to ESRD by analyzing data from 3067 African Americans in the Atherosclerosis Risk in Communities Study who did not have CKD at baseline. Carrying two risk alleles associated with a 1.49-fold increased risk of CKD (95% CI=1.02 to 2.17) and a 1.88-fold increased risk of ESRD (95% CI=1.20 to 2.93) compared with zero or one risk allele; associations persisted after adjusting for European ancestry. Among participants who developed CKD, those participants with two risk alleles were more likely to progress to ESRD than their counterparts with zero or one risk allele (HR=2.22, 95% CI=1.01 to 4.84). In conclusion, APOL1 risk variants are risk factors for the development of CKD and progression from CKD to ESRD among African Americans in the general population.
Misunderstandings in prescribing decisions in general practice: qualitative study
Authors: N Britten, F A Stevenson, C A Barry, N Barber, C P Bradley
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objectives:</b> To identify and describe misunderstandings between patients and doctors associated with prescribing decisions in general practice. <b>Design:</b> Qualitative study. <b>Setting:</b> 20 general practices in the West Midlands and south east England. <b>Participants:</b> 20 general practitioners and 35 consulting patients. <b>Main outcome measures:</b> Misunderstandings between patients and doctors that have potential or actual adverse consequences for taking medicine. <b>Results:</b> 14 categories of misunderstanding were identified relating to patient information unknown to the doctor, doctor information unknown to the patient, conflicting information, disagreement about attribution of side effects, failure of communication about doctor9s decision, and relationship factors. All the misunderstandings were associated with lack of patients9 participation in the consultation in terms of the voicing of expectations and preferences or the voicing of responses to doctors9 decisions and actions. They were all associated with potential or actual adverse outcomes such as non-adherence to treatment. Many were based on inaccurate guesses and assumptions. In particular doctors seemed unaware of the relevance of patients9 ideas about medicines for successful prescribing. <b>Conclusions:</b> Patients9 participation in the consultation and the adverse consequences of lack of participation are important. The authors are developing an educational intervention that builds on these findings.
The relationship between DNA methylation, genetic and expression inter-individual variation in untransformed human fibroblasts
Authors: James R Wagner, Stephan Busche, Bing Ge, Tony Kwan, Tomi Pastinen, Mathieu Blanchette
Journal: Genome biology (2014)

Abstract Background DNA methylation plays an essential role in the regulation of gene expression. While its presence near the transcription start site of a gene has been associated with reduced expression, the variation in methylation levels across individuals, its environmental or genetic causes, and its association with gene expression remain poorly understood. Results We report the joint analysis of sequence variants, gene expression and DNA methylation in primary fibroblast samples derived from a set of 62 unrelated individuals. Approximately 2% of the most variable CpG sites are mappable in cis to sequence variation, usually within 5 kb. Via eQTL analysis with microarray data combined with mapping of allelic expression regions, we obtained a set of 2,770 regions mappable in cis to sequence variation. In 9.5% of these expressed regions, an associated SNP was also a methylation QTL. Methylation and gene expression are often correlated without direct discernible involvement of sequence variation, but not always in the expected direction of negative for promoter CpGs and positive for gene-body CpGs. Population-level correlation between methylation and expression is strongest in a subset of developmentally significant genes, including all four HOX clusters. The presence and sign of this correlation are best predicted using specific chromatin marks rather than position of the CpG site with respect to the gene. Conclusions Our results indicate a wide variety of relationships between gene expression, DNA methylation and sequence variation in untransformed adult human fibroblasts, with considerable involvement of chromatin features and some discernible involvement of sequence variation.