bluuebunny/crossref_metadata_2025_split huggingface dataset:
A-312 Segregation in Two Families of the PCDH19Gene Deletion Associated With Infantile Epileptic Encephalopathy of X-Linked Inheritance and Expression in Female Carriers
Authors: Bellido Diaz M , De haro Romero T , Gonzalez T , de Haro T 
Published: September 2023

Abstract

Background
Developmental and epileptic encephalopathy-9 (DEE9) is an X-linked disorder characterized by seizure onset in infancy and mild to severe intellectual impairment. Autistic and psychiatric features have been reported in some individuals. The disorder affects heterozygous females only; transmitting males are unaffected. We described the segregation in two unrelated families where the proband was clinically affected as a female and another family where the proband was clinically unaffected as a male.

Methods
Array-CGH analysis was performed by a CGXTM HD v1,1 4-plex array 180 k (PerkinElmer), with an average resolution of 40 kb in the backbone and 20 kb in the regions of interest.

Results
In the first family a deletion of 809.93 Kilobases was detected in the chromosomal region Xq22.1, which includes the PCDH19 gene, in a 1 year old patient with very early onset seizures, 8 months old, inherited from an asymptomatic father. In the second family, a deletion that includes the entire PCDH19 gene was detected in a 5-year-old male patient referred to genetics for autism spectrum disorder (ASD) and not symptomatic for epilepsy; this deletion was inherited from a mother who had episodes of epilepsy in childhood.

Conclusion
The aCGH technique is currently the technique of choice to determine the presence of deletions/duplications in genes of interest with high reliability in patients with neurodevelopmental disorders such as epilepsy or ASD. The probands of these two families have been studied for different clinical pathology and in both the deletion of the complete PCDH19 gene has been detected.
The PCDH19 gene is expressed in developing human and mouse central nervous system, including the hippocampus and cortex, suggesting a role in cognitive function. Malfunction of the protocadherin19 protein is the cause of epileptic seizures in early childhood, the seizures are mostly focal and cause serial seizures (many seizures that cluster together over a few days). It is a type of epilepsy that usually begins in early childhood. Onset may occur spontaneously or in association with fever. Mutations/deletions of the PCDH19 gene are described to cause Early Childhood Epileptic Encephalopathy, with high but incomplete penetrance. DEE9 affects only females heterozygous for the deletion and is characterised by childhood onset of seizures/epilepsy, usually with mild/severe intellectual disability, with males being healthy carriers. Although the cause is not known specifically, it is thought to be related to X-chromosome silencing that occurs in females heterozygous for this mutation. It causes an autosomal dominant X-linked disorder. Some cases of males with a mosaic PCDH19 mutation/deletion have been found to be affected and it has been suggested that the presence of both the normal gene and the mutated/deleted gene is necessary to develop for this epileptic encephalopathy.
A-327 Pre-analytical and Analytical Modifications to Improve the Quality of Pediatric Lead Tests
Authors: Nassif J , Liebreich J , Granger K 
Published: September 2023

Abstract

Background
The recent decrease in the CDC Blood Lead Reference Value (BLRV) to 3.5 ug/dL has highlighted the need for systematic changes that some clinicians and laboratories need to implement to assure the quality of reported pediatric lead results. Building upon the recommendations of the Blood Lead Reference Value Workgroup, APHL has developed specific recommendations and resources designed to assist medical professionals and laboratory scientists in minimizing the likelihood of contamination when collecting and testing blood specimens. Also included are analytical practices that can improve precision, accuracy, and sensitivity of pediatric lead assays.

Methods
Evaluation of existing protocols and practices to identify potential sources of contamination and opportunities for process improvement.

Results
APHL will provide practical recommendations to systematically improve point of care and fixed laboratory testing to improve confidence in reported pediatric lead concentrations. These improved measurements will improve environmental health surveillance and inform public health intervention and patient care.

Conclusion
Rigorous pre-analytical practices including education, updated specimen collection guidance, pre-screening of collection materials, improvement of point of care technology and refinement of spectroscopic analytical methods result in less ambient contamination, improved sensitivity, precision and accuracy of pediatric lead testing. Clinician office practices, public health and commercial clinical laboratories will all benefit from implementing these strategies.
A-328 Urine Toxicology Screening: Tetrahydrocannabinol Positivity Patterns at an U.S. Urban Tertiary Care Children's Hospital
Authors: Unsihuay Vila D M , Poventud-Fuentes I , Osterhoudt K , Patel K 
Published: September 2023

Abstract

Background
Given the recent legalization of recreational and medical marijuana in different states, there is an increasing exposure of children and teenagers to marijuana products which has led to an increase in health care visits and hospitalizations. Our drug testing algorithm uses an immunoassay test for initial urinary drug screening (UDS) followed by an automatic confirmatory test only when a positive UDS result is obtained. The immunoassay test is performed in-house and detects the major metabolites of delta9- tetrahydrocannabinol (THC), the main psychoactive component of marijuana. In contrast, the liquid chromatography-tandem mass spectrometry (LC-MS/MS) confirmatory test is more specific towards THC and is carried out in an external lab. In light of the ongoing trend of marijuana exposure cases and the fact that immunoassay cross-reactivity with non-cannabinoid compounds is uncommon, we aim to assess the necessity of automatic confirmatory tests in our patient population and evaluate its impact on patient management.

Methods
We conducted a retrospective study to assess the trends in cannabinoid hospital-related encounters by age, gender, and incidence with other drugs, in our population among the main campus and satellites (November 2021–October 2022). The UDS tests that were positive for cannabinoids were further evaluated to assess their agreement with the confirmatory testing.

Results
Cannabinoid positive tests account for 62.0% (504/813) of all positive UDS tests in all our locations and 84% (425/504) of the cases did not test positive for other drug classes. Among this population, 92.7% (467/504) are in the adolescent age (≥13 years), whereas 7.3% (37/504) were children (&lt;13 years). Female population comprises 56.0% (217/504) of the cases whereas male, 43% (271/504) of the cases. The true positive rate for the immunoassay test was 99.6% (465/467) and 94.6% (35/37) for adolescents and children, respectively. Clinical decisions were made after a positive immunoassay result and before the confirmatory test as this is a send out test and takes a few days to receive the result.

Conclusion
Our evidence-based approach demonstrates unnecessary confirmatory testing for the adolescent group in our population due to a high positivity rate (99.6%). Discontinuing automatic confirmatory testing for this group will eliminate workload and reduce healthcare costs. On the other hand, automatic confirmatory testing in children will continue as these exposures are mainly considered unintentional and require more investigation.
A-333 Unusually Low Glycated Albumin Results Suggest Unexpected Interference in Study Samples from Pregnant Women
Authors: Powers Carson J , Shin A , Kabytaev K 
Published: September 2023

Abstract

Background
Glycated albumin (GA) is an alternate marker of glucose control that is recommended in situations when hemoglobin A1c is unreliable. One of us (JPC) has examined its use in pregnant women with diabetes since 2019 and regularly observed GA values of 8.0–19.4%, with occasional outliers. However, in a recently recruited cohort of 149 women with and without gestational diabetes, 58% of the samples showed GA results &lt;8.0%, despite no apparent physiological differences. Here we further investigate a subset of these samples using a liquid chromatography-mass spectrometry method (LC-MS/MS).

Methods
Glycated serum proteins (GSP) were measured using the GlycoGap kit (Diazyme Labs, Poway, CA), an enzymatic method, and subsequently converted to percent glycated albumin (GA%) using the equation provided by the manufacturer.The LC-MS/MS assay was performed according to a previously published protocol. The samples were first reduced and alkylated, then spiked with a blend of two isotope-labeled standards and digested using Glu-C enzyme. The resulting digests were analyzed using the QTRAP 6500+ (AB Sciex, Foster City, CA) coupled with a LC system (Shimadzu, Japan) in MRM mode to provide values representing the percentage of glycated to non-glycated Lys-525 in albumin (MSGA%).Samples from a previously collected cohort (A, n = 78) of pregnant women with and without diabetes, with GA% range of 8.5–24.2%, were analyzed using both methods, and a standard curve (MSGA% vs GA%) was established. Thirty-eight samples with GA &lt;8.0% (cohort B) were then analyzed using the LC-MS/MS method, and the standard curve was used to generate the expected enzymatic GA% results.

Results
The comparison of the LC-MS/MS and Diazyme methods resulted in a straight-line equation (r2 = 0.84, slope = 1.81, y-intercept = 0.79). For the cohort B samples analyzed by LC-MS/MS, the median MSGA% result was 5.89% (range: 4.32–8.95%). Based on the equation derived from the method comparison (MSGA% vs GA%), the expected median value with the Diazyme enzymatic method would have been 11.48% (range: 8.63–17.02%). These GA% values are well within the typically expected range.

Conclusion
LC-MS/MS results and GA% calculated from a method comparison curve were within the expected range while original enzymatic results were not, suggesting the presence of an interfering substance. Our hypothesis is that prenatal supplements may lead to elevated ascorbic acid, which is known to cause interference in certain enzymatic assays. We are continuing to investigate this possibility.
A-359 Performance of Measured TCO2 on the epoc Analyzer
Authors: Evans L M , Dilks M , Goldsmith B M 
Published: September 2023

Abstract

Background
The epoc Blood Analysis System (Siemens, Tarrytown, NY) performs blood gases, electrolytes, and metabolites using a Blood Gas, Electrolyte and Metabolite (BGEM) Test Card on 92 uL of whole blood. The BGEM Test Card uses potentiometric sensors to measure sodium, potassium, chloride, ionized calcium, pH, pCO2; amperometric sensors to measure pO2, glucose, creatinine, and lactate; and a conductometric sensor to measure hematocrit. Results are available in 3–10 minutes, depending upon the time of sample injection. TJUH implemented epoc in its ICUs in 2012 to provide rapid, whole blood Point of Care (POC) results and has expanded to other locations (Emergency Department, Outpatient Radiology, Cardiothoracic Surgery). While previous epoc cards provided calculated TCO2 (cTCO2), Siemens recently added measured TCO2 (mTCO2; combination of potentiometric sensors and calculation) to its BGEM card. We evaluated this card for future use.

Methods
Precision and method comparison studies were performed at our Center City location. Inter- and intra-precision studies were performed on two levels of controls (Eurotrol, Elizabethtown, KY). Whole blood was collected in heparinized syringes from 20 patients. Comparison studies were performed on the ABL800 (Radiometer, Brea, CA). We simultaneously compared epoc mTCO2 against epoc cTCO2 and against the cTCO2 on the ABL800.

Results
Intra-assay precision for epoc mTCO2 (n = 20, 2 devices) was 0.8%CV and 2.3%CV for Levels 1 and 3, respectively. Inter-assay precision for epoc mTCO2 (n = 20, 2 devices over 10 days) was 1.1%CV and 3.3%CV for Levels 1 and 3, respectively. Method comparison for epoc mTCO2 (n = 20) was: mean = 22.9, median = 22.1, r2 = 0.9174, y = 0.9751x + 1.2925. In comparison, method comparison for epoc cTCO2 (n = 20) was: mean = 24.7, median = 23.9, r2 = 0.9165 y = 0.9855x + 2.8559.

Conclusion
The epoc measured TCO2 studies show better correlation to the Radiometer ABL800 than the epoc calculated cTCO2, and it is considered acceptable for implementation at our Center City sites where epoc is currently in use.
A-368 Aspergillus Galactomannan Lateral Flow Assay with Digital Reader for the Diagnosis of Invasive Aspergillosis
Authors: Peng J , Yan J , Du J , Wang Y , Wang H , Su Y , Zhou Z 
Published: September 2023

Abstract

Background
The Novel Aspergillus Galactomannan Lateral Flow Assay(Quic GM) from Dynamiker Biotechnology (Tianjin) Co., Ltd is a fluorescent immunochromatographic cassette test using a monoclonal antibody against GM with Digital Reader (Figure 1), which was rapid and easy to operate compared with the traditional GM ELISA assay. Here we conducte a comparative study between the Dynamiker Quic GM and the Platelia GM (Bio-Rad, USA) to validate the performance of the novel assay for the diagnosis of Invasive Aspergillosis (IA).

Methods
A total of 573 serum samples and 97 BALF samples with proven IA (Serum n = 9, BALF n = 2), probable IA (Serum n = 174, BALF n = 25), possible IA (Serum n = 98, BALF n = 16) and patients not fulfilling 2019 EORTC/MSG guideline IA criteria (control, Serum n = 292, BALF n = 54) were included. All the samples were tested in parallel using the Quic GM and Platelia GM.

Results
The total coincidence rate of Quic GM compared with Platelia GM was 97.91% (Kappa value was 0.95 &gt; 0.75), 97.94% (Kappa value was 0.95 &gt; 0.75) and 97.91% (Kappa value was 0.95 &gt; 0.75) in serum samples, BALF samples and serum+BALF samples, respectively (Table 1). The concentrations generated by Quic GM and Platelia GM were linearly correlated (Serum: slope = 0.97, r2 = 0.96, P &lt; 0.0001; BALF: slope = 0.95, r2 = 0.94, P &lt; 0.0001) (Figure 2).

Conclusion
In conclusion, the Dynamiker Quic GM yielded significant consistency with Bio-Rad Platelia GM ELISA, and showed good performances for IA diagnosis, with the benefit of a relatively short handling time (around 20 min).
A-374 Analytical Performance Assessment and Comparison of Point of Care Testing (POCT) Devices for Blood Lipids Measurements
Authors: Dahya K , Pokuah F , Danilenko U , Vesper H W 
Published: September 2023

Abstract

Background
Cardiovascular diseases (CVDs) are the leading cause of death in the U.S. and worldwide. According to the World Health Organization (WHO), worldwide, 85% of CVD deaths are due to heart disease and strokes, and over 75% occur in low- and middle-income countries (LMICs). Early detection and treatment are key to preventing the consequences of CVD. Point-of-care testing (POCT) devices offer alternatives to screening large populations for CVD risk. Although POCT are increasingly used for screening, only few information is available about their accuracy and reliability.

Methods
Eight POCT devices for blood lipids that previously successfully participated in the CDC CVD Biomarker Standardization Programs were used in this preliminary study. The analytical performance for all eight devices was assessed using split sample comparisons to the CDC reference measurement procedures for measurements performed in whole blood (WB) and serum. Specifically, the accuracy of total cholesterol (TC) was determined in WB and serum. The accuracy of high-density lipoprotein-cholesterol (HDL-c), and low-density lipoprotein-cholesterol (LDL-c) was determined in serum. The precision of TC, HDL-c, LDL-c, and triglycerides (TG) was determined in WB and serum.

Results
The reference values of the specimens from 20 donors ranged between 154–279 mg/dL, 36.9–109 mg/dL, and 71.1–182 mg/dL for TC, HDL-c, and LDL-c in serum, and between 145–210 mg/dL for TC in WB. Preliminary assessments found that the mean bias for each instrument ranged from -7.86%–13.82% and from -11.90%–3.24% for TC in WB and serum, respectively. For serum HDL-c samples, the mean bias ranged from −6.81%–15.43%. The mean bias for serum LDL-c samples ranged from −22.40% to 3.08%. For three devices, approximately 30% of the WB measurements and approximately 50% of the serum measurements were reported as outside of the measurement range. The mean imprecision for each instrument ranged from 2.2%–13.75% and from 1.88%–11.76% for TC in WB and serum, respectively. For HDL-c, the mean imprecision ranged from 5.36%–23.21% and from 2.30% to 26.69% in WB and serum, respectively. The mean imprecision ranged from 4.82%–20.34% and from 3.06%–20.54% for LDL-c in WB and serum, respectively. For TG, the mean imprecision ranged from 5.78%–23.91% and from 1.71%–11.02% in WB and serum, respectively.

Conclusion
These preliminary findings about the analytical performance of POCT devices indicate notable differences in accuracy and precision for lipids measured in WB and serum, with serum measurements being more likely within performance requirements than WB measurements. Some devices appear to be more likely to report values outside the measurement range even though reference values are within the measurement range of the device. Further studies to verify these preliminary findings with more individual donor samples are underway.
A-375 Evaluation of the CLIA-Waived Afinion HbA1c Point-of-Care Test
Authors: Villasin E , Metushi I 
Published: September 2023

Abstract

Background
Point-of-care (POC) HbA1c tests can be essential in evaluation/monitoring of diabetes provided that the test has acceptable analytical performance. The Abbott Afinion HbA1c is an in vitro diagnostic test for quantification of HbA1c in human capillary and venous whole blood. This study aim was to evaluate the performance of Afinion HbA1c in whole blood EDTA patient samples.

Methods
The Afinion utilizes the boronate affinity principle for measurement of HbA1c. Hemoglobin A1c was tested on the Abbott AfinionTM 2 analyzer. Two levels of quality control (QC) and two levels of whole blood EDTA patient samples (one low and on high) were used to assess imprecision. Within-day precision was determined by assaying the 20 times in one day and between-day precision was determined by assaying the samples in duplicates over a period of 10 days. The analytical measured range (AMR) and method comparison was performed by using whole blood EDTA patient samples. Percent bias plot and Deming regression analysis was performed by EP Evaluator.

Results
Within-day and between-day precision and accuracy data are summarized in table 1 below. The assay displayed good linearity over the measured AMR. Lastly, the method comparison between Afinion vs Cobas pro, had a correlation coefficient R2 of 0.994, slope (m) of 1.14 and % bias was 2.5%. Afinion vs Trinity Biotech HPLC had R2 = 0.996, m = 1.04 and % bias was −2.3%. Afinion vs DCA Vantage had R2 = 0.991, m = 1.03 and % bias 1.5.

Conclusion
We conclude that the Abbott Afinion POC device evaluated here is precise and yields results consistent with other Clinical Chemistry analyzers such as Cobas Pro and Trinity Biotech.
A-378 Clinical Evaluation and Implementation of Rapid COVID-19 Antigen Test in Qatar
Authors: Said J S , Afreen F , Al-Wali D , Al Kuwari E A , Kabir Z M , Salem A M 
Published: September 2023

Abstract

Background
In March, the World Health Organization (WHO) declared COVID-19 as a global public health emergency. To curb the spread of virus, timely detection of infected patients and screening of suspected cases in massive population posed a challenge for the healthcare system. Rapid antigen tests (RAT) were high in demand as a fast, accurate and cost-effective screening tool to increasing the testing capacity. In this crucial timing, clinical evaluation and procurement of available COVID-19 RAT following the World Health Organization (WHO) guidelines was a huge challenge for Point of Care testing (POCT) department. The aim of this study is to highlight the challenges overcame in establishing a Point-of-care COVID-19 testing system including personnel training and building a compatible Laboratory Information System (LIS) upholding Hamad Medical Corporation (HMC) cyber security regulation.

Methods
Three regulatory approved RATs were evaluated against real-time polymerase chain reaction (RT-PCR) and analytical performance were verified. Maintaining the Clinical Laboratory Improvement Amendments (CLIA) and College of American Pathologist (CAP) standards for COVID-19 waived testing, POCT team initiated to conduct practical and educational training vastly through online platforms and face to face sessions. We utilized the extendable LIS functionality for fast medical decisions in hospitals and enabled “reason of testing” feature in Qatar's COVID-19 tracking application.

Results
Our performance verification showed 98.0% sensitivity and 100% specificity for PanbioTM COVID-19 RAT, 98.0% sensitivity and 100% specificity for Quidel SOFIA2 COVID-19 RAT and Roche COVID-19 RAT yielded a sensitivity of 97.0% and specificity of 100%. Total of 291 training sessions were conducted for 9710 clinical staffs across 17 HMC facilities and 185 private clinics. Using LIS and POC middleware features, obvious increment in RAT of more than 509 tests per day has been reported in a single emergency unit. Overall, 5.5% decrement in incorrect patient identification data using QUIDEL SOFIA2 automated device and LIS functions was recorded in laboratory quality indicator data. COVID-19 tracking application was linked to antigen results for contact tracing, isolating, and breaking the chain of transmission.

Conclusion
The methods established for the COVID-19 implementation showed acceptable performance fulfilling the elements of HMC product procurement specification and CAP Accreditation standards. Synergic actions of HMC-POCT with supportive laboratory management aided prompt decision making to optimize patient management and added efficiency to the public health control measures in Qatar.