bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enzymic assay for oxalate in unprocessed urine, as adapted for a centrifugal analyzer.
Authors: Urdal P 
Published: January 2020

Abstract
In this automated modification of the oxalate decarboxylase method, oxalate can be measured (12 per hour) in acidified but otherwise unprocessed urine. Standard curves are linear up to at least 2.5 mmol/L. When 0.50 mmol of oxalate was added per liter to samples of 18 patients' urines, a mean analytical recovery of 98.5% (SD 3.6%) was obtained. Within-series CVs were 3.4 and 1.0%, between-series CVs 7.3 and 2.7% (n = 15) for oxalate concentrations of 0.31 and 0.61 mmol/L. The lower limit of detection is 25 mumol/L. Concentrations measured with this "direct" method correlated well (r = 0.95) with those measured after precipitation with calcium and ethanol and resolubilization in dilute sulfuric acid. For 17 healthy volunteers the mean urinary excretion of oxalate was 0.37 (SD 0.14) mmol/24 h.
Assessment of analytical bias: four new ways to use recovery measurements.
Authors: Kemp G J 
Published: January 2020

Abstract
I describe three ways of using data from analytical-recovery studies to assess analytical nonlinearity, without access to samples of known concentration. I then describe a recovery-based method of assessing constant, proportional, and non-linear errors with use of as little as one sample pool of known concentration. In each case, I present the theoretical basis of the method and an outline of a practical experimental protocol.
Selenium concentrations in plasma of patients with arteriographically defined coronary atherosclerosis.
Authors: Moore J A , Noiva R , Wells I C 
Published: January 2020

Abstract
A prospective epidemiological study (Lancet ii: 175-179, 1982) implicates low concentrations of selenium in plasma in coronary atherogenesis. We examined this relationship more directly by fluorometry of selenium in the plasma of 91 hospitalized patients who were being examined by coronary arteriography for clinical evaluation of chest pain. We observed a significant, inverse correlation between the plasma selenium and severity of coronary atherosclerosis. These results confirm those of the epidemiological studies, but the role, if any, of selenium in atherogenesis still is unclear. Its concentration in plasma is decreased by ethanol and cigarette use; possibly this is the mechanism of its relation to hypertension and atherosclerosis.
Interlaboratory comparison of 25-hydroxyvitamin D determination.
Authors: Mayer E , Schmidt-Gayk H 
Published: January 2020

Abstract
This interlaboratory study on determination of 25-hydroxyvitamin D (25-OH-D) in serum involved 15 laboratories in eight European countries. All could distinguish between normal (50 +/- 31 nmol/L, mean +/- SD) and grossly increased concentrations, but for eight laboratories the results for serum samples with low and normal 25-OH-D content overlapped. In general, values were well reproducible, but interlaboratory variation in 25-OH-D measurement was large, 24,25(OH)2D3 interfering in most of the assays. We present evidence in favor of chromatography before assay, as opposed to nonchromatographic methods. Liquid chromatography with ultraviolet detection for quantifying 25-OH-D2 and 25-OH-D3 appears to be an appropriate reference method, whereas competitive protein binding assay is the method of choice for routine determinations. Control sera with subnormal, normal, and above-normal concentrations of 25-OH-D3 are needed for use in standardization of 25-OH-D assays.
A new endogenous immunoenzyme assay for prostatic acid phosphatase evaluated.
Authors: Babson A L 
Published: January 2020

Abstract
I evaluated the performance of the "ORTHO PAP-IA," an endogenous immunoenzyme assay for prostatic acid phosphatase. The procedure is based on double-antibody precipitation of the antigen, followed by quantification of its enzymic activity. The antibodies are in large excess, to speed the reactions and minimize sensitivity to variations in assay conditions. Enzymic activity is measured via an extremely sensitive colorimetric reaction, the analytical sensitivity of which exceeds that of radioimmunoassay. Absorbance is linearly related to activity concentration up to an absorbance of 4.0, and only a single calibration standard is required. Within-run CV was less than 2%, between-run CV about 4%. Neither individual blanks nor assay in duplicate is required. All reagents, including the enzyme standard, are stable solutions. Results correlated well with those by a standard radioimmunoassay (r = 0.993, n = 38).
Affinity chromatography used in distinguishing alpha-fetoprotein in serum from patients with tumors of hepatic parenchyma and of germ cells.
Authors: Buamah P K , Cornell C , Skillen A W 
Published: January 2020

Abstract
We used affinity chromatography on concanavalin A Sepharose to study the serum alpha-fetoprotein of 10 patients with histologically proven germ-cell tumors and 12 patients with primary liver cancer. Less than 50% of the fetoprotein from germ-cell tumors bound to concanavalin A, as compared with more than 80% of the alpha-fetoprotein from primary liver cancers.
Simultaneous determination of trace elements in serum by energy-dispersive x-ray fluorescence spectrometry.
Authors: Rastegar F , Maier E A , Heimburger R , Christophe C , Ruch C , Leroy M J 
Published: January 2020

Abstract
Energy-dispersive x-ray fluorescence is applied in the analysis of human serum to determine the concentrations of several elements simultaneously with minimal manipulation of the sample. The analytical procedure has been developed with standard sera, and standardization, detection limits, and reproducibility have been established. A 50-microL sample of diluted serum, to which an internal standard has been added, is deposited on a thin (4-microns thick) polypropylene film and analyzed by x-ray fluorescence. We report the statistical distributions of the concentrations of Fe, Cu, Zn, and Br obtained in the population (103 samples) studied, and report detection limits for the other 22 elements studied. The simplicity of the method, the high throughput, and the possibility of automating the measurements make this procedure suitable for screening large numbers of sera.
Carboxyhemoglobin, cotinine, and thiocyanate assay compared for distinguishing smokers from non-smokers.
Authors: Pojer R , Whitfield J B , Poulos V , Eckhard I F , Richmond R , Hensley W J 
Published: January 2020

Abstract
We compared cotinine, carboxyhemoglobin, and thiocyanate concentrations in blood sampled from 187 cigarette smokers and 181 non-smokers. All three differed significantly between smokers and non-smokers. Cotinine performed best as a test for assessing smoking status, with a sensitivity of 98% as compared with 94% for carboxyhemoglobin and 80% for thiocyanate, all at a specificity of 95%. These differences were statistically significant. Results by none of these three methods correlated well with number of cigarettes smoked per day.
An automated immunoradiometric assay for human thyrotropin.
Authors: John R , Jones M K 
Published: January 2020

Abstract
In this two-site immunoradiometric assay for thyrotropin, developed for use in the "Kemtek 3000" automated radioimmunoassay system, commercially available monoclonal antibody to thyrotropin is labeled with 125I, and the solid-phase antibody is an IgG fraction of sheep antiserum to thyrotropin, covalently coupled to reprecipitated aminocellulose. There are two incubations, totalling 3 h, the sensitivity is 0.03 milli-int. unit/L. The mean thyrotropin value for 82 healthy euthyroid subjects was 1.7 milli-int. units/L (range 0.4-3.6). For 19 overtly clinically and biochemically hyperthyroid subjects the values ranged from undetectable to 0.2 milli-int. unit/L. In this assay, euthyroid and hyperthyroid subjects can be distinguished with assay of a single basal sample. The assay appears suitable for routine use as a first-line test of thyroid function.
Highly sensitive immunoassays based on use of liposomes without complement.
Authors: Litchfield W J , Freytag J W , Adamich M 
Published: January 2020

Abstract
We describe a novel liposome-based immunoassay in which covalently linked hapten-cytolysin conjugates are used instead of complement and surface-immobilized immunoreagents. Stable, unilamellar liposomes containing entrapped alkaline phosphatase as a marker enzyme were prepared by dialysis of octyl glucoside from suspensions of cholesterol and egg yolk lecithin. The resulting vesicles could be immediately lysed by addition of either bee venom melittin or hapten-melittin conjugates. Using ouabain, an analog of digoxin, we synthesized conjugates that were more lytic than mellitin alone but that were inhibited in the presence of antibody. This inhibition was affected by adding competing free digoxin at various concentrations to obtain standard curves. The same liposome preparations could be lysed with a biotin-melittin conjugate, which was inhibited by avidin. The latter system was affected by free biotin and might be used to couple this approach to various heterogeneous immunoassays.
Detection of alpha 2-macroglobulin-associated proteases in the plasma of patients with rheumatoid arthritis.
Authors: Gaspar A , Skosey J L , Sequeira W , Teodorescu M 
Published: January 2020

Abstract
In previous work a polyclonal B cell activator has been detected in the serum of patients with rheumatoid arthritis (RA). This activator is associated with alpha 2-macroglobulin (alpha 2M) and its activity is blocked by low-Mr trypsin inhibitors, which suggests that it may be a protease-alpha 2M complex. Here we determined the possibility of developing a routine clinical chemistry test for detection of this complex in patients' blood. We measured with chromogenic substrates the total proteolytic activity of citrated plasma and of the alpha 2M immunoabsorbed from plasma. Low-Mr substrates containing Arg were degraded much better by plasma from RA patients than by plasma from patients with other arthritides. Low-Mr substrates containing Leu, Lys, or Gly or the large-Mr substrate Azocoll were not degraded by RA patients' plasma. alpha 2M from RA patients' plasma attached to a solid-phase immunoabsorbent degraded an Arg-containing tripeptide much better than did the alpha 2M from normal donors, from patients with systemic lupus erythematosus, or from those with joint inflammation of other, "non-autoimmune" origin. Although the enzyme associated with alpha 2M in the plasma from RA patients appeared to be similar to trypsin, the differences in optimal pH, cation concentration, degradation of Lys-containing substrates, and biological activity suggest otherwise. We speculate that the alpha 2M-protease complexes are generated in the immune system and contribute to the inflammatory and autoimmune phenomena in RA.
Quantification of salicylate in serum by use of salicylate hydroxylase.
Authors: You K , Bittikofer J A 
Published: January 2020

Abstract
In this enzymatic method for salicylate in serum, Pseudomonas salicylate hydroxylase (EC 1.14.13.1) is used. This stable enzyme catalyzes the stoichiometric, unidirectional conversion of salicylate and NAD(P)H to catechol and NAD(P)+ in the presence of molecular oxygen. The concentration of salicylate in a clinical sample is determined by measuring the delta A at 340 nm as compared with a standard. This new method is rapid, highly specific, requires 40 microL or less of sample, and we saw no interference by any of 61 commonly used drugs. Lipemic, icteric, or hemolyzed samples can be used. Furthermore, this method does not involve extraction, deproteinization, or derivatization. Results are precise and agree well with those obtained by the Trinder test.
Use of a rapid, sensitive immunoradiometric assay for thyrotropin to distinguish normal from hyperthyroid subjects.
Authors: Cobb W E , Lamberton R P , Jackson I M 
Published: January 2020

Abstract
Using a new three-site immunoradiometric assay for thyrotropin (TSH), we measured concentration of this hormone in the serum of 47 patients with hyperthyroidism and 46 controls. The mean and range of serum TSH concentration was significantly lower in thyrotoxic than in control subjects, and it was possible to correctly identify 96% of thyrotoxic patients on the basis of a serum TSH concentration less than 0.5 milli-int. unit/L. We conclude that such measurement is highly sensitive for distinguishing hyperthyroid from normal subjects, and that the lower limit of normal for TSH in serum is about 0.5 milli-int. unit/L.
Outcome Bias and Expertise in Investigations under International Humanitarian Law
Authors: Broude Tomer , Levy Inbar 
Published: January 2020

Abstract
Many international law decisions are made by individuals, often possessed with expertise, legal or otherwise. We examine individual international humanitarian law (IHL) decision-making on two levels: military decisions made ex ante regarding real-time operational questions under conditions of uncertainty and imperfect information, and subsequent ex post evaluations of the propriety of military decisions in the context of military investigations regarding legal responsibility with respect to proportionality and reasonableness. IHL requires ex post investigators to consider only information available at the time decisions were made. Through an experimental vignette study conducted with laypersons, legal experts and people with field experience, we test whether they are susceptible to cognitive ‘outcome bias’, specifically the extent to which the knowledge of operational outcomes, especially regarding incidental civilian harm, influences ex post normative evaluations. Our results demonstrate a general tendency towards outcome bias, which is somewhat tempered by expertise. Individuals with operational decision-making experience may be less prone to outcome bias than legal experts. We discuss possible implications for the design of military investigations relating to IHL.
Origin Recognition Complex (ORC) Evolution Is Influenced by Global Gene Duplication/Loss Patterns in Eukaryotic Genomes
Authors: Ocaña-Pallarès Eduard , Vergara Zaida , Desvoyes Bénédicte , Tejada-Jimenez Manuel , Romero-Jurado Ainoa , Galván Aurora , Fernández Emilio , Ruiz-Trillo Iñaki , Gutierrez Crisanto 
Published: January 2020

AbstractThe conservation of orthologs of most subunits of the origin recognition complex (ORC) has served to propose that the whole complex is common to all eukaryotes. However, various uncertainties have arisen concerning ORC subunit composition in a variety of lineages. Also, it is unclear whether the ancestral diversification of ORC in eukaryotes was accompanied by the neofunctionalization of some subunits, for example, role of ORC1 in centriole homeostasis. We have addressed these questions by reconstructing the distribution and evolutionary history of ORC1-5/CDC6 in a taxon-rich eukaryotic data set. First, we identified ORC subunits previously undetected in divergent lineages, which allowed us to propose a series of parsimonious scenarios for the origin of this multiprotein complex. Contrary to previous expectations, we found a global tendency in eukaryotes to increase or decrease the number of subunits as a consequence of genome duplications or streamlining, respectively. Interestingly, parasites show significantly lower number of subunits than free-living eukaryotes, especially those with the lowest genome size and gene content metrics. We also investigated the evolutionary origin of the ORC1 role in centriole homeostasis mediated by the PACT region in human cells. In particular, we tested the consequences of reducing ORC1 levels in the centriole-containing green alga Chlamydomonas reinhardtii. We found that the proportion of centrioles to flagella and nuclei was not dramatically affected. This, together with the PACT region not being significantly more conserved in centriole-bearing eukaryotes, supports the notion that this neofunctionalization of ORC1 would be a recent acquisition rather than an ancestral eukaryotic feature.
A hybrid Galerkin finite element method for seismic wave propagation in fractured media
Authors: Vamaraju Janaki , Sen Mrinal K , De Basabe Jonas , Wheeler Mary 
Published: January 2020

SUMMARYThe discontinuous Galerkin finite element method (DGM) is a promising algorithm for modelling wave propagation in fractured media. It allows for discontinuities in the displacement field to simulate fractures or faults in a model. Our approach is based on the interior-penalty formulation of DGM, and the fractures are simulated using the linear-slip model, which is incorporated into the weak formulation. On the other hand, the spectral element method (SEM) can be used to simulate elastic wave propagation in non-fractured media. SEM uses continuous basis functions which do not allow for discontinuities in the displacement field. However, the computation cost of DGM is significantly larger than SEM due primarily to increase in the number of degrees of freedom. Here we propose a hybrid Galerkin method (HGM) for elastic wave propagation in fractured media that combines the salient features of each of the algorithm resulting in significant reduction in computational cost compared to DGM. We use DGM in areas containing fractures and SEM in regions without fractures. The coupling between the domains at the interfaces is satisfied in the weak form through interface conditions. The degree of reduction in computation time depends primarily on the density of fractures in the medium. In this paper, we formulate and implement HGM for seismic wave propagation in fractured media. Using realistic 2-D/3-D numerical examples, we show that our proposed HGM outperforms DGM with reduced computation cost and memory requirement while maintaining the same level of accuracy.
Evaluating the most popular diabetes websites in the USA: a content analysis
Authors: Holtz Bree E 
Published: January 2020

Abstract
Over 1.5 million Americans are diagnosed with diabetes every year, and the majority of them go online to learn about their condition. Unfortunately, the online diabetes landscape is crowded, and the quality of website content is unknown—guidance for patients and healthcare providers regarding online diabetes information is needed. To address this, nine of the top diabetes websites in the USA were identified through a comprehensive, multiple-query search and a content analysis was conducted. Two coders, with high inter-coder reliability, evaluated these websites on six factors: (i) Design; (ii) Credibility; (iii) Accessibility; (iv) Literacy; (v) Engagement; and (vi) Diabetes Content. The analysis revealed that the websites presented most of the assessed design features. Few of the sites scored well on the credibility assessment, while the majority of sites did not note an author, editor or reviewer. With regard to accessibility, less than half of the items we assessed were met. Furthermore, the websites possessed wide variability in literacy, with an average readability grade level of 8.8. Most of the websites fared well in engagement, demonstrating multiple avenues to interact with the organization. All of the websites provided basic information regarding diabetes, but many did not include information for caregivers, providers or insurance information. In conclusion, patients and their family members will continue to seek online information about diabetes, its effects and treatment options. Therefore, this multiple-metric evaluation provides essential information for these individuals, and healthcare providers, who can now give better informed website recommendations to their patients and families.
Genomic dissection of 43 serum urate-associated loci provides multiple insights into molecular mechanisms of urate control
Authors: Boocock James , Leask Megan , Okada Yukinori ,   Asian Genetic Epidemiology Network (AGEN) Consortium, Matsuo Hirotaka , Kawamura Yusuke , Shi Yongyong , Li Changgui , Mount David B , Mandal Asim K , Wang Weiqing , Cadzow Murray , Gosling Anna L , Major Tanya J , Horsfield Julia A , Choi Hyon K , Fadason Tayaza , O’Sullivan Justin , Stahl Eli A , Merriman Tony R 
Published: January 2020

AbstractHigh serum urate is a prerequisite for gout and associated with metabolic disease. Genome-wide association studies (GWAS) have reported dozens of loci associated with serum urate control; however, there has been little progress in understanding the molecular basis of the associated loci. Here, we employed trans-ancestral meta-analysis using data from European and East Asian populations to identify 10 new loci for serum urate levels. Genome-wide colocalization with cis-expression quantitative trait loci (eQTL) identified a further five new candidate loci. By cis- and trans-eQTL colocalization analysis, we identified 34 and 20 genes, respectively, where the causal eQTL variant has a high likelihood that it is shared with the serum urate-associated locus. One new locus identified was SLC22A9 that encodes organic anion transporter 7 (OAT7). We demonstrate that OAT7 is a very weak urate-butyrate exchanger. Newly implicated genes identified in the eQTL analysis include those encoding proteins that make up the dystrophin complex, a scaffold for signaling proteins and transporters at the cell membrane; MLXIP that, with the previously identified MLXIPL, is a transcription factor that may regulate serum urate via the pentose–phosphate pathway and MRPS7 and IDH2 that encode proteins necessary for mitochondrial function. Functional fine mapping identified six loci (RREB1, INHBC, HLF, UBE2Q2, SFMBT1 and HNF4G) with colocalized eQTL containing putative causal SNPs. This systematic analysis of serum urate GWAS loci identified candidate causal genes at 24 loci and a network of previously unidentified genes likely involved in control of serum urate levels, further illuminating the molecular mechanisms of urate control.
DNMT1 mutations leading to neurodegeneration paradoxically reflect on mitochondrial metabolism
Authors: Maresca Alessandra , Del Dotto Valentina , Capristo Mariantonietta , Scimonelli Emanuela , Tagliavini Francesca , Morandi Luca , Tropeano Concetta Valentina , Caporali Leonardo , Mohamed Susan , Roberti Marina , Scandiffio Letizia , Zaffagnini Mirko , Rossi Jacopo , Cappelletti Martina , Musiani Francesco , Contin Manuela , Riva Roberto , Liguori Rocco , Pizza Fabio , La Morgia Chiara , Antelmi Elena , Loguercio Polosa Paola , Mignot Emmanuel , Zanna Claudia , Plazzi Giuseppe , Carelli Valerio 
Published: January 2020

Abstract
ADCA-DN and HSN-IE are rare neurodegenerative syndromes caused by dominant mutations in the replication foci targeting sequence (RFTS) of the DNA methyltransferase 1 (DNMT1) gene. Both phenotypes resemble mitochondrial disorders, and mitochondrial dysfunction was first observed in ADCA-DN. To explore mitochondrial involvement, we studied the effects of DNMT1 mutations in fibroblasts from four ADCA-DN and two HSN-IE patients. We documented impaired activity of purified DNMT1 mutant proteins, which in fibroblasts results in increased DNMT1 amount. We demonstrated that DNMT1 is not localized within mitochondria, but it is associated with the mitochondrial outer membrane. Concordantly, mitochondrial DNA failed to show meaningful CpG methylation. Strikingly, we found activated mitobiogenesis and OXPHOS with significant increase of H2O2, sharply contrasting with a reduced ATP content. Metabolomics profiling of mutant cells highlighted purine, arginine/urea cycle and glutamate metabolisms as the most consistently altered pathways, similar to primary mitochondrial diseases. The most severe mutations showed activation of energy shortage AMPK-dependent sensing, leading to mTORC1 inhibition. We propose that DNMT1 RFTS mutations deregulate metabolism lowering ATP levels, as a result of increased purine catabolism and urea cycle pathways. This is associated with a paradoxical mitochondrial hyper-function and increased oxidative stress, possibly resulting in neurodegeneration in non-dividing cells.