bluuebunny/crossref_metadata_2025 huggingface dataset:
B-135 Evaluation of Verification Decision Limits (VDL) for Routine Coagulation Post-Analytical Review: A Preliminary Analysis
Authors: Limpornpugdee O , Tanticharoenkarn S , Limprapassorn P , Prompetchara E
Published: October 2024

Background

A major challenge faced by medical laboratories is to meet the demand for high-throughput laboratory analysis while maintaining the quality and accuracy of the results. Manual validation remains an obstacle, with increased workloads for medical technologists leading to delayed results. The purpose of the study is to evaluate and implement VDL for routine coagulation automated post-analytical review system.

Methods

The study was conducted in the Division of Laboratory Medicine, King Chulalongkorn Memorial Hospital, Thailand. Our coagulation assay consists of activated partial thromboplastin time (APTT), and prothrombin time (PT). The VDL was a population-based percentile calculation, excluding the outlier using the Tukey method and incorporated with reference values. The decision range was implemented in the post-analytical review of the LIS system. The evaluation was carried out by using simulation analysis and post-implementation data collection to estimate the passing rate, sensitivity, and specificity.

Results

A total of 70,865 historical routine coagulation data were obtained from January 2021 to January 2022 to create VDL. The passing rate was assessed by simulation analysis using 21,277 coagulation results over 3 months(Table 1). In the initial implementation using VDL (5th, 95th percentiles combined with reference value) to the LIS in October 2023, a total of 9,792 cases were collected. The VDL identified 258 cases of aPTT and 115 cases of PT for review, while 9,534 cases of aPTT and 9,677 cases of PT were automatically released. This VDL showed a sensitivity of 99.6% and a specificity of 52.3%. Three error cases were found in partial clot specimens that the analyzer could not detect but were within the reference range.

Conclusions

This study evaluated the use of verification decision limits in an automated post-analytical review for routine coagulation tests which has the potential to improve the efficiency of the result reporting system.
B-202 Clinical and analytical performance evaluation of Savanna RVP4 panel versus three methodologies
Authors: Aldunate J , Vial M , Salgado P , Peña A , Toloza B
Published: October 2024

Background

Rapid molecular diagnosis became a key solution for healthcare institutions across the world, after COVID-19 pandemic. It has enabled diagnosis based on improved quality, accuracy, analytical sensitivity, and turnaround times for laboratory services. It also has positioned this methodology as a trusted technology for point-of-care settings. These solutions also allow to consolidate combinations of different pathogen detection in panels. This study assessed the analytical and clinical performance of the novel Savanna RVP4 panel against other available methodologies.

Methods

A prospective study was performed, considering 84 patient samples obtained from nasopharyngeal swabs. Samples were processed in parallel after collection, using Savanna RVP4, and either QIAstat-Dx Respiratory SARS-CoV Panel (59 samples), Sansure iPonatic (10 samples) and BioFire® Respiratory 2.1 (RP2.1) Panel (15 samples). Samples were collected in either MTU, commercial or homemade PBS.

Results

Overall clinical sensitivity and specificity were 96.43% and 99.64%, respectively for the aggregated panels (Table 1). By technology, the overall clinical sensitivity and specificity were 93.75% and 99.51% versus QIAstat, 100% and 100% versus Biofire, respectively. For iPonatic comparisons, no positive samples were processed and 100% of specificity was obtained. Cycle threshold (Ct) values for positive samples were compared using box plots. Ct values also showed slighlty differences, where means were lower for RSV and Flu A in Savanna (22 and 22.9 respectively) versus other PCR assays (22.5 and 24.5 respectively). For SARS-CoV-2, Ct values were higher versus other methods (19.8 vs 13.6).

Conclusions

Results obtained with Savanna RVP4 were comparable to those obtained with other methodologies, correlating with patient clinical symptoms. Samples showing disagreement for QIAstat comparison panel, in Flu A and RSV assays, corresponded to the same patient samples for the two methodologies, where Ct obtained in QIAstat were above 33. This evaluation also provides strong evidence supporting PBS usage for samples processed in Savanna RVP.
B-229 Extraction-free Nucleic Acid Sample Preparation from Inhibitor Rich Samples via Hyperbaric Heating
Authors: Hambalek J , Wright D , Babikian S , Petrullo M , Allen K , Heeren T , Peytavi R
Published: October 2024

Background

Extraction-based nucleic acid sample preparation for PCR is limited by long processing times, liquid transfers, cost, and storage requirements. Extraction-free approaches enable streamlined sample prep but are severely impacted by inhibitors present in biological sample matrices. We previously reported the use of Hyperbaric Heating (HBH) for effective organism lysis and demonstrate here its effectiveness to prepare nucleic acids for PCR from various inhibitor-rich sample matrix types.

Methods

HBH exposes the sample to high temperature/high pressure environment for a short duration. This process effectively lyses organisms and denatures inhibitors within seconds. Samples are sealed within a pressure-tight metallic vessel, then rapidly heated using magnetic induction. Within the sealed metallic vessel, vaporization of the aqueous sample raises the internal pressure, enabling an internal temperature higher than 100°C. Proprietary sample processing beads containing chelating agents and other proteins protect nucleic acids from fragmentation during heating.

Results

The efficacy of HBH for PCR amplification was tested against commercial kits and extraction-free methods. HBH treatment of nasal swab samples spiked with inactivated SARS-CoV-2 elicited detection down to 125 viral copies/mL. Viruses such as RSV and Influenza spiked in nasal swab samples demonstrated comparable PCR results as extraction prepped samples. HBH treatment of microbe samples, including Candida albicans spiked in urine and Bacillus subtilis spiked in serum, had comparable PCR threshold cycles as microbe specific DNA extraction methods (Table 1).

Conclusions

HBH is a generalizable extraction-free nucleic acid sample prep technology affording detection capabilities comparable to commercial sample prep methods. We demonstrated the use of HBH sample prep for detection of several infectious microorganisms in common biological matrices (nasal swab, serum, urine) without additional sample purification. With its ease of use, speed, and lower cost, HBH will be a key tool in applications where nucleic acid amplification is pivotal for diagnostic and research use.
B-230 Rt-pcr detection and monitoring of infection in periodontal disease: a model of herpesviral-bacterial synergism
Authors: Vigerust D J
Published: October 2024

Background

Periodontal disease results in the breakdown of tissue and ultimately bone and tooth loss. The prevalence of periodontal disease in most countries exceeds 50% and is a direct contributor to a variety of systemic chronic diseases. In addition to bacterial pathogens there is evidence of fungal and viral pathogens having a role in the genesis of inflammation and release of cytokines that stimulate bone and tooth loss. Herpes viruses such as Epstein-Barr virus (EBV), Cytomegalovirus (CMV) and Herpes Simplex 1and 2 (HSV-1 and 2), are seen in less than 5% of normal periodontal tissues but in excess of 50% in severe periodontitis. Epithelial infection with Herpesviruses can lead to impaired and inappropriate immune responses that drive immune evasion and tissue destruction. Viral infection can also alter the expression of proteins in the infected tissues that result in enhanced adherence of bacterial species like Porphyromonas gingivalis and promote active systemic disease. This viral-bacterial synergism is a mechanism of severe disease and should be proactively monitored in dental and medical patients to reduce the burden of morbidity and mortality.

Methods

Several of the eight Herpesviruses have been shown to contribute to cardiovascular disease (CVD), Alzheimer’s, GI cancers and liver disease. Our laboratory has developed and implemented as an LDT, an RT-PCR assay that detects the presence of the Keystone bacterial pathogens (Porphyrmonas gingivalis [Pg], Fusobacterium nucleatum [Fn],Treponema denticola [Td], Tannerella forsythia [Tf] and Aggregatibacter actinomycetemcomitans [Aa]), Candida spp., Streptococcus spp. related to caries formation and four Herpesviruses (EBV, CMV, HSV 1 and 2).

Results

The major pathogenic determinants of severe periodontitis are active herpesviruses, presence of keystone bacterial species, and chronic production of proinflammatory cytokines (TNF-α, IL-1, IL-6). Data from more than 500 patients demonstrates the frequent presence of EBV and CMV in patients also infected with Pg, Td and Fn suggesting a synergism that promotes aggressive periodontitis.

Conclusions

The literature and our data argue for a proactive periodontal testing program that includes viral and bacterial targets to best address and mitigate periodontal disease and the reduce risks for chronic systemic diseases such as CVD, metabolic disease and neurodegenerative disease.
B-237 Engineered Reverse Transcriptases and Taq DNA Polymerases deliver robust yield in the presence of clinically relevant inhibitors
Authors: van der Walt E , Venter P , Faurholm B , Walker J , Nevado W , Wadsworth R , Marshall C , Maasdorp H , Pavlica J , de Beer A
Published: October 2024

Background

The past five years has seen explosive growth in molecular diagnostic assays that rely on sensitive and accurate detection of nucleic acids across a wide range of sample types. As the assays are required to become increasingly sensitive, the need for highly functional and purpose-built enzymatic tools has grown. Reverse transcriptase (RT) and Taq DNA Polymerase (Taq DNAP) are commonly used to detect RNA and/or DNA viruses in patient samples for point of care (POC) diagnostics. However, crude patient samples introduce inhibitors that decrease enzyme activity and increase false negative results in POC testing. In addition, there is a need for faster turn-around time for patient diagnosis which can be enabled by engineering more active and sensitive Taq variants. Herein, we present on our engineered RT and Taq DNAP enzymes that were developed to confer greater activity, thermostability, inhibitor tolerance and/or sensitivity.

Methods

We take a 3-pronged approach to protein engineering: rational design, computational design and directed evolution. Using these techniques, we identified and characterized many RT and Taq DNAP variants. We deeply characterized each RT variant by measuring processivity, inhibitor tolerance and thermostability. First strand synthesis was done at temperatures from 42-65°C in the presence and absence of various clinically relevant inhibitors followed by qPCR to assess cDNA yield. Next, we characterized the inhibitor tolerance of the Taq variants by performing qPCR reactions in the presence of inhibitors. To determine if the Taq variant would be an appropriate fit for fast PCR, the polymerization activity of the Taq DNAP variants were characterized using a primer extension assay.

Results

Reverse transcriptases termed; StellarScript, StellarScript HT and StellarScript HT+ exhibit high processivity at 42°C. StellarScript HT+ exhibited the highest inhibitor tolerance, processivity and thermostability at temperatures up to 65°C thus making StellarScript HT+ well suited to produce high yields with clinical samples. Taq Pol variants were identified that efficiently amplify DNA in the presence of inhibitors.

Conclusions

Based on the increased polymerase activity and inhibitor tolerance, WMG Taq variants are well suited to give robust DNA yields with clinical samples. We were successful in engineering RT and Taq DNAP variants that are highly thermostable, active and inhibitor tolerant and thus will enable breakthroughs in existing POC diagnostics.
B-250 Analytical and Diagnostic Performance Evaluation of Plasma pTau217 in a Clinical Diagnostic Laboratory
Authors: Frykman H , Mammel A , Biehl D , Encarnacion M , Hallett K , Hsiung G , Mousavi A
Published: October 2024

Background

Blood-based biomarkers are a readily accessible and cost-effective screening tool for Alzheimer’s disease (AD). Phosphorylated tau 217 (pTau217) is a specific biomarker for diagnosis and differentiating of AD. It is also a reliable biomarker for facilitating more timely access to disease-modifying therapies. Here, we report the analytical and clinical performance of plasma pTau 217 using high-sensitivity methodologies in a clinical diagnostic laboratory.

Methods

The analytical performance, including precision, specificity, detection limits, and linearity, as well as analyte stability, was assessed. Plasma pTau217 levels were measured using ALZpath pTau217 assay on the Quanterix HD-X Simoa® platform or LUMIPULSE plasma pTau217 on the Lumipulse G1200 platform. Clinical Validation conducted at Neurocode USA & BC Neuroimmunology involving 263 samples with amyloid PET data, 219 healthy aging samples and 150 Pathology confirmed samples.

Results

The mean plasma pTau 217 concentrations in healthy aging samples were 0.22 ± 0.08 ng/L. ALZpath pTau217 assay has an analytical measurement range of 0.06 - 10 pg/mL, with a limit of blank (LoB) of 0.0035 ng/L, a limit of detection (LoD) of 0.0074 ng/L, and a limit of quantification (LoQ) of 0.0600 ng/L. Its linearity extends from 0.19 to 2.8 ng/L, with repeatability demonstrating intra-laboratory precision above LoQ ≤ 20% CV. Stability is maintained at 4⁰C for ≤ 1 week, at room temperature for ≤ 24 hrs, at -20⁰C for ≤ 4 weeks, and at -80⁰C for ≤ 4 weeks, with freeze/thaw cycles tolerated up to 5 times. Furthermore, no interference was detected at the maximum concentrations tested for bilirubin, hemoglobin, biotin, and heterophilic antibodies. ROC analysis yielded an AUC of 0.92 to 0.93, identifying a suitable clinical cutoff of < 0.4 ng/L.

Conclusions

The outstanding clinical and analytical performance of pTau217 supports its adoption as a robust screening tool in clinical practice, facilitating accurate and reliable diagnosis of AD by clinicians.
B-279 Evaluation of the Analytical Performance of Two Therapeutic Drug Monitoring Assays on the Atellica CI Analyzer
Authors: Huff J , Valdivia B , Wilkins G , Arrode-Bruses G , Leipold H , Snyder J
Published: October 2024

Background

The Atellica® CI Analyzer is an automated, high-throughput integrated chemistry and immunoassay analyzer utilizing both Atellica® CH and Atellica® IM Assays. This study evaluated the analytical performance of the Atellica IM Digoxin (Dig), and the Atellica CH Lithium_2 (LITH_2) Assays on the Atellica CI Analyzer.

Methods

Precision studies were performed according to CLSI EP05-A3 using native and contrived human serum samples. One aliquot of each sample pool was tested in duplicate in two runs per day ≥2 hours apart on each analyzer for ≥20 days. Precision studies were evaluated with one to three lots of reagent lot on one to two systems. Method comparison studies were performed using three reagent lots according to CLSI EP09c. Individual native and contrived human serum samples were analyzed using the Atellica IM Dig Assay on the Atellica IM Analyzer, the Atellica CH LITH_2 Assay on the Atellica CH Analyzer and both assays on the Atellica CI Analyzer.

Results

Representative precision and method comparison results for each assay are listed in the table. For the two assays tested, repeatability and within-lab %CVs were <5.4% and <8.0%, respectively. Slopes determined by the Deming linear regression model were approximately equal to 1.

Conclusions

Evaluation of the Atellica IM Dig Assay and the Atellica CH LITH_2 Assay using the Atellica CI Analyzer demonstrated good precision and equivalent performance compared to the same assays on their respective Atellica CH and Atellica IM Analyzers.
B-283 Biological Consequences of Nitrous Oxide Abuse: Insights from Targeted Metabolomics Investigation
Authors: Grzych G , Gernez E , Plasse L , Deheul S , Niguet J , Bennis A , Tard C , Douillard C , Scliffet D , Bossaert C , Girot M , Dobbelaere D , Diesnis R
Published: October 2024

Background

The recreational use of nitrous oxide (N2O), commonly known as laughing gas, has experienced a notable surge in popularity in recent times. According to the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), N2O is recognized as one of the most widely used psychoactive substances in Europe as of 2022. Its use also extends to Asia and America, according to literature. However, prolonged consumption of N2O has been associated with neurological complications linked to the functional inactivation of vitamin B12, disrupting One Carbon Metabolism. This study aims to explore the metabolic effects of N2O intoxication through a targeted metabolomics approach.

Methods

We conducted a prospective collection of clinical and biological information from 37 N2O users and 37 non-users (control group). Utilizing a targeted metabolomics method, we analyzed plasma amino acids using liquid chromatography coupled with mass spectrometry. Our statistical analysis encompassed principal component analyses, random forests, Mann-Whitney tests, Student's t-tests, and Spearman rank tests.

Results

Metabolomic analyses have demonstrated effective differentiation between patient groups. In comparison to controls, N2O consumers displayed reduced plasma levels of taurine, cystine, and methionine, alongside elevated plasma levels of serine and sarcosine. These findings suggest a potential influence of N2O on the cystine-methionine metabolic pathway. The decrease in methionine levels may be attributed to the decreased activity of methionine synthase (MS) due to vitamin B12 inactivation, which could partially explain the observed increase in serine levels. The rise in sarcosine levels could be explained by an increase in betaine-homocysteine S-methyltransferase (BHMT) activity. Moreover, dysfunction in cystathionine-β-synthase (CBS) or cystathionine γ-lyase (γ-CYS) may lead to the accumulation of upstream metabolites (such as serine) and a reduction in downstream metabolites (such as cysteine and taurine).

Conclusions

This study sheds light on potential new impacts of N2O, particularly on the plasma levels of serine, cystine, and taurine, indicating a potential modulation of enzymes involved in the conversion of homocysteine to taurine (CBS and/or γ-CYS). Additional investigations are required in a larger group of patients, which corresponds to the aims of the EFLM Task & Finish Group: Biomarkers of Diagnosis and Follow-up of Nitrous Oxide Abuse: https://www.eflm.eu/site/who-we-are/committee/science-committee/fu/tfg-biomarkers-of-diagnosis
B-289 Assessing the Shift in Positivity Rates of Cocaine and Its Metabolites in a Community Based Population: A Transition from utilization of Cutoff Concentrations to Qualitative Structure Identification
Authors: White-Al Habeeb N , Bernardin K , Standish S , Stanley K , Ang E , Catomeris P , Dunn T , Li H
Published: October 2024

Background

Semi-quantitative cutoff concentrations have traditionally been employed for urine drug detection. Research suggests that these cutoffs may be set too high, leading to the risk of overlooking positive cases. The advent of liquid chromatography-high-resolution mass spectrometry (LC-HR/MS) technology allows for the detection of drugs at lower concentrations. This study aims to assess the impact of transitioning from cutoff concentrations to qualitative structure identification on the positivity rates of cocaine and its metabolites in a community-based population.

Methods

Data analysis was conducted on results obtained from a community laboratory from April 2021 to October 2023. Screening of drugs was carried out using the Sciex X500R QTOF MS System. Cutoff concentrations were applied from April 2021 to September 2022 for screening cocaine and its metabolites (benzoylecgonine, norcocaine, and cocaethylene) in 62,816 samples. From October 2022 to October 2023, a qualitative structure identification approach was adopted for screening 47,676 samples.

Results

The previous screening for cocaine, benzoylecgonine, norcocaine, and cocaethylene was performed with a cutoff concentration of 50 ng/mL. Employing a qualitative structure identification approach, cocaine, benzoylecgonine, and cocaethylene were detectable at 5 ng/mL, while norcocaine could be identified at 10 ng/mL. Consequently, when qualitative identification was applied, the positivity rates for cocaine and its metabolites showed an increase. The prevalence of cocaine and its metabolites in the positive samples also demonstrated a corresponding shift.

Conclusions

Moving from using cutoff concentrations to employing qualitative structure identification with LC-HR/MS markedly enhances the detection of positive cases for cocaine and its metabolites. Although the detection sensitivity of drugs is improved, the presence of drugs at low concentrations can pose challenges with interpretation of results.
B-343 Development of CD40 and HER2 Bispecific Antibodies for Enhanced Efficacy against HER2-Positive Tumors
Authors: Cheng H , Zeng W , Yu L , Huang H , Wu H , Han C , Huang Y , Lou Y
Published: October 2024

Background

CD40, a member of the tumor necrosis factor superfamily, is primarily expressed on antigen-presenting cells. This receptor plays a crucial role in facilitating the interaction between dendritic cells, activating antigen-specific T cells. Agonist antibodies targeting the CD40 receptor have the potential to mimic the natural CD40 ligand, fostering dendritic cell maturation and stimulating immunity against “cold” tumors. Although this approach has shown promise in preclinical studies, translating it to clinical success has been challenging. Only modest anti-tumor activity was observed in cancer patients, and none of the developed CD40 monoclonal antibodies (mAbs) progressed beyond early clinical trials, highlighting a need for improved anti-tumor efficacy.

Methods

In this study, we successfully developed an anti-human CD40 agonist rabbit monoclonal antibody using Yurogen's proprietary SMAB(TM) platform. The most potent CD40 mAb clone was combined with trastuzumab (an anti-HER2 mAb) to create a therapeutic bispecific antibody. Our goal is to leverage immune cell activation through HER2-targeted cancer therapy to achieve enhanced anti-tumor activity. Dozens of diverse CD40xHER2 bispecific antibody designs (both symmetry and asymmetry) were explored, with careful evaluation of expression yield, purity, and binding profiles for each target respectively.

Results

A few bispecific antibody designs demonstrated robust binding to both HER2 and CD40 antigen proteins, as well as receptor-expressing cell lines. Notably, two developed bispecific antibodies exhibited potent killing of HER2-positive cancer cells with the assistance of innate immune cells.

Conclusions

In sum, this study provides novel insights into designing bispecific antibodies against HER2 and CD40, offering a promising avenue for advancing cancer immunotherapy.
B-346 Diagnostic Performance of the Atellica IM Free PSA Assay in Men Undergoing Prostate Cancer Screening
Authors: Olson Nissen K , Snyder J , Pagano M , Owusu A , Grosett M , Birmingham N , Christenson R , deFilippi C
Published: October 2024

Background

Measurement of free prostate specific antigen (fPSA) in serum is used to aid in distinguishing prostate cancer (PC) from benign prostate conditions in men 50 years or older with hsPSA of 4.0-10.0 ng/mL (µg/L) and digital rectal exam (DRE) nonsuspicious for PC. Studies were performed to evaluate clinical performance for the Atellica® IM fPSAII assay* [fPSAII/hsPSAx100 ratio].

Methods

Serum samples were prospectively collected from 1250 patients referred to an urologist for PC evaluation at 26 sites throughout the United States. At diagnostic cutoffs for %fPSAII spanning the spectrum of %fPSAII values, the percentage of PCs detected (sensitivity) and the corresponding percentage of biopsies avoided in men without PC (specificity) were tabulated. At a pre-specified sensitivity near 90%, %fPSAII specificity (relative to biopsy result) was compared to hsPSA specificity. The mean PC probabilities on biopsy and nonparametric 95% CI (2.5th and 97.5th percentiles) were calculated. The difference between these proportions was evaluated to estimate the improvement in specificity of %fPSAII relative to hsPSA alone. Difference in specificity was significant if the zero value was not bounded by 2.5th and 97.5th percentile values of the improvement estimate with a minimum of 5% improvement in specificity.

Results

Sensitivity and specificity results are presented in the table. The cutoffs provided a range of sensitivity estimates from 86%-100%. At 22% cutoff, sensitivity (90.3%) plus specificity (21.4%) is greater than 110.0%. Significant improvement in %fPSAII specificity over hsPSA alone was 8.9% with 95% CI of 6.8%-11.5%.

Conclusions

The clinical performance of the Atellica IM Analyzer fPSAII assay was acceptable and demonstrated an improvement in detection of PC than using hsPSA alone in this study.

*CAUTION: Investigational Device. Not available for sale. Future availability cannot be guaranteed. The results are preliminary and were achieved in unique setting with no expected timeline for completion.
Can longer lifespan be associated with gut microbiota involvement in lipid metabolism?
Authors: Šardzíková Sára , Gajewska Marta , Gałka Norbert , Štefánek Matúš , Baláž Andrej , Garaiová Martina , Holič Roman , Świderek Wiesław , Šoltys Katarína
Published: October 2024

Biological aging is linked to altered body composition and reduced neuroactive steroid hormones like dehydroepiandrosterone sulfate (DHEAS), which can stimulate the GABA signaling pathway via gut microbiota. Our study examined the association of gut microbiota with lifespan in mice through comprehensive analysis of its composition and functional involvement in cholesterol sulfate, a precursor of DHEAS, metabolism. We used 16S rRNA and metagenomic sequencing, followed by metabolic pathway prediction and thin layer chromatography and MALDI-TOF cholesterol sulfate identification. Significant increases in bacteria such as Bacteroides, typical for long-lived and Odoribacter and Colidextribacter, specific for short-lived mice were detected. Furthermore, for males (Rikenella and Alloprevotella) and females (Lactobacillus and Bacteroides), specific bacterial groups emerged as predictors (AUC = 1), highlighting sex-specific patterns. Long-lived mice showed a strong correlation of Bacteroides (0.918) with lipid and steroid hormone metabolism, while a negative correlation of GABAergic synapse with body weight (−0.589). We found that several Bacteroides species harboring the sulfotransferase gene and gene cluster for sulfonate donor synthesis are involved in converting cholesterol to cholesterol sulfate, significantly higher in the feces of long-lived individuals. Overall, we suggest that increased involvement of gut bacteria, mainly Bacteroides spp., in cholesterol sulfate synthesis could ameliorate aging through lipid metabolism.
Motivic Cluster Multiplication Formulas in 2-Calabi–Yau Categories
Authors: Xiao Jie , Xu Fan , Yang Fang
Published: October 2024

We introduce a notion of motivic cluster characters via virtual Poincaré polynomials, and prove a motivic version of multiplication formulas obtained by Chen–Xiao–Xu for weighted quantum cluster characters associated to a 2-Calabi–Yau triangulated category ${{\mathcal{C}}}$ with a cluster tilting object. Furthermore, a refined form of this formula is also given. When ${{\mathcal{C}}}$ is the cluster category of an acyclic quiver, our certain refined multiplication formula is a motivic version of the multiplication formula in SIGMA 19 (2023), 097-157.
Asymptotic Zeros of Poincaré Series
Authors: Kimmel Noam
Published: October 2024

We study the zeros of Poincaré series $P_{k,m}$ for the full modular group. We consider the case where $m \sim \alpha k$ for some constant $\alpha> 0$. We show that in this case a positive proportion of the zeros lie on the line $\frac{1}{2} + it$. We further show that if $\alpha> \frac{\log (2)}{2\pi }$ then the imaginary axis also contains a positive proportion of zeros. We also give a description for the location of the non-real zeros when $\alpha $ is small.
Strong pairwise interactions do not drive interactions in a plant leaf associated microbial community
Authors: Höhn Franziska , Chaudhry Vasvi , Bagci Caner , Mahmoudi Maryam , Klenk3 Elke , Berg Lara , Stincone Paolo , Hughes Chambers C , Petras Daniel , Brötz-Oesterhelt Heike , Kemen Eric , Ziemert Nadine
Published: October 2024

Microbial communities that promote plant growth show promise in reducing the impacts of climate change on plant health and productivity. Understanding microbe-microbe interactions in a community context is paramount for designing effective microbial consortia that enhance plant resilience. In this study, we investigated the dynamics of a synthetic microbial community (SynCom) assembled from Arabidopsis thaliana leaves to elucidate factors shaping community composition and stability. We found notable disparities between in vitro pairwise interactions and those inferred from correlation networks in planta. Our findings suggested that secondary metabolites, particularly antimicrobials, might mediate interactions in vitro, but are no key drivers of microbial interactions in a community context. Through co-cultivation experiments, we identified the siderophore pseudobactin as a potent antimicrobial agent against several SynCom members, but its impact on community composition in planta was negligible. Notably, dominant SynCom members, such as Pseudomonas koreensis, Flavobacterium pectinovorum, and Sporobolomyces roseus, exhibited only positive correlations, suggesting synergism based on for example exopolysaccharides and biotransformation might drive community dynamics rather than competition. Two correlations between SynCom members in the co-abundance network corresponded with their pairwise in vitro interactions, highlighting the potential for further research, and demonstrating the usefulness of correlation networks in identifying key microbe-microbe interactions. Our findings highlight the importance of considering microbiome-wide interaction studies and synthetic communities in understanding and manipulating plant microbiomes.
Hypoxia signaling in the adipose tissue
Authors: Huynh Phu M , Wang Fenfen , An Yu A
Published: October 2024

Obesity per se is rapidly emerging all over the planet and further accounts for many other life-threatening conditions, such as diabetes, cardiovascular diseases, and cancers. Decreased oxygen supply or increased relative oxygen consumption in the adipose tissue results in adipose tissue hypoxia, which is a hallmark of obesity. This review aims to provide an up-to-date overview of the hypoxia signaling in the adipose tissue. First, we summarize literature evidence to demonstrate that hypoxia is regularly observed during adipose tissue remodeling in human and rodent models of obesity. Next, we discuss how hypoxia-inducible factors (HIFs) are regulated and how adipose tissues behave in response to hypoxia. Then, the differential roles of adipose HIF-1α and HIF-2α in adipose tissue biology and obesity pathology are highlighted. Finally, the review emphasizes the importance of modulating adipose hypoxia as a therapeutic avenue to assist adipose tissues in functionally adapting to hypoxic conditions, ultimately promoting adipose health and improving outcomes due to obesity.
The formation and evolution of dark star clusters – II. The impact of primordial mass segregation
Authors: Ghasemi S Mojtaba , Rostami-Shirazi Ali , Khalaj Pouria , Zonoozi Akram Hasani , Haghi Hosein
Published: October 2024

We investigate the impact of primordial mass segregation on the formation and evolution of dark star clusters (DSCs). Considering a wide range of initial conditions, we conducted N-body simulations of globular clusters (GCs) around the Milky Way. In particular, we assume a canonical initial mass function for all GCs without natal kicks for supernova remnants, namely neutron stars or black holes. Our results demonstrate that clusters with larger degrees of primordial mass segregation reach their DSC phase earlier and spend a larger fraction of their dissolution time in such a phase, compared to clusters without mass segregation. In primordially segregated clusters, the maximum Galactocentric distance that the clusters can have to enter the DSC phase is almost twice that of the clusters without primordial mass segregation. Primordially segregated clusters evolve with a higher number of stellar mass black holes, accelerating energy creation in their central regions and consequently increasing evaporation rates and cluster sizes during dark phases. The simulations reveal that aggregating heavy components at the centre doubles the time spent in the dark phase. Additionally, the study identifies potential links between simulated dark clusters and initial conditions of Milky Way GCs, suggesting some may transition to dark phases before dissolution. Higher primordial mass segregation coefficients amplify the average binary black hole formation rate by 2.5 times, raising higher expectations for gravitational-wave emissions.
Impact of dynamical friction on the tidal formation of NGC 1052-DF2
Authors: Katayama Ryosuke , Nagamine Kentaro , Kihara Kenji
Published: October 2024

The formation of dark matter-deficient galaxies (DMDGs) through tidal interactions has been a subject of growing interest, particularly with the discovery of galaxies such as NGC 1052-DF2. Previous studies suggested that strong tidal forces could strip dark matter (DM) from satellite galaxies, but the role of dynamical friction in this process has been largely overlooked. In this paper, we present self-consistent N-body simulations that incorporate the effects of dynamical friction on the tidal formation of NGC 1052-DF2, and compare them with the one without dynamical friction. We find that dynamical friction significantly accelerates the decay of the satellite galaxy’s orbit, causing it to experience more frequent tidal stripping and leading to the earlier formation of a DM-deficient state, approximately $7\!-\!8$ Gyr after infall. This is a few Gyr earlier than simulations without dynamical friction. Our results suggest that DMDGs can form in a wider range of orbital configurations, particularly on more circular orbits, than previously thought. Furthermore, we find that globular clusters in the DM-deficient phase exhibit elevated velocity dispersion, providing an observational signature of this evolutionary stage. We also examine the evolution of satellite in the phase space of total energy versus angular momentum, and show that a vertically narrow feature in this phase space is a clear signature of pericentre passage. These findings broaden the understanding of how DMDGs form and highlight the critical role of dynamical friction in shaping the evolutionary history of satellite galaxies in massive haloes.
Local H i absorption towards the magellanic cloud foreground using ASKAP
Authors: Nguyen Hiep , McClure-Griffiths N M , Dempsey James , Dickey John M , Lee Min-Young , Lynn Callum , Murray Claire E , Stanimirović Snežana , Busch Michael P , Clark Susan E , Dawson J R , Dénes Helga , Gibson Steven , Jameson Katherine , Joncas Gilles , Kemp Ian , Leahy Denis , Ma Yik Ki , Marchal Antoine , Miville-Deschênes Marc-Antoine , Pingel Nickolas M , Seta Amit , Soler Juan D , van Loon Jacco Th
Published: October 2024

We present the largest Galactic neutral hydrogen H i absorption survey to date, utilizing the Australian SKA Pathfinder Telescope at an unprecedented spatial resolution of 30 arcsec. This survey, GASKAP-H i, unbiasedly targets 2714 continuum background sources over 250 square degrees in the direction of the Magellanic Clouds, a significant increase compared to a total of 373 sources observed by previous Galactic absorption surveys across the entire Milky Way. We aim to investigate the physical properties of cold (CNM) and warm (WNM) neutral atomic gas in the Milky Way foreground, characterized by two prominent filaments at high Galactic latitudes (between $-45^{\circ }$ and $-25^{\circ }$). We detected strong H i absorption along 462 lines of sight above the 3$\sigma$ threshold, achieving an absorption detection rate of 17 per cent. GASKAP-H i’s unprecedented angular resolution allows for simultaneous absorption and emission measurements to sample almost the same gas clouds along a line of sight. A joint Gaussian decomposition is then applied to absorption-emission spectra to provide direct estimates of H i optical depths, temperatures, and column densities for the CNM and WNM components. The thermal properties of CNM components are consistent with those previously observed along a wide range of Solar neighbourhood environments, indicating that cold H i properties are widely prevalent throughout the local interstellar medium. Across our region of interest, CNM accounts for $\sim$30 per cent of the total H i gas, with the CNM fraction increasing with column density towards the two filaments. Our analysis reveals an anticorrelation between CNM temperature and its optical depth, which implies that CNM with lower optical depth leads to a higher temperature.
Exceptional sustained long-term complete response to Tepotinib in a MET-amplified advanced intrahepatic biliary tract cancer failing Durvalumab plus Cisplatin and Gemcitabine
Authors: Reichinger Andreas , Essl Leo , Kerschner Paul , Burghofer Jonathan , Webersinke Gerald , Rumpold Holger , Doleschal Bernhard
Published: October 2024

Background

Biliary tract cancers (BTCs) are a diverse group of malignancies with varied genetic backgrounds. The prevalence of intrahepatic cholangiocarcinoma (iCC) is increasing, particularly in Western countries. Despite advancements in treatments, the prognosis for BTC remains poor. Recent molecular profiling has revealed that up to 40% of iCC cases have targetable genetic alterations. MET amplification, although rare, presents a significant target for therapy.

Case Presentation

A 25-year-old female with a history of ulcerative colitis presented with shoulder pain and a positron emission tomography–computed tomography (PET–CT) scan revealed an enlarged liver and multiple metastases. Histopathological analysis diagnosed poorly differentiated adenocarcinoma. First-line therapy with Cisplatin, Gemcitabine, and Durvalumab resulted in disease progression. Molecular profiling identified a TP53 mutation and MET amplification. Based on these findings, Tepotinib was initiated. Tepotinib treatment led to a significant reduction in tumor size and normalization of CA 19-9 levels within 2 months, achieving a complete metabolic remission lasting up to 17 months. The treatment was well tolerated with minimal side effects.

Discussion

MET-amplified BTCs are exceedingly rare, and evidence for targeted treatment is limited. This case demonstrates the efficacy of Tepotinib in a young patient with MET-amplified iCC, showing a long-term response and suggesting a potential new standard treatment option for this molecularly defined entity. This case also highlights the aggressive nature of MET-amplified tumors and the need for targeted second-line therapies.

Conclusion

Tepotinib showed remarkable efficacy in treating MET-amplified intrahepatic cholangiocarcinoma, underscoring the importance of molecular profiling in BTCs and suggesting a potential new therapeutic approach for this rare cancer subtype.
Police engagement with football fans online during the English 2022/23 season
Authors: Ralph Liam , Aitken Adam , Robinson Paul
Published: October 2024

Dialogue policing favours constructive forms of police-fan engagement, and there is overwhelming evidence that it leads to greater trust and self-regulation behaviours amongst fans. However, little is known about if and how dialogue policing can be facilitated online. To this end, five police football accounts in England were studied on the social media platform X across the 2022/23 season. Research findings show that the police used three key tactics, linked to chatting about congenial subject matter, influencing fans’ movements and behaviour, and tackling crime and disorder. On one hand, police football accounts used a soft communication approach, and yet two-way communication was rare. This is significant because it shows that the police incorporated elements of dialogue-based policing, although more must now be done by the police to speak with and not to fans.
Atlanto-occipital Dissociation
Authors: Sheppard William L. , Savage Jason W. , Moore Tim
Published: October 2024

Atlanto-occipital dissociation (AOD) is an extremely common injury but often fatal. In a systematic review from 2010, AODs were present in almost 20% of blunt trauma fatalities. It is an injury many patients do not survive; therefore, few are treated, even at high volume trauma centers. In survivors, his injury is often missed or the diagnosis is often delayed. Mortality rates commonly reach beyond 60% when injury patterns go unrecognized. Approximately 50% of patients with AOD sustain blunt cerebrovascular injury and nearly 20% of patients present with traumatic brain injury (TBI) or stroke. This pathology was once considered uniformly fatal. However, over the last 20 years, significant advancements have been made both clinically and radiographically, to better identify and manage this injury pattern. Despite improvements in clinical comprehension and improved time to diagnosis, less than 75% of cases are currently recognized within 24 hours. Less than 40% of patients who suffer AOD are independent with functionality, without neurological impairment. This article reviews current literature regarding AOD in hopes to improve timing to diagnosis, subsequent prognosis, timing to fixation or stabilization, and postoperative recovery.
Traumatic Central Cord Syndrome
Authors: Carr Matthew T. , Harrop James S. , Houten John K.
Published: October 2024

Central cord syndrome (CCS) is the most common form of incomplete spinal cord injury, with an increasing incidence with the aging population. This is a clinical diagnosis defined by weakness greater in the upper than lower extremities and often prominent sensory complaints in the hands. CCS is typically seen in individuals with underlying cervical canal stenosis from spondylosis who experience sudden forceful movement of the neck, especially hyperextension, resulting in contusion of the spinal cord. The prognosis in CCS is relatively favorable with improvement in neurological deficits, except for fine motor control of the hands. Neuropathic pain may persist even in those with excellent motor recovery. Nonoperative management may be appropriate in selected patients, but surgery is usually necessary in those with poor neurological recovery or further deterioration. The optimal timing of surgical intervention has not been defined, but recent evidence suggests that early surgery (≤24 h) may lead to greater neurological recovery, shorter hospital stay, and fewer inpatient complications. Management in any given patient must be considered in the context of the anatomy and location of spinal cord compression, the presence of fractures or ligamentous instability, the temporal course of signs and symptoms, as well as the patient’s overall health.
Use of the Electronic Health Record to Improve Nursing Chart Preparation
Authors: Sherburne Laura M. , Runge Jessica M. , Larson Abby L.
Published: October 2024

In a medical specialty clinic located in a rural community, a nursing team identified an opportunity to decrease the time nursing staff spent preparing charts for patients' upcoming clinical appointments. In collaboration with an informaticist, the nursing project team implemented a quality improvement project with a target goal of decreasing the average time spent preparing charts per patient by 20%, without increasing the number of discrepancies in the chart preparation process. The team used the define, measure, analyze, improve, and control framework to identify two interventions that could decrease time for chart preparation. A standardized chart preparation process was developed, and a condensed nursing view was created within the electronic health record. After the quality improvement project, the average time nurses spent on chart preparation per patient decreased by 18% after the standardized process and 16% after the condensed view was implemented.
Mean arterial pressure versus cardiac index for haemodynamic management and myocardial injury after hepatopancreatic surgery
Authors: Abdullah Taner , Gökduman Hürü Ceren , Enişte İşbara Alp , Kudaş İlyas , Ali Achmet , Kinaci Erdem , Özden İlgin , Gümüş Özcan Funda
Published: October 2024

BACKGROUND

Myocardial injury after noncardiac surgery (MINS) frequently complicates the peri-operative period and is associated with increased mortality.

OBJECTIVE(S)

We hypothesised that cardiac index (CI) based haemodynamic management reduces peri-operative high-sensitive troponin-T (hsTnT) elevation and MINS incidence in patients undergoing hepatic/pancreatic surgery compared to mean arterial pressure.

DESIGN

A randomised controlled study

SETTING

A single-centre study conducted in a university-affiliated tertiary hospital between June 2022 and March 2023.

PATIENTS

Ninety-one patients, who were ≥ 65 years old or ≥ 45 years old with a history of at least one cardiac risk factor were randomised to either mean arterial pressure (MAP) based (n = 45) or CI-based (n = 46) management groups, and completed the study.

INTERVENTION(S)

In group-MAP, patients received fluid boluses and/or a noradrenaline infusion to maintain MAP above the predefined threshold. In group-CI, patients received fluid boluses and/or dobutamine infusion to keep CI above the predefined threshold. When a low MAP was observed despite a normal CI, a noradrenaline infusion was started.

MAIN OUTCOME MEASURES

The primary outcome was peri-operative hsTnT elevation. The secondary outcomes were MINS incidence and 90-day mortality.

RESULTS

The median absolute troponin elevation was 4.3 ng l−1 (95% CI 3.4 to 6) for the CI-based group, and 9.4 ng l−1 (95% CI 7.7 to 12.7) for the MAP-based group (median difference: 5.1 ng l−1, 95% CI 3 to 7; P < 0.001). MINS occurred in 8 (17.4%) patients in the CI-based group and 17 (37.8%) patients in the MAP-based group (relative risk: 0.46, 95% CI: 0.22 to 0.96; P = 0.029). Two patients in group-MAP died from cardiovascular-related causes. One patient in group-CI and two in group-MAP died from sepsis-related complications (for all-cause mortality: χ
2 = 1.98, P = 0.16). MAP-AUC and CI-AUC values of the CI- and MAP-based groups were 147 vs. 179 min × mmHg (P = 0.85) and 8.4 vs. 43.2 l m−2 min−1 × min (P < 0.001), respectively.

CONCLUSIONS

CI-based haemodynamic management assures sufficient flow and consequently is associated with less peri-operative hsTnT elevation and lower incidence of MINS compared to MAP.

TRIAL REGISTRATION

Clinicaltrials.gov identifier: NCT05391087.