bluuebunny/crossref_metadata_2025_split huggingface dataset:
B-274 One-step Detection of Candida Albicans, Trichomonas Vaginalis and Gardnerella Vaginalis
Authors: Peris M , Milagro A , Gilaberte B , Gamadiel N , López M , Dehesa-García B , García-Manrique B , Mendoza C , Aabad P , Rezusta A 
Published: September 2023

Abstract

Background
Trichomonas vaginalis and Candida albicans infections and bacterial vaginosis (BV) are among the three main causes of vaginitis.The most widespread method for diagnosis is still Gram staining and culture. The disadvantages are the microscopy time required, as cultures are examined after 24–48 h. Different commercial molecular biology kits are currently available on the market to detect these pathogens in a sensitive, specific and rapid way.In vitro diagnostic products must be marketed with CE and IVD certification for marketing in the European Union and must be externally validated with clinical samples. For this reason, the company Certest Biotec proposes a collaborative study to evaluate the product VIASURE C. albicans, G. vaginalis & T. vaginalis Real Time PCR Detection Kit, in the Microbiology Laboratory of the Miguel Servet University Hospital (HUMS) in Zaragoza (Spain) using samples characterised by Gram and culture as positive or negative for C. albicans, G. vaginalis and T. vaginalis.

Methods
240 DNA extracts of clinical samples from vaginal swabs of patients with suspected vaginitis were analysed. For the validation of the kit under study, the Segene® AllplexTM Vaginitis Screening Assay was used as a reference. Discordant results will be resolved by Sanger sequencing. Preliminary results are therefore expressed as true positives, true negatives, false positives and false negatives. The use of clinical samples was approved by CEIC Aragón (CEICA): PI20/426.

Results
In the absence of resolution of the discordances by sequencing, the results were as indicated in Table 1.

Conclusion
The main advantage of using these techniques is speed, as they can provide results on the same day and reduce the time spent on microscopy and culture reading. VIASURE products are in a stabilised, ready-to-use format, which facilitates handling, avoids possible contamination, allows storage at room temperature and transport.
B-304 Performance of Alternative Proficiency Testing Program for Bayesian Forecasting Tool of Infliximab Exposure in Clinical Pharmacokinetic Laboratory
Authors: Caonguyen S , McLachlan O , Pham D , Hughes P , Dervieux T 
Published: September 2023

Abstract

Background
We have developed a Bayesian (PK) forecasting and dosing tool for Infliximab (IFX), a monoclonal antibody targeting Tumor necrosis factor α. This novel dosing tool employs machine learning and proficiency of the algorithm must be established. Our objective was to implement an alternative proficiency testing program (APT) in the routine clinical (PK) laboratory.

Methods
The test (PredictrPK® IFX) is validated and measures serum IFX and antibodies to IFX (ATI) concentrations using a homogenous mobility shift assay by size exclusion HPLC and albumin (ALB) by nephelometry. Determinations are inputted with weight, dose, and interdose interval provided on test requisition in the Bayesian forecasting PK tool which uses non-linear mixed effect to calculate the individual parameter estimates, Clearance and predicted trough concentrations. APT is conducted using five previously tested patient samples, blinded to testing personnel and retested in the same manner as the routine method of analysis every six months. APT consists of two components, a component evaluating standalone IFX, ATI, and ALB analytes, and a second component evaluating the Bayesian forecasting PK tool in estimating Clearance and trough concentrations. Criteria for acceptable performance is set at target value ± 20% for standalone analytes and forecasted PK estimates. Acceptable ATP score corresponds to 4/5 samples with passing grade.

Results
The results from two consecutive APT results with six months intervals is presented in Fig. 1. Comparing the results to the original assayed data at the time of collection, the APT results showed IFX concentration, ATI and ALB within 20% of target value. Clearance and estimated trough concentrations calculated using the Bayesian forecasting tool also met acceptability criteria (100% passing grade).

Conclusion
We have implemented an APT for Bayesian forecasting tool in the clinical PK laboratory.
B-309 Development and Validation of a LC-MS/MS Method for Highly Concentrated Tacrolimus and Cyclosporine Specimens Prepared from Clinical Pharmaceutical Products to Assess Adsorption By Feeding Tubes
Authors: Xiao Y , Leung E 
Published: September 2023

Abstract

Background
Tacrolimus and cyclosporine are common immunosuppressive drugs used in the prevention and treatment of solid-organ transplant rejection (e.g., kidney, liver, heart). Other indications include several autoimmune diseases such as Crohn’s disease, autoimmune hepatitis, and rheumatoid arthritis. To prevent toxicity while achieving therapeutic efficacy, tacrolimus and cyclosporine in whole blood specimens are commonly measured in medical centers so that their dosages can be precisely adjusted. Different from adult patients, pediatric patients often require smaller doses and the use of feeding tubes for drug administration. In order to assess nonspecific adsorption by feeding tubes, we modified our in-house clinical method to measure highly concentrated tacrolimus and cyclosporine specimens prepared from clinical pharmaceutical products.

Methods
Highly concentrated tacrolimus and cyclosporine specimens were serially diluted with dimethyl sulfoxide (2000 times for tacrolimus and 20 000 times for cyclosporine) before measurements by our clinical method using liquid chromatography mass spectrometry. The method for highly concentrated tacrolimus and cyclosporine was validated, with analytical measurement range determined with in-house prepared concentrated specimens at varying concentrations, precision (repeatability and reproducibility) assessed by multiple measurements of concentrated specimens at three different concentrations, accuracy assessed by recovery studies, and matrix effect assessed by post-column infusion and by matrix dilution with dimethyl sulfoxide.

Results
The method was linear from 10 ug/mL to 80 ug/mL for tacrolimus, and 1 mg/mL to 8 mg/mL for cyclosporine with r2 &gt; 0.99. Repeatability and reproducibility were &lt;10% CV. Minimal matrix effect was observed. Recovery studies using commercial calibrators to measure specimens prepared from reference materials and dimethyl sulfoxide identified no significant bias for tacrolimus but an average positive bias of 20% for cyclosporine, and a correction factor was used to finalize cyclosporine results for specimens prepared from clinical pharmaceutical products. The positive bias was eliminated when calibrators were prepared in dimethyl sulfoxide.

Conclusion
We have developed and validated a LC-MS/MS method for the measurement of highly concentrated tacrolimus and cyclosporine in specimens prepared from clinical pharmaceutical products. We hypothesize that one or more components in the commercial calibrators have contributed to the positive bias of cyclosporine in those specimens. Our method can be used to support studies that assess nonspecific adsorption by feeding tubes.
B-318 Development of Non-competitive Immunoassay System for Cyclosporine a Using Alpaca Naïve Library-derived VHH
Authors: Fukuya S , Tanaka M , Hotta Y , Kitamori Y , Kiyose N , Miyazaki N , Ise N , Aoyagi K 
Published: September 2023

Abstract

Background
Cyclosporine A is a potent immunosuppressive drug. It has a narrow therapeutic index, and therefore the measurement of cyclosporine’s blood concentration is essential to obtain optimal therapy. Cyclosporine A, a small cyclic polypeptide, is generally measured by competitive immunoassay, which is theoretically inferior to noncompetitive sandwich immunoassay in terms of sensitivity and specificity. In this study, we report a novel sandwich immunoassay for cyclosporine A using an alpaca naïve library-derived variable domain of heavy chain of heavy chain antibody (VHH) developed against an immunocomplex of cyclosporine A and anti-cyclosporine A mouse monoclonal antibody.

Methods
We generated a VHH against an anti-cyclosporine A mouse monoclonal antibody complexed with cyclosporine A by alpaca naïve VHH phage display library. A bivalent tandem VHH was generated using the established VHH, and a new sandwich immunoassay for measuring cyclosporine A was constructed using the tandem VHH conjugated with alkaline phosphatase. A prototype fully automated sandwich immunoassay was developed on a fully automated chemiluminescence analyzer using magnetic particles immobilized with the mouse monoclonal antibody and the tandem VHH conjugated with alkaline phosphatase. The prototype assay was further developed by implementing an automated whole blood pretreatment process with strong denaturing agents. The performances of the prototype immunoassays were investigated.

Results
The established VHH showed a highly specific reaction to the complex of cyclosporine A and the anti-cyclosporine A mouse monoclonal antibody, and a sandwich immunoassay for cyclosporine A was successfully developed using the VHH and the mouse monoclonal antibody. The tandem bivalent VHH exhibited higher reactivity to the complex than the monomeric VHH. The fully automated reagent prototype achieved a measurement range of 30 to 1500 ng/mL. Measurement of cyclosporine A in whole blood samples by the prototype reagent showed a correlation coefficient of 0.96 with mass spectrometry, and a correlation coefficient of 0.95 with a commercial IVD reagent.

Conclusion
We successfully developed a sandwich reagent prototype for cyclosporine A using VHH established by alpaca naïve VHH phage display library. This is the first report of a fully automated reagent for cyclosporine A measurement including an automated whole blood pretreatment process.
B-324 Comparison of Two Urine Fentanyl Assays on the Abbott Alinity c Analyzer
Authors: Laryea E T , Manning S , Nichols J H 
Published: September 2023

Abstract

Background
Mass spectrometry (MS) remains the gold standard, however immunoassays can provide a preliminary test result while the patient is still in the emergency room or clinic.

Methods
The ARK Fentanyl II assay (ARK Diagnostics Inc, Fremont, CA) was compared to the Immunalysis SEFRIA Fentanyl (Immunalysis Corporation, Pomona, CA) assay on the Abbott Alinity c analyzer (Abbott Park, IL) using leftover deidentified urine samples. MS analysis was performed at ARUP Laboratories (Salt Lake City, UT) to quantitate the amount of fentanyl or norfentanyl metabolite in each sample. Medications prescribed at the time of sampling were reviewed to assess for possible cross reactivity with the assays.

Results
A total of 142 urine samples were analyzed with 70 MS positive and 72 MS negative samples. Positive and negative assay specific quality control precision (N = 10) was 3.0% and 9.6% CV for the ARK Fentanyl II assay and 10.2% and 15.9% CV for the Immunalysis SEFRIA assays respectively. ARK Fentanyl II Sensitivity = 95.7%, Specificity = 94.4%, PPV = 94.4%, NPV = 95.8% and Efficiency = 95.1% compared to the Immunalysis SEFRIA Fentanyl Sensitivity = 95.7%, Specificity = 81.9%, PPV = 83.8%, NPV = 95.2% and Efficiency = 88.7%. Upon repeat analysis, 4 of 4 ARK and 6 of 13 Immunalysis false positives reported as negative, indicating some variability around the cutoff concentration. Possible carryover from high samples has also been reported (ARK Technical Note 20-001-August 2020) and high samples were analyzed prior to some of the false positive samples. Six MS positive samples were reported as negative (false negatives), 3 samples by each of the assays. However, 4/6 of those samples had combined fentanyl and norfentanyl concentrations &lt;3 ng/mL by MS.

Conclusion
The ARK Fentanyl II and Immunalysis SEFRIA assays demonstrated acceptable performance in the detection of fentanyl in our patient population.
B-381 A Multiplex Blood-based Assay Targeting DNA methylation in Peripheral Blood Mononuclear Cells Enables Early Detection of Breast Cancer
Authors: Wang C , Li J , Wang T 
Published: September 2023

Abstract

Background
The immune system can monitor the development of tumors, and the DNA methylation is involved in the body immune response to tumors. Therefore, the DNA from peripheral blood mononuclear cell (PBMC) that carries cancer-specific epigenetic aberrations may serve as a non-invasive marker for early detection of breast cancer (BC).

Methods
Genome-wide DNA methylation profiling on PBMC DNA from BC patients and healthy controls (Cohort I, n = 80) was performed in the discovery phase by Infinium 850K BeadChips. The candidate CpG sites were selected and validated in a multistep validation phase (Cohort II, n = 200) via pyrosequencing and targeted bisulfite sequencing. After that, the multiplex quantitative methylation-specific PCR assay (mBC-MSP) was established to detect BC, and the performance of this diagnostic method was analyzed in a multicenter cohort (Cohort III, n = 501).

Results
A total of 289 differentially methylated CpG positions (DMPs) between BC patients and healthy controls were identified. Among them, eight significant DMPs markers were selected and further validated using pyrosequencing and targeted bisulfite sequencing, and four hyper-methylated DMPs (cg18637238, cg16652347, cg13828440, cg11754974) passed the final validation. Then, we developed a mBC-MSP assay based on the four methylated markers. This assay exhibited excellent performance in distinguishing BC patients, with an AUC of 0.925, sensitivity of 83.1%, and specificity of 90.4%. More importantly, compared with CA153, CA125 and CEA, the mBC-MSP assay had higher sensitivity for early-stage BC (stage 0, 88.2% vs 0%, 0%, 5.9%) and minimal tumor with diameter ≤1.5 cm (91.7% vs 0%, 2.1%, 0%).

Conclusions
The mBC-MSP assay based on the four identified DNA methylation markers from PBMC can serve as a noninvasive, accurate, rapid, and high-throughput method for early diagnosis of BC, and it is more sensitive than traditional tumor markers for detecting early-stage BC and minimal tumor.
Cancer and the risk of perioperative arterial ischaemic events
Authors: Navi Babak B , Zhang Cenai , Kaiser Jed H , Liao Vanessa , Cushman Mary , Kasner Scott E , Elkind Mitchell S V , Tagawa Scott T , Guntupalli Saketh R , Gaudino Mario F L , Lee Agnes Y Y , Khorana Alok A , Kamel Hooman 
Published: September 2023

Abstract

Background and aims
Most cancer patients require surgery for diagnosis and treatment. This study evaluated whether cancer is a risk factor for perioperative arterial ischaemic events.

Methods
The primary cohort included patients registered in the National Surgical Quality Improvement Program (NSQIP) between 2006 and 2016. The secondary cohort included Healthcare Cost and Utilization Project (HCUP) claims data from 11 US states between 2016 and 2018. Study populations comprised patients who underwent inpatient (NSQIP, HCUP) or outpatient (NSQIP) surgery. Study exposures were disseminated cancer (NSQIP) and all cancers (HCUP). The primary outcome was a perioperative arterial ischaemic event, defined as myocardial infarction or stroke diagnosed within 30 days after surgery.

Results
Among 5 609 675 NSQIP surgeries, 2.2% involved patients with disseminated cancer. The perioperative arterial ischaemic event rate was 0.96% among patients with disseminated cancer vs. 0.48% among patients without (hazard ratio [HR], 2.01; 95% confidence interval [CI], 1.90–2.13). In Cox analyses adjusting for demographics, functional status, comorbidities, surgical specialty, anesthesia type, and clinical factors, disseminated cancer remained associated with higher risk of perioperative arterial ischaemic events (HR, 1.37; 95% CI, 1.28–1.46). Among 1 341 658 surgical patients in the HCUP cohort, 11.8% had a diagnosis of cancer. A perioperative arterial ischaemic event was diagnosed in 0.74% of patients with cancer vs. 0.54% of patients without cancer (HR, 1.35; 95% CI, 1.27–1.43). In Cox analyses adjusted for demographics, insurance, comorbidities, and surgery type, cancer remained associated with higher risk of perioperative arterial ischaemic events (HR, 1.31; 95% CI, 1.21–1.42).

Conclusion
Cancer is an independent risk factor for perioperative arterial ischaemic events.
Marine CSEM synthetic study to assess the detection of CO2 escape and saturation changes within a submarine chimney connected to a CO2 storage site
Authors: Yilo Naima K , Weitemeyer Karen , Minshull Timothy A , Attias Eric , Marin-Moreno Hector , Falcon-Suarez Ismael H , Gehrmann Romina , Bull Jonathan 
Published: September 2023

SUMMARY
Carbon capture and storage (CCS) within sealed geological formations is an essential strategy to reduce global greenhouse gas emissions, the primary goal of the 2015 United Nations Paris Agreement. Large-scale commercial development of geological CO2 storage requires high-resolution remote sensing methods to monitor CO2 migration during/after injection. A geological formation containing a CO2 phase in its pore space commonly exhibits higher electrical resistivity than brine-saturated (background) sediments. Here, we explore the added value of the marine controlled-source electromagnetic (CSEM) method as an additional and relevant geophysical tool to monitor moderate to significant changes in CO2 saturation within a fluid conduit breaking through the seal of a CCS injection reservoir, using a suite of synthetic studies. Our 2-D CSEM synthetic models simulate various geological scenarios incorporating the main structural features and stratigraphy of two North Sea sites, the Scanner Pockmark and the Sleipner CCS site. Our results show significant differentiation of leakage through the seal with CO2 saturation ($S_{{\rm CO}_2}$) ranging between 20 and 50 per cent, while our rock physics model predicts that detection below 20 per cent would be challenging for CSEM alone. However, we are able to detect with our 2-D inversion models the effects of saturation with 10 and 20 per cent CO2 within a chimney with 10 per cent porosity. We demonstrate that simultaneous inversion of Ey and Ez synthetic electric field data facilitates a sharper delineation of a CO2 saturated chimney structure within the seal, whereas Ez synthetic data present higher sensitivity than Ey to $S_{{\rm CO}_2}$ variation, demonstrating the importance of acquiring the full 3-D electric field. This study illustrates the value of incorporating CSEM into measurement, monitoring and verification strategies for optimal operation of marine CCS sites.
Cryo-EM and biochemical analyses of the nucleosome containing the human histone H3 variant H3.8
Authors: Hirai Seiya , Kujirai Tomoya , Akatsu Munetaka , Ogasawara Mitsuo , Ehara Haruhiko , Sekine Shun-ichi , Ohkawa Yasuyuki , Takizawa Yoshimasa , Kurumizaka Hitoshi 
Published: September 2023

Abstract
Histone H3.8 is a non-allelic human histone H3 variant derived from H3.3. H3.8 reportedly forms an unstable nucleosome, but its structure and biochemical characteristics have not been revealed yet. In the present study, we reconstituted the nucleosome containing H3.8. Consistent with previous results, the H3.8 nucleosome is thermally unstable as compared to the H3.3 nucleosome. The entry/exit DNA regions of the H3.8 nucleosome are more accessible to micrococcal nuclease than those of the H3.3 nucleosome. Nucleosome transcription assays revealed that the RNA polymerase II (RNAPII) pausing around the superhelical location (SHL) −1 position, which is about 60 base pairs from the nucleosomal DNA entry site, is drastically alleviated. On the other hand, the RNAPII pausing around the SHL(−5) position, which is about 20 base pairs from the nucleosomal DNA entry site, is substantially increased. The cryo-electron microscopy structure of the H3.8 nucleosome explains the mechanisms of the enhanced accessibility of the entry/exit DNA regions, reduced thermal stability and altered RNAPII transcription profile.
Galaxy spectral classification and feature analysis based on convolutional neural network
Authors: Wu Ying , Tao Yihan , Fan Dongwei , Cui Chenzhou , Zhang Yanxia 
Published: September 2023

ABSTRACT
Emission-line galaxy classification plays an important role in comprehending the formation and evolution of galaxies. The widely used optical spectral classification method for galaxies is the BPT diagram, which classifies emission-line galaxies on the basis of precise spectral line measurements. Various classical machine learning methods have been utilized to classify galaxy spectra. Deep learning (DL) is more feasible for a huge amount of data, as it can learn patterns autonomously from the original data. This study aims to explore the possibility of applying DL to classify galaxy spectra and improve classification efficiency. A one-dimensional convolutional neural network model called GalSpecNet was constructed to classify emission-line galaxy spectra, which recognizes star-forming, composite, active galactic nucleus (AGN), and normal galaxies with an accuracy of over 93 per cent. This study employs the Gradient-weighted Class Activation Mapping to elucidate the decision-making process of the model by inspecting spectral features that the model prioritizes for each type of galaxy. The findings suggest that the model considers features highly consistent with the conventional BPT method. Subsequently, we applied the model to the cross-matched galaxies of Sloan Digital Sky Survey Data Release 16 (DR16) and Large Sky Area Multi-Object Fiber Spectroscopic Telescope DR8 and present a catalogue comprising of 41 699 star-forming candidates and 55 103 AGN candidates. The catalogue is publicly available.
The impact of stochastic modelling on the predictive power of galaxy formation simulations
Authors: Borrow Josh , Schaller Matthieu , Bahé Yannick M , Schaye Joop , Ludlow Aaron D , Ploeckinger Sylvia , Nobels Folkert S J , Altamura Edoardo 
Published: September 2023

ABSTRACT
All modern galaxy formation models employ stochastic elements in their sub-grid prescriptions to discretize continuous equations across the time domain. In this paper, we investigate how the stochastic nature of these models, notably star formation, black hole accretion, and their associated feedback, that act on small (&lt; kpc) scales, can back-react on macroscopic galaxy properties (e.g. stellar mass and size) across long (&gt; Gyr) time-scales. We find that the scatter in scaling relations predicted by the EAGLE model implemented in the swift code can be significantly impacted by random variability between re-simulations of the same object, even when galaxies are resolved by tens of thousands of particles. We then illustrate how re-simulations of the same object can be used to better understand the underlying model, by showing how correlations between galaxy stellar mass and black hole mass disappear at the highest black hole masses (MBH &gt; 108 M⊙), indicating that the feedback cycle may be interrupted by external processes. We find that although properties that are collected cumulatively over many objects are relatively robust against random variability (e.g. the median of a scaling relation), the properties of individual galaxies (such as galaxy stellar mass) can vary by up to 25 per cent, even far into the well-resolved regime, driven by bursty physics (black hole feedback), and mergers between galaxies. We suggest that studies of individual objects within cosmological simulations be treated with caution, and that any studies aiming to closely investigate such objects must account for random variability within their results.