bluuebunny/crossref_metadata_2025_split huggingface dataset:
A-029 Modeling the Effect of Step Changes in Glucose on %Glycated Albumin vs Time
Authors: Stickle D F , DiNatale G J , Molinaro R 
Published: September 2023

Abstract

Background
Glycated albumin (GA) is often referred to as being a reflection of glucose exposure over the past 20–30 days. We examined this premise from a theoretical standpoint using a model for formation of GA and simulation of the effects of step changes in glucose concentration ([G]).

Methods
A model for glycation of albumin parallels established models for formation of hemoglobin A1c, differing only in characterization of the age distribution for albumin. Probability of survival (P(s)) of albumin at a given age (t) is based on a first-order rate constant (ke) for elimination: P(s) = exp(-ke t) [Eqn.1], where ke = 4.08e-2/d (t(1/2) = 17 d). Probability of glycation (P(g)) at a given age is given by: P(g) = (1-exp(-k[G] t)) [Eqn.2]. There is a simple analytical solution for %GA for constant [G]: %GA = 100(1-w/z), where w = ke and z = (ke+k[G]). k = 9.77e-4/d/(mmol/L) reproduces reference values for %GA [PMID: 29436378], and for which %GA = 2.41(%A1c)-0.004 (r = 0.999, for A1c range = 5%–12%). For non-constant [G], %GA must be determined by simulation of changes in P(g) using Eqn.2, calculated in small time increments, dt. Using dt = 0.01 d, we calculated changes in %GA by simulation as a function of time for two scenarios involving step changes in [G] at time = 0: A. from 10 mmol/L to 15 mmol/L (%GA ultimately moves from 19.3% to 26.4%); B. from 15 mmol/L to 10 mmol/L (%GA ultimately moves from 26.4% to 19.3%).

Results
Figure shows the fractional transition of %GA between respective starting points and ultimate endpoints vs time for scenarios A and B. In both cases, transition at 30 days was approximately 80% of the ultimate full transition.

Conclusions
Physiological model-based calculations support that description of %GA as a reflection of [G] over the past 30 days is a very reasonable one under conditions in which [G] has changed.
A-042 Comparison of the Second-Generation Parathyroid Hormone Assays: ELSA-PTH and Alinity i Intact PTH
Authors: Kang J , Park J , Choi H , Kee S 
Published: September 2023

Abstract

Background
Measurement of parathyroid hormone (PTH) level is essential in diagnosing and treating hyper- and hypoparathyroidism. Because of the various presenting forms of PTH (biologically active full-length PTH and also PTH fragments) in the blood and the lack of standardization, there can be a difference in results between the assays even when the same assay generation is used. We compared the two second-generation PTH assays, ELSA-PTH and Alinity i Intact PTH, and evaluated the analytical performance of Alinity i Intact PTH, newly adopted in the laboratory.

Methods
For method comparison, 56 remnant samples of routinely ordered sera for the PTH test were collected. ESLA-PTH assay tested on Gamma-10 contains the anti-[39-84, amino acids] PTH antibody coated on the tube, which captures PTH in the sample and is measured by the radioactivity through the bound I125-labelled anti-[1-34] PTH antibody. Alinity i Intact PTH assay performed on Alinity i system uses the anti-[39-84] PTH antibody coated on a paramagnetic microparticle and is analyzed by the emitted light through the captured acridinium-labeled anti-[1-34] PTH antibody. The correlation between the two tests was evaluated. Additionally, precision, linearity, and reference range verification were analyzed to investigate the performance of the Alinity i Intact PTH assay.

Results
Of the 56 samples, 35 (62.5%) were requested by the Nephrology department for evaluating chronic kidney disease, 16 (28.6%) by the General surgery department during and after parathyroid and thyroid surgery, and 5 (8.9%) by other departments. 52.3% of the patients were female, and the median age was 61.5 years (interquartile range: 45.3–71). The median values of ELSA-PTH and Alinity i Intact PTH were 69.0 pg/mL and 101.9 pg/mL, respectively, and the PTH values of Alinity i Intact PTH were significantly higher (P &lt; 0.0001) by the Wilcoxon test. The Pearson correlation coefficient (r) was 0.959, and the average difference between the two tests was 78.57 pg/mL. In Alinity i Intact PTH, the coefficient of variation obtained at each low (10.5 pg/mL), medium (66.6 pg/mL), high (254.6 pg/mL) levels were 1.9%, 2.4%, and 1.8% for repeatability, and 2.03%, 2.71%, and 2.65% for within-laboratory precision, respectively. Linearity was observed within the analytical measuring range of 3–3000 pg/mL. The reference range (15–68.3 pg/mL) recommended by the manufacturer was validated with 20 normal sera.

Conclusion
The PTH values of Alinity i Intact PTH were significantly higher than those of the ELSA-PTH, and both assays showed a strong correlation. Additionally, the Alinity i Intact PTH assay demonstrated acceptable analytical performance.
A-048 Accurate Measurement of Free Testosterone in Serum using Equilibrium Dialysis Coupled with ID-UHPLC-MS/MS
Authors: Zhou H , Ribera A , Danilenko U , Vesper H 
Published: September 2023

Abstract

Background
Assessment of free testosterone (FT) has been recommended in recent clinical practice guidelines as a biomarker for diagnosis and management of testosterone related disorders such as male testosterone deficiency due to hypogonadism and female androgen excess due to polycystic ovary syndrome (PCOS). FT is currently measured using direct commercial immunoassays, assays using equilibrium dialysis (ED) or other separation techniques. Though the ED approach is recognized as the recommended approach, it is laborious and technically challenging for routine clinical use. The CDC Clinical Standardization Program is developing a high throughput automated method using the ED procedure coupled with isotope dilution ultra-high-performance liquid chromatography tandem mass spectrometry (ID-UHPLC-MS/MS) that is suitable for routine patient care and large-scale epidemiologic studies.

Methods
Serum samples are dialyzed in a custom-designed multi-well plate against a protein-free HEPES buffer (pH 7.4) at 37 °C until equilibrium. After isolating endogenous FT from protein-bound testosterone by ED, isotope-labeled internal standard (13C3-testosterone) was added to the dialysate for quantification. Certified pure primary reference material (National Measurement Institute-M914) was used to prepare calibrators, enabling traceability and ensuring measurement trueness. FT was further isolated from the dialysate matrix using supported liquid extraction and a chromatographic separation from interfering compounds and quantitation by tandem MS.

Results
The measurement ranges covered 0.2–1000 ng/dL for testosterone, with the bias within ±5% and precision less than 10% CV. A total of 45 samples with a wide range of total testosterone (TT, 21–912 ng/dL) and SHBG (11–129 nmol/L) were analyzed and showed the suitability of this assay to measure the serum free testosterone levels in normal, hypogonadal males as well as in the majority of normal females and females with androgen excess. The application of 48-well format plate and automated liquid handler system significantly improves the throughput of sample preparation. In addition, comparison of the TT results measured with the presented TT method with calculated TT concentrations, suggest that on average calculation overestimates TT concentration by 34%.

Conclusion
The described high throughput method for FT allows for sufficiently accurate and precise measurement for routine applications including large epidemiologic studies to help with establishing reference intervals.
A-057 Cerebrospinal Fluid Prolactin in Patients with Neurological Disorders
Authors: Hashim I A , Abraham E 
Published: September 2023

Abstract

Introduction
Prolactin a 23 kDa glycoprotein produced by the anterior pituitary among other cells with possible immunological properties. The presence and significance of prolactin in cerebrospinal fluid (CSF) is not widely known. This study examined prolactin levels in CSF from patients being investigated for neurological disorders.

Methods
CSF samples (leftover) from patients being investigated for neuropathy were obtained and stored at 4 °C or at −20 °C if not analyzed within one week of collection. Prolactin levels were measured using a high sensitivity prolactin ELISA (R and D Systems, Inc., MN, USA) according to manufacturer’s instructions. CSF samples reported total protein and glucose levels were obtained and correlated with measured prolactin levels. Statistical analysis were performed using NCSS statistical software.

Results
A total of 53 CSF (leftover samples) were analyzed for prolactin content. Prolactin was detectable and levels ranged from 2.68 ng/mL to 12.1 ng/mL (mean 4.49 ng/mL). Total protein ranged from 21 mg/dL to 219 mg/dL (mean 67.5 mg/dL). CSF glucose levels ranged from 16 mg/dL to 114 mg/dL (mean 63.9 mg/dL). Although there was poor (r = 0.66) but significant (P &lt; 0.003) correlation between CSF prolactin and total protein levels, there was no correlation (r = −0.1) between CSF prolactin and CSF glucose levels (P = 0.6).

Conclusion
Prolactin levels was detected in CSF from patients being investigated for neurological dysfunction. There was correlation with total protein and glucose levels. The clinical significance of CSF prolactin is unknown and remains to be elucidated.
A-058 Frequency of Biochemical Assessment of Risk for Heart Failure among Diabetic Population
Authors: Joseph J , Neeley J , Hashim I A 
Published: September 2023

Abstract

Background
Diabetes remains a prevalent chronic health condition. Patients with diabetes have nearly twice the risk of developing heart failure as the general population and the American Diabetes Association recommends annual assessment by measuring N-terminal pro-B-type natriuretic peptide (NT-proBNP) or BNP among diabetic patients. We evaluated the frequency of biomarker assessment among our diabetic population.

Methods
Retrospective analysis of glycated hemoglobin (A1c) and NT-proBNP measured over a period of 21 months were performed. The frequency of NTproBNP assessment among patients with diagnostic A1c values were determined. Statical analysis were performed using Microsoft® Excel and NCSS® statistical software.

Results
A total of 74 973 A1c and 23 540 NT-proBNP measurements were performed during the study period. Among diabetics, 16% of patients received NT-proBNP testing with about 38% exhibiting elevated values.

Conclusion
This preliminary and retrospective study indicated that diabetic patients are receiving biochemical assessment for heart failure and that a significant number are of diagnostic value. It is not clear if other clinical modalities for heart failure assessment are in effect and if increased utility of biochemical assessment is required. Further studies are required to assess the utility among our patient’s population and on the best protocol to apply.
A-072 An All-Purpose Particle Enhanced Immunoturbidimetric Assay for the Comparable, Instrument-Independent Monitoring of Procalcitonin in the Management of Sepsis
Authors: Grimmler M 
Published: September 2023

Abstract

Introduction
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host immune response to infection. It is a global health concern and a leading cause of death worldwide, affecting an estimate of 48.9 million people every year. Procalcitonin (PCT) revealed to be an indispensable parameter for the management of sepsis. However, recent analysis of EQA survey results suggested crucial deviations of PCT measurements in Germany and studies by the IFCC Working Group on standardization of PCT stated the need for a higher-order reference measurement procedure.Here we present the evaluation of the all-purpose particle enhanced immunoturbidimetric assay (PETIA) of DiaSys, which can be easily applied to every high-throughput clinical chemistry analyzer. The high diversity of applications and datasets match current diagnostic and regulative needs (IVDR). Procalcitonin FS enables the equivalent and instrument-independent monitoring of PCT in the management of sepsis.

Methodology
Evaluation of Procalcitonin FS was performed on seven clinical chemistry analyzer platforms (Jeol BioMajesty® JCA-BM6010/C, DiaSys respons®920 and respons®940, Roche cobas c501, Abbott Architect c8000 and Alinity c, Beckman Olympus AU680). Measurements were performed according to Clinical and Laboratory Standards Institute (CLSI) protocols.

Results
The onboard stability reaches 8 weeks (with chimney) on BioMajesty® JCA-BM6010/C, 20 days on respons®920 and respons®940, 21 weeks on cobas c501, 9 weeks on Architect, 12 weeks on Olympus AU680 and 13 weeks on Alinity c. The calibration stability is 4 weeks (with chimney) on BioMajesty® JCA-BM6010/C, 2 weeks (with chimney) on respons®920 and respons®940, 21 weeks on cobas c501, 3 weeks on Architect, 5 weeks on Olympus AU680 and 10 weeks on Alinity c. The intra-assay precision (CV%) ranges from ≤4.57% on respons®920 up to ≤7.19% on respons®940. The Total Precision (CV%) ranges from ≤3.99% on cobas c501 up to ≤9.62% on Olympus AU680. LOB ranges from 0.07 ng/mL on BioMajesty® JCA-BM6010/C up to 0.130 ng/mL on Olympus AU680. LOQ ranges from 0.20 ng/mL on Architect up to 0.277 ng/mL on Olympus AU680. The reagent displayed a linear recovery up to 50 ng/mL and no prozone effect was detected up to 1000 ng/mL on all seven analyzers. The Passing & Bablok regression vs the reference test showed an excellent comparability/alignment between the methods (slope ≤1.11, intercept ≤0.156 ng/mL, R ≥ 0.986).

Conclusion
Evaluation work proves that DiaSys PETIA reagent Procalcitonin FS shows excellent performance on all seven clinical chemistry analyzers. In addition, the high comparability between the seven analyzers enables the reliable and instrument-independent monitoring of PCT in the management of sepsis, and thus offering a solution to the current landscape of deviating PCT measurement results.
A-085 Analytical Performance of BÜHLMANN sCAL® turbo, a New, Reliable and Precise High-Throughput Assay to Assess the Inflammatory Status of Patients
Authors: Melone A , Vogt D , Ohmann A , Moniz C , Eichmann M , Guschin D , Gerhold C , Schuster T 
Published: September 2023

Abstract

Background
Serum calprotectin plays an important pro-inflammatory role in the innate immune system and is a promising marker with several potential applications in rheumatoid arthritis, juvenile idiopathic arthritis and systemic onset juvenile idiopathic arthritis. Serum calprotectin can be a useful tool to monitor disease activity and predict treatment response in these patients.

Methods
The aim of this work was to evaluate the analytical performance of BÜHLMANN sCAL® turbo, a new turbidimetric test on clinical chemistry analyzers for the determination of calprotectin levels in serum. Assay characteristics were established according to CLSI guidelines (CLSI C28-A3, EP05-A3, EP07-A3, and EP09-A3). 111 samples were measured using 3 lots over 3 days and compared to another commercially available assay.

Results
The analytical measuring range from 0.23 to 15 µg/mL, extended to 225 µg/mL with an additional dilution in an automated rerun on a clinical chemistry analyzer, is suitable to address the described pathologies. 160 self-declared healthy adults (m/w) aged 18–83 years exhibit reference limits of 1.77 and 1.10 µg/mL when sampled either in a native tube or a gel separator tube and processed within 3.4 h after collection, respectively. With a within-laboratory precision up to 5.1% and a reproducibility up to 11.1% the method is precise, reliable and suitable for routine use. Tested concentrations of oral and injectable pharmaceuticals showed no interference. Hemolyzed samples are not recommended. It shows good comparison to an existing commercial assay with a bias of 12.5% (Bland-Altman) and a slope of 1.16 (Passing-Bablok).

Conclusion
A high-throughput test on clinical chemistry analyzers is now available with the turbidimetric BÜHLMANN sCAL® turbo allowing reliable and precise measurements of serum calprotectin levels.
A-088 Establish Laboratory Limit of Blank and Limit of Detection for LH Assay on the Ortho VITROS 3600 System
Authors: Su D , Wu H , Zhao Q 
Published: September 2023

Abstract

Background
In our lab, Luteinizing hormone (LH) was tested on VITROS 3600 system with manufacture’s declared limit of detection (LoD) 0.216 mIU/mL, limit of Blank (LoB) 0.0367 mIU/mL. It’s determined with NCCLS guideline EP17, false positives (α) less than 5% and false negatives (β) less than 1%, based on more than 700 determinations on several systems. Chinese government launched industry standard WS/T 514-2017, defining how a clinical laboratory establish its detection capability with stated proportions α = β = 5% and some other differences from EP17. Here we set up the LoB, LoD of VITROS 3600 LH assay in our lab based on Chinese industry standard.

Methods
a) LoB was designed to run 4 blank samples, LoD with 4 low positive samples, respectively with two VITROS LH kit lots, on one VITROS 3600, over two runs per day, for 3–4 days using two different calibrations, therefore we got 120 results (outliers omitted) for LoB and LoD respectively. b) Negative (blank) samples were matrix fetal bovine serum (FBS), low positive samples were in house produced, VITROS 3600 System was well maintained, fully calibrated and quality controlled. c) Data analysis: LoB and LoD sample data are not Gaussian, according to WS/T 514-2017, the LoB and LoD were computed with nonparametric statistics.

Results
Perform steps described in method for each lot reagents. LoB data distribution were non-Gaussian (as when truncated at zero). therefore the LoB can be determined by ranking the data in order from lowest to highest concentration and using the following equations, LOB = Pct100-α, here α is 0.05, P is 0.95, 60 determinations, each reagent lot arrangement position = 0.5 + 60*0.95 = 57.5, result was not an integer, LOB should be re-calculated = X57 + 0.5(X57-X58) = 0.5(X57 + X58). The final result for LoB is 0.0105.with proportions α = β = 5%, each reagent lot LoD determinations more than 50, thereof, K-S test is used for normality analysis. All results of both reagent lots have P-value less than 0.05, which means that the samples were not been generated from a normal distribution. According to WS/T 514-2017, the LoD is estimated with non-parametric statistical derivation method. All results are greater than LoB 0.0105, 0% results are lower than LoB which is less than stated probability 5%. The median value for lot 1990 is 0.0898, and lot 2010 0.0899, so LoD is 0.0899.

Conclusion
The limit of detection (LoD) for VITROS LH assay in our lab is 0.0899 mIU/mL, the limit of Blank (LoB) is 0.0105 mIU/mL, determined with WS/T 514-2017, and with proportions of false positives(α) = false negatives (β) = 5%. In our lab the detection capability is surpass to what manufacture claimed in the IFU. It could be as following factors: singleton platform in our lab, with greater stated proportions, less determinations, and consistently assigned operator. So we can conclude that this system is fit for a more sensitive detection scenario, like pediatric patients.
A-102 Development and Validation of Turbidimetric Retinol Binding Protein (RBP) Assay
Authors: Jaquemar M , Safdari A , Nilsen T , Knüttel T , Havelka A 
Published: September 2023

Abstract

Background
Retinol-binding protein (RBP) is a non-glycosylated protein synthesized by the liver. The role of RBP is to transport retinol (vitamin A) from the liver to the target tissues. RBP is also a sensitive marker of undernutrition. Serum/plasma RBP levels decrease with Vitamin A deficiency, hepatocellular insufficiency, and severe inflammation. Serum/plasma RBP levels increase with renal failure, type-2 diabetes, and steatosis.

Methods
The immunoassay was developed and validated on the turbidimetric instrument Cobas c501 from Roche Diagnostics. The antibodies against RBP in the assay react with RBP in the sample, and the turbidity formed by formation of antibody-antigen complexes is measured at 340 nm and 700 nm. The analytical sensitivity was tested in a study including 4 samples, analysed in 3 replicates over 3 days using a protocol based on the CLSI guideline EP17. The limit of quantification (LoQ) is defined as the lowest concentration of an analyte that can be reliably detected and at which the total error meets the requirements for accuracy. Interference with triglycerides, haemoglobin and bilirubin was tested using a protocol based on the CLSI guideline EP07. Precision of the assay was tested in a 22-day precision study using a protocol based on the CLSI guideline EP05. 3 controls were measured 2 times a day in 2 replicates each time.

Results
The assay has a calibration range from 7.5 to 120 mg/L. Samples with higher concentrations are automatically diluted and reanalysed. No antigen excess was observed up to 600 mg/L. Precision achieved a total CV of &lt;4 % for samples with concentrations in the range 34–63 mg/L. Analytical sensitivity of RBP was measured as 7.81 mg/L with a total error (TE) of ≤20%. No clinically relevant interference towards triglycerides (13 g/L), haemoglobin (6.9 g/L) and bilirubin (0.3 g/L) was observed.

Conclusion
The Gentian RBP assay is a turbidimetric assay based on the formation of antibody-antigen complexes and can be used for assessment of undernutrition, vitamin A deficiency, hepatocellular insufficiency, severe inflammation, renal failure, type-2 diabetes, and steatosis. The assay can be installed on high-throughput platforms from different manufacturers and provides accurate, cost efficient and fast results.
A-106 Sigma Metric Performance of Chemistries on the Abbott Alinity c Analyzer
Authors: Laryea E T , Nichols J H 
Published: September 2023

Abstract

Background
The analytical performance of the Abbott Alinity c (Abbott Park, IL) was compared to our current Abbott Architect analyzers using sigma metrics.

Methods
Sigma metrics of 28 chemistry analytes on our six Abbott Alinity analyzers was compared to three Abbott Architect 16 000 analyzers and one Architect 8000 analyzer using Bio-Rad Multiqual quality control (QC) (Hercules, CA). Method imprecision was estimated for each assay using the cumulative coefficient of variation (CV) of 12 months data for each analyzer at three QC concentrations and calculating the average sigma. Method bias was estimated by comparing each analyzer QC mean to peer group QC means. Sigma values were calculated for each method as (TEa—Bias%)/CV% using allowable total error (TEa) from three sources: the CLIA proficiency testing evaluation limits, Australasian Association of Clinical Biochemistry allowable limits of performance (RCPA quality assurance programs Pty limited, Adelaide, Australia) and desirable biological variation (Ricos C et al, Scand J Clin Lab Invest. 1999, 59(7):491–500). Average sigma values were generated for each analyte and graded as optimal &gt;6 sigma; good 5–6 sigma; marginal 3–5 sigma; or poor &lt;3 sigma.

Results
Assay sigmas varied across QC concentrations and between analyzers of the same platform. Na, Cl, and CO2 had the lowest sigma performance. Since the sigma calculations are dependent on TEa, tighter TEa limits (Ricos and RCPA) generated lower sigmas compared to the wider CLIA TEa limits especially for Ca, Cl, total bilirubin, CO2, Na, total protein, and HDL.

Conclusion
None of the chemistries met optimal six sigma performance for all analytes, concentrations of QC and sources of TEa. However, the assay performance between analyzer platforms was comparable.