bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improvement of Sample Size Calculations for Binary Diagnostic Test Assessment
Authors: Bailly Sébastien , Dupont Cyrielle , Iwaz Jean , Bossard Nadine , Rabilloud Muriel 
Published: May 2016

Objective This study aimed to formulate a new R function to improve sample size calculation for more accurate estimations of sensitivity (Se) and specificity (Sp). Methods The developed function is based on the binDesign function of the binGroup R package. This allowed the use of an “exact” method based on the binomial distribution. In addition, the function takes into account a joint testing of Se and Sp and a nonmonotonous behavior of the power function. Results Four tables were generated to display the number of cases (or controls) in joint or separate assessments for an expected combination of Se (or Sp) and a determined difference between the expected Se (or Sp) and the minimum acceptable Se (or Sp). Using the formula for a joint testing of Se and Sp, it resulted in a higher increase of the sample sizes than simply allowing for the sawtooth shape of the power curve. Conclusion Whenever equal Se and Sp values are important, a joint testing should be favored and used for sample size determination.
The Measurement of 3-Epimer 25-Hydroxyvitamin D by Mass Spectrometry in Clinical Specimens Detects Inconsequential Levels in Adult Subjects
Authors: Goldman Mildred M. , Viec Khanh V. , Caulfield Michael P. , Reitz Richard E. , McPhaul Michael J. , Clarke Nigel J. 
Published: May 2016

Background Vitamin D is derived from dietary sources or from the action of ultraviolet light on 7-dehydrocholesterol and undergoes a number of enzymatic modifications that lead to the synthesis of active vitamin D metabolites or metabolites with reduced biological activity. Among these, epimerization at the 3-hydroxyl group leads to the synthesis of 3-epimer 25-hydroxyvitamin D (3EVD). Described first in biological system experiments using in vitro incubation of vitamin D in cell culture, this molecule has been reported as having distinct activities when compared with 25-hydroxy vitamin D (25OHVD). Measurements of vitamin D have been conducted using a variety of methodologies and have led to conflicting assessments of the quantities of 3EVD3 that are measured. Method The present article describes the development and use of a simple liquid chromatography–tandem mass spectrometry method validated by the Clinical Laboratory Improvement Amendments to quantitate 3EVD3 in 3528 subjects, including 309 children (162 are <2 years) and 232 pregnant women. Results Our findings demonstrate that, although 3EVD3 constitutes a significant proportion of measureable 25OHVD3 in subjects younger than 1 year, 3EVD3 levels are negligible in most subjects older than 1 year. Conclusions It is important to choose the correct 25OHVD assay dependent on the age of the patient. Patients younger than 1 year should be run on a liquid chromatography–tandem mass spectrometry assay proven to not have potential contributions from any 3EVD present in the sample.
Use of Informatics and Information Technologies in the Clinical Research Enterprise within US Academic Medical Centers
Authors: DiLaura Robert , Turisco Fran , McGrew Cherri , Reel Stephanie , Glaser John , Crowley William F. 
Published: May 2016

Background Data on the state of information systems infrastructures used in the clinical research enterprise of academic medical centers are limited and mostly anecdotal. What has been published is slowly beginning to make important distinctions, such as clinical trials as a specialized form of clinical research and between “Informatics” in an academic setting from health care information technology. However, this field continues to undergo fundamental changes, accelerated by the National Institutes of Health's creation of Clinical and Translational Science Awards to build a new “home” for biomedical research. Methods We surveyed all Clinical Research Forum member institutions regarding their enterprise infrastructure and use of information systems in support of clinical research. The questions in this on-line study expanded on one first done in 2005. Of the 52 sites invited, 19 (37%) responded. We analyzed the responses and also made matched comparisons for those organizations that participated in both surveys. Results Although there continues to be conceptual agreement on information system elements for the clinical research enterprise, no single institution achieved the ideal, a similar result to the 2005 survey. Indeed, little progress was made over the past 2 years at most locations other than in information technology planning, strategy, and governance. Conclusions There is increased recognition of the importance of information systems infrastructure and expertise for biomedical research, but the needs are accelerating much faster than institutions can build or pay for. A much greater realization of and innovative solution for this growing chasm is urgently required.
Detection of α1 Integrin in Urine of Patients with Immunoglobulin a Nephropathy
Authors: Bank Jonathan , Ben-David Aharon , Doolman Ram , Sela Ben-Ami , Bank Ilan 
Published: May 2016

Background The α1β1 integrin is a cell surface membrane heterodimer composed of noncovalently linked α1 and β1 polypeptides that is up-regulated on activated and proliferating mesangial cells. Methods A double-sandwich enzyme-linked immunosorbent assay that detects α1 integrin in a specific and dose-dependent manner at concentrations greater than 150 ng/mL was used to evaluate whether intact α1 polypeptides are secreted in the urine samples of 29 patients with various kidney diseases and in those of 5 healthy individuals. Results α1 Integrin was detected in 8 of the 29 patients including 3 of 3 patients with biopsy-proven immunoglobulin A nephropathy and 3 of 3 clinically suspected but non-biopsy-proven immunoglobulin A nephropathy with evidence of active nephritis. No α1 integrins were found in samples of 5 healthy controls. Conclusions α1 Integrin polypeptides can be detected in human urine, particularly in immunoglobulin A nephropathy. Further extensive studies are required to clarify the significance of secretion of α1 integrins in urine of patients with kidney disease.
Ethnic Difference in Sex Gap in High-Density Lipoprotein Cholesterol between Asian Indians and Whites
Authors: Chandalia Manisha , Mohan Viswanathan , Adams-Huet Beverley , Deepa Raj , Abate Nicola 
Published: May 2016

Objective To study whether low plasma high-density lipoprotein cholesterol (HDL-C) reported in Asian Indians is common in both men and women when compared with whites and whether it is related to increased body mass index (BMI) and plasma triglyceride concentration. Design We evaluated the lipid profile and prevalence of low HDL-C (<40 mg/dL in men and <50 mg/dL in women) in the following cohorts of normoglycemic 1404 men and 1817 women: Asian Indians living in rural India; urban Chennai, India; and Dallas, TX; and whites living in Dallas, TX. Results After adjustment for age, BMI, and smoking, HDL-C was not significantly different in Asian Indian men compared with whites. However, Asian Indian women had lower HDL-C compared with white women, and rural Asian Indian women had the lowest HDL-C even in the absence of high triglycerides. Lean Asian Indian women with BMI of less than 23 kg/m2 had higher frequency of low HDL-C compared with lean white women with BMI of less than 25 kg/m2 (72%, 56%, 48%, and 25% in rural, urban, and Dallas Asian Indian and white women, respectively) and lean men (52%, 42%, 28%, and 35% in rural, urban, and Dallas Asian Indian and white men, respectively). Sex differences in HDL-C was estimated as 6.6 ± 0.5 mg/dL for Asian Indians and 15.3 ± 1.1 mg/dL for whites ( P < 0.0001 for sex difference in the 2 ethnic groups). Conclusions Increased prevalence of low HDL-C independently of obesity or hypertriglyceridemia is observed in women but not in men of Asian Indian origin. The sex gap in HDL-C is significantly smaller in Asian Indians compared with whites independent of geographical location.
Patient Experiences with MedlinePlus.gov
Authors: Smalligan Roger D. , Campbell Emily O. , Ismail Hassan M. 
Published: May 2016

Background In 2004, the American College of Physicians joined with the National Library of Medicine in an effort to help patients find reliable health information free of commercial bias at the Web site MedlinePlus.gov. The aim of this study was to evaluate the usefulness of the MedlinePlus.gov site as perceived by patients who were referred to the site by their internist. Materials and Methods A 27-item questionnaire developed by the American College of Physicians Foundation was distributed between January and May 2005 to a convenience sample of 893 adult patient volunteers attending 34 internal medicine practices across the United States. Results The questionnaire revealed that although most patients (55%) routinely look up medical information, only 43% had used MedlinePlus.gov. Of those who had used the site, 95% were satisfied with the information they found there, and 94% said the information they found at MedlinePlus.gov would help them make better health decisions. Discussion Patients who used the MedlinePlus.gov site at the recommendation of their physician found it easy to use, informative, and felt it would help them make better health decisions. Directing patients to this high quality, noncommercial, educational resource online may be an important adjunct to patient education efforts by physicians.
Cardiac Natriuretic Peptides Gene Expression and Secretion in Inflammation
Authors: Vesely David L. , de Bold Adolfo J. 
Published: May 2016

The genetic expression and secretion of the cardiac polypeptide hormones atrial natriuretic factor (ANF or ANP) and brain natriuretic peptide (BNP) have been studied mainly in the context of cardiac diseases associated with neuroendocrine and hemodynamic changes arising from cardiac dysfunction such as in chronic congestive heart failure. In this type of pathology, both ANF and BNP plasma levels change in an approximate coordinated fashion so that the use of these hormones as biomarkers of cardiac disease is, in principle, indistinctive. However, we reported that during an acute cardiac allograft rejection episode, BNP plasma levels can significantly increase in the absence of a similar increase in ANF plasma levels. We tested the hypothesis that these changes were related to cytokines and found that some pro-inflammatory cytokines, including TNFα and IL-1β, selectively promote BNP synthesis and secretion in cultures of neonatal rat ventricular cardiocytes. This effect was found related to increased BNP promoter activity and sensitive to p38 mitogen-activated protein kinase inhibition. In order to determine in vivo if the selective up-regulation of BNP would be observed in inflammatory processes other than acute cardiac allograft rejection, we carried out investigation using the experimental autoimmune myocarditis rat model, which histologically resembles human giant cell myocarditis. It was found that this model is also accompanied by a specific increase in BNP-circulating levels although the cytokines involved seem to differ from those characterized earlier through in vitro studies. Recent studies in humans have found that in sepsis, plasma BNP levels increase in the absence of hemodynamic changes. In conclusion, BNP appears to be regulated uniquely in the setting of an inflammatory process. This sets it apart from ANF in terms of potential roles in the pathogenesis of disease and in its use as a biomarker of cardiac disease.
Impaired Hepatic Ketogenesis in Moderately Obese Men with Hypertriglyceridemia
Authors: Vega Gloria Lena , Dunn Fredrick L. , Grundy Scott M. 
Published: May 2016

Background Several studies suggest that increased nonesterified fatty acid flux and increased de novo lipogenesis may contribute to hypertriglyceridemia, but few studies have examined fatty acid oxidation as a factor. Rationale Endogenous hypertriglyceridemia (increased very low density lipoprotein triglyceride) could result from ( a) re-esterification of excess nonesterified fatty acids entering the liver, ( b) activation of hepatic lipogenesis, and/or ( c) defective oxidation of hepatic fatty acids leading to greater triglyceride synthesis. Therefore, this study used plasma levels of 3-hydroxybutyrate as a marker for fatty acid oxidation. The study was carried out in hypertriglyceridemic and normotriglyceridemic subjects under 3 conditions: ( a) in the fasting state, ( b) after a fatty meal that should enhance fatty acid oxidation, and (c) after an oxandrolone challenge, which we recently showed increases fatty acid oxidation. Results In the fasting state, 3-hydroxybutyrate concentrations in hypertriglyceridemic patients were only 53% of levels in normotriglyceridemic subjects. After a fatty meal, moderate increases in 3-hydroxybutyrate were observed, but values for patients with hypertriglceridemia remained 62% of the levels in the normotriglyceridemic group. A similar pattern of response was observed with oxandrolone challenge. There were no significant changes in fasting or postprandial levels of nonesterfified fatty acids, glycerol, or triglycerides before and during the oxandrolone challenge. Conclusion Patients with endogenous hypertriglyceridemia seem to have a defect in fatty acid oxidation as indicated by reduced levels of 3-hydroxybutyrate. This defect was observed during fasting, postprandially, and during oxandrolone challenge. We propose that this defect contributes to the development of hypertriglyceridemia.
International Outsourcing of Medical Research by High-Income Countries: Changes from 1995 to 2005
Authors: Belforti Raquel K. , Wall Michal Sarah , Lindenauer Peter K. , Pekow Penelope S. , Rothberg Michael B. 
Published: May 2016

Background Medical research outsourcing provides a financial benefit to those conducting research and financial incentives to the developing countries hosting the research. Little is known about how frequently outsourcing occurs or the type of research that is outsourced. Methods To document changes in medical research outsourcing over a 10-year period, we conducted a cross-sectional comparison of 3 medical journals: Lancet, The New England Journal of Medicine, and JAMA: The Journal of the American Medical Association in the last 6 months of 1995 and 2005. The main outcome measure was the 10-year change in proportion of studies including patients from low-income countries. Findings We reviewed 598 articles. During the 10-year period, the proportion of first authors from low-income countries increased from 3% to 6% ( P = 0.21), whereas studies with participants from low-income countries increased from 8% to 22% ( P = < 0.001). In 2005, compared with studies conducted exclusively in high-income countries, those including participants from low-income countries were more likely to be randomized trials (55% vs 35%, P = 0.004), to study medications (65% vs 34%, P < 0.001), to be funded by pharmaceutical companies (33% vs 21%, P = 0.05), and to involve pediatric populations (29% vs 8%, P < 0.001). Interpretation Outsourcing of medical research seems to be increasing. Additional studies are required to know if subjects from low-income countries are being adequately protected.
Clinicopathological Characteristics and Prognostic Factors of Asymptomatic IgA Nephropathy
Authors: Shen Pei-Cheng , He Li-Qun , Tang Ying , Wang Qing , Wang Wei , Li Jie 
Published: May 2016

Aims Many patients with immunoglobulin class A (IgA) nephropathy (IgAN) present with asymptomatic urinary abnormalities. The purpose of this study was to observe the clinicopathological characteristics and prognostic factors in asymptomatic IgAN. Methods Eighty-six asymptomatic IgAN patients (49 males and 37 females) were investigated; 82 of them were followed up during a mean ± SD period of 66.7 ± 19.7 months. Results At biopsy, 18 patients (21%) presented with pure hematuria (HU), 29 patients (34%) presented with proteinuria alone (PU), and 39 patients (45%) presented concomitant hematuria and proteinuria with severe pathological lesions. Meanwhile, 16% and 26% had renal insufficiency and hypertension, respectively. Finally, urinary abnormalities of 15% of the patients disappeared, 25% of HU developed proteinuria, 47% of concomitant hematuria and proteinuria, and 32% of PU appeared to have increase of proteinuria, and 14% of PU developed hematuria. Fifteen (24%) of the patients with normal blood pressure initially became hypertensive and 18 (22%) of the patients with normal renal function initially developed renal insufficiency. Twenty-four patients (29%) had doubling of serum creatinine level, and 13 patients (16%) progressed to end-stage renal disease. Prednisone therapy and antihypertensive treatment significantly improved proteinuria and renal function deterioration. Hematuria, hypertension during follow-up, and tubulointerstitial lesions were independent risk factors predictive of the ultimate development of renal progression. Conclusions The renal outcome of asymptomatic IgAN is guarded. Hematuria, hypertension during follow-up, and tubulointerstitial lesions may be important markers to monitor renal progression in the course.
Changes in Gleason Scores for Prostate Cancer: What Should we Expect from a Measurement?
Authors: Ramos Jorge , Uchio Edward , Aslan Mihaela , Concato John 
Published: May 2016

Background Men diagnosed with prostate cancer receive therapy based on various clinical characteristics, including the Gleason score, a measurement (range, 2-10) describing a tumor's histological appearance. An upward shift has occurred in the distribution of Gleason scores during the past decade; this change was influenced by reports suggesting that lower scores (range, 2-4) should not be assigned to biopsy specimens. Methods We (1) compared Gleason scores from 1994-1995 and 2004-2005 at the same institution, (2) reviewed representative articles examining changes in Gleason scores during the last 2 decades, and (3) assessed the implications of a change in histological measurements. Results Among men diagnosed with prostate cancer at VA Connecticut, Gleason scores 2 to 4 were reported for 11.4% (19/167) of specimens in 1994-1995 but only 0.4% (1/260) of specimens in 2004-2005; this difference persisted after adjusting for age, clinical stage, and prostate-specific antigen ( P < 0.001). Similar results were evident in previous publications on this topic. A change in criteria for a clinical measurement may have unintended consequences, including problems of inconsistency across “time” and “place.” Conclusions Recent shifts in Gleason scores have led to fewer patients being diagnosed with low-grade prostate cancer; this change can have adverse impacts in clinical care and research.
The 5-Year Incidence of Type 2 Diabetes Mellitus in Women Older than 15 Years in Ankara, Turkey: A Population-Based Study
Authors: Maral Işıl , Tütüncü Neslihan Başçıl , Bakar Coşkun , Durukan Elif , Budakoğlu I.&Idot;rem , Özkan Seçil , Aycan Sefer , Aygün Remzi , Bumin Mehmet Ali 
Published: May 2016

Background Type 2 diabetes mellitus (DM) is a significant cause of morbidity and premature mortality especially in adults. In Turkey, there are few studies on DM incidence. This study aimed to determine the incidence of type 2 DM in women 15 years or older in Turkey. Methods This prospective cohort study was performed from December 2002 to May 2003. Preliminary population-based screening was performed in 1997 and 1998 on women 15 years or older living in 4 villages in the Gölbaşı, Ankara province. Five hundred sixty-three women who were considered nondiabetic in the first study comprised the population for the present study. Data collection was accomplished by using a questionnaire and randomly measuring the blood glucose levels of the women. The χ2 and Fisher exact tests were used to analyze the risk factors for DM. Results The 5-year incidences of type 2 DM, impaired glucose tolerance, and impaired fasting glucose were 2.3%, 0.4%, and 0.7%, respectively. The 5-year incidence of type 2 DM increased with age ( P < 0.05). The DM incidence was 6.2% in those with mixed-type hypertension and 4.0% in those with a body mass index of 30 kg/m2 or higher. At 5-year follow-up, age (≥35 years), hypertension, and body mass index (≥30 kg/m2) were the risk factors for incidence of abnormal glucose metabolism ( P < 0.05). Conclusions The incidence of abnormal glucose metabolism in this study is in accord with that in the literature. Our results will contribute to our understanding of the incidence of DM in women in Turkey.
Assessment of Serum Chromogranin-A as Prognostic Factor in High-Risk Prostate Cancer
Authors: Reis Leonardo O. , Vieira Larissa F.M. , Zani Emerson L. , Denardi Fernandes , de Oliveira Laurione C. , Ferreira Ubirajara 
Published: May 2016

Purpose The presence of neuroendocrine differentiation may play a key role in androgen-independent tumor progression. The prognostic significance of plasma chromogranin-A (CgA) was assessed in a series of consecutive patients with high-risk prostate cancer (PCa). Patients and Methods Twenty-three patients presenting high-risk PCa and 8 healthy individuals, as control group, had their blood samples collected to evaluate CgA, free and total prostate specific antigen, and free and total testosterone in a pilot study. The correlations of serum CgA levels with PSA, testosterone, Gleason score, number of foci of hypercaptation in bone scan, age, and outcomes were evaluated at baseline and after 12 months. Results Patients with PCa had significantly higher levels of plasma CgA (mean, 8.7; range, 1.9-73) than healthy patients (mean, 3.45; range, 0.6-5.6), P = 0.02. Analyzing only the patients group through correlation of the ranks, it was observed that CgA has low, insignificant correlations with PSA ( P = 0.07) and with metastatic extension ( P = 0.09). No association was found between the plasma CgA levels and the Gleason score ( P = 0.20), age ( P = 0.15), or disease progression ( P = 0.27). Conclusion The serum levels of CgA were significantly increased in the group with PCa compared with the healthy group. However, there were low correlations between serum CgA and known prognostic factors (such as total and free PSA, age, Gleason score, and bone metastases) or clinical deterioration. Although future studies are needed with larger samples and longer follow-up, the presented data envisage a limited role to serum CgA as high-risk PCa prognostic factor.