bluuebunny/crossref_metadata_2025_split huggingface dataset:
B-068 Plasma calprotectin as an index of draining tunnel formation in Hidradenitis suppurativa
Authors: Havelka A , Kanni T , Giamarellos-Bourboulis E J 
Published: October 2024

Abstract

Background
Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease which affects areas rich in apocrine glands. The main disease manifestations are inflammatory nodules (IN) and draining tunnels (dT). The course and progression of the disease are difficult to predict. There is currently lack of any broadly accepted biomarker which may inform on the activity of hidradenitis suppurativa (HS). Draining tunnel (dT) formation is the hallmark of HS in the affected skin. The existence of a biomarker which may predict dT formation before dTs appear in skin may become a tool for early biological treatment. Calprotectin, also known as S100 A8/A9 protein has been shown to be involved in various inflammatory conditions, including HS. Aim of this study was to evaluate circulating calprotectin as an index of dTs in the affected skin.

Methods
The study group consisted of 40 patients with confirmed HS and varying disease activity, assessed by number of dTs and International Hidradenitis Suppurativa Severity Score System (IHS 4 score) . Plasma samples were collected and stored at -80°C until analysis. Calprotectin was measured with GCAL® turbidimetric assay (Gentian AS, Norway).

Results
Fifteen patients had mild HS and 25 patients had moderate/severe HS. Positive association was found between circulating calprotectin and the absolute dT count (Pearson’s r2 = +0.750; p&lt;0.0001) and the IHS4 (International HS 4 score) (Pearson’s r2 = +0.671; p&lt;0.0001). Circulating calprotectin was significantly increased in patients with more than 2 dTs. Plasma calprotectin greater than 0.5 mg/L was associated with odds ratio 8.00 (1.87 to 34.22; p = 0.005) for 2 or more dTs.

Conclusions
Calprotectin is presented, for the first time, as a biomarker which indicates the formation of dTs in the skin. Its use as surrogate of early start of biologicals and response to treatment remains to be explored.
B-069 Characterization of a panel of antibodies as diagnostics for NASH and NAFL
Authors: van der Hoek A , Jaiu K , Gerhold J M 
Published: October 2024

Abstract

Background
Nonalcoholic fatty liver disease (NAFLD) is on the rise in Western industrialized countries and associated comorbidities like e.g. cirrhosis are a major cause of liver transplantations in the USA. In NAFLD, excess fat is accumulated in the liver whereas this build-up is not caused by alcohol. NASH (nonalcoholic steatohepatitis) and NAFL (nonalcoholic fatty liver) are two forms of NAFLD. NAFL represents a stage of the disease in which the liver does not exhibit major signs of inflammation or damage, while NASH does. NAFL does not necessarily progress to cause liver damage. NASH on the other hand may cause fibrosis and lead to cirrhosis with a risk of progression into liver cancer. Since NAFLD shows a prevalence of over 24-25% in both the USA and Europe, diagnosis moves more and more into focus. The current gold standard for NASH diagnosis is liver biopsy, and NAFLD as such can also be diagnosed by ultrasound and MRI, among others. A quest for biomarkers is ongoing to develop blood tests that allow NAFLD diagnosis by immunoassays for example. We have developed high affinity and specificity antibodies against four highly discussed marker proteins for NAFLD: RBP4 (Retinol Binding Protein 4), FGF21 (Fibroblast Growth factor 21), CHI3L1 (Chitinase-3-like protein 1) and PAI-1 (Plasminogen activator inhibitor-1). All four markers are discussed to be elevated in NAFLD patient serum.

Methods
We characterized the developed anti-RBP4 and anti-FGF21 antibodies via an in-house developed Chemiluminescence Immunoassay (CLIA).

Results
We have determined the limit of quantification (LoQ), limit of detection (LoD) and linear range of measurable concentrations for our antibody pairs. We further conducted spike and recovery experiments showing the precision of the developed antibodies against RBP4 and FGF21.

Conclusions
Together, we present antibody pairs for RBP4 and FGF21 suitable as a part of a diagnostic panel that has high potential to be applied in the diagnosis of NAFLD.
B-073 Analytical Performance of a Novel, Fully Automated Multiplexed Microarray Immunoassay Prototype for the Simultaneous Detection of Fifteen Autoantibodies Associated with Connective Tissue Diseases
Authors: Gomez G , Bijlsma D , Lukasik E , Hausmann M , Fischer C , Ghillani-Dalbin P , Miyara M , Moreau E 
Published: October 2024

Abstract

Background
There is currently a limited offer of automated multi-analyte tests for autoantibody testing in autoimmune connective tissue diseases (CTD). We assessed the analytical performance of a novel, single-use, multiplexed microarray immunoassay prototype (MosaiQ AiPlex CTDplus), used with the fully automated MosaiQ® system, for the simultaneous detection of fifteen autoantibodies associated with CTD, compared with selected CE-marked devices.

Methods
Banked human serum samples, characterized as reactive to ≥1 autoantibody or non-reactive were included. Reactive samples were characterized with FIDISTM Connective Profile (Theradiag) for CENP B, Jo-1, Ribosomal P, Scl-70, Sm, Sm/RNP, SS-A 60, TRIM21 (SS-A 52), SS-B and U1RNP; EliA CCP (Phadia) for CCP2, QUANTA Lite® Chromatin (Werfen) for Chromatin, QUANTA Flash® DFS70* (Werfen) for DFS70, Anti-dsDNA-IgG-ELISA (DRG) for dsDNA, and Immunodot (Euroimmun) for RNA polymerase III (RNAP III). For CCP2, only reactive samples were included. For the remaining analytes, non-reactive samples were characterized using immunofluorescence (ANA-Ro IgG FLUORESCENT HEp-2000®; Immuno Concepts, Germany) and ANAscreen ELISA (ORGENTEC-Diagnostika-GmbH, Germany). Each individual non-reactive sample was tested with the investigational device once; reactive samples were tested in duplicates. Positive percentage agreement (PPA) and negative percentage agreement (NPA) for individual analytes were calculated. For CCP2 only PPA is presented as no negative samples were included.

Results
Compared with relevant devices, the investigational prototype showed PPA ranging from 75% for chromatin to 99% for SS-A 60 and TRIM21. NPA ranged from 95% for chromatin, RNAP III, Scl-70 and Sm to 100% for DFS70, SS-A 60 and TRIM21. Performance details are shown in the Table.

Conclusions
The investigational prototype demonstrated substantial agreement with the compared CE-marked devices. Further studies will allow for expanded performance assessment of the investigational device. This fully-automated multiplexed platform has the potential to contribute to optimizing CTD evaluation by simplifying complex testing pathways and analyzing large number of samples per day.
B-075 Evaluation of patients with monoclonal gammopathy of undetermined significance using Optilite Freelite assays
Authors: Lakos G , Iliev V , Allen S , Rollins A , Foureau D , Bhutani M , McLendon K , Nooka A , Neish A , Birtwistle J 
Published: October 2024

Abstract

Background
Monoclonal gammopathy of undetermined significance (MGUS) is a pre-malignant disorder with a progression risk to multiple myeloma of 1% per year. Patients with MGUS may produce monoclonal intact immunoglobulins (Ig) and/or free light chains (FLC). The International Myeloma Working Group (IMWG) recommendations for the use of FLC measurements in MGUS are to establish the diagnosis of light chain only MGUS (LC-MGUS) and further to risk-stratify newly diagnosed MGUS. Once identified, MGUS is longitudinally monitored at intervals dependent on the risk of transformation. The IMWG recommends serum protein electrophoresis (SPEP) for monitoring of known MGUS with intact Ig, however others have published benefits of additionally monitoring with FLC. In this study, we evaluated the diagnostic sensitivity and specificity of the Optilite® Freelite® Kappa Free Kit and the Optilite Freelite Lambda Free Kit (The Binding Site, part of Thermo Fisher Scientific) in patients with MGUS, and the monitoring performance of Freelite results measured in serial samples from patients with clinically stable and progressive MGUS.

Methods
Serum samples from 234 patients with clinically diagnosed MGUS and 140 disease controls, taken at single time points, and serial samples (≥3) from 49 patients with MGUS were tested with the Freelite assays. Intact M-protein presence and isotype was confirmed in MGUS samples with immunofixation electrophoresis (IFE). In patients clinically diagnosed with LC-MGUS, the presence of detectable M protein on IFE was not required. The disease control cohort (non-MGUS) had disorders commonly associated with elevated polyclonal immunoglobulins (e.g autoimmune, liver, and renal diseases), confirmed by total IgG and/or IgA and/or IgM results and the absence of M-protein by IFE. Patients represented a diverse population from both European and US sources.

Results
The overall diagnostic sensitivity of the Optilite Freelite assays was 59.4%, calculated as the frequency of abnormal free light chain ratio (rFLC) in intact immunoglobulin MGUS, and abnormal rFLC with concurrent elevated involved FLC level in LC-MGUS. The diagnostic sensitivity was: 58.0% in non-IgM MGUS, 41.7% in IgM MGUS, 66.7% in biclonal MGUS and 100% in LC-MGUS. In intact (IgG/IgA/IgM) kappa MGUS, the diagnostic sensitivity was 67.5%, versus 41.5% in intact (IgG/IgA/IgM) lambda MGUS. The diagnostic specificity was 86.4%. In the 49 patients with serial samples, concentrations of involved FLC were stable in 93.3% of patients with clinically stable MGUS, whereas in patients with clinically progressive MGUS an increasing trend was seen in 50% of cases.

Conclusions
These results demonstrate that the Optilite Freelite Kappa and Lambda assays produce clinically relevant results that are useful in the evaluation of MGUS.
B-083 Sensitivity of the Sebia Hydragel 6 electrophoresis/immunofixation assay for detection of beta-2 transferrin in dilute cerebrospinal fluid (CSF): assessment by image analysis
Authors: Stickle D , Flerova E D 
Published: October 2024

Abstract

Background
Beta-2 transferrin (asialo transferrin) greater than 2-sialo transferrin is characteristic of cerebrospinal fluid (CSF). Our neurosurgery department recently requested availability of an in-house assay to evaluate post-surgical drainage fluids for presence of CSF. The Sebia Hydragel 6 beta-2 transferrin electrophoresis/immunofixation profile can be used as a qualitative (positive/negative) assay for this purpose. As a starting point for evaluation of the assay, we examined the sensitivity of the assay for detection of the beta-2 transferrin band in dilute CSF. This was performed by quantitative image analysis.

Methods
Assays were conducted according to manufacturer's instructions. Our proband sample was pooled CSF. Successive dilutions were by factors of 2 (1, 1/2, 1/4, 1/8, 1/16, 1/32). Electrophoresis/ immunofixation was performed simultaneously for these samples across lanes in 6-lane gels. We performed quantitative assessment of the electrophoretic bands for beta-2 transferrin by image analysis. The gel image was scanned to an electronic file (600 dpi png) using a desktop scanner. Grayscale pixel data were obtained using Python and the Python Image Library (PIL). Total grayscale integrals for staining of beta-2 transferrin bands were computed and compared across dilutions of the proband sample.

Results
For CSF dilutions, the assay was invariably visually positive down to dilutions of 1/16. By image analysis, this cutoff had signal/noise ratio (S/N) of 3.5. Across dilutions, band integrals were dependent on dilutions according to a simple hyperbola (representative example: see Figure).

Conclusions
The Sebia Hydragel 6 electrophoresis/immunofixation assay for qualitative assessment of presence of beta-2 transferrin was found to be suitable for unambiguous detection of beta-2 transferrin in CSF down to 1/16 dilution of CSF. By image analysis, the dose vs. response curve (density of staining for beta-2 transferrin across dilutions of CSF) was non-linear.
B-085 Optimizing Thyroglobulin Antibody Interference Thresholds to Minimize Turn-around Time
Authors: Patel S , Peck Palmer O M , Shurin M R , Wheeler S E 
Published: October 2024

Abstract

Background
Serum thyroglobulin (Tg) is a key biomarker used to detect disease recurrence in patients with differentiated thyroid cancers who have undergone complete thyroidectomy. Thyroglobulin antibodies (TgAb) can interfere with accurate measurement of serum Tg levels, producing falsely low results in automated immunoassays. Thus before measurement of Tg, TgAb levels are measured to determine if in-house immunoassays can be used or if the patient’s sample will need to be sent out for radioimmunoassay (RIA) or mass spectrometry methodologies, which are less sensitive to TgAb interference. We recently transitioned to new instrumentation and noted a sharp increase in Tg samples with TgAb interference that needed to be sent out when we used the limit of detection (LOD) of the Roche TgAb assay. This increases turnaround times for patients and increases laboratory costs. We hypothesized that the LOD of the Roche TgAb assay is below the level of interference in Tg immunoassays. To test this we compared the performance of TgAb immunoassays (IA) and Tg measurements by IA and RIA with the intention of proposing a more appropriate threshold for TgAb interference for the Roche TgAb assay.

Methods
We collected 121 serum specimens, which were above the LOD of the Roche TgAb (R-TgAb) assay, which is 10 IU/mL. These specimens were sent as part of standard care to USC for measurement of TgAb by Kronus (K-TgAb) and Tg by RIA. On these split samples we also measured Tg by Beckman Access (B-Tg). We compared the detection of TgAb by USC to varying thresholds of Roche TgAb measurements (10 IU/mL [LOD], 20 IU/mL, and 115 IU/mL [reference interval for autoimmunity]), and assessed the agreement between Tg measurements by Beckman IA and USC RIA for different Roche TgAb thresholds. Analyses were performed in Prism Graphpad using linear regression.

Results
Qualitatively, the concordance for R-TgAb to RIA (reference) at 10 IU/mL was 31%, at 20 IU/mL was 90%, and at 115 IU/mL was 80%. Quantitative agreement between the B-Tg immunoassay and RIA for the TgAb thresholds of: TgAb &gt;10 IU/mL gave an R2=0.97 for Tg comparison, &gt;20 IU/mL gave an R2=0.99, and &gt;115 IU/mL R2=0.99.

Conclusions
Prior studies have shown that TgAb immunoassays can produce significant qualitative and quantitative differences. In our study, we attempt to validate the use of the Roche immunoassay with a cutoff of 20 IU/mL to minimize interference between Tg and TgAb in order to accurately detect recurrence of thyroid cancer. We found that a TgAb cutoff of 20 IU/mL we maintained acceptable agreement between Tg methods indicating no significant interference up to 20 IU/mL. With the TgAb cutoff of 20 IU/mL, we would be able to reduce sendouts for this cohort from 121 to 42, reducing sendouts by 65% and allowing a faster turnaround time for a significant proportion of our patients.
B-092 Effect of the Increased Specificity in a Recombinant anti-tTG Assay on a Celiac Disease Diagnostic Algorithm
Authors: Ferguson A , Morris C , Garg U 
Published: October 2024

Abstract

Background
Celiac disease is an autoimmune disease where ingestion of gluten results in damage in the small intestine. Celiac disease is estimated to affect 1 in 100 people worldwide, but only 30% of individuals are correctly diagnosed. If celiac disease is neither diagnosed nor treated, this can lead to additional health problems such as type 1 diabetes, multiple sclerosis, short stature, coronary artery disease and small intestine cancers. The celiac disease diagnostic algorithm at our institution begins with determination of IgA levels in the patient. If the patient is not IgA deficient (IgA &gt; 7 mg/dL), an anti-tissue transglutaminase (anti-tTG) IgA level is determined. In patients who have anti-tTG IgA ≥ 4U/mL, an endomysial antibodies (EMA) IgA is performed by indirect immunofluorescence (IFA). Inova Diagnostics updated the reagent from human-derived native antigen to a more specific assay containing a recombinant antigen. We investigated the impact of this change on the downstream testing in our algorithm.

Methods
The new assay was implemented in August of 2023, and the monthly test counts and percentage of abnormal results were counted for both anti-tTG IgA and EMA IFA before and after the new assay was implemented.

Results
As shown in Figure 1., switching to the new recombinant anti-tTG reagent resulted in a decrease in the number of anti-tTG IgA results that were classified as abnormal. Subsequently, the abnormal samples that advanced in the algorithm for EMA IFA testing had a higher percentage of abnormal results, while the number of tests performed was lower.

Conclusions
Use of a more specific anti-tTG assay results in reduction of false positive results, and tests that continue through the celiac disease algorithm are more likely to represent a true diagnosis of celiac disease.
B-109 Six Sigma Analysis for Enhancing Biochemistry Internal Quality Control in a Private Laboratory in India
Authors: Patel T , Patel K 
Published: October 2024

Abstract

Background
This abstract outlines a comprehensive study on the application of Six Sigma methodologies to optimize internal quality control processes in a private biochemistry laboratory in India. Data collection was performed using Bio-Rad Assayed Chemistry Control on the Roche cobas 6000 instrument, facilitated by Bio-Rad Unity software. The study adheres to Clinical Laboratory Improvement Amendments (CLIA) 2024 guidelines, specifically focusing on Total Error (TEa).

Methods
The analytical performances of Cobas c501 insturment as analyse by running biochemical tests (urea, creatinine, uric acid, total bilirubin, AST, Amylase, Lipase, CK, LD, ALT, ALP, LDH, HDL-C, Ca2+, cholesterol, TG, HDL LDL, total protein, albumin, Na+, K+, and Cl−) and glucose on Cobas 400 were evaluated. Biases and CV were obtained from internal quality control programs using biorad unity software. The performance of each instrument was assessed using the σ scale; the benchmark performance was &lt;3 σ (improvement needed); “world-class” quality was six sigma.

Results
Analytes such as “Alk PO4,” “ALT,” “Amylase,” “Bilirubin,” “CK,” “GGT,” “LD,” “Phosphorus,” “HDL,” “LDL Cholesterol,” “Triglycerides,” and “Uric acid” exhibited impressive sigma scores exceeding 6. Meanwhile, analytes including “Calcium,” “Total Cholesterol,” “Potassium,” “Total Protein,” “Urea,” and “Glucose” achieved sigma scores between 4 and 6, demonstrating noteworthy performance within acceptable bounds.

Conclusions
This study contributes valuable insights to laboratory management, specifically in the context of biochemistry testing in private Indian laboratories. The adoption of Six Sigma principles, coupled with adherence to CLIA 2024 guidelines and the utilization of advanced instrumentation and software, ensures compliance with regulatory requirements and fosters a culture of continuous improvement. This positions the laboratory to deliver high-quality and reliable results in the dynamic landscape of healthcare diagnostics.
B-118 Comparison of Statistical Methods, Chauvenet Test, and Interquartile Deviation for Urinary Sediment Inter Microscopists Evaluation
Authors: Ramadan-Boscolo D R , Banzato J M , Utiyama A H , de Andrade S S , Tufik S 
Published: October 2024

Abstract

Background
Comparison among microscopists is a quality process aimed at achieving comparability of analyses among collaborators who perform microscopy or manual analysis examinations, as in the case of urinary sediment examination. The current laboratory process evaluates red blood cell and white blood cell counts among microscopists within the same unit, aiming to identify discrepant counts through the application of statistical tools, with Chauvenet Statistics and Interquartile Deviation (IQD) being the most common in the literature. The purpose was to systematically compare Chauvenet Statistics and IQD as evaluation criteria for the comparison among microscopists for urinary sediment examination in our laboratories.

Methods
A total of 45 laboratory units within a total of 684 participants were analyzed throughout 2023. The results reported by microscopists from the same unit were evaluated using Chauvenet Statistics and IQD, calculating the adequacy rate for each type of assessment.

Results
Adopting IQD as the evaluation criterion, adequacy rates of 94.20% for red blood cell counts and 93.73% for white blood cell counts were observed. Using Chauvenet Statistics, the adequacy rates were 96.20% for red blood cells and 95.65% for white blood cells. This difference stems from 233 results identified as inadequate by the IQD method but deemed adequate by Chauvenet Statistics. In these cases, the results did not exhibit a normal distribution, approaching an expected distribution for categorical (discrete) variables. Additionally, 35 results identified as inadequate by Chauvenet Statistics were evaluated as adequate by the IQD method. These occurrences were observed when the reported results approached a normal distribution.

Conclusions
Regarding Chauvenet Statistics, IQD is a more efficient statistical tool for use as an evaluation criterion in the comparison among microscopists who perform red and white blood cell counts for urinary sediment examination in the selected laboratory units. However, the present study illustrated that each of the statistical tools will be more efficient in identifying outliers depending on the dataset analyzed. Therefore, it is important to consider the laboratory's epidemiology and population to decide which statistical tool is most suitable for each scenario.
B-119 Comparative performance of GPT-4 and CNV-ETLAI in extracting copy number variations from medical journals: Bridging the gap between large language models and specialized NLP tools in genomic data interpretation
Authors: Choi J 
Published: October 2024

Abstract

Background
Copy Number Variations (CNVs) are critical genetic markers in diversity and disease, yet their accurate extraction from medical literature remains challenging due to the complexity of genetic data. While specialized NLP models like CNV-ETLAI have been developed for this task, the advent of Large Language Models (LLMs) such as GPT-4 presents a potential alternative with broader applicability. This study evaluates the efficacy of GPT-4 against CNV-ETLAI in extracting CNVs from medical journal articles, aiming to enhance genetic research and clinical decision-making.

Methods
We configured GPT-4 to process and interpret medical journal PDFs, designing custom prompts for CNV information extraction. The performance of GPT-4 was benchmarked against CNV-ETLAI using a dataset of 146 true positive CNVs extracted from 23 journal articles. Performance metrics focused on accuracy in extracting CNVs from both text and tables, recognizing the importance of structured data interpretation in genomic analysis.

Results
CNV-ETLAI demonstrated superior accuracy, achieving a 98% success rate in CNV extraction, compared to GPT-4’s 49%. Specifically, CNV-ETLAI outperformed GPT-4 in table extraction accuracy (99% vs. 41.2%) and context extraction accuracy (96% vs. 63.2%). Despite GPT-4's lower performance, its capacity for improvement and adaptability was noted, indicating potential future applicability in medical data extraction.

Conclusions
The study highlights CNV-ETLAI's current superiority in extracting CNVs from medical texts, particularly in interpreting structured data like tables. However, the adaptability and potential for growth in LLMs like GPT-4 suggest they could soon become valuable tools for medical data extraction, offering a more versatile and powerful solution across a broader range of applications. The promise of LLMs, despite their current limitations, underscores the need for continued research and development in AI technologies for genomic data interpretation.