bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting the Severity of Acute Pancreatitis by Rapid Measurement of Trypsinogen-2 in Urine
Authors: Lempinen Marko , Kylänpää-Bäck Marja-Leena , Stenman Ulf-Håkan , Puolakkainen Pauli , Haapiainen Reijo , Finne Patrik , Korvuo Armi , Kemppainen Esko 
Published: January 2020

AbstractBackground: Early identification of patients at risk of developing a severe attack of acute pancreatitis (AP) is of great importance because rapid therapeutic interventions improve outcome. At a cutoff of 50 μg/L, trypsinogen-2 measured by a rapid urinary dipstick is a sensitive and specific diagnostic test in AP. The trypsinogen-2 concentration correlates with the severity of the disease, and a test with a higher cutoff might therefore be useful for prediction of disease severity.Methods: We increased the detection limit of the urinary trypsinogen-2 test strip (Actim Pancreatitis) from 50 μg/L to 2000 μg/L and evaluated the prognostic value of this test. The results were compared with those obtained with serum C-reactive protein and the acute physiology and chronic health evaluation II (APACHE II) score. The study population consisted of 150 consecutive patients with AP (42 with severe disease).Results: The sensitivity of the rapid urinary test strip (detection limit, 2000 μg/L) for prediction of severe AP, both on admission and at 24 h, was 62%; specificities were 87% and 85%, respectively, positive predictive values were 65% and 62%, and negative predictive values were 85% and 85%. C-Reactive protein had a sensitivity of only 38% on admission, but at 24 h, it was 83%; specificities were 90% and 70%, respectively, whereas positive predictive values were 59% and 52%, and NPVs were 79% and 91%, respectively. On admission the positive-likelihood ratio for the urinary trypsinogen-2 test strip was 4.8, and at 24 h it was 4.2; for C-reactive protein, the values were 3.7 and 2.7, respectively.Conclusions: The urinary trypsinogen-2 dipstick is a simple and rapid method for prediction of severe acute pancreatitis.
Detection of Early Pregnancy Forms of Human Chorionic Gonadotropin by Home Pregnancy Test Devices
Authors: Butler Stephen A , Khanlian Sarah A , Cole Laurence A 
Published: January 2020

Abstract
Background: Home pregnancy testing devices claim &gt;99% diagnostic accuracy for pregnancy and utility on the first day of the missed menses or earlier. We investigated the forms of human chorionic gonadotropin (hCG) in early pregnancy urines, the diagnostic accuracy claim, and the abilities of 15 devices to detect the different forms of hCG.
Methods: We measured the concentrations of regular hCG and hyperglycosylated hCG (H-hCG, a large hCG variant) in 592 urines. Fifteen home devices were tested according to manufacturers’ instructions with regular hCG and H-hCG diluted in urine.
Results: H-hCG was the principal hCG-related molecule in pregnancy urine in the 2 weeks following the missed menses (61% and 50% of total immunoreactivity in the 4th and 5th completed weeks of pregnancy, respectively). Of 15 home test devices, 2 had a detection limit of 6.3 IU/L for regular hCG, but poorer detection of H-hCG. Two devices detected 13 IU/L regular hCG, one with similar detection and one with poorer detection of H-hCG. Ten devices detected 25 IU/L regular hCG, 6 with poorer detection of H-hCG. One device detected 50 IU/L regular hCG, but better detected H-hCG. Overall, 9 of 15 devices did not detect H-hCG as well as regular hCG.
Conclusions: H-hCG is the principal hCG immunoreactivity in early pregnancy urine. Home tests vary widely in detection limits for regular hCG (6.3–50 IU/L), and 9 of 15 devices (60%) had poorer detection limits for H-hCG than for hCG. The variation in analytical detection limits appears contradictory to the common claim for all devices of &gt;99% detection of pregnancy on the first day of the missed menses or earlier. We suggest that manufacturers calibrate devices for both hCG and H-hCG and determine the detection rates for pregnancy rather than the proportion of positive results at arbitrary hCG concentrations.
Effect of Outliers and Nonhealthy Individuals on Reference Interval Estimation
Authors: Horn Paul S , Feng Lan , Li Yanmei , Pesce Amadeo J 
Published: January 2020

Abstract
Background: Improvement in reference interval estimation using a new outlier detection technique, even with a physician-determined healthy sample, is examined. The effect of including physician-determined nonhealthy individuals in the sample is evaluated.
Methods: Traditional data transformation coupled with robust and exploratory outlier detection methodology were used in conjunction with various reference interval determination techniques. A simulation study was used to examine the effects of outliers on known reference intervals. Physician-defined healthy groups with and without nonhealthy individuals were compared on real data.
Results: With 5% outliers in simulated samples, the described outlier detection techniques had narrower reference intervals. Application of the technique to real data provided reference intervals that were, on average, 10% narrower than those obtained when outlier detection was not used. Only 1.6% of the samples were identified as outliers and removed from reference interval determination in both the healthy and combined samples.
Conclusions: Even in healthy samples, outliers may exist. Combining traditional and robust statistical techniques provide a good method of identifying outliers in a reference interval setting. Laboratories in general do not have a well-defined healthy group from which to compute reference intervals. The effect of nonhealthy individuals in the computation increases reference interval width by ∼10%. However, there is a large deviation among analytes.
Effect of Hemochromatosis Genotype and Lifestyle Factors on Iron and Red Cell Indices in a Community Population
Authors: Rossi Enrico , Bulsara Max K , Olynyk John K , Cullen Digby J , Summerville Lesa , Powell Lawrie W 
Published: January 2020

Abstract
Background: Heterozygotes for the C282Y mutation of the HFE gene may have altered hematology indices and higher iron stores than wild-type subjects.
Methods: We performed a cross-sectional analysis of 1488 females and 1522 males 20–79 years of age drawn from the Busselton (Australia) population study to assess the effects of HFE genotype, age, gender, and lifestyle on serum iron and hematology indices.
Results: Male C282Y heterozygotes had increased transferrin saturation compared with the wild-type genotype. Neither male nor female heterozygotes had significantly increased ferritin values compared with the wild-type genotype. Younger (20–29 years) wild-type males, but not heterozygous males, had significantly lower ferritin values than wild-type males in the older age groups. Compound heterozygous subjects had increased means for serum iron, transferrin saturation, corpuscular volume, and corpuscular hemoglobin compared with the wild-type genotype, and the males also had increased ferritin values (medians 323 vs 177 μg/L; P = 0.003). In both male and female wild-type subjects, an increased body mass index was associated with decreased serum iron and transferrin saturation and increased ferritin values. There was a significant increase in ferritin concentrations in both genders with increasing frequency of red meat consumption above a baseline of 1–2 times per week and alcohol intakes &gt;10 g/day.
Conclusions: Male C282Y heterozygotes had significantly increased transferrin saturation values. Compound heterozygous (C282Y/H63D) subjects formed a separate category of C282Y heterozygotes in whom both iron and red cell indices were significantly increased compared with the wild-type genotype.
Novel, Aberrantly Truncated Isoform of Serum CD13 in a Family with High Serum Aminopeptidase N (CD13) Activity
Authors: Kawai Makoto , Hara Yukichi , Miyazato Itsuro , Hosaki Seijin 
Published: January 2020

AbstractBackground: We previously reported a family in which the propositus and both her father and paternal grandmother had high serum aminopeptidase N (CD13; EC 3.4.11.2) activity (autosomal dominant). The molecular mass of the serum CD13 polypeptide of the propositus was larger than that of normal CD13, suggesting either a mutation in the CD13 gene or an abnormality in posttranslational modification of CD13 polypeptide in this family.Methods: Reverse transcription-PCR and direct sequencing were performed with leukocyte CD13 mRNA from the propositus. Two-dimensional electrophoresis and N-terminal amino acid sequencing were performed with serum CD13 from the propositus, the father of the propositus, and healthy volunteers.Results: The sequence of the CD13 cDNA of the propositus was essentially identical with that reported previously. However, the CD13 polypeptide of the propositus and the father of the propositus was truncated, lacking amino acids 1–43 of intact CD13 (43-truncated CD13), whereas CD13 lacking residues 1–58 (58-truncated CD13) and 43-truncated CD13 were detected in serum from healthy volunteers.Conclusions: In serum from healthy volunteers, we found both 58-truncated CD13, a major isoform reported previously, and 43-truncated CD13, a novel, minor isoform with a larger polypeptide. In serum of the family, 43-truncated CD13 was extremely concentrated, suggesting that proteolytic cleavage of CD13 amino acids 43 and 44 (43-truncation) is abnormally promoted. Because no mutation was found in the CD13 cDNA from the propositus, increased serum CD13 in this family seems to be caused by a mutation in a gene that regulates 43-truncation protease activity.
Immunofluorometric Assay of Human Kallikrein 10 and Its Identification in Biological Fluids and Tissues
Authors: Luo Liu-Ying , Grass Linda , Howarth David J C , Thibault Pierre , Ong Huy , Diamandis Eleftherios P 
Published: January 2020

Abstract
Background: The human kallikrein 10 gene [KLK10, also known as normal epithelial cell-specific 1 gene (NES1)] is a member of the human kallikrein gene family. The KLK10 gene encodes for a secreted serine protease (hK10). We hypothesize that hK10 is secreted into various biological fluids and that its concentration changes in some disease states. The aim of this study was to develop a sensitive and specific immunoassay for hK10.
Methods: Recombinant hK10 protein was produced and purified using a Pichia pastoris yeast expression system. The protein was used as an immunogen to generate mouse and rabbit polyclonal anti-hK10 antisera. A sandwich-type immunofluorometric assay was then developed using these antibodies.
Results: The hK10 immunoassay has a detection limit of 0.05 μg/L. The assay is specific for hK10 and has no detectable cross-reactivity with other homologous kallikrein proteins, such as prostate-specific antigen (hK3), human glandular kallikrein 2 (hK2), and human kallikrein 6 (hK6). The assay was linear from 0 to 20 μg/L with within- and between-run CVs &lt;10%. hK10 is expressed in many tissues, including the salivary glands, skin, and colon and is also detectable in biological fluids, including breast milk, seminal plasma, cerebrospinal fluid, amniotic fluid, and serum.
Conclusions: We report development of the first immunofluorometric assay for hK10 and describe the distribution of hK10 in biological fluids and tissue extracts. This assay can be used to examine the value of hK10 as a disease biomarker.
Performance Characteristics of a Carbon Isotope Ratio Method for Detecting Doping with Testosterone Based on Urine Diols: Controls and Athletes with Elevated Testosterone/Epitestosterone Ratios
Authors: Aguilera Rodrigo , Chapman Thomas E , Starcevic Borislav , Hatton Caroline K , Catlin Don H 
Published: January 2020

Abstract
Background: Carbon isotope ratio methods are used in doping control to determine whether urinary steroids are endogenous or pharmaceutical.
Methods: Gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) was used to determine the δ13C values for 5β-androstane-3α,17β-diyl diacetate (5βA), 5α-androstane-3α,17β-diyl diacetate (5αA), and 5β-pregnane-3α,20α-diyl diacetate (5βP) in a control group of 73 healthy males and 6 athletes with testosterone/epitestosterone ratios (T/E) &gt;6.
Results: The within-assay precision SDs for 5βA, 5αA, and 5βP were ± 0.27‰, ± 0.38‰, and ± 0.28‰, respectively. The between-assay precision SDs ranged from ± 0.40‰ to ± 0.52‰. The system suitability and batch acceptance scheme is based on SDs. For the control group, the mean δ13C (SD) values were −25.69‰ (± 0.92‰), −26.35‰ (± 0.68‰), and −24.26‰ (± 0.70‰), for 5βA, 5αA, and 5βP, respectively. 5βP was greater than 5βA and 5αA (P &lt;0.01), and 5βA was greater than 5αA (P &lt;0.01). The means − 3 SD were −28.46‰, −28.39‰, and −26.37‰ for 5βA, 5αA, and 5βP, respectively. The maximum difference between 5βP and 5βA was 3.2‰, and the maximum 5βA/5βP was 1.13. Three athletes with chronically elevated T/Es had δ13C values consistent with testosterone administration and three did not.
Conclusions: This GC-C-IRMS assay of urine diols has low within- and between-assay SDs; therefore, analysis of one urine sample suffices for doping control. The means, SDs, ±3 SDs, and ranges of δ13C values in a control group are established. In comparison, testosterone users have low 5βA and 5αA, large differences between 5βA or 5αA and 5βP, and high 5βA/5βP and 5αA/5βP ratios.
Variability and Classification Accuracy of Serial High-Sensitivity C-Reactive Protein Measurements in Healthy Adults
Authors: Ockene Ira S , Matthews Charles E , Rifai Nader , Ridker Paul M , Reed George , Stanek Edward 
Published: January 2020

AbstractBackground: Increased concentrations of high-sensitivity C-reactive protein (hs-CRP), a marker of systemic inflammation, are associated with increased risk for coronary heart disease. Because of its relationship to inflammation, hs-CRP has considerable biologic variation. This study was carried out to characterize CRP variation and to compare it to another risk factor, total serum cholesterol.Methods: One hundred thirteen individuals were scheduled to have five measurements each of hs-CRP and total cholesterol carried out at quarterly intervals over a 1-year period. Variations of hs-CRP and total cholesterol were characterized, and classification accuracy was described and compared for both.Results: The relative variation was comparable for hs-CRP and total cholesterol. When classified by quartile, 63% of first and second hs-CRP measurements were in agreement; for total cholesterol it was 60%. Ninety percent of hs-CRP measurements were within one quartile of each other. This relationship was not altered by the use of log-transformed hs-CRP data.Conclusion: hs-CRP has a degree of measurement stability that is similar to that of total cholesterol.
Solid-Phase PCR with Hybridization and Time-resolved Fluorometry for Detection of HLA-B27
Authors: Sjöroos Minna , Ilonen Jorma , Lövgren Timo 
Published: January 2020

Abstract
Background: Preactivated solid surfaces provide new possibilities for multiple consecutive reactions in a microtiter plate format. In this study, a combination of PCR and subsequent hybridization in the same microtiter well was applied for the detection of HLA-B27 alleles.
Methods: A multiplex solid-phase PCR to amplify the HLA-B27 alleles together with β-actin as an amplification control gene was performed on the NucleoLinkTM (Nunc) surface. PCR was followed by hybridization and detection with time-resolved fluorescence. For the covalent capture of the PCR primers onto the solid support via a 1-(3-dimethylamino-propyl)-3-ethylcarbodiimide hydrochloride-mediated reaction, different 5′-end modifications of oligonucleotides were tested [amination, phosphorylation, and a poly(dT)10 linker].
Results: For covalent immobilization of the primers, amination of the 5′ end combined with use of the poly(dT)10 linker was superior. At least 19.5% of the primer added per well was attached via a stable bond. When the standard time-resolved, fluorescence-based HLA-B27 detection system was compared with the newly developed method in a sample series of 82 genomic DNAs and the corresponding dried-blood spots, all results were in full agreement.
Conclusions: The new solid-phase PCR approach can be applied for multiple-target DNA detection. PCR followed by hybridization can be accomplished in a few hours using precoated strips and dried-blood spot PCR templates.
Biochemical Markers of Bone Formation in Patients with Plasma Cell Dyscrasias and Benign Osteoporosis
Authors: Woitge Henning W , Horn Eva , Keck Andrea V , Auler Beatrice , Seibel Markus J , Pecherstorfer Martin 
Published: January 2020

AbstractBackground: Myeloma-induced bone loss is related to an uncoupling of bone formation and bone resorption. The aim of the present study was to assess the potential clinical value of biochemical markers of bone formation in the work up of patients with plasma cell dyscrasias.Methods: Serum total alkaline phosphatase, bone-specific alkaline phosphatase (BAP), and osteocalcin (OC) were measured in 43 patients with newly diagnosed multiple myeloma (MM), in 40 patients with monoclonal gammopathy of undetermined significance (MGUS), in 40 patients with untreated benign vertebral osteoporosis (OPO), and in 48 healthy adults.Results: In MM and MGUS patients, serum BAP, but not serum OC, was lower than in healthy controls (P &lt;0.05). Serum OC was higher in patients with OPO than in healthy controls (P &lt;0.05). The strongest associations between markers were found in OPO patients and in healthy adults. MM patients with early-stage disease or without detectable osteolysis had decreased serum BAP values (P &lt;0.05). Serum OC was higher in MM patients with stage III disease (P &lt;0.05) than in healthy controls. MM patients with OPO-like bone involvement had lower BAP values than sex- and age-matched MGUS patients with OPO-like bone involvement and patients with benign OPO (P &lt;0.05).Conclusions: In patients with plasma cell dyscrasias, serum BAP, rather than serum OC, appears to reflect a suppressed bone formation rate and may be helpful in the differentiation between benign and myeloma-induced OPO. However, the overall clinical use of biochemical markers of bone formation in patients with plasma cell dyscrasia appears limited.
Molecular Diagnosis of Mycobacteria
Authors: Soini Hanna , Musser James M 
Published: January 2020

AbstractTuberculosis is one of the leading infectious diseases in the world and is responsible for more than 2 million deaths and 8 million new cases annually. Because of the slow growth rate of the causative agent Mycobacterium tuberculosis, isolation, identification, and drug susceptibility testing of this organism and other clinically important mycobacteria can take several weeks or longer. During the past several years, many molecular methods have been developed for direct detection, species identification, and drug susceptibility testing of mycobacteria. These methods can potentially reduce the diagnostic time from weeks to days. Currently, two nucleic acid amplification methods, the Enhanced Mycobacterium tuberculosis Direct Test (Gen-Probe) and the Amplicor Mycobacterium tuberculosis Test (Roche Diagnostic Systems), have been approved by the Food and Drug Administration for direct detection of M. tuberculosis from clinical specimens. PCR-based sequencing has become commonly used to identify many mycobacterial species. DNA probes have been widely used for species determination of the most commonly encountered mycobacteria. High-density oligonucleotide arrays (DNA microarrays) also have been applied to simultaneous species identification and detection of mutations that confer rifampin resistance in mycobacteria.
Development of a Rapid and Sensitive Immunofluorometric Assay for Glutathione S-Transferase A
Authors: Dajani Laila K , Paus Elisabeth , Warren David J 
Published: January 2020

Abstract
Background: The short half-life of the α-class glutathione S-transferases (GSTAs) in plasma combined with their even distribution throughout the liver lobule suggests that they may be useful complements to the more traditionally used liver markers. However, the currently available assays for measuring GSTAs in biological fluids have a poor dynamic range and are cumbersome, requiring multiple steps and prolonged incubation times.
Methods: Hybridomas that secrete monoclonal antibodies to human GSTAs were produced and used to develop a rapid one-step immunometric assay for the determination of GSTA in serum. The assay uses a time-resolved immunofluorometric assay (TR-IFMA) format and requires 35 min of incubation. The reference interval was determined using 208 serum samples from healthy blood donors. We also compared our TR-IFMA with a commercially available enzyme immunoassay (EIA) for GSTAs.
Results: The assay had a detection limit of 0.07 μg/L with a measuring range up to 625 μg/L. Within-run imprecision (CV) was 1.8–2.6% over the concentrations of GSTA tested (2.5–311 μg/L), with a between-run CV of &lt;5%. In healthy blood donors, the median values and reference intervals were 2.0 μg/L and 0.6–7.2 μg/L for females and 2.6 μg/L and 0.7–9.8 μg/L for males, respectively. GSTA concentrations determined with the TR-IFMA correlated well with those obtained using a commercially available EIA.
Conclusions: This report describes a new assay for monitoring the concentrations of GSTAs in human serum. The method may be useful in further evaluating the potential of monitoring serum GSTAs in the routine clinical setting.
Analysis of Volatile Disease Markers in Blood
Authors: Miekisch Wolfram , Schubert Jochen K , Vagts Dierk A , Geiger Klaus 
Published: January 2020

AbstractBackground: The diagnostic potential of breath analysis has been limited by a lack of knowledge on origin, distribution, and metabolism of the exhaled substances. To overcome this problem, we developed a method to assess trace amounts of hydrocarbons (pentane and isoprene), ketones (acetone), halogenated compounds (isoflurane), and thioethers (dimethyl sulfide) in the blood of humans and animals.Methods: Arterial and venous blood samples were taken from mechanically ventilated patients. Additional blood samples were taken from selected vascular compartments of 19 mechanically ventilated pigs. Volatile substances were concentrated by means of solid-phase microextraction (SPME), separated by gas chromatography, and identified by mass spectrometry.Results: Detection limits were 0.02–0.10 nmol/L. Venous concentrations in pigs were 0.2–1.3 nmol/L for isoprene, 0–0.3 nmol/L for pentane, and 1.2–15.1 nmol/L for dimethyl sulfide. In pigs, substances were not equally distributed among vascular compartments. In humans, median arteriovenous concentration differences were 3.58 nmol/L for isoprene and 1.56 nmol/L for pentane. These values were comparable to pulmonary excretion rates reported in the literature. Acute respiratory distress syndrome (ARDS) patients had lower isoprene concentration differences than patients without ARDS.Conclusions: The SPME method can detect volatile substances in very low concentrations in the blood of humans and animals. Analysis of volatile substances in vascular compartments will enlarge the diagnostic potential of breath analysis.