bluuebunny/crossref_metadata_2025 huggingface dataset:
On the rôle of singular functions in extending the probabilistic symbol to its most general class
Authors: Rickelhoff Sebastian , Schnurr Alexander
Published: September 2023

The probabilistic symbol is the right-hand side derivative of the characteristic functions corresponding to the one-dimensional marginals of a stochastic process. This object, as long as the derivative exists, provides crucial information concerning the stochastic process. For a Lévy process, one obtains the characteristic exponent while the symbol of a (rich) Feller process coincides with the classical symbol which is well known from the theory of pseudodifferential operators.

Leaving these classes behind, the most general class of processes for which the symbol still exists are Lévy-type processes. It has been an open question, whether further generalizations are possible within the framework of Markov processes. We answer this question in the present article: within the class of Hunt semimartingales, Lévy-type processes are exactly those for which the probabilistic symbol exists. Leaving Hunt behind, one can construct processes admitting a symbol. However, we show, that the applicability of the symbol might be lost for these processes. Surprisingly, in our proofs the upper and lower Dini derivatives corresponding to certain singular functions play an important rôle.
Socially Acquired Nocebo Effects Generalize but Are Not Attenuated by Choice
Authors: Saunders Cosette , Colagiuri Ben , Barnes Kirsten
Published: September 2023

Background

Socially observing a negative treatment-related experience has been shown to modulate our own experience with the same intervention, leading to worsened health outcomes. However, whether this social learning generalizes to similar but distinct interventions has not been explored nor what manipulations can reduce these effects.

Purpose

To determine whether socially acquired nocebo effects can be generated by observing a negative experience with a similar, but distinct intervention, and whether choice can reduce these effects.

Methods

Across three experiments, a community sample of healthy adults (N = 336) either watched a confederate report cybersickness to the same Virtual Reality (VR) activity they were assigned to (Social Modeling: Consistent); a similar, but different VR activity (Social Modeling: Inconsistent); or did not view the confederate (No Social Modeling). Participants were either given choice over the VR (Choice) or assigned by the experimenter (No Choice).

Results

Across the experiments, there was significantly greater cybersickness in both Social Modeling groups relative to No Social Modeling, while the two Social Modeling groups did not differ. There was no significant effect of Choice or a Choice by Social Modeling interaction. Social Modeling elicited greater anxiety and expectancies for cybersickness. Furthermore, these mechanisms mediated the association between social modeling and cybersickness.

Conclusions

Socially acquired side-effects were demonstrated to generalize to similar, but distinct interventions, highlighting the diffuse and robust effect social modeling can have on our experiences. However, choice did not attenuate the experience of cybersickness, highlighting the need for alternative methods to counteract the effect of social modeling.
Simulating structurally variable nuclear pore complexes for microscopy
Authors: Theiss Maria , Hériché Jean-Karim , Russell Craig , Helekal David , Soppitt Alisdair , Ries Jonas , Ellenberg Jan , Brazma Alvis , Uhlmann Virginie
Published: September 2023

Motivation

The nuclear pore complex (NPC) is the only passageway for macromolecules between nucleus and cytoplasm, and an important reference standard in microscopy: it is massive and stereotypically arranged. The average architecture of NPC proteins has been resolved with pseudoatomic precision, however observed NPC heterogeneities evidence a high degree of divergence from this average. Single-molecule localization microscopy (SMLM) images NPCs at protein-level resolution, whereupon image analysis software studies NPC variability. However, the true picture of this variability is unknown. In quantitative image analysis experiments, it is thus difficult to distinguish intrinsically high SMLM noise from variability of the underlying structure.

Results

We introduce CIR4MICS (‘ceramics’, Configurable, Irregular Rings FOR MICroscopy Simulations), a pipeline that synthesizes ground truth datasets of structurally variable NPCs based on architectural models of the true NPC. Users can select one or more N- or C-terminally tagged NPC proteins, and simulate a wide range of geometric variations. We also represent the NPC as a spring-model such that arbitrary deforming forces, of user-defined magnitudes, simulate irregularly shaped variations. Further, we provide annotated reference datasets of simulated human NPCs, which facilitate a side-by-side comparison with real data. To demonstrate, we synthetically replicate a geometric analysis of real NPC radii and reveal that a range of simulated variability parameters can lead to observed results. Our simulator is therefore valuable to test the capabilities of image analysis methods, as well as to inform experimentalists about the requirements of hypothesis-driven imaging studies.

Availability and implementation

Code: https://github.com/uhlmanngroup/cir4mics. Simulated data: BioStudies S-BSST1058.
Splicing transcriptome-wide association study to identify splicing events for pancreatic cancer risk
Authors: Liu Duo , Bae Ye Eun , Zhu Jingjing , Zhang Zichen , Sun Yanfa , Deng Youping , Wu Chong , Wu Lang
Published: September 2023

A large proportion of the heritability of pancreatic cancer risk remains elusive, and the contribution of specific mRNA splicing events to pancreatic cancer susceptibility has not been systematically evaluated. In this study, we performed a large splicing transcriptome-wide association study (spTWAS) using three modeling strategies (Enet, LASSO and MCP) to develop alternative splicing genetic prediction models for identifying novel susceptibility loci and splicing introns for pancreatic cancer risk by assessing 8275 pancreatic cancer cases and 6723 controls of European ancestry. Data from 305 subjects of whom the majority are of European descent in the Genotype-Tissue Expression Project (GTEx) were used and both cis-acting and promoter–enhancer interaction regions were considered to build these models. We identified nine splicing events of seven genes (ABO, UQCRC1, STARD3, ETAA1, CELA3B, LGR4 and SFT2D1) that showed an association of genetically predicted expression with pancreatic cancer risk at a false discovery rate ≤0.05. Of these genes, UQCRC1 and LGR4 have not yet been reported to be associated with pancreatic cancer risk. Fine-mapping analyses supported likely causal associations corresponding to six splicing events of three genes (P4HTM, ABO and PGAP3). Our study identified novel genes and splicing events associated with pancreatic cancer risk, which can improve our understanding of the etiology of this deadly malignancy.
Curcumin artefacta
Authors: Kanagarajan Amuthavalli , Mittal Setu , Chandrasekaran Shanmugasekar , Shanmugasundaram Priyanka
Published: September 2023

Ultraviolet-induced fluorescence dermoscopy (UVFD) utilizes 365 nm UV light to induce fluorescence. Curcumin, the bioactive product of turmeric produces artefactual fluorescence when seen under UVFD. The purpose of this case report is to share this observation, which can help prevent misdiagnosis.
Effects of BNT162b2 Messenger RNA Vaccine and ChAdOx1 Adenovirus Vector Vaccine on Deaths From COVID-19 in Adults Aged ≥70 Years
Authors: Lopez Bernal Jamie , Andrews Nick , Gower Charlotte , Stowe Julia , Tessier Elise , Simmons Ruth , Ramsay Mary
Published: September 2023

We estimated the risk of death from coronavirus disease 2019 in vaccinated compared with unvaccinated patients. The risk of death was reduced 44% after 1 dose of the Pfizer-BioNTech BNT162b2 vaccine, 55% after 1 dose of the Oxford-Astrazeneca ChAdOx1 vaccine, and 69% after 2 doses of the BNT162b2 vaccine. This is above the protection provided against infection.
A-030 Indicators Generated from Salivary Cortisol Measurement to Assess Circadian Rhythm: Comparison of Immunoassay and Liquid Chromatography-Tandem Mass Spectrometry
Authors: Lee A , Jang S , Kim J , Jang J , Kim I , Lee S , Seok J
Published: September 2023

Background

Salivary cortisol is considered a reliable alternative to serum-free cortisol for evaluating hypothalamic-pituitary-adrenal axis rhythmicity. Its advantages include free hormone measurement, non-invasiveness, precision, and cost-effectiveness. Several cortisol indicators in serially collected saliva have been used in research studies to evaluate the circadian rhythm. We aimed to find if the distribution of those indicators is affected by the specific assay platform used.

Methods

Four-time points of saliva specimens were obtained immediately after awakening, 30 min and 60 min post-awakening, and in the nighttime from 49 subjects (aged between 19 and 25, mean ± SD: 28.9 ± 8.4 years). Salivary cortisol was analyzed by ELISA method using the Cortisol Saliva ELISA kit (IBL, Hamburg, Germany). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay was performed on the API 4000 triple quadrupole mass spectrometer coupled with an Agilent 1200 liquid chromatography system. Four cortisol indicators (DCS (diurnal cortisol slope), CARi (cortisol awakening response by an absolute increase within 30 min of awakening), AUCg (area under the curve with respect to ground), and AUCi (AUC with respect to increasing)) were calculated from each patient by the method. Correlation between the two methods was evaluated for overall cortisol concentrations, DCS, CARi, AUCg, and AUCi.

Results

The cortisol concentrations between the two methods strongly correlated (r = 0.973) but with a mean bias of 3.4 nmol/L (95% CI −3.8 to −2.9). Four cortisol indicators strongly correlated between the two methods, but showed significant differences. DCS data generated from LC-MS/MS measurement was more broadly distributed than those from ELISA. On the contrary, CARi data generated from ELISA measurement dispersed more than those from LC-MS/MS.

Conclusion

The concentrations of salivary cortisol strongly correlated between ELISA and LC-MS/MS, though considerable proportional bias between the two methods. The cortisol indicators generated from different methods can affect its distribution, therefore possibly affecting its discrimination power.
A-031 Global Discovery of Serological Metabolome Uncovers Unique Molecular Signature for Early Onset of Type 2 Diabetes Mellitus: A Retrospective Study in Chinese Population
Authors: Zhu L , Wu Y
Published: September 2023

Background

Type 2 diabetes mellitus (T2DM) is a multifaceted disorder affecting epidermic proportion at global scope. Defective insulin secretion by pancreatic β-cells and the inability of insulin-sensitive tissues to respond appropriately to insulin are the primary causes of T2DM. Early detection of people at high risk of developing T2DM is of great importance as interventions such as dietary control and intentional weight loss can effectively improve the insulin sensitivity and prevent the disease incidence. However, circulating biomarkers that are indicative of early diabetic onset at asymptomatic stage have not been well described. Here, we aim to identify new serological markers indicating early asymptomatic onset of T2DM by MS-based metabolomic discovery.

Methods

Three independent cohorts were assembled for the study. The discovery cohort included sera from 25 patients with T2DM and 25 healthy controls. The validation cohort included sera from 15 patients with T2DM and 15 healthy controls. The testing cohort included sera from 111 patients with pre-diabetes and 89 healthy controls. Untargeted approach was used to characterize the serological metabolome by high performance liquid chromatography-high resolution mass spectrometry.

Results

The univariate analysis identified 11 metabolites that were significantly altered in patients with T2DM across discovery and validation cohorts. After evaluated by the testing cohort, 8 of 11 metabolites, such as hexose, N-acetyl-glucosamine, and alpha-ketobutyrate, remained statistically significant in patients with prediabetes as compared to healthy controls. The multivariate analysis based on 8 significant metabolites revealed distinct patterns of metabolic perturbation at the early onset of T2DM. To gain mechanistic insights into the disease pathophysiology, pathway enrichment and correlation network analyses were conducted to unveil the molecular crosstalk underlying the disturbed metabolic network in the pathogenesis of T2DM.

Conclusion

Our study not only identified serological biomarkers detecting early asymptomatic onset of T2DM but also provided additional insights into the disease pathophysiology.
A-087 Relationship among Different Inflammatory Markers in Patients with COVID-19 Infections
Authors: Yadav R , Chopra P , Sehgal T , Datta S K , Ningombam A , Ahirwar A
Published: September 2023

Introduction

Acute phase reactants (APRs) are inflammation biomarkers that exhibit significant changes in their serum concentrations due to infectious and noninfectious conditions. APRs such as C-reactive protein (CRP), Interleukin-6 (IL-6), Ferritin, Lactate dehydrogenase (LDH); coagulation biomarkers such as D-dimer, Fibrinogen; cardiac biomarkers such as Creatine kinase-MB (CK-MB), and hematological biomarkers such as Neutrophil to Lymphocyte ratio (NLR) have been used extensively during the COVID-19 pandemic for early diagnosis, monitoring of response to treatment and prognostication. Amongst these, CRP, although a non-specific marker of inflammation has been widely used in COVID-19 patients.

Objectives

In this study, we tried to evaluate the relationship of the other markers like IL-6, Ferritin, LDH, D-dimer, Fibrinogen, CK-MB and NLR with CRP levels in COVID-19 patients.

Methods

This cross-sectional study was carried out in a tertiary care hospital, New Delhi India, July 2020 to Dec 2020. Total 282 adults, confirmed COVID positive by RT-PCR were included in the study. The investigations were performed on day 0 or day 1 of COVID positivity. Correlation of CRP with other markers was studied by regression analysis using Minitab ver.17.

Results

Among the 282 patients, gender distribution was 190 males to 92 females with an average age of 52.5 ± 15.1 years. All the markers were observed to have non-parametric distribution. CRP was raised in 92.5% cases (n = 239), IL-6 in 83.2% (n = 279), Ferritin in 66.8% (n = 238), LDH in 99.1% (n = 233), D-dimer in 96.6% (n = 30), Fibrinogen in 68.4% (n = 19), CK-MB in 84.6% (n = 98) and NLR of more than 4 in 82.8% (n = 280). The median and range for the different markers were as follows: CRP (44.8 U/L; 15.6–736), IL-6 (67.3 pg/mL; 0.8–1624), LDH (608.0 U/L; 161–6705), Ferritin (643.5 ng/mL; 7.9–11 932), D-dimer (7 µg/mL; 0–5250), NLR (9.43; 0.05–157.17); Fibrinogen (475 mg/dL; 285–759) CK-MB (9.9 mg/L; 0.1–46.7) respectively. Significant correlation was not observed between CRP and any of the inflammatory markers.

Conclusion

Inflammatory markers are raised in most patients with COVID-19, however, all markers are not raised in all patients. Sequential evaluation of these markers may be beneficial rather than at one time point.
A-099 Assessment of Stability of Routine Clinical Biochemical Results in 24-h Urine Specimen Under Conditions Simulating Various Preanalytical Variables
Authors: Chae H , Jang H , Cha K , Oh E
Published: September 2023

Background

The preanalytical phase has long been recognized as a source of substantial variability for 24-h urine samples. Hence, we examined the stability of analyte concentrations of 14 clinical biochemistry parameters commonly requested in a 24-h urine sample. The effects of various preanalytical variables simulating preexamination processes of the testing process were assessed.

Methods

We aimed to examine the effect of time delay in sample processing (up to 7 days), storage temperature (at 4 °C and room temperature), storage container (24-h urine bag, styrofoam box), and the effect of addition of toluene as preservative. The effect of the variables on clinical biochemistry parameters (uric acid, calcium, amylase, LDH, total protein, urea nitrogen, magnesium, phophorus, glucose, creatinine, sodium, potassium, chloride, and micro-albumin) in 24-h urine samples were assessed.

Results

Most of the analytes (uric acid, calcium, amylase, total protein, urea nitrogen, magnesium, creatinine, sodium, chloride, and micro-albumin) showed values not significantly different (≤± 5%) from baseline after 7 days of storage regardless of the storage temperature or addition of preservative. Three analytes were stable ≤24-h: phosphorus and glucose were stable up to 24-h and potassium up to 4-h. The addition of toluene had significant positive interference with LDH measurements.

Conclusion

According to our results, major analytes (uric acid, calcium, amylase, total protein, urea nitrogen, magnesium, creatinine, sodium, chloride, and micro-albumin) were stable up to 7 days in ambient storage conditions and toluene as a preservative was not necessary. However, a few analytes (phosphate, glucose, and potassium) were much more unstable and allowed ≤24-h or ≤4-h of storage in ambient or refrigerated conditions.
A-117 Performance Evaluation of five Sentinel Diagnostics’ Assays on Beckman Coulter DxC 500 AU Clinical Chemistry Analyzer
Authors: Cugini A , O’Meara D , Di Gennaro F , Di Rocco N , Assalini C , Lucini R , Brambilla S
Published: September 2023

Objective

The aim of this study is to evaluate the analytical performances of the following Sentinel Diagnostics’ assays: ACE Liquid, Lp(a) Ultra, Pancreatic Amylase, Lipase NG, Albumin BCP on the Beckman Coulter DxC 500 AU Clinical Chemistry Analyzer.

Methods

Performance evaluation included Limit of Blank (LoB), Limit of Detection (LoD), Limit of Quantitation (LoQ), linearity, intra assay precision, inter assay precision, calibration stability, on board reagent stability and instrument correlation, following the current CLSI guidelines protocols. Analytical Measuring Range (AMR) was defined through linearity and sensitivity.

Results

Summary of the analytical performances for all the assays tested is reported in table below.

Conclusions

All assays showed good results for the parameters tested on the Beckman Coulter DxC 500 AU Clinical Chemistry Analyzer making these kits very suitable for a routine measurement of these analytes.
A-120 Performance Evaluation of Three Sentinel Diagnostics’ Assays on Roche Cobas c 303 Analytical Unit
Authors: De Lorenzis M , Di Gennaro F , Valdambrini M , De Angelis L , Lucini R , Brambilla S
Published: September 2023

Objective

The aim of this study is to evaluate the analytical performances of the following Sentinel Diagnostics’ assays: Total Bile Acid Liquid, Copper, Aldolase, on Roche cobas c 303 analytical unit.

Methods

Performance evaluation included Limit of Blank (LoB), Limit of Detection (LoD), Limit of Quantitation (LoQ), linearity, intra assay precision, inter assay precision, on board reagent stability, prozone effect, instrument correlation following the current CLSI guidelines protocols. Data were evaluated using Microsoft Excel statistical tool Analyse-it. Analytical Measuring Range (AMR) was defined through linearity and sensitivity.

Results

Summary of the analytical performances for all the assays tested is reported in table below.

Conclusion

All assays showed good results for all the parameters tested on Roche cobas c 303 analytical unit making these kits very suitable for a routine measurement of these analytes.
A-121 Performance evaluation of two Sentinel Diagnostics’ assays on Roche cobas c 503 analytical unit
Authors: De Lorenzis M , Di Gennaro F , De Angelis L , Lucini R , Brambilla S
Published: September 2023

Objective

The aim of this study is to evaluate the analytical performances of the following Sentinel Diagnostics’ assays: Zinc, Total Bile Acid Liquid on Roche cobas c 503 analytical unit.

Background

Zinc is a component of metalloenzymes involved in nucleic acid and protein synthesis, therefore it is a necessary complement for cell replication. Acute zinc deficiency can result in skin lesions, irritability, loss of hair, growth retardation. Also impaired immunological function is associated with zinc insufficiency. Total Bile Acids (TBA) are metabolized in the liver and hence serve as a marker for liver function. Serum TBA are increased in patients with acute hepatitis, chronic hepatitis, liver sclerosis and liver cancer.

Methods

Performance evaluation included Limit of Blank (LoB), Limit of Detection (LoD), Limit of Quantitation (LoQ), linearity, intra assay precision, inter assay precision, calibration stability, on board reagent stability, and instrument correlation following the current CLSI guidelines protocols. Data were evaluated using Microsoft Excel statistical tool Analyse-it. Analytical Measuring Range (AMR) was defined through linearity and sensitivity.

Results

Summary of the analytical performances for both the assays tested is reported in table below.

Conclusions

Both assays showed good results for all the parameters tested on Roche cobas c 503 analytical unit making these kits very suitable for a routine measurement of these analytes.
A-142 Comparison of Alinity c Hemoglobin A1c Immunoassay with Premier Hb9210 Automated HPLC Assay: Very Few Patients May be Outside Reportable Range Using Alinity c.
Authors: Walton A
Published: September 2023

Background

Hemoglobin A1c (HbA1c; glycosylated hemoglobin) is used for diagnosis and monitoring of patients with diabetes. In the clinical laboratory both immunoassays and high-performance liquid chromatography (HPLC) based tests are available for such measurement. We use Premier Hb9210 analyzer (HPLC method; Trinity Biotech, Jamestown, NY) for measuring HBA1c in whole blood. As our laboratory is transitioning to Abbott chemistry systems, we compared HbA1c values obtained by the Alinity c and Premier Hb9210.

Methods

The Premier Hb9210 analyzer is based on boronate affinity high performance liquid chromatography with output in 66 sec. The analytical measurement range is 3.8 to 18.5% although values as low as 2% can be reported by the analyzer but result may not be accurate. The Alinity c Hemoglobin A1c assay measures both total hemoglobin and HbA1c (enzymatic assay) in whole blood and then calculates %HbA1c. The analytical measurement range of this assay is 4 to 14% of HbA1c. Specimens cannot be diluted for Alinity c HbA1c measurement.

Results

Alinity c HbA1c has excellent total precision (0.4% at HbA1c of 5.1% and 0.25% at Hb A1c of 9.4%). In contrast, Premier HB9210 has total precision of 1.89% at HbA1c of 5.5% and 1.81% at HbA1c of 8.4%. However, analytical measurement range of Premier HB9219 is slightly wider compared Alinity c assay. Plotting HbA1c results obtained by the Premier Hb9210 analyzer in the x-axis and the corresponding values obtained by the Alinity c assay, we observed the following regression equation: y = 0.9499 x + 0.1108 ( n = 50, 0.99). The 95% confidence interval of the slope was 0.9241 to 0.9757. Rarely, we get specimen where HbA1c is between 3.8 and 4.0% (42 specimens out of 52 803 between 2/7/22 to 2/7/23; 0.08%) or above 14% (174 specimens out of 52 802; same period; 0.33%) and these specimens would not produce any result with Alinity c assay. We recently observed HbA1c result of 2.4 % in a sickle cell patient (reported as <3.8% per our lab policy).

Discussion

Our result indicates that HbA1c immunoassay on the Alinity c analyzer showed values comparable to HPLC method. However, for very few patients HbA1c may exceed 14% due to uncontrollable diabetes. Because specimen cannot be diluted, real value could not be measured using Alinity c but can be measured by the HPLC method.

Conclusions

We conclude that HbA1c assay on the Alinity c analyzer is a viable alternative to HPLC for measuring HbA1c in clinical laboratory. However, for very few patients (sickle cell trait, uncontrolled diabetes), HbA1c may be outside the range of Alinity c, requiring HPLC analysis.
A-146 A Review of RDW-CV and RDW-SD Measurements in Patients With Iron Deficiency Anemia in an Acute Care Hospital in Singapore
Authors: Chen Z , Ilagan F , Heng P , Prasad V
Published: September 2023

Background

Red Cell Distribution Width (RDW) is a routinely available parameter on automated haematology analysers. This parameter is often used to help in the diagnosis of iron deficiency anaemia. RDW quantitatively measures the degree of anisocytosis of the red blood cells. The more common way of reporting RDW is RDW-CV, which is based on the coefficient of variation of the red blood cell distribution volume and is calculated using mean red cell volume. RDW can also be presented as RDW-SD, which is a direct measurement of the width of the red blood cell distribution curve and is not influenced by mean red cell volume. Conventionally, laboratories report RDW-CV as part of the red blood cell indices in full blood count (FBC) reports. However, it has been proposed that RDW-SD is a better indicator of iron deficiency anaemia compared to RDW-CV. The authors seek to review and assess the clinical utility of both RDW measurements in patients with iron deficiency anaemia in an acute care hospital in Singapore.

Methods

RDW data of samples from 271 unique individuals from Sysmex XN-9000 (Sysmex, Japan) automated haematology analysers over a period of two months were reviewed. These individuals were selected as they had plasma iron measured in the same blood collection. The individuals were sorted into two groups based on the plasma iron measurement: with iron deficiency (80%) and without iron deficiency (20%). The correlation of RDW-CV and RDW-SD with the plasma iron concentration of the individuals was studied. The RDW-CV reference range used were established for the local population by an in-house reference range validation study while that of the RDW-SD is from a recent Participant Summary Report for a College of American Pathologists (CAP) Hematology Automated Differential survey (FH9-B 2022). The sensitivity, specificity, predictive values, and overall efficiency of RDW-CV and RDW-SD were calculated and compared using the data collected.

Results

The sensitivity and specificity of RDW-CV in detecting iron deficiency anaemia are 45.2% and 68.5%. The positive and negative predictive values for RDW-CV are 85.2% and 23.7% respectively. The sensitivity and specificity of RDW-SD in detecting iron deficiency are 33.2% and 64.8%. The positive and negative predictive value of RDW-SD are 79.1% and 19.4% respectively. The overall efficiency of RDW-CV is 49.8%, significantly higher than 39.4% of RDW-SD.

Conclusion

This retrospective study suggested that RDW-CV is still a better blood cell index than RDW-SD in the differential diagnosis of iron deficiency anaemia in a predominantly Asian population. However, the use of RDW-SD reference range that is appropriate for the local population may improve the clinical utility of the RDW-SD.
A-160 Factor VIII Chromogenic Low Activity Sample Analysis in a Low Calibration Curve Model
Authors: de Paula R F , Ramos G R , Yanquen M , Borella C , Perez C M
Published: September 2023

Background

Adequate laboratorial diagnostics of hemophilia is essential and could be done by chromogenic and one-stage assays based on APTT methodologies. Adverse effects of medications became less severe recently, but it remains important to be aware of to ensure that treatment is effective and ensure the best possible conditions for affected individuals. Classification of hemophilia according to FVIII activity: mild 25%–5%; moderate, 5%–1% and severe <1%. For new therapies such as emicizumab and some drugs with an extended half-life, the World Federation of Hemophilia recommends the use of a chromogenic assay of FVIII containing bovine FX for monitoring factor FVIII activity. Objetive: evaluate the applicability of a low calibration curve (LCC) in the chromogenic factor VIII (FVIII-Chr) assay by standardizing the dilution of the standard (calibrator) and thus ensuring the accuracy of the analyses in the lower values like severe hemophilia range.

Methods

The samples were obtained from H&H LAB SAS, which guarantees all requirements. Sysmex® CS 2100i Siemens Healthineers. Calibration was performed with Standard Human Plasma (SHP), together with FVIII-Chr. Quality Control (QC); the accuracy of the LCC was checked.

Results

Preparation of the LCC: SHP reconstitution, followed by 1:10 dilution between the SHP and the plasma deficient in FVIII. The curve was named FVIII-Chr Low. QC was performed through pathological control (PC) with 2 dilutions: 1) identical to the formation of the low curve, i.e., dilution 1:10 (2.3%–3.9%). 2) dilution 1:30 (0.2%–2%) to accommodate the range of activity comprising severe hemophilia. The values found confirms the curve’s quality.

Discussion

This study sought to develop a way to detect FVIII activities <1.5% in a reproductive manner, even with a reduced “N” number of samples for severe state. The chromogenic test presents a limit of detection for the optical density of D.O. 0.0080 reporting <0,3% FVIII-Chr activity, which is very close to the most diluted point of the LCC.

Conclusion

QC performance with PC 1/10 and 1/30 showed excellent reproducibility. With the protocol FVIII Low and LCC (SHP + PDF) it is possible to obtain results of FVIII-Chr <1.0% compatible patients with severe hemophilia clinical condition.
A-165 Test Harmonisation Is a Key Enabler of Pathology Transformation
Authors: Ellison T , Cane P , MacFarlane C , James D
Published: September 2023

Background

In April 2021 a new joint venture was formed to deliver and transform services across South East London. Two large NHS Foundation Trusts (Guy’s and St Thomas’, and King’s College hospitals) partnered with SYNLAB who are specialist pathology providers, bringing extensive global experience and expertise in setting up, transforming and running diagnostic services. The Trusts had been working in partnership for many years but were operating in numerous areas as two separate entities. There was duplication of services and tests, with different analytical platforms and very different ways of working, which led to variations in resulting and reporting. Our aim was to establish a single consolidated service, with a harmonised test catalogue, facilitating the provision of consistent results regardless of the origin of sample, and to have a single governance framework to drive improved accountability and optimisation of resources. Our view was that test harmonisation was essential to enable the deployment of a common core Laboratory Information Management System (LIMS) from the 24 legacy systems, and that the harmonisation process should be clinically led.

Method

We established forums (through a series of workshops) for comprehensive engagement and dialogue to allow key clinical leads from all services to meet and agree the path forward. After extensive collaborative engagement, a new model was created with a single “Strategic Clinical Lead” with pan-site responsibility appointed for each service from the existing senior clinical staff. The Strategic Clinical Lead works with their colleagues to drive consensus, seeking wide stakeholder engagement from end service users as required.

Results

From an initial repertoire of circa 7100 tests, test harmonisation has resulted in a 25% reduction, and in some services such as Virology, we identified 31% duplication in tests. The establishment of the new clinical model has resulted in improved efficiency and better use of resources including staffing as well as a reduction of variation of services. Importantly, test harmonisation is essential to move samples seamlessly in a hub and spoke model. The implementation of a single common core LIMS this year will significantly improve business continuity by facilitating seamless transfer of work between sites.

Conclusion

Extensive clinical engagement is key to transforming pathology services. The benefits of consolidation include an overall reduction in process variation leading to improved standardisation and therefore enhanced patient safety as a result of consistency in result reporting. We established a framework and new clinical model which has resulted in improved links between staff across all sites who are working collaboratively on the new target operating model (hub and spokes) which will be live in April 2024.
A-166 Severity of Harm Category Designation Survey Results
Authors: Peltier L , Van Aelst S , Peeters B , Raimbourg J , Yundt-Pacheco J
Published: September 2023

Background

ISO document 14971-Application of Risk Management to Medical Devices and CLSI document EP23-Laboratory Quality Control Based on Risk Management use a Severity of Harm model to designate maximum acceptable probability of patient harm (risk) based on the severity of the consequence to the patient.

When designing a risk managed quality control program for the clinical diagnostic laboratory, the starting point is to select Severity of Harm categories for each analyte being tested. As each Severity of Harm Category (Negligible,Minor,Serious,Critical,Catastrophic) can be mapped to a corresponding maximum acceptable probability of patient harm from erroneous results (0.01,0.001,0.0001, 0.00001,0.000001). The laboratory can then design quality control strategies that have a predicted probability of patient harm below this maximum for a risk managed quality control program.

Unfortunately, there is little guidance on setting Severity of Harm designations, and they are by nature, subjective. To remedy this, we conducted a survey of laboratory professionals, asking them to rate the Severity of Harm for 20 analytes.

Method

An international Severity of Harm survey was conducted to solicit Severity of Harm designations for analytes in the clinical diagnostic laboratory. 261 respondents from 42 countries answered the question: “How would you rate the severity of patient harm if a clinician would interpret incorrect reported results from these analytes in the most unfavorable situation?”.

The available ratings were described as:

Results

Conclusion

While Severity of Harm designations are specific to the local clinical system, guidance can be provided by collecting the opinion of a wide variety of clinical laboratory professionals. This provides support for the clinical diagnostic community in building risk managed quality control programs.
A-175 Objective Indexes for Comparing Platelet Usage Among Peer Hospitals During the COVID-19 Pandemic
Authors: Tu Y , Hsueh Y , Cheng Y , Lin T , Chiueh T
Published: September 2023

Background

Besides hospital size, clinical diagnosis and severity of patients’ cases determine the total platelet transfusions of each hospital. Therefore, the appropriateness of platelet usage could not be simply compared with the total units of platelet usage among hospitals of different sizes. This study aimed to establish objective indexes that can appropriately reflect the differences in platelet usage in various hospitals.

Methods

We used three objective indexes X, Y, and Z to compare the appropriateness of platelet transfusions among different hospitals. Instead of considering various factors such as hospital size, patient population, and disease diagnosis individually, three indexes were generated by dividing the annual total units of platelet usage by total annual reimbursement, the total number of admissions, and the average total reimbursement per admission for each hospital, respectively.

Results

Total units of platelet usage were only directly related to the sizes of hospitals. New indexes X and Y alleviated the hospital size-dependent difference. Index Y was considered a better option than index X, as its value fluctuated less during the COVID-19 pandemic. Index Z was adjusted with the average total reimbursement per admission, and its results showed that more patients of higher disease complexity did not result in more platelet usage during the COVID-19 pandemic.

Conclusion

These three objective indexes are suitable for peer comparison and monitoring the platelet usage of hospitals irrespective of their size.
A-179 Implementation of an Electronic Competency Evaluation System for Point of Care Testing
Authors: Sanchez N , Coughlin V , Okulewicz A , Urena C , Mauriello M , Chen D
Published: September 2023

Background

Management of training and competency evaluation for point of care testing personnel is essential to hospital operations. Typically, documentation for training and competency of point of care operators is a paper based manual process and managed by the POCT team. The responsibilities include maintaining these records for the duration of employment and thereafter and retrieving records for regulatory inspections. It is a challenge for any POCT team in a hospital system with a high volume of operators. In an effort to streamline this process, an electronic training and competency format for the operators of point of care glucose meter was developed and implemented in our hospital system.

Method

Initial training and competency requires in person delivery which must capture specific elements of competency and must be traceable to the trainer and trainee. Leveraging a survey based online training platform (Qualtrics) as the repository of the training record, the paper based training checklist was converted to an online format accessed via QR (Quick Response) code. Delivery of the training is performed by a certified trainer or preceptor under observation. The training checklist and competency quiz are documented directly in Qualtrics capturing all of the data required for traceability. The evaluation record of each new trainee is available to the POCT Team in real time.

Results

The online format of initial training and competency was validated by comparing the paper based version to the electronic version. Functionality of the electronic version was confirmed and accuracy of the checklist answers were validated. This electronic format was implemented for initial operator training and evaluation in January 2023. Over 150 trainees have successfully completed the electronic training checklist and competency quiz.

Discussion and Conclusion

The implementation of an electronic evaluation tool for operators of point of care blood glucose testing has streamlined the process of documentation management in a secure, reliable and transparent way. It also helps to standardize the training process and minimize errors related to a manual process. These documents are readily available and can be retrieved upon request. The implementation of the electronic training evaluation system through Qualtrics coupled with our existing electronic re-certification process will allow us to transition to a fully paperless evaluation/documentation workflow.
A-183 Improving Turnaround Time of Critical Value Reporting by Reducing Redundant Workflow
Authors: Chuang F
Published: September 2023

Background

Most laboratories and hospital patient safety committee define the critical value parameter together, and laboratory should notice the doctor when critical value reporting. “Critical value” as a result refers to the patient may be life-threatening or in imminent danger and require immediate treatment by a doctor. Especially, Troponin-I result is greatly affect door to balloon time. As soon as the critical value reporting, the patient will get therapy earlier. For patient safety, we implemented some methods to reduce the turnaround time of critical value reporting.

Methods

(1) Shorten the distance between specimen receiver and testing operator from 2 meter to 0 meter. Specimens are analyzed sooner due to reduced unnecessary walk. (2) Assess the difference of results between first and second exam, there are no significant difference. Reducing unnecessary repeat test to report critical value as soon as possible. (3) Reading barcode by both clockwise and counterclockwise way to improve barcode reading performance of analyzer, and reducing unnecessary re-label or manual operate.

Results

Emergency patient critical value report in 30 min completion rate increased from 80.5% to 93.3%. Inpatient critical value report in 60 min completion rate increased from 94.1% to 96.6%. Troponin-I report in 30 min completion rate increased from 89.3% to 97.0%.

Conclusion

Doctors treat according to result from laboratory, and delayed report is an impediment to patient care. Particularly critical value reports, that causes delays in urgent patient treatment. We reduced unnecessary work to short turnaround time for critical value reporting, patient will get better therapy faster, and further improve patient safety.
A-187 The Effect of Ambient Temperature on Potassium During Hot Months: The Seasonal Pseudohypokalemia Delima!
Authors: Khoury R , Gudaitis P , Gandhi A , Gudaitis D
Published: September 2023

Background

Laboratory tests are vital tools for the clinicians and it is becoming more and more the most the decision maker for the management of patients. Blood samples are drawn from patients and transported to the laboratory for analysis; samples are exposed to various temperatures during transportation which could have an effect on test results. We studied the effect of seasonal change on the potassium results using lithium heparin plasma tubes.

Method

We compared the results collected from one day/month each from January 2022 to August 2022 from patients residing in Long-Term Care Facilities and were transported to the laboratory during which the samples were exposed to ambient temperature. A total of 16 086 specimens were collected using Lithium heparin plasma tubes up to 8/8/2022, sample on 8/15/22 were collected using serum gel separation tubes. Statistical analysis was done using Analyse-it.

Results

our results showed an increase in hypokalemia with the increase in ambient temperature, the highest incidence of hypokalemia was during the month of June to August which corresponds with the higher ambient temperature. There was an increase in hypoglycemia at the same time of the increase in hypokalemia. The percentage of samples with hypokalemia was normalized when serum (SST) tubes were used.

Conclusion

Seasonal pseudohypokalemia is phenomena that is seen when the samples are transported to the laboratory from different collection sites during the hot temperature. The increase in hypokalemia could be due to an increase in glucose metabolism and the cellular uptake of potassium or could be mediated by sodium-potassium-exchange-ATPase. Serum samples were less affected by the temperature change than lithium heparin plasma. It is very important to emphasis on the temperature during transporting samples to the laboratory to avoid seasonal pseudohypokalemia in the hot temperature season and hyperkalemia during the cold temperature season.
A-206 Association of Lipids and Glucose with High-sensitivity CRP (hs-CRP) in a Community-based Adult Population
Authors: Li H , White Al-Habeeb N , Catomeris P
Published: September 2023

Background

Research and clinical studies have established a pivotal role of inflammation in the development and progression of both cardiac and vascular diseases, responsive to injurious factors such as smoking, hypertension, dyslipidemia, and hyperglycemia. This study analyzed the association of various lipids, HbA1c and glucose with high-sensitivity CRP (hs-CRP), a marker of low-grade chronic inflammation, in a community-based adult population.

Methods

Data analysis was carried out on within-collection results obtained from adults (> = 20 yrs) from 2019 to 2022. Tests included hs-CRP, with cholesterol (n = 74 560), triglycerides (n = 74 551), LDL-C (n = 73 426), HDL-C (n = 74 458), non-HDL-C (n = 69 808), ApoB (n = 3122), Lp(a) (n = 4444), fasting glucose (n = 42 954) or HbA1c (n = 62 486). All tests were performed on Roche Cobas instrumentation. Chi square tests were performed to evaluate the association between each lipid and glycemic indicator with hs-CRP. Relative risk (RR) and odds ratio (OR) were calculated to assess the strength of the association.

Results

Chi-square test demonstrated association of hs-CRP with HDL-C, triglycerides, HbA1c, non-HDL-C, LDL-C, fasting glucose, cholesterol and ApoB, but not Lp(a). Increased risk and odds to have elevated hs-CRP (3.0 -10.0 mg/L) were observed with abnormal glucose and lipid levels. Higher RR and OR were seen with decreased HDL-C and elevated HbA1c, fasting glucose, triglycerides, and non-HDL-C. Slightly increased RR and OR were also observed with elevated LDL-C, ApoB, but not Lp(a).

Conclusion

Glucose and most lipid parameters were associated with hs-CRP. Stronger association was observed with HDL-C and carbohydrates (glucose and triglycerides), followed by triglycerides-rich non-HDL-C. LDL-C, ApoB and cholesterol had weaker association, and Lp(a) had no association with hs-CRP. This observation from a large data set from a community population may provide helpful insight to prevention and clinical management of low-grade chronic inflammation.
A-219 A Multiplexed Targeted Assay for Gangliosides Using Liquid Chromatography-Tandem Mass Spectrometry
Authors: Kim J , Byeon S , Oglesbee D , Matern D , Schultz M J , Pandey A
Published: September 2023

Background

Gangliosides are a family of complex lipids that are molecules composed of glycosphingolipid with one or more sialic acid linked on the sugar moieties. Gangliosides are recognized to play an important role in many biological processes and the alterations in ganglioside profiles have been observed in some neurodegenerative diseases, neuropathies and lysosomal disorders. Gangliosidoses are a group of inherited lysosomal enzyme deficiencies characterized by an accumulation of incompletely degraded gangliosides in the lysosome. While the diagnosis of gangliosidoses can be accomplished by measurement of enzymatic activities and/or molecular genetic testing, biomarker analysis could facilitate monitoring affected patients, including those enrolled in clinical trials of new treatment approaches (ie., substrate reduction or gene therapies). We developed a rapid and sensitive LC-MS/MS assay that allows simultaneous quantification of multiple gangliosides and other glycosphingolipids and tested it in serum and plasma of patients with a diagnosis of GM2-gangliosidosis.

Methods

Gangliosides and other glycosphingolipids were extracted from 20 µL serum or plasma using chloroform:methanol (1:2, v/v). A multiplexed LC-MS/MS assay was developed that targeted several ganglioside species (GM3, GM2, GM1, GD3, GD2, GD1, GT3, GT2, GT1 and GQ1) along with several glycosphingolipid species (GlcCer, LacCer, Gb3, Gb4 and GA2). This assay was performed on a triple quadrupole mass spectrometer with scheduled MRM in both negative and positive ion modes after internal standards (GM3 18:0-d5, GM1 17:0, GA2 17:0 and Gb3 18:0-d3) were spiked into clinical samples.

Results

The multiplexed targeted assay applied to serum and plasma from controls (47 and 49 samples, respectively) and three GM2-gangliosidosis patients for identification and quantification of the targeted gangliosides and other glycosphingolipids. The abundance of GM2 and GM1 gangliosides inserum and plasma of patients with GM2-gangliosidosis was significantly higher than in the control group (P  <  0.0001) whereas GM3 levels were significantly lower (P <  0.005). Other gangliosides including GD3, GD2, GD1 and GT1 and glycosphingolipids such as GlcCer, LacCer and Gb3 were not significantly different between these patients and controls.

Conclusion

A multiplexed targeted assay for glycosphingolipids including gangliosides was developed. This assay will be further validated for potential use in the diagnosis and monitoring of patients with additional gangliosidoses.