bluuebunny/crossref_metadata_2025 huggingface dataset:
A-271 Verification of a multiplexed STI Pathogen Microarray Test with Saliva Collected With SDNA-1000 Kit
Authors: Quinter C R , Serrett J , Jensen M M , Vigerust D , Gupta R , Peek J
Published: September 2023

Background

Sexually transmitted infections (STI) spread through oral sex potentially cause infections of the mouth, throat, genitals, or rectum. Saliva may be an important source of transmission of STI following oral sex. Multiplexed STI assays are useful diagnostically for patients with risk factors for STI as co-infections occur frequently.

Methods

Alimetrix STI is a multiplexed laboratory developed test for the identification of STI pathogens present in clinical specimens. DNA was collected in SDNA-1000 devices, extracted, purified, underwent multiplex PCR, and labeled amplicons were hybridized to a microarray with gene-specific 50mer capture probes. Fluorescently tagged amplicons were detected on a microarray scanner. Verification included analytical sensitivity (Limit of Detection (LOD), competition, and inclusivity), stability, and analytical specificity (exclusivity, precision and accuracy). Pathogens included in the multiplexed microarray included N. gonorrhea, C. trachomatis, T. vaginalis, T. pallidum , herpes 1 and 2, M. genitalium, U. urealyticum, and monkeypox.

Results

LOD for each pathogen in the Spectrum Solutions SDNA Collection System, throat swab, and first catch urine is found in Table 1. Competition of organisms showed the ability to co-detect up to 5 organisms from a single sample. Saliva collected using Spectrum Solutions SDNA Collection System was stable for 35 days at room temperature enabling discreet at home collection. Inclusivity showed related strains were detectable at 1× LOD, while maintaining 100% precision, 100% accuracy, and 97% exclusivity for high concentrations of closely related analytes in normal flora.

Conclusion

Control of STI associated with oral sex is dependent upon the demonstration of all pathogens present. Saliva collected in the SDNA-1000 device a high degree of sensitivity, precision, and accuracy, as well as the ability to detect multiple analytes (co-infection) within a given sample. Saliva is a clinically informative specimen source useful for the diagnosis, monitoring, and management of patients with oral and systemic disease.
A-296 Validation of a Real Time PCR Kit for the Detection and Differentiation of MRSA, MSSA and MRCoNS in Respiratory Clinical Samples
Authors: Franco-Marín E , Dehesa-García B , Escolar C , García-Manrique B , Cebollada R , Monforte-Cirac M , Millán-Lou M , Alonso H , Aspiroz-Sancho C
Published: September 2023

Background

Staphylococcus aureus infections are remarkable due to their high morbimortality. In addition, antibiotic resistance of these bacteria is a cause of concern since it worsens the patient prognosis and it is associated to higher morbidity, mortality and cost of treatment. The aim of this study was to assess the clinical performance of the assay VIASURE Methicillin resistant Staphylococcus aureus Real Time Detection Kit in clinical and epidemiological respiratory samples.

Methods

Respiratory samples were collected from patients admitted to intesive care or ward of the Hospital Royo Villanova (Zaragoza, Spain). A total of 653 respiratory samples (both clinical and epidemiological) were employed: 189 nasal swab, 103 pharyngeal, 161 bronchoalveolar aspirate (BAS), 154 bronchoalveolar lavage (BAL) and 46 sputa samples previously characterised using culture methods. Results were compared with other commercial validated molecular assay (RIDA®GENE MRSA (R-biopharm)) presenting the same molecular targets as the assay under study. The characterisation performed by VIASURE is based on the combined results of the three targets S. aureus SA 442/coA, mecA/mecC and Sccmec-orfX junction and may report the following genotypes: methicillin-resistant Staphylococcus aureus (MRSA), methicillin-susceptible Staphylococcus aureus (MSSA)), methicillin-resistant coagulase negative Staphylococcus (MRCoNS) and methicillin-susceptible Staphylococcus aureus and methicillin-resistant coagulase-negative Staphylococcus (MSSA and MRCoNS).

Results

VIASURE assay correctly reported MRSA/MSSA/MRCoNS genotyping results with sensitivity and specificity values over 90% in all sample matrixes (Table 1).

Conclusion

The diagnostic performance of the assay under study demonstrated to be suitable tool for the molecular diagnosis of coagulase negative Staphylococci, S. aureus and their methicillin resistance causing mutation when compared with reference methods.
A-300 Evaluation of Different Storage Conditions of Nasopharyngeal Swabs for the Detection of Influenza A, Influenza B and RSV
Authors: Martínez-Santolaria M , Sota-Diez C , García-Manrique B , Machetti-Mareca E
Published: September 2023

Background

Every year, Influenza A (FluA), Influenza B (FluB) and Respiratory Syncytial Virus (RSV) affect our communities and increase the number of patients in our health systems. Molecular techniques, such as real-time PCR have become essential, not only for the diagnostic but also for the epidemiological studies. High amounts of samples or retrospective analysis need the use of samples stored at different conditions. For this reason, a stability study of nasopharyngeal swabs (NP) in Viral Transport Medium (VTM) for FluA, FluB and RSV was performed.

Methods

Twenty-eight negative FluA, FluB and RSV NP samples in VTM (Vircell, Spain) were used in this study. All samples were mixed into one pool and divided into 7 aliquots. One of them served as a negative control. The others were enriched (each) with different concentrations of viral cultures from ATCC (VR-95PQ™, VR1804PQ™, VR26PQ™) to obtain two positive samples for each pathogen. Samples were stored under specific conditions of time and temperature before being processed: 1 and 2 days stored at 25°C, 3 and 6 days stored at 4°C, and 8, 30 and 180 days stored at −20°C. Each condition was extracted in triplicate with the MagDEA Dx SV kit, using the magLEAD® 12gC instrument (Precision System Science Co.) and analysed with VIASURE SARS-CoV-2, Flu & RSV Real Time PCR Detection Kit (Certest Biotec S.L) in triplicate on CFX96™ Real-Time PCR Detection System (Bio-Rad). The results were compared with the data obtained on the first day (0 h).

Results

All positive samples were detected in all conditions and matrices. No amplifications were observed in negative samples. There were no major differences compared with the data obtained on the first day. However, a Cq delay of around 1 unit was observed in all pathogens when samples were stored 2 days at 25°C. For this reason, this storage condition would not be recommended.

Conclusion

NP samples in VTM for the detection of FluA, FluB and RSV can be stored at 25°C for up to 1 day, 4°C for up to 6 days, or frozen at −20°C for up to 180 days.
A-372 Increased Sensitivity in Detection of SARS-CoV-2 Antigen Using RADI COVID-19 Ag Rapid Test
Authors: Kee S , Choi J , Jeon J , Heo M , Park J , Choi H
Published: September 2023

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapid point-of-care antigen tests can provide easy and fast results for the diagnosis of coronavirus disease 2019 (COVID-19). However, due to the lower sensitivity of rapid antigen tests relative to reverse transcription polymerase chain reaction (RT-PCR), they might miss many infectious COVID-19 cases. We evaluated and compared a new rapid antigen test with the current approved one.

Methods

The RADI COVID-19 Ag Rapid Test (KH Medical, Hanam, Korea) was validated with a total of 1054 pre-confirmed residual nasopharyngeal swab samples (258 positives and 796 negatives) by PowerChek 2019-nCoV Real-time PCR (Kogene Biotech, Seoul, Korea). Among them, 258 positives and 546 negatives were used to compare the RADI COVID-19 Ag Rapid Test with the STANDARD Q COVID-19 Ag Test (SD Biosensor, Suwon, Korea).

Results

Using RT-PCR results as the reference, the overall sensitivity and specificity of RADI COVID-19 Ag Rapid Test were 82.2% (212/258; 95% confidence interval, CI [76.9–86.6]) and 99.1% (789/796; 95% CI [98.2–99.7]), respectively. The positive predictive value and negative predictive value were 96.8% (212/219; 95% CI [93.5–98.5]) and 94.5% (789/835; 95% CI [93.0–95.7]), respectively. The accuracy was 95.0% (1001/1054; 95% CI [93.5–96.2]) with Cohen's kappa value of 0.86 (95% CI [0.82–0.89]). The positive percent agreement and negative percent agreement of the RADI COVID-19 Ag Rapid Test for STANDARD Q COVID-19 Ag Test were 97.0% (159/164; 95% CI [93.0–99.0]) and 90.6% (580/640; 95% CI [88.1–92.8]), respectively, and those of STANDARD™ Q COVID-19 Ag Test for RADI COVID-19 Ag Rapid Test were 72.6% (159/219; 95% CI [66.2–78.4] and 99.2% (580/585; 95% CI [98.0–99.7], respectively. The overall percent agreement between the two rapid antigen assays was 91.9% (739/804; 95% CI [89.8–93.7]) with Cohen's kappa value of 0.78 (95% CI [0.73–0.83]). Among the 65 discrepant samples between the two rapid antigen assays, 56 were positive as per RT-PCR, which showed 53 samples negative for STANDARD Q COVID-19 Ag Test and 3 samples negative for RADI COVID-19 Ag Rapid Test. The median E gene Ct value of the 65 discrepant samples was 28.2 (interquartile range: 26.1–32.3).

Conclusion

RADI COVID-19 Ag Rapid Test provides acceptable sensitivity and specificity according to the validation criteria for KFDA immunological test product approval. Furthermore, RADI COVID-19 Ag Rapid Test shows improved sensitivity compared to the current approved rapid antigen test.
B-012 Validation of a Urine Ammonium Assay on Roche Cobas c502 Chemistry Analyzer
Authors: Song L , Tong K H , Fournier M I
Published: September 2023

Background

Urine ammonium (uNH4+) excretion is critical for the maintenance of acid-base balance and reduced uNH4+ excretion can cause retention of hydrogen ions resulting in metabolic acidosis in patients with chronic kidney disease (CKD). In addition, study found that declined urine ammonium excretion is an independent factor for predicting the worsening of kidney function. However, urine ammonium assay is not readily available on automated chemistry analyzers. We developed a protocol for the determination of urine ammonium levels using an ammonia assay for plasma samples on an automated chemistry analyzer. In this report, we present the urine ammonium protocol used in our laboratory and the validation of the urine ammonium assay.

Methods

All urine samples were diluted 100 times with deionized water and ammonium in the diluted samples was measured using the NH2L2 ammonia II assay on Roche cobas c502 chemistry analyzer. When a urine sample containing ammonium level less than 1.06 mmol/L, a 50-fold dilution was performed. Recovery was determined in six urine samples when 9 parts of the urine were mixed with one part of a standard 200 mmol/L ammonium solution (made with Ammonium Chloride from Thermo Scientific). Linearity was determined by serial dilutions of a sample containing 187 mmol/L ammonium. Limit of quantitation was determined using a 50-fold dilution protocol. The reference interval of 3–65 mmol/L was verified using 64 urine samples from volunteer donors and patient without CKD and metabolic acidosis. The stability was determined by testing two samples kept at room temperature for 0, 8, and 24 hour, respectively. The within-run precisions were determined by testing three urine samples 20 times in a run, and the between-run precisions were determined by testing three samples 2 times a day for 10 days, respectively.

Results

Recovery was 95.8% to 102.2% in six urine samples contained varying amount of ammonium ranged between 6.0 mmol/L to 22.2 mmol/L. Linearity was 0.5–99 mmol/L. Limit of quantification was 0.5 mmol/L. The reference interval of 3–65 mmol/L was verified. Urine ammonium was stable up to 24 h at room temperature. For within-run precision, the coefficient of variation (CV) was 1.51%, 0.49%, and 0.54% for samples containing 6.0 mmol/L, 27.7 mmol/L, and 75.7 mmol/L ammonium, respectively. For between-run precision, the CV was 2.54%, 5.98%, and 6.13% for samples containing 4.4 mmol/L, 27.9 mmol/L, and 55.1 mmol/L ammonium, respectively.

Conclusion

Urine ammonium levels can be determined using the NH2L2 ammonia II assay on Roche cobas c502 chemistry analyzer after manual dilution of urine samples 100 times with deionized water. The limit of quantitation is extended to 0.5 mmol/L when urine samples are diluted 50 times with deionized water.
B-045 A Descriptive Study of the Clinical Impacts on COVID-19 Survivors Using Telemonitoring (The TeleCOVID Study)
Authors: Chow J S
Published: September 2023

Background

There is increasing evidence that COVID-19 survivors are at increased risk of experiencing a wide range of cardiovascular complications post infection; however, there are no validated models or clear guidelines for remotely monitoring the cardiac health of COVID-19 survivors. This study aims to test a virtual, in-home healthcare monitoring model of care for detection of clinical symptoms and impacts on COVID-19 survivors. It also aims to demonstrate system usability and feasibility.

Methods

This open label, prospective, descriptive study was conducted in South Western Sydney. Included in the study were patients admitted to the hospital with the diagnosis of COVID-19 between June 2021 and November 2021. Eligible participants after consent were provided with a pulse oximeter to measure oxygen saturation and a S-Patch EX to monitor their electrocardiogram (ECG) for a duration of 3 months. Data was transmitted in real-time to a mobile phone via Bluetooth technology and results were sent to the study team via a cloud-based platform. All the data was reviewed in a timely manner by the investigator team, for post COVID-19 related symptoms, such as reduction in oxygen saturation and arrhythmia. This study was designed for feasibility in real clinical setting implementation, enabling the study team to develop and utilise a virtual, in-home healthcare monitoring model of care to detect post COVID-19 clinical symptoms and impacts on COVID-19 survivors.

Results

During the study period, 23 patients provided consent for participation. Out of which 19 patients commenced monitoring. Sixteen patients with 81 (73.6%) valid tests were included in the analysis and amongst them seven patients were detected by artificial intelligence to have cardiac arrhythmias but not clinically symptomatic. The patients with arrhythmias had a higher occurrence of supraventricular ectopy, and most of them took at least 2 tests before detection. Notably, patients with arrhythmia had significantly more tests than those without (t-test, t (13) = 2.29, P < 0.05).

Conclusions

Preliminary observations have identified cardiac arrhythmias on prolonged cardiac monitoring in 7 out of the first 16 participants who completed their 3 months follow-up. This has allowed early escalation to their treating doctors for further investigations and early interventions.
B-064 Analytical and Diagnostic Performances of Anti-Integrin Antibody System in Inflammatory Bowel Disease
Authors: Schwalbe M , McLachlan O , Everts-van der Wind A , Dervieux T
Published: September 2023

Background

Anti-integrin αvβ6 autoantibodies may have value in the diagnosis of Inflammatory Bowel Disease (IBD) and more specifically Ulcerative Colitis (UC). Our objective was to establish the analytical and diagnostic performance of this novel autoantibody system in distinguishing IBD from a group of Normal Healthy Volunteers (NHV) and UC from Crohn’s Disease (CD).

Methods

All testing was performed using a Tecan Evo200 equipped with 8-channel and 96-channel arms, plate washer, and plate reader. The ELISA assay used calibration controls and diluted serum samples added to ELISA plates coated with Integrin αvβ6 antigen. Anti-human IgG horseradish peroxidase complexed with Anti-integrin αvβ6 antibodies was detected using colorimetry. The analytical performance was evaluated by using repeatability and reproducibility with coefficient of variation (CV) calculated. The diagnostic performances were evaluated by testing specimens collected from consented subjects available from a biobank in autoimmune gastrointestinal diseases. This consisted of 60 NHV, and 187 IBD (91 CD and 96 UC). Sensitivity, specificity, diagnostic odds ratio (OR), positive and negative predictive values (PPV and NPV) were estimated.

Results

Intra-assay CVs ranged from 1.5% to 5.2% over dynamic range. Inter-assay CVs were below 10%. Median titers were below 5 U/mL for NHV and CD, and 26 U/mL for UC (Fig. 1). Cutoff of 5 U/mL was 100% specific for UC and CD. Sensitivity for UC and CD was 80% (77/96), and 15% (14/91), respectively. Diagnostic Odds Ratio yielded 22.3-fold (95% CI: 10.5–47.5) higher likelihood of UC than CD in the presence of Anti-integrin αvβ6 titers above cutoff, with PPV and NPV values of 84% (76%-90%) and 81% (74%–87%), respectively (50% pre-test).

Conclusion

We have established the analytical performance of an Anti-integrin αvβ6 autoantibody ELISA assay. These preliminary data suggests that the Anti-Integrin αvβ6 autoantibody system is highly specific for UC with high sensitivity and specificity.
B-124 Applicability of measurement uncertainty in the validity of results in the clinical laboratory
Authors: Martinez Nieto O , Garzón A , Barrera V , Romero A , Garzón A , Hernández N
Published: September 2023

Background

The results of the clinical laboratory must comply with attributes of precision, veracity, and accuracy to guarantee the validity of the result; since the assurance of analytical quality, different performance evaluation strategies have been applied with the use of tools such as total permissible error (ETa) and sigma metric. However, based on the requirements to qualify for the accreditation process by standards such as ISO 15189 and ISO 17025, the concept of the “measurement uncertainty” of the measured magnitude values was introduced, giving special relevance in the interpretation of the values obtained, therefore it is important to consider its estimation and evaluation as a tool that contributes to patient safety in the interpretation of clinical decision limits.

Methods

Uncertainty estimation was performed for forty-one measurands that were previously selected considering the variables of clinical risk and processing volume. The estimation of uncertainty, ETa and sigma metric were made with the RANDOX Acusera software 24/7 online from the information obtained from the internal quality control data and the scheme of the external quality evaluation. The uncertainty obtained was compared against four criteria of acceptability of uncertainty.

Results

After comparing the uncertainty obtained against the four criteria of acceptability of uncertainty, it was found that the most demanding criterion is that derived from the reference biological interval. The implementation of this criterion would allow objective comparability of performance between laboratories. Conclusions: The estimation of uncertainty as an indicator of the validity of the results provides relevant information in the interpretation of the results that are within the limits of clinical decision, while the ET and sigma metric contribute to the monitoring and control of the performance of the analysis or measurement procedure.

Conclusion

We observed that the efforts of the laboratory for minimizing the variation sources that can affect the analytical accuracy have been prolific. Total Error quantification, Sigma 6 and MU have a correlation, favorably impacting the tests performance. Aiming to guarantee a constant improvement of the results’ quality, the Total Error and MU goals must be periodically revised, ensuring their utility throughout time.
B-135 Research Trends and Hotspots of Glial Fibrillary Acidic Protein in Body Fluid for Alzheimer’s Disease: A Bibliometric Analysis
Authors: Zou Y , Qiu L
Published: September 2023

Background

As the most common form of dementia, Alzheimer’s disease (AD) is prevalent worldwide. An increasing number of studies have focused on glial fibrillary acidic protein (GFAP), an astrocytic cytoskeletal protein, for the development, diagnosis and prognosis of AD. Therefore, this study aimed to analyze trends and hotspots of GFAP in body fluid for AD by using a bibliometric method, which is missing in current publications.

Methods

We systematically searched the Web of Science Core Collection for published papers on GFAP in body fluid and AD. All articles and reviews from inception to December 31, 2022, were included in this study. Full records and cited references of all publications were derived, imported into Microsoft Excel, and analyzed by BIBLIOMETRC Online analysis platform and VOSviewer software.

Results

A total of 2269 publications including 2166 articles were ultimately included based on the inclusion criteria. The data showed that the number of published papers on GFAP in body fluid and AD is annually increasing, which was published in 81 countries/regions and 527 academic journals. Separately, the top 3 prolific countries/regions and institutions were USA, China and England, Univ Gothenburg (Sweden), Univ Fed Rio Grande do Sul (Brasilia) and UCL Queen Square Institute of Neurology (England). Journal of Alzheimer’s Disease, Brain Research, and Neuroscience contributed the most publications; Zetterberg, Henrik from Univ Gothenburg, Blennow, Kaj from Univ Gothenburg and Verkhratsky, Alexei from the University of Manchester were the top 3 prolific and cited authors. The most published and linked meaningful keywords included oxidative stress, inflammation, microglia, hippocampus and amyloid, which also annually increased in recent publications.

Conclusion

Based on a bibliometric analysis, the number of publications on GFAP in body fluid and AD are rapidly increasing, especially in the past several years. Oxidative stress and inflammation are research hotspots, and the diagnostic performance of GFAP in body fluid need to be further summarized and verified.
B-210 Spectrum of Germline Mutation with Characteristic MLH1 Hotspots and High Concordance with MMR Deficiency Phenotype in Lynch Syndrome Patients in Taiwan
Authors: Chang P Y , Chang S C , Wang M C , Chen C C , Chiang J M
Published: September 2023

Background

Patients carried defects on cancer susceptibility genes or had cancer family history have at least twice the risk of developing cancer than the general population, with both early onset and multiple cancers features. For elucidating the carrier rate of cancer susceptibility genes in patients with inherited colorectal cancer (CRC) and endometrial cancer (EnCa) in Taiwan, we established a NCCN guided 30-gene panel which included four DNA Mismatch Repair (MMR) genes to detect the germline mutation of patients with Lynch Syndrome. Correlation of genotype and phenotype of MMR enzymes are under investigation as well.

Methods

Sixty-eight blood samples were collected from unrelated cancer patients, 42 of them were from patients with inherited colon cancer, 13 from patients with diagnosis of both CRC and endometrial cancer and 13 from patients with early onset EnCa. 30-gene panel was performed by next generation sequencing (NGS) platform and variants were annotated following ACMG guideline. MMR protein expression in tumor tissue sections were identified by conventional immunohistochemistry (IHC) stain. Loss of nuclear staining were classified as MMR deficiency.

Results

Average age of first tumor onset of 68 patients were 49.2 years old. 54% (37/68) of the subjects had at least one germline mutations with pathogenic effect or deleterious variant predicted by in silico protein function software. Five of them carried two heterozygous mutations. Total 42 mutations appeared majority on three MMR genes, MLH1 (17/42, 40%), MSH2 (10/42, 24%) and MSH6 (6/42, 11%) with notified three hotspots on MLH1 p.R265C (7/17, 41%); p.T117M (2/17, 12%) and p.K618del(2/17, 12%). The rest mutations spread sporadically on nine genes (PMS2, TP53, CHEK2, POLE, POLD1, ATM, EPCAM, MLH3 and RNF43). For exploring the effect of germline mutation on MMR protein expression status on tissue, we compared the MMR IHC results and the germline mutation pattern. As high as 57% concordance between phenotype and genotype were found. We also collected six blood samples from relatives of our CRC cohort to demonstrate the inheritance and pathogenesis of the germline mutation. Exactly the same germline mutations can be found in diseased relatives among different generation or siblings.

Conclusion

In spite of having founder mutations on MLH1 gene in Taiwanese Lynch syndrome, most of the germline mutations randomly occurred in MMR-related genes. Comprehensive cancer susceptible gene screening panel by NGS is a cost-effective way to identify the inherited status of individuals with family cancer history and serves as a surrogate tool to predict MMR protein expression. Genetic counseling and prophylactic therapeutic information can be provided for positive cases for better cancer prevention.
B-277 Analytical Validation of Whole Blood Suitability for MeMed BV, A Host-protein Test for Differentiating Between Bacterial and Viral Infection
Authors: Hainrichson1 M , Simon E , Kalfon R , Senderovich N , Shamir N , Kaminer-Israeli Y , Navon R , Halabi S , Klein-Kremer A , Eden E
Published: September 2023

Background

MeMed BV® is an FDA-cleared test for differentiating bacterial and viral infections. It is based on computational integration of serum levels of TNF-related apoptosis-induced ligand (TRAIL), interferon gamma-induced protein-10 (IP-10), and C-reactive protein (CRP). The test result is a score between 0 and 100 that correlates with increasing likelihood of bacterial infection (or co-infection). Here, we assessed the analytical performance of MeMed BV using whole blood (WB).

Methods

Precision for each BV analyte and the score were assessed using 3 clinical WB samples representing bacterial, viral and equivocal scores. Each specimen was analyzed in four runs on five MeMed Key® analyzers in accordance with CLSI EP05-A3 Evaluation of Precision of Quantitative Measurement Procedures. For the matrix comparison study, paired samples of serum and WB were collected from patients with suspected acute bacterial/viral infection. The study was performed in accordance with CLSI EP35Ed1E Assessment of Equivalence or Suitability of Specimen Types. Limit of Quantitation was established based on CLSI EP17-A2 Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures.

Results

Precision results passed the pre-determined acceptance criteria for the analytes and score. The precision coefficient of variation range was 4.6%–6.9%, 3.1%–5.8%, and 4.0%–12.0% for TRAIL, IP-10 and CRP, respectively. The precision standard deviation for the score was 0.0–3.0 score units.

For the matrix comparison study, 216 patients were recruited, aged 1–92 years (median 42.0) and 45.8% female. Passing-Bablok regression analysis of test scores from serum vs WB yielded a slope of 1.00 (95% confidence interval, CI 0.99–1.00) and intercept of 0.00 (95%CI 0.00–0.06) fulfilling pre-defined acceptance criteria (Fig. 1). Limit of Quantitation was established to be 1mg/L, 100 pg/mL, and 15 pg/mL for CRP, IP-10 and TRAIL, respectively, the same values as for serum.Fig. 1.

Conclusion

Suitability of MeMed BV® for whole blood was demonstrated.
B-337 Case Report: Fatal Opioid Overdose Induced by Over-the-Counter Cold Medication Diphenhydramine
Authors: Whitt A , Jortani S
Published: September 2023

Background

Accidental drug-related deaths frequently arise following ingestion of multiple co-intoxicants, including opioid analgesics. Hydrocodone, the most prescribed opioid for pain management, is metabolized by hepatic enzymes CYP2D6 and CYP3A4 to the pharmacologically active metabolite hydromorphone and the inactive metabolite norhydrocodone, respectively. As a result, inhibition of CYP2D6 by other pharmacologic agents can impair the analgesic properties of hydrocodone and prolong its half-life in circulation. One such example is diphenhydramine, which is a potent inhibitor of CYP2D6 activity. This case highlights a drug-drug interaction likely resulting in an accidental fatal opioid overdose.

Case Presentation

A 58-year-old female had longstanding prescriptions for hydrocodone/acetaminophen (Norco® 10/325), alprazolam, carisoprodol, and diltiazem. The decedent had recently taken an over-the-counter cold medication, diphenhydramine (Benadryl), shortly preceding death. A toxicology report (NMS labs, Horsham, PA) from a post-mortem femoral blood sample detected the presence of the following therapeutic compounds by High Performance Liquid Chromatography/Time of Flight-Mass Spectrometry (LC/TOF-MS) analysis: acetaminophen (14 μg/mL), hydrocodone (410 ng/mL), dihydrocodeine (hydrocodol, 24 ng/mL), alprazolam (42 ng/mL), carisoprodol (88 ng/mL), diltiazem (110 ng/mL), and diphenhydramine (150 ng/mL). Hydromorphone, the active metabolite of hydrocodone, was not detected (<2 ng/mL). With the exception of hydrocodone, which was present at fatal concentrations, all other compounds were within therapeutic range. Together, these observations are strongly suggestive of a drug-drug interaction leading to impaired hydrocodone metabolism.

Conclusions

This case report highlights a fatal opioid overdose as a result of CYP2D6 inhibition by diphenhydramine, a readily available over-the-counter medication. Post-mortem toxicological analysis revealed hydrocodone was present in lethal concentrations, whereas its pharmacologically active metabolite, hydromorphone, was undetectable at time of autopsy. Further, the patient was prescribed a formulation of hydrocodone in combination with acetaminophen, which was present at therapeutic concentrations despite the two drugs having similar elimination half-lives. These toxicological findings suggest administration of diphenhydramine precipitated a deadly accumulation of hydrocodone in the deceased. Overall, this case report underscores the importance of understanding and preventing harmful drug-drug interactions in patients taking opioid medications for pain management.
B-390 Next-generation Sequencing Panel to Detect Homologous Recombination Deficiency (HRD) Biomarkers in Brazilian Ovarian Cancer Samples
Authors: de Lima A B , Leite L R , Freire M C , Zauli D A
Published: September 2023

Background

Homologous recombination deficiency (HRD) has been used as a biomarker of PARP inhibitors (PARPi) sensitivity in ovarian cancer (OC), especially in high-grade serous (HGS) types. Initially, only likely pathogenic (LPV) and pathogenic variants (PV) in BRCA1/2 were screened to define PARPi eligibility. However, LPV and PV are shown in less than 20% of OC, which restricted PARPi therapies to a small group. Advances in OC biology knowledge identified other markers that also contribute to HRD. Nowadays, is estimated that almost 50% of OC have HRD. When HRD is present, DNA damage is not properly repaired and the accumulated genomic changes over time are called Genomic Scars (GS). In this sense, Next Generation Sequencing (NGS) is important in GS detection due to searching different loci simultaneously, allowing an estimate of the GS score related to the HRD. So, this work aims to describe the profile of samples requesting an NGS test to detect HRD biomarkers.

Methods

Were evaluated anonymized data of 76 formalin-fixed, paraffin-embedded (FFPE) samples with OC diagnosis. The samples’ quality was evaluated with TapeStation 4200 and Qubit Fluorometer. Libraries were prepared with AmoyDx® HRD Focus Kit and sequenced with NextSeq 500. Data analysis was performed with ANDAS software.

Results

The HRD-positive percentage was 59,2% (45/76), being mostly BRCA wild type. Almost 15% of all samples presented PV or LPV in BRCA1 or 2, which was more frequent in BRCA1 (∼82%). The allele frequencies (AF) detected ranged from 5% to 83%. Two of the detected variants (classified as LPV) are not yet registered in databases. The HRD-negative group represented 34,2% (26/76), and 6,6% of performed tests had inconclusive results. Some requests (data not included) were not performed due to insufficient material, low quality, or FFPE block age greater than two years, which are limiting factors of this kind of test.

Conclusion

The availability of validated HRD testing options is essential to extend the reach to patients who may benefit from PARPi. In this analysis, most of the BRCA1/2 PV or LPV had AF above 50%, which can help oncologists to suggest germline PV investigation for these patients and also their families. Besides, our data showed a slightly higher HRD-positive rate than reported in the literature, although other works have already described rates above 60%. It reinforces the importance to monitor the HRD status of Brazilian samples to obtain a more assertive profile to the clinical practice.
B-391 Is Comprehensive Cancer Panel By Next-generation Sequencing (NGS) More Efficient Than Cancer-specific NGS Panel in the Management of Non-small Cell Lung Cancer Patients?
Authors: Alvim L B , Marinho F L , Freire M C , Zauli D A
Published: September 2023

Background

: Genetic tests play an integral part in the diagnosis, treatment and prognosis of lung cancer patients. Comprehensive cancer panels using next-generation sequencing (NGS) are gradually becoming the standard tool and replacing the previous approach of single-gene or cancer-specific testing. In this study, we compared the performance of two commercially available NGS gene panels of different sizes concerning their clinical utility in the management of non-small cell lung cancer (NSCLC) patients.

Methods

A total of 65 tumor samples were sequenced with both lung cancer NGS panel (Lung-panel), 12 genes, and comprehensive cancer NGS panel (Pan-panel), 161 genes, following the manufacturer’s protocol.

Results

The Pan-panel detected 159 variants in 93.8% (61/65) patient samples; 37.7% (60/159) of these variants were classified as clinically relevant (tier I or II) with 68.3% (41/60) containing therapy approved and 31.7% (19/60) eligible for a clinical trial. The Lung-panel covered 51 of the 159 (32.0%) variants reported by the larger panel in 72.3% (47/65) tumor samples and all genetic alterations detected (51/51) were indicated as clinically relevant with 78.4% (40/51) described therapy-related variants and 21.6% (11/51) with a genomically matched clinical trial. While the Pan-panel detected more variants, additional variants beyond those included in the Lung-panel had no impact on NSCLC patient management. Even more remarkably, the cancer-specific panel despite covering a smaller genomic region than the comprehensive panel (28.7 kbp vs 329.4 kbp) was more informative in the context of FDA-approved therapy or biomarkers included in NCCN or ESMO guidelines that predict response or resistance to therapies in this cancer type, 78.4% and 68.3%, respectively.

Conclusion

Overall, this comparative analysis of the clinical utility of NGS panels of different sizes indicates that cancer-specific NGS panels containing carefully selected genes are as informative as larger panels when the primary goal is to identify clinically actionable mutations, particularly in patients with NSCLC. Furthermore, this approach presents a better balance among accurate identification of genomic variants, sensitivity, turnaround time, and cost-effectiveness for cancers with well-characterized molecular targets as shown in this study. Larger panels should be used in patients with rare and understudied forms of cancer or in academic reference centers where clinical and translational research is conducted.
Lattice-Based Homomorphic Encryption For Privacy-Preserving Smart Meter Data Analytics
Authors: Marandi Ali , Alves Pedro Geraldo M R , Aranha Diego F , Jacobsen Rune Hylsberg
Published: September 2023

Privacy-preserving smart meter data collection and analysis are critical for optimizing smart grid environments without compromising privacy. Using homomorphic encryption techniques, smart meters can encrypt collected data to ensure confidentiality, and other untrusted nodes can further compute over the encrypted data without having to recover the underlying plaintext. As an illustrative example, this approach can be useful to compute the monthly electricity consumption without violating consumer privacy by collecting fine-granular data through small increments of time. Toward that end, we propose an architecture for privacy-preserving smart meter data collection, aggregation and analysis based on lattice-based homomorphic encryption. Furthermore, we compare the proposed method with the Paillier and Boneh–Goh–Nissim (BGN) cryptosystems, which are popular alternatives for homomorphic encryption in smart grids. We consider different services with different requirements in terms of multiplicative depth, e.g. billing, variance and nonlinear support vector machine classification. Accordingly, we measure and show the practical overhead of using the proposed homomorphic encryption method in terms of communication traffic (ciphertext size) and latency. Our results show that lattice-based homomorphic encryption is more efficient than Paillier and BGN for both multiplication and addition operations while offering more flexibility in terms of the computation that can be evaluated homomorphically.
Patient-reported Outcome Measures in Ileoanal Pouch Surgery: a Systematic Review
Authors: Warsop Zakary Ismail , Manzo Carlo Alberto , Yu Natalie , Yusuf Bilal , Kontovounisios Christos , Celentano Valerio
Published: September 2023

Objective

To summarise frequency, type, and heterogeneity of patient-reported outcomes measures [PROMs] in papers reporting on outcomes after ileal pouch anal anastomosis [IPAA].

Background

Prevalence of ulcerative colitis [UC] has risen in Western countries, and one in three patients requires surgery. IPAA is a frequently performed procedure for UC, and a lack of standardisation is manifest in reporting outcomes for inflammatory bowel disease [IBD] despite the clear need for inclusion of PROMs as primary outcomes in IBD trials.

Methods

Scopus, Pubmed, and Web of Science databases were searched from January 2010 to January 2023 for studies investigating outcomes in IPAA surgery. The primary outcome was the proportion of studies reporting outcomes for IPAA surgery for UC, which included PROMs.

Results

The search identified a total of 8028 studies which, after de-duplication and exclusion, were reduced to 79 articles assessing outcomes after IPAA surgery. In all 44 [55.7%] reported PROMs, with 23 including validated questionnaires and 21 papers using authors’ questions, 22 different PROMs were identified, with bowel function as the most investigated item. The majority of studies [67/79, 85%] were retrospective, only 14/79 [18%] were prospective papers and only two were [2.5%] randomised, controlled trials.

Conclusions

Only half of the papers reviewed used PROMs. The main reported item is bowel function and urogenital, social, and psychological functions are the most neglected. There is lack of standardisation for use of PROMs in IPAA. Complexity of UC and of outcomes after IPAA demands a change in clinical practice and follow-up, given how crucial PROMs are, compared with their non-routine use.
The behavioral response to the putative necromones from dead Tribolium castaneum (Coleoptera: Tenebrionidae) in traps by conspecifics as a function of density and time since capture
Authors: Harman Rachel R , Morrison William R , Bruce Alexander , Ranabhat Sabita , Quellhorst Hannah E , Wilkins Rachel V , Campbell James F , Gerken Alison R
Published: September 2023

Long-term trapping programs of stored product pests provide information for timely and accurate pest management. Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae) is a highly successful external-infesting grain pest and is frequently monitored using a commercial pitfall trap that combines pheromonal and kairomonal stimuli. However, an often overlooked component of lure-based traps is the potential for the volatile plume to change over time as individuals are captured. These now-dead insects may then release necromones altering the captures of conspecifics. In this study, we evaluated changes in (i) the behavior of T. castaneum and (ii) the relative change in volatiles over time since dead insects were added and among different densities of dead conspecifics in a commercially available kairomone oil. We used multiple behavior assays, including wind tunnel, release-recapture, and 2-way olfactometer, and performed chemical analyses via headspace collection and gas chromatography coupled with mass spectrometry. Tribolium castaneum response to the kairomone lure was not consistent among assays of density of conspecifics between 4 and 40 adults after 24 or 96 h, or time of seeding over 1–96 h or 8–11 days prior. Tested strains collected in 2012 and 2019 ruled out strain-specific differences. Oil batch effects were also ruled out as a factor contributing to the response of T. castaneum. The relative volatile composition was generally stable among the treatments despite using different seeding densities and seeding times. Given that attraction and relative volatile composition were generally unaffected by prior captures, long-term monitoring programs may be robust in their interpretability over time.
Egg size variation in the context of polyandry: a case study using long-term field data from snowy plovers
Authors: Eberhart-Hertel Luke J , Rodrigues Lourenço Falcão , Krietsch Johannes , Hertel Anne G , Cruz-López Medardo , Vázquez-Rojas Karina Alejandra , González-Medina Erick , Schroeder Julia , Küpper Clemens
Published: September 2023

Gamete size variation between the sexes is central to the concept of sex roles, however, to what extent gamete size variation within the sexes relates to sex role variation remains unclear. Comparative and theoretical studies suggest that, when clutch size is invariable, polyandry is linked to a reduction of egg size, while increased female–female competition for mates favors early breeding when females cannot monopolize multiple males. To understand whether and how breeding phenology, egg size, and mating behavior are related at the individual level, we studied the reproductive histories of 424 snowy plover females observed in the wild over a 15-year period. Egg size, but not polyandry, were highly repeatable for individual females. Consistent with theoretical predictions, we found that polyandrous females were the earliest breeders and that early clutches contained smaller eggs than clutches initiated later. Neither egg size nor mating behavior showed clear signs of an age-related deterioration, on the contrary, prior experience acquired either through age or local recruitment enabled females to nest early. Taken together, these results suggest that gamete size variation is not linked to mating behavior at the individual level, and, consequently, the adaptive potential of such variation appears to be limited.
The TNF∆ARE Model of Crohn’s Disease-like Ileitis
Authors: Metwaly Amira , Haller Dirk
Published: September 2023

Crohn’s disease (CD) is one of the 2 main phenotypes of inflammatory bowel diseases (IBDs); CD ischaracterized by a discontinuous, spontaneously recurring, transmural immunopathology that largely affects the terminal ileum. Crohn’s disease exhibits both a relapsing and progressive course, and its prevalence is on the rise globally, mirroring the trends of industrialization. While the precise pathogenesis of CD remains unknown, various factors including immune cell dysregulation, microbial dysbiosis, genetic susceptibility, and environmental factors have been implicated in disease etiology. Animal models, particularly ileitis mouse models, have provided valuable tools for studying the specific mechanisms underlying CD, allowing longitudinal assessment and sampling in interventional preclinical studies. Furthermore, animal models assess to evaluate the distinct role that bacterial and dietary antigens play in causing inflammation, using germ-free animals, involving the introduction of individual bacteria (monoassociation studies), and experimenting with well-defined dietary components. An ideal animal model for studying IBD, specifically CD, should exhibit an inherent intestinal condition that arises spontaneously and closely mimics the distinct transmural inflammation observed in the human disease, particularly in the terminal ileum. We have recently characterized the impact of disease-relevant, noninfectious microbiota and specific bacteria in a mouse model that replicates CD-like ileitis, capturing the intricate nature of human CD, namely the TNF∆ARE mouse model. Using germ-free mice, we studied the impact of different diets on the expansion of disease-relevant pathobionts and on the severity of inflammation. In this review article, we review some of the currently available ileitis mouse models and discuss in detail the TNF∆ARE model of CD-like Ileitis.
On the Gaussian Projection Inequalities
Authors: Lin Youjiang , Xing Sudan
Published: September 2023

We provide an overview of projection bodies in Gaussian probability space for sets of finite Gaussian perimeter and their corresponding applications in functions of Bounded variation space. On the one hand, we study the properties of Gaussian projection bodies for sets of finite Gaussian perimeter under Ehrhard symmetrization and establish a Gaussian projection-type inequality. This inequality concludes that Ehrhard symmetrization contracts the Minkowski symmetrization of the Gaussian projection body for set of finite Gaussian perimeter $E$. On the other hand, we investigate the functional “lifting” of Ehrhard symmetrization and establish the affine Gaussian Pólya–Szegö-type inequalities in terms of the functional Ehrhard symmetrization.
Quantification of Total Sulfite in Shrimps by BIOFISH 300 SUL Method: First Action 2021.09
Authors: Garate Jone , Jaureguibeitia Arrate , Gonzalez Roberto , Ortiz de Zarate Itziar , Salleres Sandra
Published: September 2023

Background

Sulfite is the oldest and most widely used additive in our food supply with antioxidant and preservative properties. Due to its allergenic-like reactions and other adverse health effects, its use is regulated by international regulatory bodies. Therefore, food industries as well as regulatory laboratories must ensure that the maximum concentration of sulfite permitted is not exceeded. The AOAC INTERNATIONAL-approved official method for the quantification of sulfites is the Optimized Monier–Williams Method (AOAC Official Method 990.28), which consists of a time-consuming titration.

Objective

The present study aims to demonstrate the reliability of the BIOFISH 300 SUL, a simple, fast, and accurate method, as an alternative, for the quantification of total sulfites in shrimp, with a lower LOQ than that of the OMA 990.28, set at 10 mg/Kg.

Methods

The BIOFISH 300 SUL method is a highly specific biosensor based on its proprietary enzyme-based electrode, for the rapid quantification of total sulfite. The test kit consists of an electrochemical reader (biosensor BIOFISH 300) and disposable electrodes (Biotest) that are capable of providing an electrical signal proportional to the amount of sulfite in the sample analyzed. The method mainly consists of the extraction of sulfite from the solid matrix in an aqueous solution, and its subsequent quantification by the device in less than 3 min.

Results

Comparative studies between BIOFISH 300 SUL and OMA 990.28 were conducted for naturally contaminated and spiked samples of raw and boiled shrimp with sulfite levels covering the 7–150 mg/kg range in order to determine linearity, recovery, repeatability, intermediate reproducibility, and accuracy.

Conclusion

The BIOFISH 300 SUL method demonstrated high accuracy and precision for the whole range of quantification (7–150 mg/kg). Its ease of use and fast response make it the ideal technology to be implemented by the industry.

Highlights

BIOFISH 300 SUL was adopted as a First Action Official MethodSM by the AOAC Expert Review Panel for Sulfites in Seafood Methods in February 2021 after rigorous review.