bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polymorphisms in the Transcobalamin Gene: Association with Plasma Homocysteine in Healthy Individuals and Vascular Disease Patients
Authors: Lievers Karin JA , Afman Lydia A , Kluijtmans Leo AJ , Boers Godfried HJ , Verhoef Petra , den Heijer Martin , Trijbels Frans JM , Blom Henk J 
Published: January 2020

AbstractBackground: Hyperhomocysteinemia is an independent risk factor for cardiovascular disease (CVD). Intracellular vitamin B12 deficiency may lead to increased plasma total homocysteine (tHcy) concentrations and because transcobalamin (TC) is the plasma transporter that delivers vitamin B12 to cells, genetic variation in the TC gene may affect intracellular vitamin B12 availability and, consequently, tHcy concentrations.Methods: We examined five sequence variants, i.e., I23V, G94S, P259R, S348F, and R399Q, in the TC gene as possible determinants of tHcy and, concordantly, as possible risk factors for CVD in 190 vascular disease patients and 601 controls. We also studied potential effect-modification of vitamin B12 by genotype.Results: In individuals with high vitamin B12, 259PP individuals had lower tHcy concentrations than 259PR and 259RR individuals. Homozygous 23VV individuals had lower fasting tHcy concentrations than their 23IV and 23II peers. None of the genotypes defined by the three other sequence variants showed an association with tHcy concentrations, nor was any TC genotype associated with an increased CVD risk.Conclusions: In individuals in the highest quartile of the vitamin B12 distribution (&gt;299 pmol/L), tHcy concentrations are lower in 259PP homozygotes than in 259PR and 259RR individuals. Therefore, 259PP individuals, who represent &gt;25% of the general population, may be more susceptible to reduction of plasma tHcy concentrations by increasing the vitamin B12 status.
Quantitative and Compositional Study of Cardiolipin in Platelets by Electrospray Ionization Mass Spectrometry: Application for the Identification of Barth Syndrome Patients
Authors: Valianpour Fredoen , Wanders Ronald JA , Barth Peter G , Overmars Henk , van Gennip Albert H 
Published: January 2020

AbstractBackground: The concentration of cardiolipin (CL) in cultured skin fibroblasts is a useful indicator of Barth syndrome (BTHS; MIM 302060), but the sampling and culturing of fibroblasts are burdensome and time-consuming procedures. We investigated whether the analysis of CL in platelets might help to identify BTHS in patients suspected of having this condition.Methods: We used HPLC and online electrospray ionization mass spectrometry (HPLC-ESI-MS) to quantify CL molecular species. The CL content of platelets was studied in blood samples of BTHS and non-BTHS patients. Control blood samples drawn from healthy adults were collected and analyzed within 24 h (n = 10) and 48 h (n = 10) to characterize any effect of sample shipping time on the CL content in platelets. Samples were collected from children 1–10 years of age who were not affected by BTHS (n = 6) and from BTHS patients (n = 4) and analyzed within 24 h. Results for all four groups were compared by a Student t-test for all individual analyses.Results: We found different CL molecular species, e.g., (C18:2)4-CL. BTHS patients had a specific decrease of tetralinoleyl-CL concentrations in platelets (0.1–0.5 nmol/mg of protein; n = 4) compared with all control groups (2.3–5.5 nmol/mg of protein; n = 26). Only minor differences were observed among the different control groups.Conclusions: Quantitative and compositional analyses of CL in platelets by the proposed method allow identification of BTHS patients more rapidly than gene analysis or analysis of CL in cultured skin fibroblasts. The abnormality of CL may explain the abnormal mitochondrial function observed in BTHS. The differences between the control groups did not cause any complication.
Flow Cytometric Quantification of Competitive Reverse Transcription-PCR Products
Authors: Wedemeyer Niels , Pötter Thomas , Wetzlich Steffi , Göhde Wolfgang 
Published: January 2020

Abstract
Background: Competitive PCR of reverse transcribed mRNA sequences is used to quantify transcripts, but the usual approaches are labor-intensive and time-consuming. We describe the non-gel-based quantification of competitive reverse transcription (RT)-PCR products with use of microparticles and flow cytometry.
Methods: PCR products of a target sequence and an internal control sequence (competitor) were labeled during PCR using digoxigenin (DIG)- and dinitrophenol (DNP)-labeled primer, respectively, allowing specific binding to microparticles coated with the corresponding antibody. Both amplification products were biotinylated to enable fluorescence labeling with streptavidin-R-phycoerythrin. The mean fluorescence intensity of each microparticle population, corresponding to the amount of bound PCR product, was measured in a flow cytometer. We constructed microparticles coated with antibodies against DIG and DNP to specifically capture PCR products derived from target and competitor sequences, respectively.
Results: As required for a reliable competitive PCR assay, nearly identical kinetics were found for the amplification of target and competitor sequences when using only one competitive primer. The method was applied to examine interleukin-8 expression in human lymphocytes after x-irradiation. One hour after irradiation, the concentration of transcripts decreased by half.
Conclusions: The flow cytometric assay for the quantification of competitive RT-PCR products avoids additional hybridization steps and antibody labeling. The use of paramagnetic microparticles would also enable the complete automation of this method.
Single-Point Cardiac Troponin T at Coronary Care Unit Discharge after Myocardial Infarction Correlates with Infarct Size and Ejection Fraction
Authors: Panteghini Mauro , Cuccia Claudio , Bonetti Graziella , Giubbini Raffaele , Pagani Franca , Bonini Elena 
Published: January 2020

Abstract
Background: One of the major concerns in replacing creatine kinase MB (CK-MB) with cardiac troponins is the lack of evidence of the ability of troponins to estimate the size of acute myocardial infarction (AMI). We investigated the ability of a single measurement of cardiac troponin T (cTnT) at coronary care unit (CCU) discharge to estimate infarct size and assess left ventricular (LV) function in AMI patients.
Methods: We studied 65 AMI patients in whom infarct size was estimated by CK-MB peak concentrations and gated single-photon emission computed tomography (SPECT) myocardial perfusion using technetium-99m sestamibi and LV function by SPECT imaging. Measurements of cTnT and SPECT were performed 72 h (median) after admission (range, 40–160 h). SPECT was also repeated 3 months later.
Results: We found a significant correlation between cTnT and both the peak CK-MB concentrations (r = 0.76; P &lt;0.001) and the perfusion defect size at SPECT (r = 0.62; P &lt;0.001). cTnT was inversely related to LV ejection fraction (LVEF) assessed both early (r = −0.56; P &lt;0.001) and 3 months after AMI (r = −0.70; P &lt;0.001). cTnT &gt;2.98 μg/L predicted a LVEF &lt;40% at 3 months with a sensitivity of 86.7%, specificity of 81.4%, and a likelihood ratio for a positive test of 4.7 (95% confidence interval, 4.0–5.4).
Conclusions: A single cTnT measurement at CCU discharge after AMI is useful as a noninvasive estimate of infarct size and for the assessment of LV function in routine clinical setting.
Serum Reference Intervals and Diagnostic Ranges for Free κ and Free λ Immunoglobulin Light Chains: Relative Sensitivity for Detection of Monoclonal Light Chains
Authors: Katzmann Jerry A , Clark Raynell J , Abraham Roshini S , Bryant Sandra , Lymp James F , Bradwell Arthur R , Kyle Robert A 
Published: January 2020

AbstractBackground: The detection of monoclonal free light chains (FLCs) is an important diagnostic aid for a variety of monoclonal gammopathies and is especially important in light-chain diseases, such as light-chain myeloma, primary systemic amyloidosis, and light-chain-deposition disease. These diseases are more prevalent in the elderly, and assays to detect and quantify abnormal amounts of FLCs require reference intervals that include elderly donors.Methods: We used an automated immunoassay for FLCs and sera from a population 21–90 years of age. We used the calculated reference and diagnostic intervals to compare FLC results with those obtained by immunofixation (IFE) to detect low concentrations of monoclonal κ and λ FLCs in the sera of patients with monoclonal gammopathies.Results: Serum κ and λ FLCs increased with population age, with an apparent change for those &gt;80 years. This trend was lost when the FLC concentration was normalized to cystatin C concentration. The ratio of κ FLC to λ FLC (FLC K/L) did not exhibit an age-dependent trend. The diagnostic interval for FLC K/L was 0.26–1.65. The 95% reference interval for κ FLC was 3.3–19.4 mg/L, and that for λ FLC was 5.7–26.3 mg/L. Detection and quantification of monoclonal FLCs by nephelometry were more sensitive than IFE in serum samples from patients with primary systemic amyloidosis and light-chain-deposition disease.Conclusions: Reference and diagnostic intervals for serum FLCs have been developed for use with a new, automated immunoassay that makes the detection and quantification of monoclonal FLCs easier and more sensitive than with current methods. The serum FLC assay complements IFE and allows quantification of FLCs in light-chain-disease patients who have no detectable serum or urine M-spike.
Selection, Preparation, and Characterization of Commutable Frozen Human Serum Pools as Potential Secondary Reference Materials for Lipid and Apolipoprotein Measurements: Study within the Framework of the Dutch Project “Calibration 2000”
Authors: Cobbaert Christa , Weykamp Cas , Baadenhuijsen Henk , Kuypers Aldy , Lindemans Jan , Jansen Rob 
Published: January 2020

AbstractBackground: The Dutch project “Calibration 2000” aims at harmonization of laboratory results via calibration by development of matrix-based secondary reference materials. We considered the selection, preparation, and characterization of 34 potential reference materials (PRMs).Methods: Sixteen PRMs were prepared either strictly according to the NCCLS C37-A protocol or in a less stringent and more convenient way. In addition, 18 commercial, so-called human serum-based calibrators or controls were purchased and tested. Lipoprotein integrity was evaluated by examining the physicochemical characteristics of the materials. Commutability of the PRMs was assessed in 86 Dutch clinical laboratories, using a multicenter split-patient-sample between-field-method (twin-study) design. Normalized residuals of the PRMs with respect to the patient regression lines were calculated; in addition, the extra contribution of each PRM to the total measurement uncertainty (CVNetto) was calculated. On the basis of these results, the most native PRM was selected to investigate its potential to reduce interlaboratory variation and to improve lipid and apolipoprotein standardization.Results: In general, only the NCCLS C37-A-type materials displayed normalized residuals below the decision limit for commutability and had small CVNetto values ranging between 0 and 3.8%. This contrasts with the findings in regularly pooled frozen sera and lyophilized cryoprotected PRMs. In two subsequent external quality assessment surveys, the NCCLS type C37-A materials contributed to reducing the intermethod lipid and (apo)lipoprotein variation to ∼2–4%.Conclusions: NCCLS C37-A materials have a strong potential as secondary reference materials, not only for cholesterol but also for HDL-cholesterol, LDL-cholesterol, triglyceride, and apolipoprotein measurements.
Homogeneous, Nonradioactive, Enzymatic Assay for Plasma Pyridoxal 5-Phosphate
Authors: Han Qinghong , Xu Mingxu , Tang Li , Tan Xuezhong , Tan Xiuying , Tan Yuying , Hoffman Robert M 
Published: January 2020

AbstractBackground: Pyridoxal 5′-phosphate (PLP) is the biologically active form of vitamin B6. Clinical studies suggest that low PLP concentrations are an independent risk factor for cardiovascular and other diseases. However, PLP concentrations are not routinely diagnosed because of the lack of a homogeneous, nonradioactive assay. We describe a homogeneous, nonradioactive, enzymatic PLP assay that uses the apo form of the PLP-dependent recombinant enzyme, homocysteine-α,γ-lyase (rHCYase).Methods: PLP was removed from holoenzyme rHCYase by incubation with hydroxylamine to obtain apo-rHCYase. The restoration of enzymatic activity by reconstitution of the holoenzyme was linearly related to the amount of PLP bound to the enzyme. The amplification principle of the assay allowed nanomolar concentrations of PLP to be measured by the conversion (by reconstituted holo-rHCYase) of millimolar concentrations of homocysteine to H2S. N,N-Dibutylphenylenediamine (DBPDA) was used for determination of H2S, the combination of which forms a chromophore with high absorbance. The assay was initiated by incubation of 5 μL of plasma with apo-rHCYase in a binding buffer for 60 min at 37 °C. Homocysteine (2.5 mmol/L) was added to the assay buffer and incubated at 37 °C for 20 min. The DBPDA reaction was allowed to progress for 10 min and then read at 675 nm.Results: The PLP enzymatic assay has a lower limit of detection of 5 nmol/L and is linear to 200 nmol/L. The recovery of PLP was 98%. The mean within- and between-run CVs were 9.6% and 12%, respectively. Correlation of 45 samples in the PLP enzymatic assay and the B63H radioenzymatic assay (American Laboratory Products Co., Ltd.) yielded: y = 0.9367x + 10.569 (R2 = 0.9201).Conclusions: This new PLP assay is the first homogeneous, nonradioactive, vitamin B6 diagnostic method. The assay is applicable to chemistry automated analyzers and may have wide clinical use.
Unveiling the roles of interspecific competition and local adaptation in phenotypic differentiation of parapatric frogs
Authors: Huang Yan , Wang Xiaoyi , Yang Xin , Jiang Jianping , Hu Junhua 
Published: January 2020

AbstractUnderstanding how ecological processes affect phenotypic evolution has been and continues to be an important goal of ecology and evolutionary biology. Interspecific competition for resources can be a selective force driving phenotypic differentiation that reduces competition among sympatric species (character divergence), enabling closely-related species to coexist. However, although patterns of character divergence are well documented in both empirical and theoretical researches, how local adaptation to abiotic environment affects trait evolution in the face of interspecific competition is less known. Here, we investigate how patterns in morphological traits of 2 parapatric frog species, Feirana quadranus and F. taihangnica, vary among allopatric and sympatric regions using range-wide data derived from extensive field surveys. Feirana quadranus was overall larger than F. taihangnica in body size (i.e., snout–vent length [SVL]), and the difference between SVL of both species in sympatry was larger than that in allopatry. From allopatry to sympatry, the 2 species diverged in foot and hand traits, but converged in eye size and interorbital span, even when we controlled for the effects of geographic gradients. Sympatric divergence in SVL, hand and foot traits is likely acting as a case of evolutionary shift caused by interspecific competition. In contrast, sympatric convergence of eye-related traits may derive at least partly from adaptation to local environments. These results imply the relative roles of interspecific competition and local adaptation in shaping phenotypic diversification. Our findings illustrate how traits evolve in parapatric species pair due to sympatric divergent and convergent evolution. It thus provides insights into understanding underlying evolutionary processes of parapatric species, that is, competition and local adaptation.
Do healthy doctors deliver better messages of health promotion to their patients?: Data from the SUN cohort study
Authors: Carlos Silvia , Rico-Campà Anaïs , de la Fuente-Arrillaga Carmen , Echavarri María , Fernandez-Montero Alejandro , Gea Alfredo , Salazar Camino , Martínez-González Miguel Angel 
Published: January 2020

AbstractBackgroundHealthy lifestyle adherence is associated with lower chronic disease morbidity/mortality. The role of doctors, as counselors and role models, is essential. Among physicians participating in a prospective cohort, we investigated the behavioral counseling on diet and lifestyle provided to their patients in association with their own personal behaviors.MethodsWe assessed 890 doctors aged ≤65 years participating in the ‘Seguimiento Universidad de Navarra’ (SUN) cohort, who replied to an online questionnaire regarding their practices on behavioral counseling and drug prescription to their patients. Data were combined with previous baseline information on their personal healthy habits.ResultsAmong doctors, 31% reported &lt;10 min per visit; 73% counseled 60–100% of their patients on smoking cessation, 58% on physical activity, 54% on weight control, 51% on healthy nutrition, 44% on alcohol avoidance/reduction and 28% recommended alcohol moderate consumption. The percentage of doctors that counseled 100% of their patients about lifestyle was 43% for smoking cessation, 15% for exercise and 13% for weight control and nutrition. Better doctor’s adherence to the Mediterranean dietary pattern was associated with more frequent and longer nutrition counseling. Higher practice of physical activity was associated with longer time on counseling about exercise to their patients. Among doctors both current and former smoking were inversely associated with the frequency and duration of their smoking cessation/avoidance counseling practices.ConclusionsPersonal behavioral changes among doctors and better training of medical doctors on a personal healthy diet and lifestyle are likely to contribute to improve the behavioral counseling given to patients.
Spatial statism: Afterword to the Foreword by Ran Hirschl and Ayelet Shachar
Authors: Doyle Oran 
Published: January 2020

Abstract
“Spatial statism” challenges us to pay greater attention to the spatial dimension of public law and provides a critique of how states dominate that geographic space. In this Afterword, I suggest that the spatial dimension of public law can be helpfully understood as a special case of the geographic dimension of law in general. State domination of geographic space warrants critical attention, particularly in the context of migration regulation. But we must also pay attention to the advantages of states as the primary locus of constitutional authority.
Prescribing Patterns of Psychotropic Drugs and Risk of Violent Behavior: A Prospective, Multicenter Study in Italy
Authors: di Giacomo E , Stefana A , Candini V , Bianconi G , Canal L , Clerici M , Conte G , Ferla M T , Iozzino L , Sbravati G , Tura G , Micciolo R , de Girolamo G ,   VIORMED-2 Group, Bava Mattia , Carrà Giuseppe , Gamba Giulia , Martinazzoli Assunta , Mina Giuliana , Ornaghi Alessandra , Travasso Bruno , Vita Antonio 
Published: January 2020

Abstract

Background
This prospective cohort study aimed at evaluating patterns of polypharmacy and aggressive and violent behavior during a 1-year follow-up in patients with severe mental disorders.

Methods
A total of 340 patients (125 inpatients from residential facilities and 215 outpatients) were evaluated at baseline with the Structured Clinical Interview for DSM-IV Axis I and II, Brief Psychiatric Rating Scale, Specific Levels of Functioning scale, Brown-Goodwin Lifetime History of Aggression, Buss-Durkee Hostility Inventory, Barratt Impulsiveness Scale, and State-Trait Anger Expression Inventory-2. Aggressive behavior was rated every 15 days with the Modified Overt Aggression Scale and treatment compliance with the Medication Adherence Rating Scale.

Results
The whole sample was prescribed mainly antipsychotics with high levels of polypharmacy. Clozapine prescription and higher compliance were associated with lower levels of aggressive and violent behavior. Patients with a history of violence who took clozapine were prescribed the highest number of drugs. The patterns of cumulative Modified Overt Aggression Scale mean scores of patients taking clozapine (n = 46), other antipsychotics (n = 257), and no antipsychotics (n = 37) were significantly different (P = .001). Patients taking clozapine showed a time trend at 1-year follow-up (24 evaluations) indicating a significantly lower level of aggressive behavior. Patient higher compliance was also associated with lower Modified Overt Aggression Scale ratings during the 1-year follow-up.

Conclusion
Both inpatients and outpatients showed high levels of polypharmacy. Clozapine prescription was associated with lower Modified Overt Aggression Scale ratings compared with any other antipsychotics or other psychotropic drugs. Higher compliance was associated with lower levels of aggressive and violent behavior.
A hybrid preventive maintenance model for systems with partially observable degradation
Authors: Finkelstein Maxim , Cha Ji Hwan , Levitin Gregory 
Published: January 2020

AbstractA new model of hybrid preventive maintenance of systems with partially observable degradation is developed. This model combines condition-based maintenance with age replacement maintenance in the proposed, specific way. A system, subject to a shock process, is replaced on failure or at some time ${T}_S$ if the number of shocks experienced by this time is greater than or equal to m or at time $T&gt;{T}_S$ otherwise, whichever occurs first. Each shock increases the failure rate of the system at the random time of its occurrence, thus forming a corresponding shot-noise process. The real deterioration of the system is partially observed via observation of the shock process at time ${T}_S$. The corresponding optimization problem is solved and a detailed numerical example demonstrates that the long-run cost rate for the proposed optimal hybrid strategy is smaller than that for the standard optimal age replacement policy.
Development of data dictionary for neonatal intensive care unit: advancement towards a better critical care unit
Authors: Singh Harpreet , Kaur Ravneet , Saluja Satish , Cho Su Jin , Kaur Avneet , Pandey Ashish Kumar , Gupta Shubham , Das Ritu , Kumar Praveen , Palma Jonathan , Yadav Gautam , Sun Yao 
Published: January 2020

Abstract

Background
Critical care units (CCUs) with extensive use of various monitoring devices generate massive data. To utilize the valuable information of these devices; data are collected and stored using systems like clinical information system and laboratory information management system. These systems are proprietary, allow limited access to their database and, have the vendor-specific clinical implementation. In this study, we focus on developing an open-source web-based meta-data repository for CCU representing stay of the patient with relevant details.

Methods
After developing the web-based open-source repository named data dictionary (DD), we analyzed prospective data from 2 sites for 4 months for data quality dimensions (completeness, timeliness, validity, accuracy, and consistency), morbidity, and clinical outcomes. We used a regression model to highlight the significance of practice variations linked with various quality indicators.

Results
DD with 1555 fields (89.6% categorical and 11.4% text fields) is presented to cover the clinical workflow of a CCU. The overall quality of 1795 patient days data with respect to standard quality dimensions is 87%. The data exhibit 88% completeness, 97% accuracy, 91% timeliness, and 94% validity in terms of representing CCU processes. The data scores only 67% in terms of consistency. Furthermore, quality indicators and practice variations are strongly correlated (P &lt; 0.05).

Conclusion
This study documents DD for standardized data collection in CCU. DD provides robust data and insights for audit purposes and pathways for CCU to target practice improvements leading to specific quality improvements.