tbuckley/cabot-search huggingface dataset:
Considerations in the Statistical Analysis of Hemodialysis Patient Survival
Authors: Christos Argyropoulos, Chung-Chou H. Chang, Laura Plantinga, Nancy Fink, Neil Powe, Mark Unruh
Journal: Journal of the American Society of Nephrology (2009)

The association of hemodialysis dosage with patient survival is controversial. Here, we tested the hypothesis that methods for survival analysis may influence conclusions regarding dialysis dosage and mortality. We analyzed all-cause mortality by proportional hazards and accelerated failure time regression models in a cohort of incident hemodialysis patients who were followed for 9 yr. Both models identified age, race, heart failure, physical functioning, and comorbidity scores as important predictors of patient survival. Using proportional hazards, there was no statistically significant association between mortality and Kt/V (hazard ratio 0.72; 95% confidence interval 0.45 to 1.14). In contrast, using accelerated failure time models, each 0.1-U increment of Kt/V improved adjusted median patient survival by 3.50% (95% confidence interval 0.20 to 7.08%). Proportional hazard models also yielded less accurate estimates for median survival. These findings are consistent with an additive damage model for the survival of patients who are on hemodialysis. In this conceptual model, the assumptions of the proportional hazard model are violated, leading to underestimation of the importance of dialysis dosage. These results suggest that future studies of dialysis adequacy should consider this additive damage model when selecting methods for survival analysis. Accelerated failure time models may be useful adjuncts to the Cox model when studying outcomes of dialysis patients.
Cytokine and chemokine expression in cigarette smoke-induced lung injury in guinea pigs
Authors: S. Kubo, M. Kobayashi, Y. Masunaga, H. Ishii, Y. Hirano, K. Takahashi, Y. Shimizu
Journal: European Respiratory Journal (2005)

The guinea pig model of cigarette smoke (CS)-induced lung injury is known to exhibit many pathophysiological similarities to chronic obstructive pulmonary disease (COPD), but the expression profiles of inflammatory mediators in the lung are poorly understood. Quantitative real-time RT-PCR was used in this study to investigate the pulmonary expression profiles of cytokine and chemokine mRNA in response to single or repeated CS exposure in guinea pigs. A single CS exposure did not induce obvious inflammatory cell infiltration into the lungs, but it led to significant increases in the mRNA expression of tumour necrosis factor-α, interleukin (IL)-1β, IL-8, and monocyte chemoattractant protein (MCP)-1, and decreases in IL-5 and granulocyte-macrophage colony-stimulating factor. Repeated CS exposure induced many features of COPD, such as marked accumulation of macrophages and neutrophils, augmented protease activities, lung structural alterations and increased airway resistance, accompanied by significant increases in the mRNA expression of IL-1β and MCP-1 and decreases in IL-2, IL-5, transforming growth factor-β, and eotaxin. In conclusion, in guinea pigs, inflammatory mediator changes in the lungs following cigarette smoke exposure are largely similar to those reported for smokers and/or chronic obstructive pulmonary disease patients. This model will therefore be useful to further understand the pathogenesis of chronic obstructive pulmonary disease.
Ultrasound transmission time: an in vivo guide to nail thickness
Authors: A.Y. FINLAY, H. MOSELEY, T.C. DUGGAN
Journal: British Journal of Dermatology (1987)

Human fingernail thickness was measured distally in 39 subjects using an adapted electronic micrometer and ultrasound transmission time was measured both distally and proximally. Distal ultrasound nail transmission time correlated well with micrometer measurements. There was a clear rank order of distal and proximal nail transmission times: thumb > index > middle > ring > little fingers. Male nails had greater transmission times than female nails on the ring and little fingers. Distal nail transmission time was 8.8%, less than proximal transmission time.
Gender, Cytidine Deaminase, and 5-Aza/Decitabine—Letter
Authors: Joseph Ciccolini, Godefridus J. Peters, Elisa Giovannetti
Journal: Clinical Cancer Research (2013)

We have read with interest the observational study by Mahfouz and colleagues ([1][1]), who examined the role of cytidine deaminase (CDA) on outcomes of patients treated with 5-azacytidine or decitabine. Surprisingly, gender emerged as the main determinant of CDA levels, and consequently, male
Leptin acts as a growth factor for colorectal tumours at stages subsequent to tumour initiation in murine colon carcinogenesis
Authors: H. Endo, K. Hosono, T. Uchiyama, E. Sakai, M. Sugiyama, H. Takahashi, N. Nakajima, K. Wada, K. Takeda, H. Nakagama, A. Nakajima
Journal: Gut (2011)

<h3>Background and aims</h3> Obesity increases the risk of colorectal cancer (CRC). Serum leptin levels are markedly elevated in obese individuals, but the involvement of leptin in CRC growth remains unclear. We explored the hypothesis that leptin signalling regulates the growth of CRC, by examining the effects of leptin deficiency on murine colon tumour growth. <h3>Methods</h3> We used genetic (leptin-deficient and leptin receptor-deficient) models of obesity and investigated carcinogen-induced colon polyp formation and cell proliferation in the colonic epithelium. Colonic tissues and cell lines were analysed by histopathology and molecular-biology methods. <h3>Results</h3> A significant increase in the proliferative activity of normal colonic epithelial cells was observed in the obesity model; on the other hand, significant decrease of tumour cell proliferation was observed in leptin-deficient tumours, and tumour growth was dramatically inhibited in leptin-deficient and leptin-receptor-deficient mice despite the animals exhibiting severe obesity. Notably, a marked increase of the leptin receptor (ObR) expression levels was observed in colon tumours as compared to the normal epithelium. Nuclear β-catenin staining was pronounced in all tumours, irrespective of leptin deficiency, whereas altered cellular localisation of β-catenin was not observed in the normal colonic epithelial cells. In vitro, β-catenin knockdown decreased ObR expression, and stimulation of recombinant Wnt increased ObR expression. In addition, the proliferative and survival effects of leptin were found to be mediated by the ObR/signal transducer and activator of transcription 3 (STAT3) signalling in colon tumours. <h3>Conclusions</h3> Our findings indicate that leptin is important for CRC growth in obesity, and acts as a growth factor for CRC at stages subsequent to tumour initiation in colorectal carcinogenesis. Thus, inhibition of leptin signalling may be an effective strategy for therapy and prevention of colonic adenoma and cancer, which show activation of Wnt signalling.
Bronchial asthma causing symptoms suggestive of angina pectoris
Authors: D. Kiss, W. Veegh, D. Schragel, C. Bachl, C. Stöllberger, K. Sertl
Journal: European Respiratory Journal (2003)

Many patients undergoing pharmacological stress echocardiography for assessing symptoms suggestive of coronary artery disease are found to have a normal test. This study was performed to evaluate whether asthma symptoms simulate angina pectoris. A total 41 consecutive patients who had a negative pharmacological stress echocardiography and had been evaluated for angina pectoris were studied. Patients with previously known coronary artery disease or obstructive lung disease were excluded. Lung function testing was performed and the authors proceeded either with the administration of a bronchodilator or with methacholine challenge testing. A questionnaire was applied to assess the symptoms dyspnoea, chest tightness and substernal burning at the end of the challenge test. In addition, patients were asked if they were experiencing those symptoms that made them seek medical attention. From the 41 patients tested, 26 patients showed a significant bronchial hyperreactivity (mean±sd provocative concentration causing a 20% fall in the forced expiratory volume in one second 5.93±4.50 mg·mL −1 ). A total of 20 patients confirmed having those symptoms that led to cardiac evaluation. It was concluded that symptoms suggestive of angina pectoris might represent bronchial asthma. This should be considered in the differential diagnosis of angina pectoris.
Enhancing T cell persistence of CAR-redirected T cells in solid tumors
Authors: Sonia Guedan, Shannon E McGettigan, Avery D Posey, Jihyun Lee, Omkar Kawalekar, Prachi R Patel, Brian Keith, Carl June
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts T cell persistence is likely to promote long-term anti-tumor effects after adoptive T cell transfer. We have recently shown that incorporation of the ICOS intracellular domain into chimeric antigen receptors (CARs) significantly increased Th17 cell persistence in vivo , compared
Phagocyte-specific S100 proteins and high-sensitivity C reactive protein as biomarkers for a risk-adapted treatment to maintain remission in juvenile idiopathic arthritis: a comparative study
Authors: Joachim Gerss, Johannes Roth, Dirk Holzinger, Nicolino Ruperto, Helmut Wittkowski, Michael Frosch, Nico Wulffraat, Lucy Wedderburn, Valda Stanevicha, Dimitrina Mihaylova, Miroslav Harjacek, Claudio Len, Claudia Toppino, Massimo Masi, Kirsten Minden, Traudel Saurenmann, Yosef Uziel, Richard Vesely, Maria Teresa Apaz, Rolf-Michael Kuester, Maria Jesus Rua Elorduy, Ruben Burgos-Vargas, Maka Ioseliani, Silvia Magni-Manzoni, Erbil Unsal, Jordi Anton, Zsolt Balogh, Stefan Hagelberg, Henryka Mazur-Zielinska, Tsivia Tauber, Alberto Martini, Dirk Foell
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> Juvenile idiopathic arthritis (JIA) is a chronic inflammatory joint disease affecting children. Even if remission is successfully induced, about half of the patients experience a relapse after stopping anti-inflammatory therapy. The present study investigated whether patients with JIA at risk of relapse can be identified by biomarkers even if clinical signs of disease activity are absent. <h3>Methods</h3> Patients fulfilling the criteria of inactive disease on medication were included at the time when all medication was withdrawn. The phagocyte activation markers S100A12 and myeloid-related proteins 8/14 (MRP8/14) were compared as well as the acute phase reactant high-sensitivity C reactive protein (hsCRP) as predictive biomarkers for the risk of a flare within a time frame of 6 months. <h3>Results</h3> 35 of 188 enrolled patients experienced a flare within 6 months. Clinical or standard laboratory parameters could not differentiate between patients at risk of relapse and those not at risk. S100A12 and MRP8/14 levels were significantly higher in patients who subsequently developed flares than in patients with stable remission. The best single biomarker for the prediction of flare was S100A12 (HR 2.81). The predictive performance may be improved if a combination with hsCRP is used. <h3>Conclusions</h3> Subclinical disease activity may result in unstable remission (ie, a status of clinical but not immunological remission). Biomarkers such as S100A12 and MRP8/14 inform about the activation status of innate immunity at the molecular level and thereby identify patients with unstable remission and an increased risk of relapse.
Screening in women’s health, with emphasis on fetal Down’s syndrome, breast cancer and osteoporosis
Authors: Hajo I.J. Wildschut, T.J. Peters, Carl P. Weiner
Journal: Human Reproduction Update (2006)

Screening tests have become increasingly popular in women’s health care over the last two decades. The initiative for screening is typically generated by either an agency or the health care professional being consulted for some reason. In many instances, however, the demand for screening tests is patient driven with the health care provider being poorly prepared to determine the usefulness of screening. This review illustrates the complexity of screening using three disorders where early detection and treatment have the potential to improve the quality and longevity of life. Prenatal diagnosis of Down’s syndrome does not offer the parents the opportunity for cure but does offer the opportunity for education and rational choice as the impact of the diagnosis on the family is weighed. The evidence for breast cancer screening is more persuasive for older than younger women, but even in older women, there is a balance of risks and benefits. Treatment options for osteoporosis have improved in terms of reductions in fracture risk as well as beneficial effects on bone density, but evidence of the effectiveness of a screening programme for this condition in an unselected population is lacking. Ultimately, it is crucial that women be provided with clear and comprehensive information about the screening programme, in terms of possible gains but also costs of various kinds: physical, economic and psychological.
Can India pull off its ambitious National Health Mission?
Authors: Jeetha D'Silva
Journal: BMJ (2013)

<h3>Abstract</h3> <h3>Objectives</h3> To identify serum protein biomarkers which might separate early inflammatory arthritis (EIA) patients with psoriatic arthritis (PsA) from those with rheumatoid arthritis (RA) to provide an accurate diagnosis and support appropriate early intervention. <h3>Methods</h3> In an initial protein discovery phase, the serum proteome of a cohort of patients with PsA and RA was interrogated using unbiased liquid chromatography mass spectrometry (LC-MS/MS) (n=64 patients), a multiplexed antibody assay (Luminex) for 48 proteins (n=64 patients) and an aptamer-based assay (SOMAscan) targeting 1,129 proteins (n=36 patients). Subsequently, analytically validated targeted multiple reaction monitoring (MRM) assays were developed to further evaluate those proteins identified as discriminatory during the discovery. During an initial verification phase, MRM assays were developed to a panel of 150 proteins (by measuring a total of 233 peptides) and used to re-evaluate the discovery cohort (n=60). During a second verification phase, the panel of proteins was expanded to include an additional 23 proteins identified in other proteomic discovery analyses of arthritis patients. The expanded panel was evaluated using a second, independent cohort of PsA and RA patients (n=167). <h3>Results</h3> Multivariate analysis of the protein discovery data revealed that it was possible to discriminate PsA from RA patients with an area under the curve (AUC) of 0.94 for nLC-MS/MS, 0.69 for Luminex based measurements; 0.73 for SOMAscan analysis. During the initial verification phase, random forest models confirmed that proteins measured by MRM could differentiate PsA and RA patients with an AUC of 0.79 and during the second phase of verification the expanded panel could segregate the two disease groups with an AUC of 0.85. <h3>Conclusion</h3> We report a serum protein biomarker panel which can separate EIA patients with PsA from those with RA. We suggest that the routine use of such a panel in EIA patients will improve clinical decision making and with continued evaluation and refinement using additional patient cohorts will support the development of a diagnostic test for patients with PsA.
Spliced-Leader trans-Splicing in Freshwater Planarians
Authors: Ricardo M. Zayas, Tyler D. Bold, Phillip A. Newmark
Journal: Molecular Biology and Evolution (2005)

trans-Splicing, in which a spliced-leader (SL) RNA is appended to the most 5′ exon of independently transcribed pre-mRNAs, has been described in a wide range of eukaryotes, from protozoans to chordates. Here we describe trans-splicing in the freshwater planarian Schmidtea mediterranea, a free-living member of the phylum Platyhelminthes. Analysis of an expressed sequence tag (EST) collection from this organism showed that over 300 transcripts shared one of two ∼35-base sequences (Smed SL-1 and SL-2) at their 5′ ends. Examination of genomic sequences encoding representatives of these transcripts revealed that these shared sequences were transcribed elsewhere in the genome. RNA blot analysis, 5′ and 3′ rapid amplification of cDNA ends, as well as genomic sequence data showed that 42-nt SL sequences were derived from small RNAs of ∼110 nt. Similar sequences were also found at the 5′ ends of ESTs from the planarian Dugesia japonica. trans-Splicing has already been described in numerous representatives of the phylum Platyhelminthes (trematodes, cestodes, and polyclads); its presence in two representatives of the triclads supports the hypothesis that this mode of RNA processing is ancestral within this group. The upcoming complete genome sequence of S. mediterranea, combined with this animal's experimental accessibility and susceptibility to RNAi, provide another model organism in which to study the function of the still-enigmatic trans-splicing.
Selective Stimulation of Renal Nerves in the Anesthetized Dog
Authors: RONALD G. LA GRANGE, CHARLES H. SLOOP, HERMAN E. SCHMID
Journal: Circulation Research (1973)

The combined effects of low-frequency stimulation of the renal sympathetic nerves and reductions in renal arterial blood pressure on various hemodynamic parameters of the in situ kidney and on renal venous renin levels were determined in 17 dogs. Autoregulation of flow (measured using noncannulating electromagnetic probes) and glomerular filtration (measured using continuous extraction of 131 I-iothalamate) was followed before, during, and after nerve stimulation. Stimulation of isolated renal nerves (0.5 msec, 10-15 v, 0.1-3.0/sec) produced distinct changes in the release of renin with only minimal changes in the autoregulatory curves for glomerular filtration rate and renal plasma flow. Reducing arterial blood pressure from 150 to 50 mm Hg caused an increase in the release of renin from 4 to 35 ng/ml hour -1 . Stimulation of the renal nerves increased renin production at both pressures (from 4 to 10 ng/ml hour -1 at 150 mm Hg and from 35 to 50 ng/ml hour -1 at 50 mm Hg). In fact, renal nerve stimulation elicited increases in renin release at all pressures examined. In contrast, sodium excretion following nerve stimulation was depressed at comparable sodium loads in spite of minimal changes in renal hemodynamics. It appears that the effect of the renal sympathetic nerves on renin release is evident at all pressures; however, the sympathetic nerves are proportionately more important at pressures above 100 mm Hg and the renal artery pressure plays a greater role at pressures below 115-100 mm Hg.
It’s a Sign of Spring
Authors: Molly O’Dell
Journal: JAMA (2010)

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Noninvasive Diagnosis of Coronary Artery Disease in Patients With Diabetes by Dobutamine Stress Real-Time Myocardial Contrast Perfusion Imaging
Authors: Abdou Elhendy, Jeane M. Tsutsui, Edward L. O’Leary, Feng Xie, Anna C. McGrain, Thomas R. Porter
Journal: Diabetes Care (2005)

OBJECTIVE—The aim of this study was to assess the accuracy of real-time myocardial contrast perfusion imaging (MCPI) during dobutamine stress in the diagnosis and localization of coronary artery disease (CAD) in patients with diabetes. Myocardial contrast echocardiography is a new technique that allows evaluation of myocardial perfusion. Its utility in diabetic patients has not been defined. RESEARCH DESIGN AND METHODS—Dobutamine-atropine stress test was performed in conjunction with MCPI using Optison or Definity at rest and at peak stress in 128 patients with diabetes and suspected CAD who underwent coronary angiography within 1 month. CAD was defined as ≥50% stenosis in one or more coronary artery. MCPI was considered diagnostic of CAD in the presence of reversible perfusion abnormalities. The normalcy rate of MCPI was additionally determined in 18 asymptomatic nondiabetic patients with low probability. RESULTS—CAD was detected in 101 (79%) patients by angiography. Reversible perfusion abnormalities were detected in 90 patients with and 13 patients without CAD. The overall sensitivity of MCPI was 89% (95% CI 83–95), specificity 52% (33–71), and accuracy 81% (75–88). Reversible abnormalities were detected in two or more vascular distributions in 44 of 56 patients with multivessel CAD and in 8 of 63 patients without (sensitivity 68%, specificity 87%, positive predictive value 84%, and accuracy 79%). Regional sensitivity was 75% (65–85) for left anterior descending CAD, 71% (60–83) for left circumflex, and 67% (55–78) for right CAD. MCPI was normal in 16 of the 18 patients with low clinical probability of CAD (normalcy rate 89%). CONCLUSIONS—MCPI is a useful noninvasive technique for the diagnosis and localization of CAD in diabetic patients. The extent of perfusion abnormalities can identify patients with multivessel CAD with a moderate sensitivity and high specificity.