bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationships and Clinical Utility of Creatinine, Cystatin C, eGFRs, GFRs, and Clearances
Authors: Toffaletti John G 
Published: July 2018

Abstract

Background
This review addresses techniques for glomerular filtration rate (GFR), either measured by clearance tests such as with creatinine, iothalamate, inulin, or iohexol [measured GFR (mGFR)] or calculated by equations that determine the estimated GFR (eGFR) from serum measurements of creatinine and/or cystatin C. However, mGFR tests are slow and impractical for routine use. Therefore, calculations of eGFRs have been developed that have advantages over the mGFRs.

Content
The eGFR is a serum creatinine and/or cystatin C adjusted for age, sex, and race, with mathematical manipulations to produce an average numerical agreement with the mGFR. However, all comparisons between eGFR and mGFR show wide scatter that appears to be related to the large variability of the mGFR. Procedures for mGFR often do not agree with each other and have both wide population variation (similar to plasma creatinine and cystatin C) and within-individual variation that is much larger than creatinine or cystatin C. Whether the measured GFR is even equivalent to serum creatinine and/or cystatin C for detecting early clinical changes in chronic kidney disease will be addressed.

Summary
Procedures for measuring GFR are tedious and expensive, and have both wide population variation (similar to plasma creatinine and cystatin C), and within-individual variation that is much larger than either creatinine or cystatin C. Because the normal range for mGFR overlaps considerably with the stages 1 and 2 of chronic kidney disease, mGFR has significant clinical limitations. Instead of trying to mimic mGFRs, the focus should be on using eGFRs on their own clinical merits to detect impaired kidney function.
Analytical and Clinical Validation of Two Commercially Available Immunoassays Used in the Detection of TSHR Antibodies
Authors: Kemble David J , Jackson Tara , Morrison Mike , Cervinski Mark A , Nerenz Robert D 
Published: July 2018

Abstract

Background
Graves disease is caused by autoantibodies that target the thyroid-stimulating hormone receptor (TSHR). Anti-TSHR autoantibody measurement is routinely performed to differentiate between Graves disease and other causes of hyperthyroidism. We evaluated the clinical performance of a reference laboratory bioassay [the Thyretain thyroid-stimulating immunoglobulin (TSI) Bioassay by Diagnostic Hybrids] and 2 commercially available immunoassays: the TSI Bridge immunoassay by Siemens and the thyroid-stimulating hormone receptor antibody (TRAb) immunoassay by Roche. We further evaluated the analytical performance of the Siemens TSI and Roche TRAb assays.

Methods
We performed method comparisons using 125 patient specimens submitted for TSI testing for clinical purposes. Concordance of patient results was assessed between the 3 methods, and chart review was performed to further evaluate samples that generated discordant results. All 3 methods were also evaluated for potential interference caused by human chorionic gonadotropin (hCG).

Results
The Roche and Siemens assays demonstrated acceptable day-to-day precision, within-run precision, and precision at the clinical decision cutoffs. Despite manufacturer-defined analytical measuring ranges up to 40 IU/L, the Roche and Siemens assays were linear to 20 IU/L and 15 IU/L, respectively. hCG concentrations up to 150000 IU/L did not interfere with any of the methods evaluated. Moderate agreement between methods was observed when testing patient specimens that generated negative (≤1.3) or weakly positive (1.4–3.8) results by the Thyretain assay. One hundred percent agreement was observed when the Thyretain assay was strongly positive (≥3.9).

Conclusions
The 3 commercially available anti-TSHR autoantibody measurement methods demonstrated equivalent performance in patients with untreated Graves disease. Discordant results were observed when testing specimens collected from patients undergoing treatment for Graves disease. In these patients, the Siemens TSI assay more frequently generated results consistent with clinical history, results of other laboratory tests, and imaging studies than the Thyretain Bioassay and Roche TRAb assay.
A Simplified Sample Preparation Method for the Assessment of Plasma Ascorbic Acid in Clinical Settings
Authors: Liu Yuguan , Becker Margaret , Brown Jillian , Sirover William , Handelman Garry J 
Published: July 2018

Abstract

Background
Vitamin C deficiency is difficult to diagnose on the basis of clinical presentation alone and requires plasma levels for confirmation. Reference laboratories typically specify shipment of plasma on dry ice. This requirement may complicate clinic work flow and delay vitamin C measurement. Additionally, patients with vitamin C deficiency may experience unnecessary testing and increased health-care costs, as other diagnoses are often considered first. We examined an alternative, more practical shipping method.

Methods
Plasma was collected from 17 healthy volunteers by use of heparin tubes with gel separators, and all tubes were centrifuged immediately to separate the plasma layer from the cells. Baseline vitamin C was measured in plasma obtained immediately after specimen collection. Remaining sample tubes were held in Styrofoam containers with cold packs for 30 h or 48 h, followed by vitamin C measurement. Additional samples were exposed to conditions that simulated harsher shipping conditions.

Results
Mean plasma vitamin C was 69.6 μmol/L (SD = 21.5 μmol/L). Vitamin C losses were 5.4% at 30 h (SD = 5.55%, P &lt; 0.05) and 7.6% at 48 h (SD = 5.56%, P &lt; 0.05), which is slightly more than freeze-and-thaw treatment (average loss of 1.4%, SD = 6.9%, NS). The vitamin C method had an intraday variation of 1.88%. Vigorous shaking of 2 samples for 24 h resulted in a −1.9% change in 1 sample, and a +4.1% change in another sample. Exposure of the shipping container to elevated temperature (35 °C for 30 h) did not change the internal temperature of the container.

Conclusions
The shipping procedure uses routine sample handling, standard vacutainers, and can be replicated by health-care centers seeking to evaluate patient vitamin C status.
Price of High-Throughput 25-Hydroxyvitamin D Immunoassays: Frequency of Inaccurate Results
Authors: Tolan Nicole V , Yoon Edward J , Brady Ashley R , Horowitz Gary L 
Published: July 2018

Abstract

Background
With a 10-year sustained increase in 25-hydroxyvitamin D [25(OH)D] testing, laboratories have swapped their LC-MS/MS methods for high-throughput automated immunoassays. Although it is generally well-known that immunoassays have poor recoveries for 25-hydroxyvitamin D2 [25(OH)D2], the frequency and extent to which this impacts total 25(OH)D have not been previously demonstrated. We evaluated 3 automated immunoassays against the first FDA-cleared CDC/NIST-traceable LC-MS/MS method.

Methods
Method comparison was performed for the Siemens ADVIA Centaur, Roche Elecsys Cobas, and Abbott Architect 25(OH)D immunoassay methods in real patient samples (n = 105). We calculated the mean bias in samples containing &gt;20 ng/mL 25(OH)D2 and estimated the percent 25(OH)D2 cross-reactivities. We determined the prevalence of appreciable concentrations of 25(OH)D2 in our patient population through random sampling (n = 120) and projected the frequency of inaccurate 25(OH)D immunoassay results.

Results
Linear regression for 25(OH)D was y = 1.09x − 4.44 (Centaur), y = 0.84 + 0.43 (Cobas), and y = 0.83x − 0.48 (Architect). The mean biases of 25(OH)D concentrations were 5.6 (11.0) ng/mL (Centaur), −17.5 (7.2) ng/mL (Cobas), and −20.3 (9.8) ng/mL (Architect) in samples containing &gt;20 ng/mL 25(OH)D2. The observed percent cross-reactivities for 25(OH)D2 were 115% (Centaur), 52% (Cobas), and 44% (Architect). We estimate that 8% of our population has &gt;20 ng/mL 25(OH)D2, thereby compromising the accuracy of 25(OH)D results in &gt;3000 samples annually.

Conclusions
We demonstrate that immunoassay manufacturer package inserts indicate much better recoveries of 25(OH)D2 than what is observed in unadulterated real patient samples. We estimate the frequency of inaccurate total 25(OH)D determination by these immunoassay methods to be largely dependent on the concentration of 25(OH)D2 in each sample.
Genotype–Phenotype Correlations of Glucose-6-Phosphate–Deficient Variants Throughout an Activity Distribution
Authors: Powers Jennifer L , Best D Hunter , Grenache David G 
Published: July 2018

Abstract

Background
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked disorder that may manifest as neonatal jaundice or acute hemolytic anemia. Quantitative assessment of G6PD activity in erythrocytes is required to definitively diagnose a deficiency. Most males and homozygous females have low enzyme activities, whereas heterozygous females may have a range of activities. We sought to examine G6PD genotype–phenotype associations to identify an activity cutoff above which G6PD deficiency is unlikely.

Methods
Ninety-five residual samples were randomly selected to represent the various regions of a G6PD activity distribution. DNA was isolated from the leukocyte fraction and sequenced using the Sanger method. ROC curves were used to establish cutoffs.

Results
Thirteen variant alleles were identified, including 1 not previously reported. In the very deficient activity range, we found males and homozygous females of both class II and III variants. In the deficient category, we found predominantly class III males and heterozygous females. The presumed deficient category contained class III and IV variants and nonvariants. An activity cutoff of &lt;7.85 U/g hemoglobin (Hb) was 100% sensitive and 94% specific for identifying a G6PD-deficient male, and a cutoff of &lt;8.95 U/g Hb was 90% sensitive and 82% specific for a deficient female.

Conclusions
The observed activity groupings were not because of a particular variant class. Cutoffs to identify the presence of a deficiency variant for males and females may be useful when trying to decide whether to recommend genetic analysis.
Evaluation of the Elecsys Syphilis Immunoassay for Detection of Syphilis in Populations at Risk of Disease in the US and Argentina
Authors: Christenson Robert H , Lessig Marvin , Miles Gabrielle , Luebcke Silke , Stillions Cheryl , Jones Prentiss 
Published: July 2018

Abstract

Background
The Elecsys® syphilis immunoassay is an automated, qualitative immunoassay that uses a double-antigen sandwich format to detect antibodies to Treponema pallidum in human serum and plasma. We aimed to validate performance of the immunoassay in various populations at risk for syphilis infection in the US and Argentina.

Methods
Samples were obtained for a number of study cohorts, including participants from routine syphilis testing at high or low risk for syphilis, HIV-positive patients, pregnant women, and patients in various stages of syphilis infection. The primary objective was to validate the Elecsys syphilis immunoassay by comparing it with a composite testing algorithm using US Food and Drug Administration (FDA)-approved tests, including the predicate IMMULITE 2000 syphilis screening assay, the rapid plasma reagin, and the T. pallidum particle agglutination assay.

Results
Complete algorithm testing was performed on all 2660 collected samples. Acceptable precision was demonstrated in all samples. Comparison of the Elecsys syphilis immunoassay with the final syphilis status for all samples yielded a diagnostic sensitivity of 99.5% (95% CI, 98.21–99.94) and a diagnostic specificity of 99.2% (95% CI, 98.69–99.49). Overall, the lower limit of the 95% CIs for sensitivity and specificity met the expected performance of ≥95%.

Conclusion
This is the first study that confirms the high sensitivity and specificity of the Elecsys syphilis immunoassay in US and Argentinian cohorts and highlights the assay's usefulness as an alternative to current tests for the diagnosis of syphilis infection in a broad range of participant cohorts.
Multiplex Allele-Specific PCR for Simultaneous Detection of H63D and C282Y HFE Mutations in Hereditary Hemochromatosis
Authors: Arts Heleen H , Eng Barry , Waye John S 
Published: July 2018

Abstract

Background
Hereditary hemochromatosis (HH) is characterized by excessive iron absorption in the intestine, which can lead to failure of vital organs such as the heart, liver, and pancreas. Among northern Europeans, HH is most often associated with the C282Y and H63D mutations of the HFE gene. We developed a test that allows screening for both mutations in a single reaction.

Methods
A multiplex allele-specific PCR was developed for simultaneous genotyping of the H63D and C282Y HFE mutations. PCR fragments were designed such that the resulting PCR product can be analyzed in a single polyacrylamide gel lane.

Results
Test results from our multiplex assay were concordant with genotypes of 55 Canadian patients with suspected hemochromatosis, which had previously been established by allele-specific PCRs that targeted H63D and C282Y in separate reactions.

Conclusions
Molecular diagnostic detection of H63D and C282Y mutations can be achieved by a variety of methods, but these are not necessarily time-efficient or economical. Multiplex allele-specific PCR is an excellent tool for molecular diagnostic screening for H63D and C282Y mutations in patients with suspected hemochromatosis. This method is inexpensive, accurate, and highly efficient in terms of labor, throughput, and turnaround time.
CRP-Based Cardiovascular Risk Assessment: New Conventional CRP Assay Fit for Purpose?
Authors: Coelho Graça Didia , Golaz Olivier , Magnin Jean-Luc , Fleurkens Hans , Rossier Michel F , Lescuyer Pierre , Vuilleumier Nicolas 
Published: July 2018

Abstract

Background
Subclinical inflammation was shown to play a role in the context of cardiovascular disorder processes. American College of Cardiology/American Heart Association guidelines on cardiovascular risk assessment in specific clinical contexts recommend the use of C-reactive protein (CRP) measurement with high sensitive (hs)-CRP assays that meet the precision requirements for values &lt;2 mg/L. Until now, only hs-CRP assays reached the required limit of quantification. However, new regular CRP assays allow measuring CRP down to 0.6 mg/L.

Methods
A multisite comparative study between hs-CRP and a new conventional CRP assay (Tina-quant) was performed to evaluate the possibility of using regular CRP assays for cardiovascular risk assessment.

Results
A satisfactory concordance was observed between regular CRP assays and the hs-CRP assay. Both assays met the analytical precision requirements at the different cutpoints tested (1.00, 2.00, and 3.00 mg/L).

Conclusion
These results suggest that this new regular CRP assay can be used for cardiovascular risk assessment, which is expected to provide substantial operational and financial advantages when compared with hs-CRP assays.
Heavy metals assessment of soils in and around Kama-Otto and Kwotto artisanal mining of mica, cassiterite and tantalite in Nasarawa state, Nigeria
Authors: Isa Osu Usman , Edith Bolanle Agbaji , Hadiza Omenesa 
Published: July 2018

This study assesses the level of heavy metal in Soils within the vicinity of artisanal mining of Mica, Cassiterite and Tantalite in Nasarawa State, Nigeria. Soil samples of Kama-otto and Kwotto artisanal mining were collected and analyzed using mass-plasma Atomic emission spectroscopy (MP-AES). Samples were also collected in Angwan-Mada, a non-artisanal mining environment, for comparison. Pollution assessment of soil samples using the following geochemical parameters such as contamination factor (CF), pollution load index (PLI), and Enrichment factor (EF), Nemerow index method (IIN) and Geo-accumulating index (Igeo) were carried out. The results indicate an elevation in pollution status in the order of Kama-otto mining, Kwotto mining, Kama-otto, Kwotto and Angwan-mada. The concentrations of Cd, Cr and Mn were significant in the sampled areas (P < 0.05).Â Â
Synthesis, characterization, x-ray diffraction studies and biological activities of iron(III) and cobalt(II) complexes with alanine
Authors: Musa Shuaibu , O. Idris S , D. Onu A 
Published: July 2018

The resulted complexes produced between Fe (III) and Co (II) with biological molecules like amino acids play an important role in human life. They can be used as bioactive compounds as well as in industries. Fe (III) and Co (II) complexes are synthesized with Alanine amino acid. The complexes were characterized by X-ray diffraction, magnetic suscetivility, elemental analysis (AAS), molar conductance, melting point, infrared and uv-visible spectrophotometry analyses. The elemental analyses were used to determine the chelation ratio, 1:3(metal: ligands) for iron (III) Alanine and 1:2 ratio for cobalt (II) Alanine. The molar conductivity of the complexes show that the complexes are not electrolytic in nature. The x-ray data suggest monoclinic crystal system for all the complexes with the exception of Co-alanine, which is hexagonal. The magnetic susceptivility and electronic spectra suggest the complexes are high spin with octahedral geometry.The complexes show enhance activity in comparable to the amino acid.Â Â
Reflexiones sobre la guitarra clásica en Colombia: conversación con Irene Gómez
Authors: Gómez Irene , Gómez Moreno Pedro Pablo 
Published: July 2018

En esta conversación se realiza un recorrido por varias de las dimensiones de la trayectoria artística de una de las guitarristas colombianas más importantes: Irene Gómez. En su transcurso, se abordan temas que tienen que ver con la escena de la guitarra clásica, la formación musical, la ética de la artista y su particular perspectiva sobre la interpretación, la investigación y el acercamiento a los públicos que significa llevar la música al corazón de los oyentes, así como los proyectos en curso de la artista.
Frequency of MTHFR GENE C677T Polymorphism for Non-Syndromic Autism Spectrum Disorder Patients
Authors: Laksono Bremmy , Maskoen Ani Melani , Winarni Tri Indah , Taufik Syarief , Faradz Sultana MH 
Published: July 2018

Background: The folate metabolism is a pathway that may involve in the non-syndromic Autism Spectrum Disorder (ASD). Methylenetetrahydrofolate reductase enzyme has a key role in folate metabolism. The C677T polymorphism of MTHFR gene could reduce the effectiveness of the enzyme.Objectives: To evaluate the frequency of MTHFR geneC677T polymorphism for non-syndromic ASD patients.Method: Thirty-four DNA samples were taken from each group. PCR mixture was consisted of 1µL DNA, 2.5µL PCR buffer, 0.5µL dNTP, 1.5µL MgCL2, 0.125µLTaqenzyme, 0.5µLofforwardandreverseprimerandaquabidesttoreach a volume of 25 µL. The PCR profiles were initiation 95ºC for 5 min, denaturation 94ºC for 1min, annealing 55ºCfor 45 seconds, and elongation 72ºC for30 seconds. The cycles were done in 35 times an dfinal elongation was at 72ºC for 5min. The PCR product was 198bp, and then digested by the Hinfl enzyme for 16hours at 37°C, and visualized using2%agarosegeland then electrophoresed for 30 minutes at 100 volts.Result: Non-syndromic ASD samples showed none had homozygote mutant type (677TT), 3 (8.8%) samples had heterozygote (677CT)and 31 (91.2%) samples had wild type (677CC). Meanwhile, normal control showed only 1 (2.9%)sample had homozygote mutant type(677TT), 9 (26.5%) samples had heterozygote (677CT)and 24 (70.6%) samples had wild type (677CC).Conclusion: The frequency of MTHFR geneC677T polymorphism in patients with non-syndromic ASD and controls are not significantly different.
Genetic Analysis for the Diagnosis of Disorders of Sexual Development in Indonesia
Authors: Faradz Sultana MH 
Published: July 2018

Disorders of sex development (DSD) is defined by congenital conditions in which development of chromosomal, gonadal, or anatomical sex is atypical, while in clinical practice this term means any abnormality of the external genitalia. DSD patients have been managed by a multidisciplinary gender team in our center as collaboration between Dr. Kariadi province referral hospital and Faculty of Medicine Diponegoro University. Diagnosis should be established by specific physical examination hormonal, chromosomal and DNA studies; and imaging for most of the cases depending on indication.Since 2004 the involvement of molecular and cytogenetic analysis so far can diagnosed many of the DSD cases. Most of the genetically proven cases were Congenital Adrenal hyperplasia, Androgen Insensitivity syndrome and sex chromosomal DSD that lead abnormal gonadal development. Many of them remain undiagnosed, further testing such as advanced DNA study should be carried out in collaboration with other center in overseas.The novel genes were found in some cases that contributed for the management of DSD. Information for medical professionals, patients, family members and community about the availability and necessity of DSD diagnosis should be delivered to improve DSD management and patient quality of life.
Physiological Starvation PromotesCaenorhabditis elegansVulval Induction
Authors: Grimbert Stéphanie , Vargas Velazquez Amhed Missael , Braendle Christian 
Published: July 2018

AbstractStudying how molecular pathways respond to ecologically relevant environmental variation is fundamental to understand organismal development and its evolution. Here we characterize how starvation modulates Caenorhabditis elegans vulval cell fate patterning – an environmentally sensitive process, with a nevertheless robust output. Past research has shown many vulval mutants affecting EGF-Ras-MAPK, Delta-Notch and Wnt pathways to be suppressed by environmental factors, such as starvation. Here we aimed to resolve previous, seemingly contradictory, observations on how starvation modulates levels of vulval induction. Using the strong starvation suppression of the Vulvaless phenotype of lin-3/egf reduction-of-function mutations as an experimental paradigm, we first tested for a possible involvement of the sensory system in relaying starvation signals to affect vulval induction: mutation of various sensory inputs, DAF-2/Insulin or DAF-7/TGF-β signaling did not abolish lin-3(rf) starvation suppression. In contrast, nutrient deprivation induced by mutation of the intestinal peptide transporter gene pept-1 or the TOR pathway component rsks-1 (the ortholog of mammalian P70S6K) very strongly suppressed lin-3(rf) mutant phenotypes. Therefore, physiologically starved animals induced by these mutations tightly recapitulated the effects of external starvation on vulval induction. While both starvation and pept-1 RNAi were sufficient to increase Ras and Notch pathway activities in vulval cells, the highly penetrant Vulvaless phenotype of a tissue-specific null allele of lin-3 was not suppressed by either condition. This and additional results indicate that partial lin-3 expression is required for starvation to affect vulval induction. These results suggest a cross-talk between nutrient deprivation, TOR-S6K and EGF-Ras-MAPK signaling during C. elegans vulval induction.