bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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 (&lt;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

Abstract

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

Abstract

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

Abstract
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

Abstract

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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract

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.
Two cases of concurrent carcinoma showing thymus-like differentiation (CASTLE) coexisting with papillary thyroid carcinoma
Authors: Zhao Qi , Bian Xuehai 
Published: September 2023

AbstractCarcinoma showing thymus-like differentiation (CASTLE), which emerges within the thyroid gland or the adjacent soft tissues of the neck, is a rare malignant neoplasm found globally. The occurrence of CASTLE in conjunction with papillary thyroid carcinoma is an even more infrequent phenomenon. The ensuing sections elaborate upon the clinical attributes characteristic of CASTLE.