bluuebunny/crossref_metadata_2025_split huggingface dataset:
Connectivity from Source to Action
Authors: Aller Raymond D 
Published: January 2020

Abstract
Recent advances in electronic connectivity technology make conceivable almost instantaneous movement of data from the patient or laboratory to any other point in the healthcare system. The Internet, combined with new standards for wireless data transmission, has erased many of the previous physical barriers. Interface engines and formatting/content standards have facilitated the connection of multiple disparate systems in medicine. However, major logical barriers persist, and overcoming these barriers is key to achieving functional connectivity. These include fundamental issues of patient safety (such as reliably identifying the patient), capture of the most clinically meaningful data (patient history, physical examination findings, physician diagnostic impressions, and full range of orders), unambiguous identification of data elements, and synchronization of control files among multiple different systems within the healthcare enterprise. Fortunately, tools exist to address each of these areas. This report cites illustrative examples of such tools.
The Total Laboratory Solution: A New Laboratory E-Business Model Based on a Vertical Laboratory Meta-Network
Authors: Friedman Bruce A 
Published: January 2020

Abstract
Major forces are now reshaping all businesses on a global basis, including the healthcare and clinical laboratory industries. One of the major forces at work is information technology (IT), which now provides the opportunity to create a new economic and business model for the clinical laboratory industry based on the creation of an integrated vertical meta-network, referred to here as the “total laboratory solution” (TLS). Participants at the most basic level of such a network would include a hospital-based laboratory, a reference laboratory, a laboratory information system/application service provider/laboratory portal vendor, an in vitro diagnostic manufacturer, and a pharmaceutical/biotechnology manufacturer. It is suggested that each of these participants would add value to the network primarily in its area of core competency. Subvariants of such a network have evolved over recent years, but a TLS comprising all or most of these participants does not exist at this time. Although the TLS, enabled by IT and closely akin to the various e-businesses that are now taking shape, offers many advantages from a theoretical perspective over the current laboratory business model, its success will depend largely on (a) market forces, (b) how the collaborative networks are organized and managed, and (c) whether the network can offer healthcare organizations higher quality testing services at lower cost. If the concept is successful, new demands will be placed on hospital-based laboratory professionals to shift the range of professional services that they offer toward clinical consulting, integration of laboratory information from multiple sources, and laboratory information management. These information management and integration tasks can only increase in complexity in the future as new genomic and proteomics testing modalities are developed and come on-line in clinical laboratories.
Guidelines and Algorithms: Perceptions of Why and When They Are Successful and How to Improve Them
Authors: Keffer Joseph H 
Published: January 2020

Abstract
Medicine is increasingly complex, a reality created by the explosion of knowledge during the last 50 years. The cost of applying this knowledge creates a daunting economic challenge. As a result, there has been a profusion of guidelines intended to influence medical practice. This report explores the interrelated issues and concepts that impact the value and success of guidelines. These include medical quality and error, compliance, and the impact on outcomes in an evidence-based medicine context. Lessons learned from previous guidelines must be understood in relation to human behavior. Legal implications of the guidelines must be considered because both an increase and a decrease in liability can be anticipated. Many products have been labeled “advocacy guidelines” with a negative context. They are believed to express motivation rather than optimizing care. The ideal of professionalism is challenged, and there is potential for the growing use of guidelines in enforcing punitive actions. Constructive experience has emphasized the appropriate required elements for practice guidelines: a systematic review of the literature, an assessment of the volume and level of the evidence, and development of a review process by an appropriate multidisciplinary group for consistency, clinical impact, and resource implications leading to clearly stated and reasonable recommendations. The dissemination of guidelines, beyond conventional publication in a journal, will impact the success of the intended outcomes. The exploitation of electronic avenues, including the Internet and the evolving interactive electronic medical record, seems to be essential for future success in these endeavors.
Mitochondrial Gene Mutations in the tRNALeu(UUR) Region and Diabetes: Prevalence and Clinical Phenotypes in Japan
Authors: Ohkubo Kumiko , Yamano Akemi , Nagashima Mariko , Mori Yumiko , Anzai Keizo , Akehi Yuko , Nomiyama Riku , Asano Takashi , Urae Akinori , Ono Junko 
Published: January 2020

Abstract
Background: Mitochondrial gene mutations play a role in the development of diabetes mellitus. We have assessed the frequency of the A3243G and other mitochondrial mutations in Japan and in the relationship to clinical features of diabetes.
Methods: DNA was obtained from peripheral leukocytes of 240 patients with diabetes mellitus (39 with type 1; 188 with type 2; 13 with gestational diabetes) and 125 control subjects. We used PCR-restriction fragment length polymorphism analysis (ApaI) for A3243G and PCR-single-strand conformation polymorphism analysis to determine the mutations in the mitochondrial gene including nucleotide position 3243.
Results: The A3243G mutation was found in seven patients, and an inverse relationship was observed between the degree of heteroplasmy and the age at onset of diabetes. A3156G, G3357A, C3375A, and T3394C were detected in addition. Those who shared the same mutation showed similar clinical characteristics, thus representing a putative clinical subtype. The patients with A3156G had a sudden onset of hyperglycemia and showed a rapid progression to an insulin-dependent state with positive anti-glutamic acid decarboxylase antibody. Those with T3394C showed a mild defect in glucose-stimulated insulin secretion, and hyperglycemia appeared after adding such factors as aging or obesity.
Conclusions: The identification of mitochondrial gene mutations allows preclinical diagnosis of diabetes and prediction of the age at onset by evaluating the degree of heteroplasmy in cases with A3243G. Mutation detection may also be important for patient management and identification of affected family members.
Multivariate Discriminant Function Based on Six Biochemical Markers in Blood Can Predict the Cirrhotic Evolution of Chronic Hepatitis
Authors: Fortunato Giuliana , Castaldo Giuseppe , Oriani Giovannangelo , Cerini Raimondo , Intrieri Mariano , Molinaro Eugenia , Gentile Ivan , Borgia Guglielmo , Piazza Marcello , Salvatore Francesco , Sacchetti Lucia 
Published: January 2020

Abstract
Background: Serologic markers have been proposed for monitoring hepatic fibrosis in chronic active liver disease. Because none of these markers, when used singly, is totally satisfactory, we developed and evaluated a multivariate approach.
Methods: We studied two cohorts of chronic hepatitis (54 patients) and cirrhosis patients (49 patients) to identify a panel of biochemical markers that discriminates between the two diseases. Using multivariate discriminant analysis, we selected a function, based on the concentrations of six biochemical markers (fibronectin, prothrombin, pseudocholinesterase, alanine aminotransferase, manganese superoxide dismutase, and N-acetyl-β-glucosaminidase). We then prospectively validated this function on a second temporal cohort of patients.
Results: Multivariate discriminant analysis correctly classified 93.7% of patients (94.3% of chronic hepatitis and 92.9% of cirrhosis patients) in the first cohort and 85% of patients (89.5% of chronic hepatitis patients and 81% of cirrhosis patients) in the second cohort.
Conclusions: Discriminant analysis of results of six inexpensive biochemical markers provides a high predictive value for differentiation between liver cirrhosis and chronic hepatitis. Consequently, these biochemical markers condensed into a multivariate discriminant analysis value for each patient provide information that can be contributory for subsequent options during the evolution of the natural history of chronic hepatitis.
Differential DNA Methylation between Fetus and Mother as a Strategy for Detecting Fetal DNA in Maternal Plasma
Authors: Poon Leo LM , Leung Tse N , Lau Tze K , Chow Katherine CK , Lo YM Dennis 
Published: January 2020

Abstract
Background: Fetal DNA has been detected in maternal plasma by the use of genetic differences between mother and fetus. We explore the possibility of using epigenetic markers for the specific detection of fetal DNA in maternal plasma.
Methods: A differentially methylated region in the human IGF2-H19 locus and a single-nucleotide polymorphism in this region were chosen for the study. The methylation status in this region is maintained in such a way that the paternal allele is methylated and the maternal allele is unmethylated. The single-nucleotide polymorphism was typed by direct sequencing of PCR products. The methylation status of this region was ascertained by bisulfite conversion and methylation-specific PCR. Differentially methylated fetal alleles were detected in maternal plasma by direct sequencing and a primer-extension assay.
Results: Women in the second (n = 21; 17–21 weeks) and third (n = 18; 37–42 weeks) trimesters of pregnancy were recruited. Among these 39 volunteers, the 16 who were heterozygous for the single-nucleotide polymorphism were chosen for further analysis. In 11 of these 16 cases, paternally inherited methylated fetal alleles were different from the methylated alleles of the respective mothers. Using direct sequencing, we detected paternally inherited methylated fetal DNA in 6 of 11 (55%) cases. In 8 of the 16 heterozygous cases, the fetuses possessed an unmethylated maternally inherited allele that was different from the unmethylated allele of the mother. Using a primer-extension assay, we detected fetal-derived maternally inherited alleles in maternal plasma of four of eight (50%) cases.
Conclusions: These results represent the first use of fetal epigenetic markers in noninvasive prenatal analysis. These data may also have implications for the investigation of other types of chimerism.
The History and Future of the Fluorescence Activated Cell Sorter and Flow Cytometry: A View from Stanford
Authors: Herzenberg Leonard A , Parks David , Sahaf Bita , Perez Omar , Roederer Mario , Herzenberg Leonore A 
Published: January 2020

Abstract
The Fluorescence Activated Cell Sorter (FACS) was invented in the late 1960s by Bonner, Sweet, Hulett, Herzenberg, and others to do flow cytometry and cell sorting of viable cells. Becton Dickinson Immunocytometry Systems introduced the commercial machines in the early 1970s, using the Stanford patent and expertise supplied by the Herzenberg Laboratory and a Becton Dickinson engineering group under Bernie Shoor. Over the years, we have increased the number of measured FACS dimensions (parameters) and the speed of sorting to where we now simultaneously measure 12 fluorescent colors plus 2 scatter parameters. In this history, I illustrate the great utility of this state-of-the-art instrument, which allows us to simultaneously stain, analyze, and then sort cells from small samples of human blood cells from AIDS patients, infants, stem cell transplant patients, and others. I also illustrate analysis and sorting of multiple subpopulations of lymphocytes by use of 8–12 colors. In addition, I review single cell sorting used to clone and analyze hybridomas and discuss other applications of FACS developed over the past 30 years, as well as give our ideas on the future of FACS. These ideas are currently being implemented in new programs using the internet for data storage and analysis as well as developing new fluorochromes, e.g., green fluorescent protein and tandem dyes, with applications in such areas as apoptosis, gene expression, cytokine expression, cell biochemistry, redox regulation, and AIDS. Finally, I describe new FACS methods for measuring activated kinases and phosphatases and redox active enzymes in individual cells simultaneously with cell surface phenotyping. Thus, key functions can be studied in various subsets of cells without the need for prior sorting.
Screening for Primary Aldosteronism: Implications of an Increased Plasma Aldosterone/Renin Ratio
Authors: Schwartz Gary L , Chapman Arlene B , Boerwinkle Eric , Kisabeth Robert M , Turner Stephen T 
Published: January 2020

Abstract
Background: The value of the ratio of plasma aldosterone concentration (aldosterone) to plasma renin activity (renin) to identify patients at risk for primary aldosteronism is controversial. We determined the sensitivity, specificity, and predictive value of the ratio to identify combinations of renin and aldosterone compatible with primary aldosteronism.
Methods: The ratio was calculated in 505 adults with essential hypertension (143 black women, 82 black men, 122 white women, and 158 white men). We used a conventional cutpoint for an increased ratio (i.e., 20 mL/dL · h). The primary combination of renin and aldosterone considered compatible with primary aldosteronism was increased aldosterone for the concomitant renin, defined as aldosterone in the highest quartile predicted by linear regression on renin. Renin was considered low if it was in the lowest quartile of the sample distribution.
Results: The sensitivity of the ratio to identify individuals with increased aldosterone for the concomitant renin was 66% (80% in blacks and 56% in whites; P = 0.009), and the specificity of the ratio was 67% (46% in blacks and 84% in whites; P &lt;0.0001). In 36% of instances of an increased ratio, it was a measure of low renin alone without increased aldosterone for renin (32% in blacks and 45% in whites; P = 0.072). The positive predictive value of the ratio to identify individuals with increased aldosterone for the concomitant renin was 34% (49% in whites and 27% in blacks; P &lt;0.002).
Conclusion: The aldosterone/renin ratio lacks sensitivity and specificity and has only a modest predictive value for combinations of renin and aldosterone that are compatible with primary aldosteronism.
Comparison of Procedures for Evaluating Laboratory Performance in External Quality Assessment Schemes for Lead in Blood and Aluminum in Serum Demonstrates the Need for Common Quality Specifications
Authors: Taylor Andrew , Angerer Jurgen , Claeys Francoise , Kristiansen Jesper , Mazarrasa Olav , Menditto Antonio , Patriarca Marina , Pineau Alain , Schoeters Ilse , Sykes Christophe , Valkonen Sinikka , Weykamp Cas 
Published: January 2020

Abstract
Background: The different scoring methods used by eight European External Quality Assessment Schemes (EQASs) for occupational and environmental laboratory medicine were compared to develop suitable quality specifications as a step toward harmonization.
Methods: Real results for blood lead and serum aluminum assays, reported by participants in Italian and United Kingdom EQASs, were evaluated according to individual scheme scoring criteria. The same results were then used to produce z scores using scheme-based between-laboratory SDs as the estimate of variability to determine whether simple performance-derived quality specifications produced better agreement among schemes.
Results: The schemes gave conflicting assessments of participants’ performance, and participants judged to be successful by one scheme could be defined as performing inadequately by another. An approach proposed by Kenny et al. (Scand J Clin Lab Invest 1999;59:585), which uses clinical inputs to set targets for analytical imprecision, bias, and total error allowable, was then used to elaborate quality specifications.
Conclusions: We suggest that the CLIA ′88 recommendations for blood lead (± 40 μg/L or ± 10% of the target concentration, whichever is the greater) could be used as a quality specification, although a revision to ± 30 μg/L or ± 10% is recommended. For serum aluminum, a suitable quality specification of ± 5 μg/L or ± 20% of the target concentration, whichever is the greater, is suggested. These specifications may be used to compare laboratory performance across schemes.
Clinical Performance of an In-Line, ex Vivo Point-of-Care Monitor: A Multicenter Study
Authors: Billman Glenn F , Hughes Amy B , Dudell Golde G , Waldman Elizabeth , Adcock Lisa M , Hall Dan M , Orsini Edmund N , Koska Adolph J , Van Marter Linda J , Finer Neil N , Kulhavy Jeff C , Feld Ronald D , Widness John A 
Published: January 2020

AbstractBackground: The management of critically ill infants and neonates includes frequent determination of arterial blood gas, electrolyte, and hematocrit values. An objective of attached point-of-care patient monitoring is to provide clinically relevant data without the adverse consequences associated with serial phlebotomy.Methods: We prospectively determined the mean difference (and SD of the difference) from laboratory methods of an in-line, ex vivo monitor, the VIA LVM Blood Gas and Chemistry Monitoring System® (VIA LVM Monitor; Metracor Technologies, Inc.), in 100 critically ill neonates and infants at seven children’s hospitals. In doing so, we examined monitor stability with continuous use. In vivo patient test results from laboratory benchtop analyzers were compared with those from the VIA LVM Monitor on paired samples. In a separate in vitro comparison, benchtop analyzer and monitor test results were compared on whole-blood split samples.Results: A total of 1414 concurrent, paired-sample measurements were obtained. The mean differences (SD of differences) from laboratory methods and r values for the combined data for the VIA LVM Monitor from the seven sites were 0.001 (0.026) and 0.97 for pH, 0.7 (3.6) mmHg and 0.94 for Pco2, 4.2 (9.6) mmHg and 0.98 for Po2, 0.0 (2.9) mmol/L and 0.87 for sodium, 0.1 (0.2) mmol/L and 0.96 for potassium, and 0.3% (2.9%) and 0.90 for hematocrit. Performance results were similar among the study sites with increasing time of monitor use and between in vivo paired-sample and in vitro split-sample test results.Conclusion: The VIA LVM Monitor can be used to assess critically ill neonates and infants.
Reagent-free, Simultaneous Determination of Serum Cholesterol in HDL and LDL by Infrared Spectroscopy
Authors: Liu Kan-Zhi , Shaw R Anthony , Man Angela , Dembinski Thomas C , Mantsch Henry H 
Published: January 2020

Abstract
Background: The purpose of this study was to assess the feasibility of infrared (IR) spectroscopy for the simultaneous quantification of serum LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C) concentrations.
Methods: Serum samples (n = 90) were obtained. Duplicate aliquots (5 μL) of the serum specimens were dried onto IR-transparent barium fluoride substrates, and transmission IR spectra were measured for the dry films. In parallel, the HDL-C and LDL-C concentrations were determined separately for each specimen by standard methods (the Friedewald formula for LDL-C and an automated homogeneous HDL-C assay). The proposed IR method was then developed with a partial least-squares (PLS) regression analysis to quantitatively correlate IR spectral features with the clinical analytical results for 60 randomly chosen specimens. The resulting quantification methods were then validated with the remaining 30 specimens. The PLS model for LDL-C used two spectral ranges (1700–1800 and 2800–3000 cm−1) and eight PLS factors, whereas the PLS model for HDL-C used three spectral ranges (800–1500, 1700–1800, and 2800–3500 cm−1) with six factors.
Results: For the 60 specimens used to train the IR-based method, the SE between IR-predicted values and the clinical laboratory assays was 0.22 mmol/L for LDL-C and 0.15 mmol/L for HDL-C (r = 0.98 for LDL-C; r = 0.91 for HDL-C). The corresponding SEs for the test spectra were 0.34 mmol/L (r = 0.96) and 0.26 mmol/L (r = 0.82) for LDL-C and HDL-C, respectively. The precision for the IR-based assays was estimated by the SD of duplicate measurements to be 0.11 mmol/L (LDL-C) and 0.09 mmol/L (HDL-C).
Conclusions: IR spectroscopy has the potential to become the clinical method of choice for quick and simultaneous determinations of LDL-C and HDL-C.
Homogeneous Amplification and Mutation Scanning of the p53 Gene Using Fluorescent Melting Curves
Authors: Millward Haleigh , Samowitz Wade , Wittwer Carl T , Bernard Philip S 
Published: January 2020

Abstract
Background: In malignancy, gene mutations frequently occur in tumor suppressor genes such as p53 and are sporadically located. We describe a homogeneous method for amplification and mutation scanning, and apply the method to the p53 gene.
Methods: Using a series of overlapping fluorescein-labeled oligonucleotides complementary to a wild-type p53 sequence, we detected somatic mutations in colorectal cancers by aberrant probe:target melting temperatures (Tm). The probes were designed so that fluorescence decreased on target annealing as a result of deoxyguanosine quenching. Probes were walked along the sequence to be scanned, using two to three probes per cuvette and placing overlapping probes in separate reactions. After amplification, the reaction was cooled to anneal probes and then slowly heated (0.1 °C/s) while fluorescence was continuously monitored. Somatic mutations in tumor tissue were detected by changes from a characteristic wild-type melting curve profile using leukocyte DNA.
Results: A complete scanning of the DNA binding domain (exons 5–8) of the p53 gene was completed in a single run (∼30 min) starting from genomic leukocyte DNA. To show proof-of-principle, p53 exons 6–8 from 63 colon cancers were probe-scanned and showed 100% agreement with direct sequencing for detecting alterations from wild-type DNA.
Conclusions: p53 mutation scanning by single-labeled hybridization probes is a homogeneous, rapid, and sensitive method with application in both research and clinical diagnostics.