bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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

Abstract

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

Abstract
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

Abstract
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

Abstract
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 $\alpha&gt; 0$. 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 $\alpha&gt; \frac{\log (2)}{2\pi }$ 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

Abstract
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

Abstract
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

ABSTRACT
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

ABSTRACT
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

ABSTRACT
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

Abstract

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

ABSTRACT
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.
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.