bluuebunny/crossref_metadata_2025_split huggingface dataset:
B-356 Advancements in Commercial Viability of a Blood Test for the Early Detection of Breast Cancer
Authors: Kehelpanalla C , Pascovici D , Li D , Heffernan K , David M , Huynh K , Lamoury G , Ekroos K , Meikle P J , Batarseh A M 
Published: September 2023

Abstract

Background
Mammography is the current diagnostic standard for breast cancer screening and monitoring. However, accessibility challenges, accuracy issues and patient discomfort all contribute to reduced patient compliance and utilization, resulting in a need for more effective diagnostic tools. A blood test to detect early-stage breast cancer is sought to increase the screening detection rate, provide more accurate monitoring tools, and improve outcomes for patients. We have previously reported a series of lipidomic studies and derived a lipid signature from plasma enriched extracellular vesicles (EVs) that effectively distinguished people with localized breast cancer from cancer-free controls. Here we report on a significant refinement to the test methodology allowing the assessment of the lipid signature directly from plasma samples and its performance, with the aim of advancing the commercial viability of the test as we move towards clinical application.

Methods
Lipids in EVs from fasted breast cancer and control blood samples (4 separate cohorts (n = 793)) were extracted and analysed by liquid chromatography-high resolution mass spectrometry (LC-HRAM-MS). Over 400 manually curated lipids were quantified. From these, an independent review and retrospective analysis of the data established a lipid signature. The lipid signature was modelled on each of the cohorts using leave-one-out internal cross-validation. Following variable selection, a lipid signature capable of distinguishing breast cancer samples from controls was derived. Furthermore, we investigated if the lipid signature can be assessed from plasma instead of EVs with the aim of further streamlining the process. We analysed the lipids in cancer and control plasma samples (n = 256) previously used for EV preparations, corresponding to patients from Cohorts 3 and 4, and applied the signature derived using EVs on plasma lipidomic data. NIST Standard Reference Material (SRM) 1950-Metabolites in Frozen Human Plasma was used for inter-laboratory quality control.

Results
Breast cancer subjects were differentiated from controls by the lipid signature with an area under the curve (AUC) of 0.77–0.89 across four cohorts. Assessing the signature directly from plasma, the test achieved a comparable AUC of 0.84. This improvement would make the test more clinically viable and easier to perform.

Conclusion
We derived a lipid signature, which shows high potential for distinguishing breast cancer samples from controls directly from plasma instead of EVs, reducing the test complexity. Ongoing studies will optimize the plasma lipidomic signature and prospectively compare the test against mammographic and pathological diagnoses.
B-360 Usefulness of the Ratios of CYFRA21-1 and p53 Autoantibody Immune Complexes to Their Free Antigens in Lung Cancer
Authors: Hong Y , Kim H , Lee J , Oh A , Kim H 
Published: September 2023

Abstract

Background
Autoantibodies against specific cancer-associated antigens are produced in the early stages of tumorigenesis. In lung cancer, the possibility of autoantibodies as diagnostic biomarkers has been proposed. This study was to evaluate the usefulness of novel DNA-guided sandwich immunoassay detecting CYFRA21-1 and p53 autoantibody immune complexes and their free antigens in diagnosis of lung cancer.

Methods
In total, 100 patients with lung cancer and 119 healthy controls were analyzed with 9G testTM Lung/Cancer (Biometrix Technology, South Korea) measuring plasma autoantibody immune complexes (CYFRA21-1 with anti-CYFRA21-1 autoantibody immune complex (CIC), p53 with anti-p53 autoantibody immune complex (PIC)) and their free antigens (CYFRA 21-1 and p53). The ratios of CIC to CYFRA21-1 (CIC/CYFRA21-1) and PIC to p53 (PIC/p53), and the multiplication of the two ratios, named as LC index were calculated.

Results
The levels of CIC and PIC were significantly increased in lung cancer compared with those in healthy control (P = 0.0062 and P = 0.0026, respectively), while free antigens didn’t distinguish between lung cancer and healthy control. The ratios CIC/CYFRA21-1 and PIC/p53 were significantly higher in lung cancer than those in healthy control (all, P &lt; 0.0001). Diagnostic performances expressed as area under the curve (AUC) were higher in the ratios of autoantibody immune complexes to each free antigen (PIC/p53 and CIC/CYFRA21-1) than autoantibody immune complexes (PIC and CIC) (AUC; 0.887, 0.847 vs 0.618, 0.608, respectively). The most excellent diagnostic performance was proven with LC index at diagnostic cut-off 3.60, which showed 81% sensitivity and 95% specificity with 0.945 AUC (P &lt; 0.001). It was more sensitive to early lung cancer than to advanced lung cancer (sensitivity 87.5% vs 72.7%).

Conclusion
The ratios of CIC to CYFRA21-1 and PIC to p53 are useful biomarkers in lung cancer diagnosis and the combination of the ratios, LC index could be complementary tool for lung cancer screening with radiological tests.
B-379 Analytical Performance of Two Tumor Marker Immunoassays on the Atellica CI 1900 Analyzer
Authors: Quintanilla M , Baldys A , Thakur K , Arrode-Bruses G , Rhea-McManus J , Leipold H 
Published: September 2023

Abstract

Background
The Atellica® CI 1900 Analyzer is an automated, mid-throughput, integrated chemistry and immunoassay analyzer utilizing both Atellica CH and Atellica IM assays. This study was designed to evaluate the analytical performance of the Atellica IM Carcinoembryonic Antigen (CEA) and Alpha Fetoprotein (AFP) assays* on the Atellica CI 1900 Analyzer.

Methods
The Atellica CI 1900 CEA and AFP assays use the same reagents and calibrators as the comparable Atellica IM assays. Precision and method comparison (MC) were used as performance indicators for the Atellica CI 1900 Analyzer. Precision studies were performed according to CLSI EP05-A3 using quality control, native, and contrived human serum samples. One aliquot of each sample pool was tested in duplicate in two runs per day ≥2 h apart on each analyzer for ≥20 days. MC studies were performed according to CLSI EP09-A3. Individual native and contrived human serum samples were analyzed using the Atellica IM assays on both the Atellica IM and Atellica CI 1900 Analyzers.

Results
Representative precision and MC results observed for each assay across indicated sample ranges are listed in the table. Slopes determined by the Deming linear regression model were approximately equal to 1.

Conclusion
Evaluation of the CEA and AFP assays using the Atellica CI 1900 Analyzer demonstrated good precision and equivalent performance compared to the same assays on the Atellica IM Analyzer.
*The products/features mentioned here are not commercially available in all countries. Their future availability cannot be guaranteed.
B-380 Drift of Freelite on Optilite
Authors: Griffiths M H , Kulasingam V , Cheng P L , Wang X Y , Schneider R J 
Published: September 2023

Abstract

Background
Serum free light chains (sFLC) which include kappa (KFLC), lambda (LFLC) and their ratio (K/L) are used for diagnosis and monitoring of plasma cell dyscrasias (PCDs). In 2002, the Binding Site Freelite assay established reference intervals (RIs) for KFLC, LFLC and K/L. Since that time, renal RIs have been proposed and drift for the Freelite assays has been reported. The objective of this study was to evaluate healthy and renal insufficiency population RIs and examine retrospective data to ascertain the reported assay drift.

Methods
260 serum samples were measured using the Freelite assay on the Optilite. Creatinine was measured on the Abbott Alinity and eGFR was calculated. Binding Site’s RIs for KFLC, LFLC and K/L were compared to samples with ≥60 eGFR and ≤59 eGFR samples were compared to the hypergammaglobulinemia population from a previous report in 2002. IFE was used to exclude samples with detectable monoclonal proteins. Retrospective data from University Health Network (UHN) was examined.

Results
The comparison results for the samples are in the tables below:
The data suggest that Freelite has drifted up approximately 300% for KFLC, 150% for LFLC and 200% for K/L. Using 220 000 data points from UHN and applying these recalibration factors, the normal KFLC vs LFLC bivariate distribution appears centered to the well-known ‘0.26–1.65’ K/L 100% diagnostic range.

Conclusions
Drift of Freelite is confirmed with this study and recalibration factors for Freelite are proposed which are lower KFLC values by 300% and lower LFLC values by 150% for K/L to be centered to 0.26–1.65. Institutions should review their data with Freelite on Optilite and any clinical data to confirm this finding. Drift of this magnitude has the potential to cause false positives for kappa and false negatives for lambda in the diagnosis and monitoring of PCDs.
B-389 Validation of One-step In-house RT-qPCR Method for Detecting MLL::AF4 Fusion
Authors: Marques F K , Zauli D A 
Published: September 2023

Abstract

Background
Rearrangements of mixed lineage leukemia gene (MLL) with 1 of &gt;130 alternative partner genes is a recurrent cytogenetic finding in both acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) and is generally associated with a poor prognosis. Among the most common MLL rearrangement is t(4;11)(q21;q23), forming the MLL::AF4 (also known as KMT2A::AFF1) fusion gene. Unique among MLL rearrangements, MLL::AF4 is almost exclusively associated with pro-B cell ALL and is prototypical of infant ALL, where it carries a very poor prognosis. At least 10 different MLL-AF4 fusion transcripts have been found, due to break-points in different introns, some transcripts being more frequent in either adult or infant ALL. Fast and reliable diagnostic tests represent an important tool in clinical laboratories to detect these rearrangements and . In this context, this work aimed to validate a qualitative method to detect the main MLL::AF4 fusion isoforms.

Methods
We evaluated the performance of the Hs03043614_ft (e10e4, e9e4 and e9e5) and Hs03024412_ft (e11e4) inventoried TaqMan assays (Thermo Fisher Scientific). Total mRNA from negative and positive samples for each fusion was extracted by the TRIzol reagent according to the manufacturer’s instructions. All assays were performed using TaqMan RNA-to-Ct 1-Step kit (Thermo Fisher Scientific). The inventoried ABL1 assay (Thermo Fisher Scientific) was used as endogenous control. Using positive samples, negative samples and controls of each fusion were performed: sequence verification tests, standardization of RNA input, evaluation of reaction efficiency and determination of the detection limit (LOD). The performance of the assays was evaluated with ABL1 control separately from the fusions.

Results
Our results showed that both assays worked well for the detection of specific fusions. The best RNA input for the reactions was 200 ng. The efficiencies reactions were: a) with ABL1 in separate reactions: 92.6% and 110.0% for Hs03043614_ft and Hs03024412_ft assays, respectively; The literature recommends the limit of efficiency was between 90% and 110%. The LODs with ABL1 in separate reactions were 10−3 for both assays, respectively. There was no unspecific amplification in negative samples.

Conclusion
The TaqMan assays with RT one-step protocol evaluated are highly sensitive, fast, and reliable tools for detecting the most frequent MLL::AF4 fusion transcripts.
Acquired cardiovascular disease in adults with congenital heart disease
Authors: Brida Margarita , De Rosa Salvatore , Legendre Antoine , Ladouceur Magalie , Dos Subira Laura , Scognamiglio Giancarlo , Di Mario Carlo , Roos-Hesselink Jolien , Goossens Eva , Diller Gerhard , Gatzoulis Michael A 
Published: September 2023

Abstract
Rates of successful surgical repair and life expectancy for patients with congenital heart disease have increased dramatically in recent decades. Thanks to advances in diagnosis, treatment, and follow-up care, an ever-increasing number of individuals with congenital heart disease are reaching advanced age. The exposure to cardiovascular risk factors during their lifetime is modifying the outlook and late clinical trajectory of adult congenital heart disease (ACHD). Their disease burden is shifting from congenital to acquired, primarily atherosclerotic cardiovascular disease (ASCVD) with worrisome consequences. In addition, the complex background of ACHD often curbs appropriate preventive strategies by general practitioners or adult cardiologists. Comprehensive guidance for the prevention and management of acquired heart disease in ACHD patients is currently not available, as this topic has not been covered by the European Society of Cardiology (ESC) guidelines on cardiovascular disease prevention or the ESC guidelines for the management of ACHD. In this document, a state-of-the-art overview of acquired heart disease in ACHD patients and guidance on ASCVD prevention for both ACHD specialists and non-ACHD cardiologists are provided. The aim is to provide a clinical consensus statement to foster the development of a sustainable strategy for the prevention of ASCVD in a practical and simple-to-follow way in this ever-growing cardiovascular cohort, thus reducing their cardiovascular burden.
‘Un jugement politique’: race, policy and punishment in colonial Saint-Domingue before 1789
Authors: Christie Nancy , Gauvreau Michael 
Published: September 2023

Abstract
This article analyses the trial of Félicité, an enslaved woman in Port-au-Prince, who was convicted of theft and arson in 1787 and sentenced to be executed. The case is of interest to historians, as it is one of the few complete surviving records of slave testimony from Saint-Domingue. By examining the testimony of Félicité and a number of her fellow slaves and free people of colour, the case sheds new light on the sociability and economic life of urban slaves, explores the meaning of marronage, questions the extent to which racial solidarity existed between slaves and free people of colour and probes the assertions of recent scholarship regarding the use of slave testimony as autobiographical narrative. In addition, the article advances the argument that the outcome of the trial revealed a number of fault-lines within the white governing classes, particularly over the question of the intersection between humanitarianism and judicial decision-making.
A review of misfit functions for adjoint full waveform inversion in seismology
Authors: Gao Yajian , Tilmann Frederik , Rietbrock Andreas 
Published: September 2023

SUMMARY
In seismological full waveform inversion, the choice of misfit functions plays a critical role in quantifying the discrepancy between observed and synthetic data, affecting convergence rate and also final results. We revisit and compare six commonly used misfit functions, including cross-correlation time-shift (CC), least-square waveform difference (L2), multitaper time-shift (MT), exponentiated phase shift (EP), time–frequency phase shift (TF) and zero-lag cross-correlation coefficient (CCC), with respect to their definitions, adjoint sources and misfit kernels for velocity perturbations. Synthetic tests are performed for several canonical models.
First, we simulated wave propagation in a model with a single rectangular anomaly with sharp boundaries and a smoothed variant of that model. We analysed the resulting misfit kernels first for the P-wave phase, which is highly distorted in the sharp model due to strong heterogeneities, and mostly experiences traveltime perturbations in the smooth model. Second, we considered a model where a laterally limited region is subject to layered anomalies (low velocity in the middle crust and high velocity in the lower crust) and determine misfit kernels for S and surface waves in this model. Based on these two simplified seismological scenarios, we further perform iterative test inversions using different misfit functions.
Combining the features of misfit kernels and synthetic inversion results, we find that CCC, L2 and EP are the most effective at identifying the sharpness of velocity anomalies from the direct body waves and their scattered phases. Consequently, inversion based on those misfit measures yielded the best recovery in the inversion test. For surface and S waves from crustal sources, TF appears to be the most effective in constraining the heterogeneous structure in the crust but needs more iterations for convergence than other misfit functions.
N-glycomic profiling of capsid proteins from Adeno-Associated Virus serotypes
Authors: Xie Yongjing , Butler Michael 
Published: September 2023

Abstract
Adeno-associated virus (AAV) vector has become the leading platform for gene delivery. Each serotype exhibits a different tissue tropism, immunogenicity, and in vivo transduction performance. Therefore, selecting the most suitable AAV serotype is critical for efficient gene delivery to target cells or tissues. Genome divergence among different serotypes is due mainly to the hypervariable regions of the AAV capsid proteins. However, the heterogeneity of capsid glycosylation is largely unexplored. In the present study, the N-glycosylation profiles of capsid proteins of AAV serotypes 1 to 9 have been systemically characterized and compared using a previously developed high-throughput and high-sensitivity N-glycan profiling platform. The results showed that all 9 investigated AAV serotypes were glycosylated, with comparable profiles. The most conspicuous feature was the high abundance mannosylated N-glycans, including FM3, M5, M6, M7, M8, and M9, that dominated the chromatograms within a range of 74 to 83%. Another feature was the relatively lower abundance of fucosylated and sialylated N-glycan structures, in the range of 23%–40% and 10%–17%, respectively. However, the exact N-glycan composition differed. These differences may be utilized to identify potential structural relationships between the 9 AAV serotypes. The current research lays the foundation for gaining better understanding of the importance of N-glycans on the AAV capsid surface that may play a significant role in tissue tropism, interaction with cell surface receptors, cellular uptake, and intracellular processing.
The conceptualization and development of critical health literacy in children: a scoping review
Authors: Jenkins Catherine L , Sykes Susie , Wills Jane 
Published: September 2023

AbstractThe cognitive and social practices associated with critical health literacy, such as critical appraisal of health messages and participation in political processes to address wider determinants of health, are of lifelong benefit. Understanding how and where critical health literacy development can be supported early in the life course may improve health outcomes now and in the future. This scoping review focuses on how critical health literacy in children is conceptualized and the supportive environments available for its development. Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines are used in reporting. Evidence retrieved was eligible for inclusion if it contained a substantive conceptual or empirical study of critical health literacy in populations aged 7–11 (middle childhood). From the included 18 peer-reviewed and grey literature sources, schools are identified as the setting most associated with the development of critical health literacy in the target age group. However, the action-oriented dimension of critical health literacy is rarely supported in the school setting. The review concludes that further research is needed to clarify how and where to support children to develop critical health literacy in and outside of school settings.
Identification of a muscle-specific isoform of VMA21 as a potent actor in X-linked myopathy with excessive autophagy pathogenesis
Authors: Cocchiararo Ilaria , Cattaneo Olivia , Rajendran Jayasimman , Chabry Florent , Cornut Mélanie , Soldati Hadrien , Bigot Anne , Mamchaoui Kamel , Gibertini Sara , Bouche Axelle , Ham Daniel J , Laumonier Thomas , Prola Alexandre , Castets Perrine 
Published: September 2023

AbstractDefective lysosomal acidification is responsible for a large range of multi-systemic disorders associated with impaired autophagy. Diseases caused by mutations in the VMA21 gene stand as exceptions, specifically affecting skeletal muscle (X-linked Myopathy with Excessive Autophagy, XMEA) or liver (Congenital Disorder of Glycosylation). VMA21 chaperones vacuolar (v-) ATPase assembly, which is ubiquitously required for proper lysosomal acidification. The reason VMA21 deficiencies affect specific, but divergent tissues remains unknown. Here, we show that VMA21 encodes a yet-unreported long protein isoform, in addition to the previously described short isoform, which we name VMA21-120 and VMA21-101, respectively. In contrast to the ubiquitous pattern of VMA21-101, VMA21-120 was predominantly expressed in skeletal muscle, and rapidly up-regulated upon differentiation of mouse and human muscle precursors. Accordingly, VMA21-120 accumulated during development, regeneration and denervation of mouse skeletal muscle. In contrast, neither induction nor blockade of autophagy, in vitro and in vivo, strongly affected VMA21 isoform expression. Interestingly, VMA21-101 and VMA21-120 both localized to the sarcoplasmic reticulum of muscle cells, and interacted with the v-ATPase. While VMA21 deficiency impairs autophagy, VMA21-101 or VMA21-120 overexpression had limited impact on autophagic flux in muscle cells. Importantly, XMEA-associated mutations lead to both VMA21-101 deficiency and loss of VMA21-120 expression. These results provide important insights into the clinical diversity of VMA21-related diseases and uncover a muscle-specific VMA21 isoform that potently contributes to XMEA pathogenesis.
Which airways should we treat? Structure–function relationships and estimation of the singular input modes from the forward model alone
Authors: Donovan Graham M 
Published: September 2023

Abstract
Structure–function relationships occur throughout the sciences. Motivated by optimization of such systems, we develop a framework for estimating the input modes from the singular value decomposition from the action of the forward operator alone. These can then be used to determine the input (structure) changes, which induce the largest output (function) changes. The accuracy of the estimate is determined by reference to the method of snapshots. The proposed method is demonstrated on several example problems, and finally used to approximate the optimal airway treatment set for a problem in respiratory physiology.