bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of cardiac troponin subunit release into serum after acute myocardial infarction and comparison of assays for troponin T and I
Authors: Wu Alan H B , Feng Yue-Jin , Moore Robert , Apple Fred S , McPherson Paul H , Buechler Kenneth F , Bodor Geza , for for the American Association , Standardization Clinical Chemistry Subcommittee on cTnI 
Published: July 2020

Abstract
We examined the release of cardiac troponin T (cTnT) and I (cTnI) into the blood of patients after acute myocardial infarction (AMI). Three postAMI serum samples were applied in separate analytical runs onto a calibrated gel filtration column (Sephacryl S-200), and the proteins were separated by molecular weight. Using commercial cTnT and cTnI assays measured on collected fractions, we found that troponin was released into blood as a ternary complex of cTnT-I-C, a binary complex of cTnI-C, and free cTnT, with no free cTnI within the limits of the analytical methodologies. The serum samples were also examined after incubation with EDTA and heparin. EDTA broke up troponin complexes into individual subunits, whereas heparin had no effect on the assays tested. We added free cTnC subunits to 24 AMI serum samples and found no marked increase in the total cTnI concentrations, using an immunoassay that gave higher values for the cTnI-C complex than free cTnI. To characterize the cross-reactivity of cTnT and cTnI assays, purified troponin standards in nine different forms were prepared, added to serum and plasma pools, and tested in nine quantitative commercial and pre-market assays for cTnI and one approved assay for cTnT. All nine cTnI assays recognized each of the troponin I forms (complexed and free). In five of these assays, the relative responses for cTnI were nearly equimolar. For the remainder, the response was substantially greater for complexed cTnI than for free cTnI. Moreover, there was a substantial difference in the absolute concentration of results between cTnI assays. The commercial cTnT assay recognized binary and ternary complexes of troponin on a near equimolar basis. We conclude that all assays are useful for detection of cardiac injury. However, there are differences in absolute cTnI results due to a lack of mass standardization and heterogeneity in the cross-reactivities of antibodies to various troponin I forms.
Biochemical hallmarks of tyrosine hydroxylase deficiency
Authors: Bräutigam Christa , Wevers Ron A , Jansen Riet J T , Smeitink Jan A M , Andel Johanneke F de Rijk-van , Gabreëls Fons J M , Hoffmann Georg F 
Published: July 2020

AbstractWe report the biochemical hallmarks of tyrosine hydroxylase deficiency with emphasis on reliable diagnostic strategies of four new cases of an inborn error of tyrosine hydroxylase (TH). Three of our patients from different parts of the Netherlands were found homozygous for a mutation in exon 6 (G698A) of the TH gene, and one patient was found compound heterozygous for the same mutation and an additional mutation in exon 3. The first clinical symptoms of hypokinesia, rigidity of arms and legs and axial hypotonia, developed between 3 and 7 months of age. Cerebrospinal fluid investigations revealed a characteristic metabolite constellation in every case: low homovanillic acid (HVA) and 3-methoxy-4-hydroxy-phenylethyleneglycol concentrations in the presence of normal reference range 5-hydroxyindolacetic acid concentrations. Strict adherence to a standardized lumbar puncture protocol and adequate age-related reference values are essential for diagnosis of this “new” treatable neurometabolic disorder. Urinary measurements of HVA, vanillylmandelic acid, and catecholamines can lead to false-negative conclusions. All patients showed a remarkable clinical improvement on a low dose of l-dihydroxyphenylalanine/(S)-2-(3,4-dihydroxybenzyl)-2-hydrazinpropionic acid. During treatment, cerebrospinal fluid HVA, and 3-methoxy-4-hydroxy-phenylethyleneglycol increased substantially.
Miniaturization of analytical systems
Authors: Kricka Larry J 
Published: July 2020

Abstract
Miniaturization has been a long-term trend in clinical diagnostics instrumentation. Now a range of new technologies, including micromachining and molecular self-assembly, are providing the means for further size reduction of analyzers to devices with micro- to nanometer dimensions and submicroliter volumes. Many analytical techniques (e.g., mass spectrometry and electrophoresis) have been successfully implemented on microchips made from silicon, glass, or plastic. The new impetus for miniaturization stems from the perceived benefits of faster, easier, less costly, and more convenient analyses and by the needs of the pharmaceutical industry for microscale, massively parallel drug discovery assays. Perfecting a user-friendly interface between a human and a microchip and determining the realistic lower limit for sample volume are key issues in the future implementation of these devices. Resolution of these issues will be important for the long-term success of microminiature analyzers; in the meantime, the scope, diversity, and rate of progress in the development of these devices promises products in the near future.
Escalation firebreaks in the cyber, conventional, and nuclear domains: moving beyond effects-based logics
Authors: Kreps Sarah , Schneider Jacquelyn 
Published: July 2020

Abstract
Despite the growing literature on cyber security, most studies have sidestepped important questions of how conflict escalates in the cyber domain. To better understand this dynamic, we advance two main theoretical pathways of escalation, one in which actors respond with increasing intensity based on the effect of an attack, irrespective of how it is conducted (through cyber, conventional, or nuclear) and another in which the means of attack determines the actor’s willingness to escalate. We then test those effects- and means-based pathways with an original experiment that probes support for escalation, focusing on the American public, a key actor in debates about nuclear escalation and deterrence. Our study suggests that cyberattacks create a threshold that restrains the escalation of conflict. Americans are less likely to support retaliation with force when the scenario involves a cyberattack even when they perceive the magnitude of attacks across domains to be comparable. Our findings provide support for cyber strategies based on assumptions of cyber thresholds, while also casting doubt on the credibility of cyber deterrence by punishment. More broadly, our research suggests effects-based theories of escalation may not help understand the impact of emerging technologies on strategic stability.
Ventricular fibrillation associated with vasospastic angina pectoris in Fabry disease: a case report
Authors: Kodama Kenji , Ozawa Tomoya , Dochi Kenichi , Ueno Yoshiki 
Published: July 2020

Abstract

Background
Fabry disease (FD) is an X-linked lysosomal storage disorder resulting from a deficiency in alpha-galactosidase A. The major causes of death due to cardiac complications include life-threatening arrhythmias. In addition, life-threatening arrhythmias may be related to myocardial fibrosis assessed by late gadolinium enhancement (LGE).

Case summary
A 43-year-old man with sinus bradycardia and left ventricular hypertrophy was referred to our cardiology department. Family history includes unexplained hypertrophy and sick sinus syndrome in mother. Additionally, his plasma alpha-galactosidase A activity was low. He was subsequently diagnosed with FD. Enzyme replacement therapy using 1.0 mg/kg agalsidase-β was initiated. During the fifth administration, he developed ventricular fibrillation (VF). Electrocardiography conducted immediately before VF revealed ST elevation in the inferior leads with reciprocated ST depression. Cardiac magnetic resonance imaging showed no LGE in the myocardium. Coronary angiography showed no organic stenosis; moreover, coronary spasms were induced by an intracoronary acetylcholine injection. Ventricular fibrillation was not observed as the patient received calcium antagonists.

Discussion
This report suggests that vasospastic angina pectoris is associated with life-threatening arrhythmias in patient with FD without LGE.
Incidence, characteristics, determinants, and prognostic impact of recurrent syncope
Authors: Zimmermann Tobias , du Fay de Lavallaz Jeanne , Nestelberger Thomas , Gualandro Danielle M , Strebel Ivo , Badertscher Patrick , Lopez-Ayala Pedro , Widmer Velina , Freese Michael , Miró Òscar , Christ Michael , Cullen Louise , Than Martin , Martin-Sanchez F Javier , Di Somma Salvatore , Peacock W Frank , Keller Dagmar I , Boeddinghaus Jasper , Twerenbold Raphael , Wussler Desiree , Koechlin Luca , Walter Joan E , Bürgler Franz , Geigy Nicolas , Kühne Michael , Reichlin Tobias , Lohrmann Jens , Mueller Christian 
Published: July 2020

AbstractAims The aim of this study is to characterize recurrent syncope, including sex-specific aspects, and its impact on death and major adverse cardiovascular events (MACE).Methods and resultsWe characterized recurrent syncope in a large international multicentre study, enrolling patients ≥40 years presenting to the emergency department (ED) with a syncopal event within the last 12 h. Syncope aetiology was centrally adjudicated by two independent cardiologists using all information becoming available during syncope work-up and long-term follow-up. Overall, 1790 patients were eligible for this analysis. Incidence of recurrent syncope was 20% [95% confidence interval (CI) 18–22%] within the first 24 months. Patients with an adjudicated final diagnosis of cardiac syncope (hazard ratio (HR) 1.50, 95% CI 1.11–2.01) or syncope with an unknown aetiology even after central adjudication (HR 2.11, 95% CI 1.54–2.89) had an increased risk for syncope recurrence. Least Absolute Shrinkage and Selection Operator regression fit on all patient information available early in the ED identified &gt;3 previous episodes of syncope as the only independent predictor for recurrent syncope (HR 2.13, 95% CI 1.64–2.75). Recurrent syncope carried an increased risk for death (HR 1.87, 95% CI 1.26–2.77) and MACE (HR 2.69, 95% CI 2.02–3.59) over 24 months of follow-up, however, with a time-dependent effect. These findings were confirmed in a sensitivity analysis excluding patients with syncope recurrence or MACE before or during ED evaluation.Conclusion Recurrence rates of syncope are substantial and vary depending on syncope aetiology. Importantly, recurrent syncope carries a time-dependent increased risk for death and MACE.Trial registrationBAsel Syncope EvaLuation (BASEL IX, ClinicalTrials.gov registry number NCT01548352).
Fine-scale population structure in the UK Biobank: implications for genome-wide association studies
Authors: Cook James P , Mahajan Anubha , Morris Andrew P 
Published: July 2020

Abstract
The UK Biobank is a prospective study of more than 500 000 participants, which has aggregated data from questionnaires, physical measures, biomarkers, imaging and follow-up for a wide range of health-related outcomes, together with genome-wide genotyping supplemented with high-density imputation. Previous studies have highlighted fine-scale population structure in the UK on a North-West to South-East cline, but the impact of unmeasured geographical confounding on genome-wide association studies (GWAS) of complex human traits in the UK Biobank has not been investigated. We considered 368 325 white British individuals from the UK Biobank and performed GWAS of their birth location. We demonstrate that widely used approaches to adjust for population structure, including principal component analysis and mixed modelling with a random effect for a genetic relationship matrix, cannot fully account for the fine-scale geographical confounding in the UK Biobank. We observe significant genetic correlation of birth location with a range of lifestyle-related traits, including body-mass index and fat mass, hypertension and lung function, even after adjustment for population structure. Variants driving associations with birth location are also strongly associated with many of these lifestyle-related traits after correction for population structure, indicating that there could be environmental factors that are confounded with geography that have not been adequately accounted for. Our findings highlight the need for caution in the interpretation of lifestyle-related trait GWAS in UK Biobank, particularly in loci demonstrating strong residual association with birth location.
No Change in Surgical and Hospitalization Trends Despite Higher Exposure to Anti-Tumor Necrosis Factor in Inflammatory Bowel Disease in the Québec Provincial Database From 1996 to 2015
Authors: Verdon Christine , Reinglas Jason , Coulombe Janie , Gonczi Lorant , Bessissow Talat , Afif Waqqas , Vutcovici Maria , Wild Gary , Seidman Ernest G , Bitton Alain , Brassard Paul , Lakatos Peter L 
Published: July 2020

Abstract

Background
Crohn disease (CD) and ulcerative colitis (UC) have high health care expenditures because of medications, hospitalizations, and surgeries. We evaluated disease outcomes and treatment algorithms of patients with inflammatory bowel disease (IBD) in Québec, comparing periods before and after 2010.

Methods
The province of Québec’s public health administrative database was used to identify newly diagnosed patients with IBD between 1996 and 2015. The primary and secondary outcomes included time to and probability of first and second IBD-related hospitalizations, first and second major surgery, and medication exposures. Medication prescriptions were collected from the public prescription database.

Results
We identified 34,644 newly diagnosed patients with IBD (CD = 59.5%). The probability of the first major surgery increased after 2010 in patients with CD (5 years postdiagnosis before and after 2010: 8% [SD = 0.2%] vs 15% [SD = 0.6%]; P &lt; 0.0001) and patients with UC (6% [SD = 0.2%] vs 10% [SD = 0.6%] ;P &lt; 0.0001). The probability of the second major surgery was unchanged in patients with CD. Hospitalization rates remained unchanged. Patients on anti-tumor necrosis factor (anti-TNF) medications had the lowest probability of hospitalizations (overall 5-year probability in patients with IBD stratified by maximal therapeutic step: 5-aminosalicylic acids 37% [SD = 0.6%]; anti-TNFs 31% [SD = 1.8%]; P &lt; 0.0001). Anti-TNFs were more commonly prescribed for patients with CD after 2010 (4% [SD = 0.2%] vs 16% [SD = 0.6%]; P &lt; 0.0001) in the public health insurance plan, especially younger patients. Corticosteroid exposure was unchanged before and after 2010. Immunosuppressant use was low but increased after 2010. The use of 5-ASAs was stable in patients with UC but decreased in patients with CD.

Conclusions
The probability of first and second hospitalizations remained unchanged in Québec and the probability of major surgery was low overall but did increase despite the higher and earlier use of anti-TNFs.
Persistent COVID-19 in an Immunocompromised Patient Temporarily Responsive to Two Courses of Remdesivir Therapy
Authors: Helleberg Marie , Niemann Carsten Utoft , Moestrup Kasper Sommerlund , Kirk Ole , Lebech Anne-Mette , Lane Clifford , Lundgren Jens 
Published: July 2020

Abstract
The antiviral drug remdesivir has been shown clinically effective for treatment of COVID-19. We here demonstrate suppressive but not curative effect of remdesivir in an immunocompromised patient. A man in his fifties treated with chemoimmunotherapy for chronic lymphocytic leukemia experienced a 9-week course of COVID-19 with high fever and severe viral pneumonia. During two 10-day courses of remdesivir starting 24 and 45 days after fever onset, pneumonia and spiking fevers remitted, but relapsed after discontinuation. Kinetics of temperature, C-reactive protein, and lymphocyte counts mirrored the remitting/relapsing SARS-CoV-2 infection. Combination therapy or longer treatment duration may be needed in immunocompromised patients.
Accelerated Solvent Extraction of Vitamin K1 in Medical Foods in Conjunction with Matrix Solid-Phase Dispersion
Authors: Chase G William , Thompson Brian 
Published: July 2020

Abstract
An extraction technique is described for vitamin K1 in medical foods, using accelerated solvent extraction (ASE) in conjunction with matrix solid-phase dispersion (MSPD). The medical food sample is treated as it would be with MSPD extraction, followed by ASE for a hands-free automated extraction. The vitamin K1 in the ASE extract is then quantitated by reversed-phase liquid chromatography with fluorescence detection. The chromatography specifications are identical to those in previous work that used MSPD only, with a limit of detection of 6.6 pg and a limit of quantitation of 22 pg on column. Recoveries, which were determined for an analyte-fortified zero control reference material for medical foods, averaged 97.6% (n = 25) for vitamin K1. The method provides a rapid, automatic, specific, and easily controlled assay for vitamin K1 in fortified medical foods with minimal solvent usage.
Determination of Lead, Cadmium, Zinc, Copper, and Iron in Foods by Atomic Absorption Spectrometry after Microwave Digestion: NMKL1 Collaborative Study
Authors: Jorhem Lars , Engman Joakim ,   Collaborators:, Arvidsson B-M , Åsman B , Åstrand C , Gjerstad K O , Haugsnes J , Heldal V , Holm K , Jensen A M , Johansson M , Jonsson L , Liukkonen-Lilja H , Niemi E , Thorn C , Utterström K , Venäläinen E-R , Waaler T 
Published: July 2020

Abstract
A method for determination of lead, cadmium, zinc, copper, and iron by atomic absorption spectrometry (AAS) after microwave digestion was subjected to a collaborative study in which 16 laboratories participated [including users of inductively coupled plasma (ICP) and ICP–mass spectrometry (MS)]. The types of samples included in the study were minced fish, wheat bran, milk powder, bovine and pig liver, mushroom, 2 simulated diets, and bovine muscle; the last 4 were certified reference materials. These were analyzed as single (4 samples), double blind (1 sample), or split level (2 samples) samples. Before the collaborative study, a pretrial was conducted in which 4 ready-made solutions and one fish tissue sample were analyzed for Pb and Cu. The reproducibility relative standard deviation (RSDR) values, for results above the detection limit, ranged from 59% at 0.155 mg/kg to 16% at 1.62 mg/kg for Pb, from 28% at 0.0124 mg/kg to 11% at 0.482 mg/kg for Cd, from 9.3% at 35.3 mg/kg to 1.7% at 147 mg/kg for Zn, from 39% at 0.241 mg/kg to 3.0% at 63.4 mg/kg for Cu, and from 17% at 7.4 mg/kg to 5.9% at 303 mg/kg for Fe. The RSDR values agreed well with the norms described by the International Union of Pure and Applied Chemistry. As a complement to the AAS determinations, a number of laboratories analyzed the samples either by ICP or by ICP–MS. The results of these analyses agreed well with the AAS results. On the basis of the results of the collaborative study, the method was adopted Official First Action by AOAC INTERNATIONAL.
Semi-Automated Direct Epifluorescent Filter Technique for Total Bacterial Count in Raw Milk
Authors: Hermida María , Taboada Margarita , Menéndez Santiago , Rodríguez-Otero José Luis 
Published: July 2020

Abstract
The Direct Epifluorescent Filter Technique (DEFT) and the reference method of counting total bacterial colonies on Petri dishes were compared. IDF Standards 128 (1985) and 161A (1995) were applied. A total of 496 samples of milk were analyzed. Colony forming units per μL milk were transformed to decimal logarithmic units: log (cfu/μL). The repeatability standard deviation, Sr = 0.114, was typical for a routine microbiological method. To study the carryover at different levels of bacteria, 3 tests were performed on milk samples of approximately 100, 700, and &gt;1000 cfu/μL. For the first 2 experiments, no carryover was detected; in the milk sample with &gt;1000 cfu/μL, the carryover was &lt;0.12%. When the DEFT counts were regressed versus the reference method, the values of the slope and intercept were 0.92 and 0.17, respectively; the correlation coefficient was r = 0.84; and the residual standard deviation was Syx = 0.287. The paired t-test showed that the reference method and DEFT do not give significantly different results (p = 0.05).
Determination of Iodine-131 at Low Levels in Milk: Collaborative Study
Authors: Baratta Edmong J , Easterly David G ,   Collaborators:, Bell S A , Cheng C-S , Daly J , Fuhrmann G C , Kapish J B , Kingan K L , Larsen I L , Schlenker J M , Sheibley R H , Silverstone M , Uyesugi G S 
Published: July 2020

Abstract
The official method for the determination of iodine-131 in milk has a lower limit of detection (LLD) of 10 pCi/L (0.37 Bq/L). The Nuclear Regulatory Commission had recommended that a method claiming to have an LLD of &lt;0.3 pCi/L (&lt;1.1E-02 Bq/L) be used. That method, which is capable of measuring iodine-131 below the level of detection of the Official Method, was collaboratively studied. The method uses a palladium iodide precipitate to concentrate the iodine-131 and measures (counts) its 364 keV gamma energy in coincidence with the beta decay or with a low-background beta-counting system. The study was performed by using 3 concentrations of iodine- 131 in milk: 2.6, 5.0, and 8.0 pCi/L (9.62E-02, 1.85E-01, and 2.96E-01 Bq/L, respectively). Eleven laboratories agreed to participate in the study. Eight laboratories submitted data for the study. The averages of the results were 2.68, 5.30, and 8.12 pCi/L (9.92E-02, 1.96E-01, and 3.00E-01 Bq/L, respectively), respectively. The intra- and interlaboratory variations were acceptable. The method was adopted First Action by AOAC INTERNATIONAL.
Investigation of Ketoconazole Copper(II) and Cobalt(II) Complexes and Their Spectrophotometric Applications
Authors: El-Ragehy Nirman A , El-Saharty Yasser S 
Published: July 2020

Abstract
Ketoconazole, as a ligand, reacts quantitatively with copper(II) and cobalt(II) to form blue-colored, stable complexes in dichloromethane. These complexes can be spectrophotometrically measured at 720 and 612.5 nm in the case of Cu(II) or Co(II), respectively. Different factors affecting the reaction such as pH, reagent concentration, solvent effect, and time were studied. By using Job's method of continuous variation, the stoichiometry of the reaction was found to be in the ratio of 1:2, metal:drug, with Cu(II) and Co(II). The stability of the complexes formed was also studied. The reaction products were isolated for further investigation. The complexes have apparent molar absorptivities of 35.36 ± 1.95 and 59.62 ± 1.87 for Cu(II) and Co(II), respectively. Suggested procedures based on the stoichiometric reaction were successfully applied to the analysis of the pure drug and its pharmaceutical formulations. The validity of the procedures was further ascertained by the method of standard additions. The developed method was found to be simple, accurate, and precise when compared with the official method of the British Pharmacopoeia.