bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computer-supported Detection of M-Components and Evaluation of Immunoglobulins after Capillary Electrophoresis
Authors: Jonsson Magnus , Carlson Joyce , Jeppsson Jan-Olof , Simonsson Per 
Published: January 2020

Abstract
Background: Electrophoresis of serum samples allows detection of monoclonal gammopathies indicative of multiple myeloma, Waldenström macroglobulinemia, monoclonal gammopathy of undetermined significance, and amyloidosis. Present methods of high-resolution agarose gel electrophoresis (HRAGE) and immunofixation electrophoresis (IFE) are manual and labor-intensive. Capillary zone electrophoresis (CZE) allows rapid automated protein separation and produces digital absorbance data, appropriate as input for a computerized decision support system.
Methods: Using the Beckman Paragon CZE 2000 instrument, we analyzed 711 routine clinical samples, including 95 monoclonal components (MCs) and 9 cases of Bence Jones myeloma, in both the CZE and HRAGE systems. Mathematical algorithms developed for the detection of monoclonal immunoglobulins (MCs) in the γ- and β-regions of the electropherogram were tested on the entire material. Additional algorithms evaluating oligoclonality and polyclonal concentrations of immunoglobulins were also tested.
Results: CZE electropherograms corresponded well with HRAGE. Only one IgG MC of 1 g/L, visible on HRAGE, was not visible after CZE. Algorithms detected 94 of 95 MCs (98.9%) and 100% of those visible after CZE. Of 607 samples lacking an MC on HRAGE, only 3 were identified by the algorithms (specificity, 99%). Algorithms evaluating total gammaglobulinemia and oligoclonality also identified several cases of Bence Jones myeloma.
Conclusions: The use of capillary electrophoresis provides a modern, rapid, and cost-effective method of analyzing serum proteins. The additional option of computerized decision support, which provides rapid and standardized interpretations, should increase the clinical availability and usefulness of protein analyses in the future.
Microvolume Blood-Sampling Device with Low Hemolysis and High Consistent Yield of Serum Components
Authors: Tanaka Yoshiyuki , Noda Yuichiro , Kobayashi Mayumi , Yamada Yasuko , Hirao Konomu 
Published: January 2020

Abstract
Background: Blood sampling by finger puncture is convenient, but the need for centrifugation and the problem of hemolysis remain, as does instability when samples must be shipped for analysis. We aimed to develop a blood-sampling device that provided high yields of serum with limited hemolysis and enabled preservation of serum components for at least 7 days at room temperature.
Methods: For separation of blood cells, we devised a grooved, asymmetric, polysulfonate membrane impregnated with sucrose. We evaluated hemoglobin (Hb) concentrations in the serum, assay values for 15 frequently measured serum components (including glucose), and the stability of analytes in the device.
Results: In sera from the new device, the Hb concentration was ≤0.43 mg/L. Recovered serum contained 65.0% ± 4.2% (mean ± SD; n = 41) of each of the serum components obtained by centrifugation. Serum components were stable in the device for 10 days at room temperature (25 °C).
Conclusions: The newly developed device allows recovery of 60% of serum components from microvolumes of blood by finger puncture with neither degradation of analytes at room temperature nor hemolysis.
Detection of Acetylcodeine in Urine as an Indicator of Illicit Heroin Use: Method Validation and Results of a Pilot Study
Authors: Staub Christian , Marset Miguel , Mino Annie , Mangin Patrice 
Published: January 2020

Abstract
Background: Acetylcodeine (AC), an impurity of illicit heroin synthesis, has been suggested as an interesting biomarker of illicit heroin use.
Methods: Procedures were developed for quantification of (a) morphine, 6-monoacetylmorphine (6-AM), and codeine in urine and (b) diacetylmorphine and AC in urine. Solid-phase extraction of the analytes was performed, and the extracted analytes were analyzed by selected-ion monitoring with gas chromatography–mass spectrometry. This procedure required prior derivatization with propionic anhydride.
Results: Different validation parameters were determined, such as linearity, reproducibility, extraction recoveries, and cutoffs. Seventy-one urine specimens of illicit heroin abusers and 44 urine specimens of subjects in a heroin maintenance program were analyzed. AC was detected in 85.9% of the samples of the first group but not in any of the samples from subjects taking medical heroin. In the two groups, there were 94.4% and 84.1% 6-AM positive urine specimens, respectively. Detection times were determined for AC and codeine by parallel administration of heroin containing various percentages of AC to four voluntary patients in a heroin maintenance program. The measured detection times were 8 and 23 h for AC and codeine, respectively.
Conclusions: These results indicate that, together with detection of 6-AM in urine, AC is a suitable marker of illicit heroin use.
Compound Heterozygous Familial Hypercholesterolemia and Familial Defective Apolipoprotein B-100 Produce Exaggerated Hypercholesterolemia
Authors: Tai E Shyong , Koay Evelyn S C , Chan Edmund , Seng Tzer Jing , Loh Lih Ming , Sethi Sunil K , Tan Chee Eng 
Published: January 2020

AbstractBackground: Familial hypercholesterolemia (FH) and familial defective apolipoprotein B-100 (FDB) represent ligand-receptor disorders that are complementary. Individuals with both FH and FDB are unusual. We report a family with both disorders and the impact of the mutations on the phenotypes of the family members.Methods: We used single strand conformation polymorphism (SSCP) and denaturing gradient gel electrophoresis (DGGE) for genetic analysis of all 18 exons and the promoter region of the LDL receptor and DGGE for genetic analysis of the apolipoprotein B-100 (apo B-100) gene. The functional significance of the apo B-100 mutation was studied using a U937 cell proliferation assay. Fasting serum lipid profiles were determined for the index case and seven first-degree relatives.Results: One of the patient’s sisters had a missense mutation (Asp407→Lys) in exon 9 of the LDL receptor and a serum LDL-cholesterol concentration of 4.07 mmol/L. Four other first-degree relatives had hyperlipidemia but no LDL-receptor mutation. However, these subjects had a mutation of the apo B-100 gene (Arg3500→Trp). The cell proliferation rate of U937 cells fed with LDL from other subjects with the same mutation was fourfold less than that of controls. The index case had both FH- and FDB-related mutations. Her serum LDL-cholesterol (9.47 mmol/L) was higher than all other relatives tested.Conclusions: Existence of both FH and FDB should be considered in families with LDL-receptor mutations in some but not all individuals with hypercholesterolemia or when some individuals in families with FH exhibit exaggerated hypercholesterolemia.
Rapid Determination of Transferrin Isoforms by Immunoaffinity Liquid Chromatography and Electrospray Mass Spectrometry
Authors: Lacey Jean M , Bergen H Robert , Magera Mark J , Naylor Stephen , O’Brien John F 
Published: January 2020

AbstractBackground: Congenital disorders of glycosylation (CDG) are autosomal recessive disorders that produce increased serum carbohydrate-deficient transferrin (CDT) isoforms. Methods to resolve CDT from fully glycosylated transferrin (Trf) have been based on a neutral shift in the isoelectric focusing (IEF) pattern or on a reduction in the negative charge, allowing resolution by anion-exchange chromatography. Our purpose was to develop a method of resolution and relative quantification of Trf isoforms using online immunoaffinity liquid chromatography–mass spectrometry (LC-MS).Methods: Serum (25 μL) was diluted with 100 μL of water before application to an immunoaffinity column that sequestered Trf isoforms. Trf isoforms were eluted from the immunoaffinity column, concentrated on a C4 column, eluted from the C4 column, and introduced into the mass spectrometer. Analysis of the Trf isoforms was entirely automated and completed in &lt;10 min per sample.Results: The LC-MS method demonstrated that the major abnormal Trf isoforms in CDG lack one complete oligosaccharide structure (mono-oligosaccharide) or both oligosaccharide structures (a-oligosaccharide), but not the sialic acids, as presumed on the basis of IEF methods. Calculation of relative ratios among three possible species (mono-/di-oligosaccharide and a-/di-oligosaccharide) is reproducible [mean intra- and interassay CVs were 9.3% (n = 10) and 10% (n = 5), respectively]. A reference range for patients &lt;18 years was determined by analysis of 209 samples (for mono-/di-oligosaccharide, the median was 0.041 and the range was 0.018–0.083; for a-/di-oligosaccharide, the median was 0.007 and the range was 0.002–0.036). Comparison of data obtained with an affinity chromatography-IEF method and the LC-MS method demonstrated equivalence in the interpreted results (n = 170).Conclusions: Advantages of the LC-MS method include improved sensitivity, minimal sample preparation, and an analysis time of &lt;10 min. The method was automated, which allowed high throughput, with &gt;100 samples analyzed in a single day. Moreover, the nature of the oligosaccharide defect in CDG is accurately reflected by mass resolution, and subtle oligosaccharide truncations may also be detected by this method.
Plasma Protein Contents Determined by Fourier-Transform Infrared Spectrometry
Authors: Petibois Cyril , Cazorla Georges , Cassaigne André , Déléris Gérard 
Published: January 2020

Abstract
Background: Fourier-transform infrared (FT-IR) spectrometry has been used to measure small molecules in plasma. We wished to extend this use to measurement of plasma proteins.
Methods: We analyzed plasma proteins, glucose, lactate, and urea in 49 blood samples from 35 healthy subjects and 14 patients. For determining the concentration of each biomolecule, the method used the following steps: (a) The biomolecule was sought for which the correlation between spectral range areas of plasma FT-IR spectra and concentrations determined by comparison method was greatest. (b) The IR absorption of the biomolecule at the most characteristic spectral range was calculated by analyzing pure samples of known concentrations. (c) The plasma concentration of the biomolecule was determined using the FT-IR absorption of the pure compound and the integration value obtained for the plasma FT-IR spectra. (d) The spectral contribution of the biomolecule was subtracted from the plasma FT-IR spectra, and the resulting spectra were saved for further analyses. (e) The same method was then applied to determining the concentrations of other biomolecules by sequentially comparing the resulting FT-IR spectra.
Results: Results agreed with those obtained by clinical methods for the following biomolecules when analyzed in the following order: albumin, glucose, fibrinogen, IgG2, lactate, IgG1, α1-antitrypsin, α2-macroglobulin, transferrin, apolipoprotein (Apo)-A1, urea, Apo-B, IgM, Apo-C3, IgA, IgG4, IgG3, IgD, haptoglobin, and α1-acid glycoprotein.
Conclusion: FT-IR spectrometry is a useful tool for determining concentrations of several plasma biomolecules.
Evaluation of the TAS Analyzer and the Low-Range Heparin Management Test in Patients Undergoing Extracorporeal Membrane Oxygenation
Authors: Ambrose Theresa M , Parvin Curtis A , Mendeloff Eric , Luchtman-Jones Lori 
Published: January 2020

Abstract
Background: The new Low-Range Heparin Management Test (LHMT), a method for point-of-care testing (POCT) of heparinization, has been designed to function at the low to moderate heparin concentrations typically found in patients undergoing extracorporeal membrane oxygenation (ECMO). In this study, the new method is compared with two POCT methods and a laboratory-based anti-Xa assay.
Methods: We obtained 760 whole blood samples from 13 patients undergoing ECMO. All samples were tested immediately by the LHMT, the Activated Clotting Time (ACT) test, and its low-range counterpart (ACT-LR). Aliquots from the same blood draw were frozen for later anti-Xa analysis using the Diagnostica Stago method on the Roche Cobas Fara-II.
Results: The precision was best for duplicate citrated LHMT samples (CV = 3.1%). LHMT clotting times (overall median, 162 s) were typically shorter than ACT or ACT-LR times (247 and 235 s, respectively). The relationship between the LHMT and the other POCT methods differed significantly from patient to patient (P &lt;0.0001), and a meaningful single relationship between the methods could not be obtained. The overall correlation coefficient between clotting time values and actual heparin concentrations was ≤0.48 for each of the instruments tested, although time plots of each analyzer’s data suggested that they detected heparin dosage changes within single patients.
Conclusions: The performance of the LHMT on the TAS Analyzer is equivalent to that of currently commercially available POCT methods. The lack of agreement between absolute clotting time values and heparin concentrations suggests the need for reexamination of current ECMO patient management strategy.
Hereditary Hemochromatosis Since Discovery of the HFE Gene
Authors: Lyon Elaine , Frank Elizabeth L 
Published: January 2020

Abstract
Background: Hereditary hemochromatosis is an inherited disorder of iron metabolism that is characterized by excessive iron deposition in major organs of the body. Chronic increased iron absorption leads to multiorgan dysfunction. Since the discovery of the gene responsible for the majority of cases, research has progressed rapidly to identify the gene product, the effects of mutations, and the implications for different populations. The protein product of the HFE gene is a transmembrane glycoprotein, termed HFE, that modulates iron uptake. Mutations in the HFE protein compromise its function and produce disease symptoms. Two mutations, C282Y and H63D, have been linked to the majority of disease cases.
Approach: We reviewed the recent literature for the molecular basis of hereditary hemochromatosis. Genotypic information was combined with biochemical and clinical phenotypic information to achieve a better understanding of the disease mechanism.
Content: This review provides a comprehensive discussion of known mutations in the HFE gene and their phenotypic expression. Diagnostic criteria using molecular genetic techniques in conjunction with traditional biochemical tests are provided. Current methods and limitations of molecular testing are examined in detail. A strategy for population screening and an algorithm for diagnosis that incorporates molecular testing are presented. Treatment by therapeutic phlebotomy and the use of blood obtained from hemochromatosis patients are discussed.
Summary: Although the disease mechanism has not been completely elucidated, phenotypic and penetrance data are becoming available. Controversy still exists concerning the role of genetic testing in diagnosis and population screening.
Infrared Analysis of Urinary Calculi by a Single Reflection Accessory and a Neural Network Interpretation Algorithm
Authors: Volmer Marcel , de Vries Jules C M , Goldschmidt Henk M J 
Published: January 2020

Abstract
Background: Preparation of KBr tablets, used for Fourier transform infrared (FT-IR) analysis of urinary calculus composition, is time-consuming and often hampered by pellet breakage. We developed a new FT-IR method for urinary calculus analysis. This method makes use of a Golden Gate Single Refection Diamond Attenuated Total Reflection sample holder, a computer library, and an artificial neural network (ANN) for spectral interpretation.
Methods: The library was prepared from 25 pure components and 236 binary and ternary mixtures of the 8 most commonly occurring components. The ANN was trained and validated with 248 similar mixtures and tested with 92 patient samples, respectively.
Results: The optimum ANN model yielded root mean square errors of 1.5% and 2.3% for the training and validation sets, respectively. Fourteen simple expert rules were added to correct systematic network inaccuracies. Results of 92 consecutive patient samples were compared with those of a FT-IR method with KBr tablets, based on an initial computerized library search followed by visual inspection. The bias was significantly different from zero for brushite (−0.8%) and the concomitantly occurring whewellite (−2.8%) and weddellite (3.8%), but not for ammonium hydrogen urate (−0.1%), carbonate apatite (0.5%), cystine (0.0%), struvite (0.4%), and uric acid (−0.1%). The 95% level of agreement of all results was 9%.
Conclusions: The new Golden Gate method is superior because of its smaller sample size, user-friendliness, robustness, and speed. Expert knowledge for spectral interpretation is minimized by the combination of a library search and ANN prediction, but visual inspection remains necessary.
Simultaneous Multianalyte ELISA Performed on a Microarray Platform
Authors: Wiese Rick , Belosludtsev Yuri , Powdrill Tom , Thompson Patricia , Hogan Mike 
Published: January 2020

Abstract
Background: A logical progression of the widely used microtiter plate ELISA is toward a protein array format that allows simultaneous detection of multiple analytes at multiple array addresses within a single well. Here we describe the construction and use of such a multiplex ELISA to measure prostate-specific antigen (PSA), α1-antichymotrypsin-bound PSA (PSA-ACT), and interleukin-6 (IL-6).
Methods: We silanized glass plates and printed the appropriate capture antibodies to allow for the construction of “sandwich” ELISA quantification assays. We examined specificity of the assay for appropriate antigen, assembled calibration curves, and obtained PSA concentrations for 14 human serum samples. We compared the serum PSA concentrations derived through the use of our array with values obtained independently using a standard ELISA method.
Results: R 2 values generated by our microarray for the PSA and PSA-ACT calibration curves were 0.989 and 0.979, respectively. Analyte concentrations used for the construction of these curves were 0.31–20 μg of protein/L of diluent. IL-6 calibration curve concentrations were 4.9–300 ng of IL-6/L of diluent. The R2 value for the IL-6 calibration curve was 0.983. The 14 human serum samples screened by this micro-ELISA technique for PSA concentrations generated a regression equation (linear) with a slope of 0.83 ± 0.10 and intercept of 0.74 ± 0.70 (R2 = 0.88).
Conclusions: Multiplexed ELISA arrays are a feasible option for analyte quantification in complex biologic samples.
Quantitative Measurement of Porphobilinogen in Urine by Stable-Isotope Dilution Liquid Chromatography-Tandem Mass Spectrometry
Authors: Ford Roddey E , Magera Mark J , Kloke Karen M , Chezick Paul A , Fauq Abdul , McConnell Joseph P 
Published: January 2020

AbstractBackground: Measurement of porphobilinogen (PBG) is useful in the diagnosis of the acute neurologic porphyrias. Currently used colorimetric assays lack analytical and clinical sensitivity and specificity.Methods: We developed a liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS) method for the measurement of PBG in 1 mL of urine, using 5-(aminoethyl)-4-(carboxymethyl) 1H-2,4-[13C]pyrolle-3-propanoic acid ([2,4-13C]PBG; 2.75 μg) as internal standard. After solid-phase extraction, LC-MS/MS analysis was performed in the selected-reaction monitoring (SRM) mode. PBG and [2,4-13C]PBG were monitored through their own precursor and product ion settings (m/z 227 to 210 and m/z 229 to 212, respectively). The retention time of PBG and [2,4-13C]PBG was 1.0 min in a 2.3-min analysis.Results: Daily calibrations (n = 6) between 0.1 and 2.0 mg/L were linear and reproducible. Inter- and intraassay CVs were 3.2–3.5% and 2.6–3.1%, respectively, at mean concentrations of 0.24, 1.18, and 2.15 mg/L. The regression equation for the comparison between an anion-exchange column method (y) and the LC-MS/MS method (x) was: y = 0.84x + 0.74 (Sy|x = 5.8 mg/24 h; r = 0.85; n = 100). In 47 volunteers, PBG excretion was 0.02–0.42 mg/24 h, lower than reported reference intervals (up to 2.0 mg/24 h) based on colorimetric methods. In 85 samples with PBG ≤0.5 by LC-MS/MS, 8 (9.4%) had values ≥2.0 mg/24 h by the anion-exchange method (mean ± SD, 4.3 ± 1.8 mg/24 h). In 11 patients with confirmed diagnoses of acute porphyria and increased PBG by LC-MS/MS, 2 had values within the reported reference intervals by a quantitative anion-exchange method.Conclusions: The quantitative LC-MS/MS method for PBG measurement exhibits greater analytical specificity and improved clinical sensitivity and specificity than currently available methods.
Multicenter Evaluation of an Artificial Neural Network to Increase the Prostate Cancer Detection Rate and Reduce Unnecessary Biopsies
Authors: Stephan Carsten , Cammann Henning , Semjonow Axel , Diamandis Eleftherios P , Wymenga Leon FA , Lein Michael , Sinha Pranav , Loening Stefan A , Jung Klaus 
Published: January 2020

Abstract
Background: The percentage of free prostate-specific antigen (%fPSA) has been shown to improve specificity for the diagnosis of prostate cancer (PCa) over total PSA (tPSA). A multicenter study was performed to evaluate the diagnostic value of a %fPSA-based artificial neural network (ANN) in men with tPSA concentrations between 2 and 20 μg/L for detecting patients with increased risk of a positive prostate biopsy for cancer.
Methods: We enrolled 1188 men from six different hospitals with PCa or benign prostates between 1996 and 2001. We used a newly developed ANN with input data of tPSA, %fPSA, patient age, prostate volume, and digital rectal examination (DRE) status to calculate the risk for the presence of PCa within different tPSA ranges (2–4, 4.1–10, 2–10, 10.1–20, and 2–20 μg/L) at the 90% and 95% specificity or sensitivity cutoffs, depending on the tPSA concentration. ROC analysis and cutoff calculations were used to estimate the diagnostic improvement of the ANN compared with %fPSA alone.
Results: In the low tPSA range (2–4 μg/L), the ANN detected 72% and 65% of cancers at specificities of 90% or 95%, respectively. At 4–10 μg/L tPSA, the ANN detected 90% and 95% of cancers with specificities of 62% and 41%, respectively. Use of the ANN with 2–10 μg/L tPSA enhanced the specificity of %fPSA by 20–22%, thus reducing the number of unnecessary biopsies.
Conclusions: Enhanced accuracy of PCa detection over that obtained using %fPSA alone can be achieved with a %fPSA-based ANN that also includes clinical information from DRE and prostate volume measurements.
Structure Fault Tolerance of Recursive Interconnection Networks
Authors: Sabir Eminjan , Meng Jixiang 
Published: January 2020

Abstract
Motivated by effects caused by structure link faults in networks, we study the following graph theoretical problem. Let $T$ be a connected subgraph of a graph $G$ except for $K_{1}$. The $T$-structure edge-connectivity $\lambda (G;T)$ (resp. $T$-substructure edge-connectivity $\lambda ^s(G;T)$) of $G$ is the minimum cardinality of a set of edge-disjoint subgraphs $\mathcal{F}=\{T_{1},T_{2},\ldots ,T_{m}\}$ (resp. $\mathcal{F}=\{T_{1}^{^{\prime}},T_{2}^{^{\prime}},\ldots ,T_{m}^{^{\prime}}\}$) such that $T_{i}$ is isomorphic to $T$ (resp. $T_{i}^{^{\prime}}$ is a connected subgraph of $T$) for every $1 \le i \le m$, and $E(\mathcal{F})$’s removal leaves the remaining graph disconnected. In this paper, we determine both $\lambda (G;T)$ and $\lambda ^{s}(G;T)$ for $(1)$ the hypercube $Q_{n}$ and $T\in \{K_{1,1},K_{1,2},K_{1,3},P_{4},Q_{1},Q_{2},Q_{3}\}$; $(2)$ the $k$-ary $n$-cube $Q^{k}_{n}$ $(k\ge 3)$ and $T\in \{K_{1,1},K_{1,2},K_{1,3},Q^{3}_{1},Q^{4}_{1}\}$; $(3)$ the balanced hypercube $BH_{n}$ and $T\in \{K_{1,1},K_{1,2},BH_{1}\}$. We also extend some known results.