bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting polycomb repressor complex 2‐mediated bivalent promoter epigenetic silencing of secreted frizzled‐related protein 1 inhibits cholangiocarcinoma progression
Authors: Wu Guanhua , Wang Qi , Wang Da , Xiong Fei , Liu Wenzheng , Chen Junsheng , Wang Bing , Huang Wenhua , Wang Xin , Chen Yongjun 
Published: December 2023

AbstractBackgroundCholangiocarcinoma (CCA) refers to a collection of malignancies that are associated with a dismal prognosis. Currently, surgical resection is the only way to cure patients with CCA. Available systemic therapy is limited to gemcitabine plus cisplatin; however, this treatment is palliative in nature. Therefore, there is still a need to explore new effective therapeutic targets to intervene against CCA.MethodsWe analyzed the expression of EZH2 and the prognosis of patients in CCA. The proliferation, migration and invasion of CCA cells after gene knockdown and overexpression were examined and validated by a xenograft model and a primary CCA mouse model with corresponding gene intervention. Targeting DNA methylation, and RNA‐sequencing‐based transcriptomic analysis in EZH2 and SUZ12 knockout CCA cells was performed. Bisulfite sequencing polymerase chain reaction (PCR), chromatin immunoprecipitation‐quantitative PCR (ChIP‐qPCR) and reverse‐ChIP assays were performed for research purposes.ResultsIncreased expression of EZH2 in CCA exhibited a significantly poorer prognosis. DNA hypomethylation of the promoter and increased mRNA levels of secreted frizzled‐related protein 1 (SFRP1) were observed in CCA cells following the inhibition of polycomb repressor complex 2 (PRC2), which was achieved through a knockout of EZH2, SUZ12 and EED, respectively, or treatment with GSK126 and GSK343. Targeting the SFRP1 promoter DNA hypermethylation with dCas9‐DNMT3a decreased the mRNA level of SFRP1. The expression of SFRP1 is regulated by both H3K27me3 and DNA methylation and H3K27me3 plays a crucial role in promoting SFRP1 promotor DNA methylation. GSK343 is a small molecule inhibitor that targets the catalytic activity of EZH2. It effectively inhibits the progression and development of subcutaneous xenografts and primary CCA mouse models.ConclusionOverall, our data strongly suggested that targeting PRC2 promotes the expression of SFRP1, thereby inhibiting the progression of CCA.Key Points/Headlights
Cholangiocarcinoma (CCA) exhibits elevated expression of EZH2, SUZ12 and EED, resulting in increased levels of H3K27me3.
Targeting polycomb repressor complex 2 (PRC2) leads to the removal of H3K27me3 from the secreted frizzled‐related protein 1 (SFRP1) promoter and DNA hypomethylation, thereby activating the transcription of SFRP1.
Inhibiting PRC2, including the use of EZH2 inhibitors, holds promise as a potential strategy for developing anti‐cancer drugs for CCA.
Blood‐based biomarkers in Alzheimer's disease: Future directions for implementation
Authors: Suridjan Ivonne , van der Flier Wiesje M. , Monsch Andreas U. , Burnie Nerida , Baldor Robert , Sabbagh Marwan , Vilaseca Josep , Cai Dongming , Carboni Margherita , Lah James J. 
Published: December 2023

AbstractINTRODUCTIONDisease‐modifying therapies (DMTs) for Alzheimer's disease (AD) will increase diagnostic demand. A non‐invasive blood‐based biomarker (BBBM) test for detection of amyloid‐β pathology may reduce diagnostic barriers and facilitate DMT initiation.OBJECTIVETo explore heterogeneity in AD care pathways and potential role of BBBM tests.METHODSSurvey of 213 healthcare professionals/payers in US/China/UK/Germany/Spain/France and two advisory boards (US/Europe).RESULTSCurrent diagnostic pathways are heterogeneous, meaning many AD patients are missed while low‐risk patients undergo unnecessary procedures. Confirmatory amyloid testing (cerebrospinal fluid biomarkers/positron emission tomography) is utilized in few patients, resulting in diagnostic/treatment delays. A high negative‐predictive‐value test could streamline the diagnostic pathway by reducing unnecessary procedures in low‐risk patients; supporting confirmatory testing where needed. Imminent approval of DMTs will increase need for fast and reliable AD diagnostic tests.DISCUSSIONAn easy‐to‐use, accurate, non‐invasive BBBM test for amyloid pathology could guide diagnostic procedures or referral, streamlining early diagnosis and DMT initiation.Highlights
This study explored AD care pathways and how BBBM may meet diagnostic demands
Current diagnostic pathways are heterogeneous, with country and setting variations
Many AD patients are missed, while low‐risk patients undergo unnecessary procedures
An easy‐to‐use, accurate, non‐invasive BBBM test for amyloid pathology is needed
This test could streamline early diagnosis of amyloid pathology and DMT initiation
Factors influencing the in situ formation of Δ9‐THC from cannabidiol during GC–MS analysis
Authors: Cheng Ya‐Chih , Kerrigan Sarah 
Published: December 2023

AbstractGas chromatography–mass spectrometry (GC‐MS) is widely used for the identification of cannabinoids in seized plant material. Conditions used for instrumental analysis should maximize decarboxylation, while minimizing the in situ production of Δ9‐THC inside the GC inlet. In this study, decarboxylation of the acidic Δ9‐THC precursor and in situ degradation of cannabidiol (CBD) were investigated using seven commercial GC liners with different deactivation chemistries and geometries. While the inlet temperature was previously optimized at 250°C in a previously validated assay, we systematically examined the temperature‐dependent decarboxylation of tetrahydrocannabinolic acid‐A (Δ9‐THCA‐A) and cyclization of CBD between 230°C and 310°C using different liners using favorable and unfavorable conditions. Significant differences in decarboxylation rate and CBD cyclization were observed between different liner types. While no temperature‐dependent differences in decarboxylation rate were observed within liner type, liner‐dependent differences were observed (α = 0.05), particularly between those with different geometry. In contrast, temperature and liner‐dependent differences were observed for in situ formation of Δ9‐THC (α = 0.05). This was influenced by liner geometry and to a smaller extent by surface deactivation. Effects were exacerbated with liner usage. While significant differences were observed using new and used GC liners, differences between liners of the same type but different lot numbers were not observed. Inter‐instrument differences using the same liner were also evaluated and had minimal effect. Liner‐ and temperature‐dependent effects were also confirmed using more than 20 cannabis plant extracts. Careful selection of liner, inlet conditions, and regular preventive maintenance can mitigate the risks associated with in situ formation Δ9‐THC from CBD.
Carbon black/acrylonitrile‐butadiene‐styrene composite material incorporated with silver nanoparticles: A new sensitive and cost‐effective electrochemical platform for trace lead detection in seawater samples
Authors: do Nascimento Suéllen F. L. , de Faria Lucas V. , da S. Cabral Taíssa , P. Lisboa Thalles , de S. Borges Pedro H. , Nossol Edson , S. Semaan Felipe , Dornellas Rafael M. , Pacheco Wagner F. 
Published: December 2023

AbstractA novel composite material based on acrylonitrile‐butadiene‐styrene (ABS) and carbon black (CB) was proposed here. Different ratios between CB and ABS (40 : 60–60 : 40 %, w/w) were studied to obtain a substrate with improved electrochemical properties. These materials were characterized by techniques such as cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), Raman and Fourier transform infrared (FT‐IR) spectroscopies and scanning electron microscopy (SEM). Under the CB/ABS substrate (50 : 50 %, w/w), a lower charge transfer resistance (854 Ω) and a higher heterogeneous electron transfer constant (K0=1.551×10−3 cm s−1) were found, indicating a kinetically more favorable reaction. To improve the electroanalytical performance of the CB/ABS electrode (50 : 50 %, w/w), silver nanoparticles (AgNPs) were electrodeposited using recycled silver from photographic waste, whose presence was confirmed by SEM imaging and Raman spectra. A method using square wave anodic stripping voltammetry (SWASV) and Pb2+ as model species was developed, where a wider linear working range (4.0 to 40.0 μg L−1) and lower detection limit (0.4 μg L−1) were achieved for the modified electrode. The electrode modification process was highly reproducible (RSD=9.7 %, n=9, inter‐electrode), with precise electrochemical responses (RSD=3.6 %, n=9, intra‐electrode). The applicability was demonstrated in two seawater samples, where recovery levels between 94 and 106 %, as well as statistically similar results to those obtained by atomic absorption spectroscopy, attested to the reliability of the analysis. Furthermore, it is noteworthy that an appropriate selectivity was achieved even in the presence of other metallic species. The proposed composite material is low‐cost, robust, versatile, and can be a promising tool for additive manufacturing of electrochemical sensors.
Site‐specific response spectra developed by considering near‐fault motion with finite‐fault simulation in Taiwan
Authors: Huang Jyun‐Yan , Chao Shu‐Hsien , Lin Che‐Min , Chou Chung‐Che , Loh Chin‐Hsiung , Wu Chiun‐Lin 
Published: December 2023

AbstractA new methodology is proposed for developing a scenario‐based site‐specific response spectrum (RS) considering near‐fault effects in Taiwan. First, source parameters, together with reference rock site conditions, are defined according to the available geological and geophysical information at a target site close to a potential active fault in northern Taiwan. Secondly, the scenario‐based response spectrum for a reference rock site condition is developed theoretically through an empirical approach by using a ground motion prediction equation (GMPE). The effect of the pulse period and the occurrence probability of near‐fault pulse‐like ground motion on RS is evaluated by using the ground motion simulation (GMS) technique, in which the stochastic finite‐fault simulation method is validated and applied for evaluating velocity pulse. Third, site‐specific site amplification is incorporated into RS through a site transfer function calculated from the measured horizontal‐to‐vertical Fourier spectral ratio through the microtremor (MHVR) of the target site. Finally, the design spectrum of the target site is compared with the derived site‐specific RS to evaluate the impact of the neighbor fault on the structure of the target site.
A wellbore fluid performance parameters–temperature–pressure coupling prediction model during the managed pressure cementing injection stage
Authors: Liu Jinlu , Li Jun , Yang Hongwei , Li Hui , Liu Gonghui 
Published: December 2023

AbstractManaged pressure cementing (MPC) is a new technology based on managed pressure drilling, which has a greater advantage in facing narrow density window formations. However, the existing pressure prediction models during MPC injection stage consider fewer factors and have lower accuracy. To this end, combined with the characteristics of the injection stage, a predictive model of the distribution of annular fluid type was first proposed. Then, based on the experimental results, fluid density and rheology as a function of temperature and pressure were fitted. The governing equation of temperature‐pressure field was established. Eventually the fluid performance parameters–temperature–pressure coupling prediction model was developed in this paper. By comparing the predicted pump pressure with the measured pump pressure, the maximum relative error is not more than 10%. Using this model, the fluid type distribution, temperature field distribution, and pressure field distribution were investigated. The results indicated that the distribution of fluid types in the wellbore presented a complex variation, with up to 10 fluids in the casing and up to five fluids in the annulus. The trend of temperature field is complex, with three turning points. The larger the formation temperature gradient, the higher the fluid temperature in the annulus. The influence law of fluid heat conduction coefficient is reversed at 6750 m. Decreasing drilling fluid density will trigger gas channeling, while increasing drilling fluid density will increase the risk of fracturing formation, and safe operation can be realized by MPC. The variation of the static pressure in the casing is more complicated than in the annulus and the annular circulation pressure in the eccentric casing is smaller than that of the concentric casing, which is due to the smaller annular friction pressure. This study can provide a theoretical basis for the prediction of hydrodynamic parameters during the MPC injection stage.
Early detection of white matter hyperintensities usingSHIVA‐WMHdetector
Authors: Tsuchida Ami , Boutinaud Philippe , Verrecchia Violaine , Tzourio Christophe , Debette Stéphanie , Joliot Marc 
Published: December 2023

AbstractWhite matter hyperintensities (WMHs) are well‐established markers of cerebral small vessel disease, and are associated with an increased risk of stroke, dementia, and mortality. Although their prevalence increases with age, small and punctate WMHs have been reported with surprisingly high frequency even in young, neurologically asymptomatic adults. However, most automated methods to segment WMH published to date are not optimized for detecting small and sparse WMH. Here we present the SHIVA‐WMH tool, a deep‐learning (DL)‐based automatic WMH segmentation tool that has been trained with manual segmentations of WMH in a wide range of WMH severity. We show that it is able to detect WMH with high efficiency in subjects with only small punctate WMH as well as in subjects with large WMHs (i.e., with confluency) in evaluation datasets from three distinct databases: magnetic resonance imaging‐Share consisting of young university students, MICCAI 2017 WMH challenge dataset consisting of older patients from memory clinics, and UK Biobank with community‐dwelling middle‐aged and older adults. Across these three cohorts with a wide‐ranging WMH load, our tool achieved voxel‐level and individual lesion cluster‐level Dice scores of 0.66 and 0.71, respectively, which were higher than for three reference tools tested: the lesion prediction algorithm implemented in the lesion segmentation toolbox (LPA: Schmidt), PGS tool, a DL‐based algorithm and the current winner of the MICCAI 2017 WMH challenge (Park et al.), and HyperMapper tool (Mojiri Forooshani et al.), another DL‐based method with high reported performance in subjects with mild WMH burden. Our tool is publicly and openly available to the research community to facilitate investigations of WMH across a wide range of severity in other cohorts, and to contribute to our understanding of the emergence and progression of WMH.
Impacted spike frequency adaptation associated with reduction of KCNQ2/3 exacerbates seizure activity in temporal lobe epilepsy
Authors: Jiang Shicheng , Liu Bei , Lin Kaiwen , Li Lianjun , Li Rongrong , Tan Shuo , Zhang Xinyu , Jiang Lei , Ni Hong , Wang Yuanyuan , Ding Haihu , Hu Jing , Qian Hao , Ge Rongjing 
Published: December 2023

AbstractNumerous epilepsy‐related genes have been identified in recent decades by unbiased genome‐wide screens. However, the available druggable targets for temporal lobe epilepsy (TLE) remain limited. Furthermore, a substantial pool of candidate genes potentially applicable to TLE therapy awaits further validation. In this study, we reveal the significant role of KCNQ2 and KCNQ3, two M‐type potassium channel genes, in the onset of seizures in TLE. Our investigation began with a quantitative analysis of two publicly available TLE patient databases to establish a correlation between seizure onset and the downregulated expression of KCNQ2/3. We then replicated these pathological changes in a pilocarpine seizure mouse model and observed a decrease in spike frequency adaptation due to the affected M‐currents in dentate gyrus granule neurons. In addition, we performed a small‐scale simulation of the dentate gyrus network and confirmed that the impaired spike frequency adaptation of granule cells facilitated epileptiform activity throughout the network. This, in turn, resulted in prolonged seizure duration and reduced interictal intervals. Our findings shed light on an underlying mechanism contributing to ictogenesis in the TLE hippocampus and suggest a promising target for the development of antiepileptic drugs.
Investigating consumer stated preferences for orange juice: The influence of behavioral traits
Authors: Orivri Glory E. , Kassas Bachir , Lai John , House Lisa , Nayga Rodolfo M. 
Published: December 2023

AbstractThis study aims to investigate consumer acceptance of gene‐edited orange juice, focusing on the influence of behavioral traits. Specifically, we conducted an online survey of US orange juice consumers, using a choice experiment to elicit consumers' preferences for gene editing (GE) versus gene modification (GM) in orange juice. We find that consumers require a significantly larger discount for GM than for GE, and this preference for GE is influenced by multiple behavioral traits. We used a latent cla4ss approach to further analyze choice behavior among consumer segments. Findings indicate significant heterogeneity in preferences across consumer segments, which can be explained by behavioral traits and individual‐specific characteristics.
Correlation between membrane proteins and sizes of extracellular vesicles and particles: A potential signature for cancer diagnosis
Authors: Zhai Chunhui , Xie Feng , Xu Jiaying , Yang Yuting , Zheng Weiqiang , Hu Haiyan , Ding Xianting , Yu Hui 
Published: December 2023

AbstractExtracellular vesicles and particles (EVPs) are recognized as ideal liquid biopsy tools for cancer detection, and membrane proteins are commonly used EVP biomarkers. However, bulk analysis of EVP membrane protein biomarkers typically fails to meet the clinical requirement for diagnostic accuracy. We investigated the correlation between the membrane protein expression level, the binding kinetics to aptamers and the sizes of EVPs with interferometric plasmonic microscopy (iPM), and demonstrated the implementation of the correlative signature to determine cancer types. Using EVPs collected from both cell model and clinical plasma samples with liver, lung, breast, or prostate cancer, we found that the selective set of membrane protein expression levels of five protein markers and their binding kinetics were highly heterogeneous across various sizes of EVPs, resulting in the low overall accuracy (<50%) in cancer classification with bulk analysis of all populations. By grouping the EVPs into three subpopulations according to their sizes, the overall accuracy could be increased to about 70%. We further grouped the EVPs into subpopulations with a 10 nm interval in sizes and analysed the correlation between the membrane proteins and sizes with a machine learning algorithm. The results show that the overall accuracy to discriminate cancer types could be improved to 85%. Therefore, this work highlights the significance of size‐dependent subtyping of EVPs and suggests that the correlation between the selective set of membrane proteins and sizes of EVP can serve as a signature for clinical cancer diagnosis.
Single‐particle analysis of circulating bacterial extracellular vesicles reveals their biogenesis, changes in blood and links to intestinal barrier
Authors: Ou Zihao , Situ Bo , Huang Xinyue , Xue Yicong , He Xiaojing , Li Qianbei , Ou Dejin , He Bairong , Chen Jing , Huang Yiyao , Deng Lulu , Zhang Minying , Wang Qian , Zheng Lei 
Published: December 2023

AbstractBacterial extracellular vesicles (BEVs) are nano‐size particles secreted by bacteria that carry various bioactive components. These vesicles are thought to provide a new window into the mechanisms by which bacteria affect their hosts, but their fundamental proprieties within human remain poorly understood. Here, we developed a single‐vesicle analytical platform that enabled BEV detection in complex biological samples of host. Using this platform, we found the presence of BEVs in the host circulation and they were mainly derived from gut microbes. We showed that the levels of circulating BEVs in humans significantly increased with aging due to an age‐related increase in intestinal permeability. Significantly different levels of BEVs in blood were also found in patients with colorectal cancer and colitis. Together, our study provides new insights into circulating BEV biology and reveals their potential as a new class of biomarkers.
Psychosocial issues and coping strategies in families affected by long‐chain fatty acid oxidation disorders
Authors: Thiel Maren , Garbade Sven F. , Rosenbaum‐Fabian Stefanie , Spiekerkoetter Ute , Grünert Sarah C. 
Published: December 2023

AbstractLong‐chain fatty acid oxidation disorders (lcFAODs) are associated with a high disease burden due to both the risk of metabolic decompensation as well as chronic, partly irreversible complications in some. Little research has been performed on the impact of these disorders on the daily life of parents and caregivers. We performed a web‐based questionnaire study among parents/caregivers of patients affected with lcFAODs. The questionnaire focused on challenges at different ages of the child, on disease management issues, schooling, family and social life as well as the parental job situation, and their overall attitude toward the disease and the future life of their child. Data were collected from parents/caregivers of 63 patients (87 respondents, 63% mothers, 36% fathers) with lcFAODs (median age of patients 8.0 years, range 0–25 years, long‐chain 3‐hydrocyacyl‐CoA dehydrogenase deficiency 40%, mitochondrial trifunctional protein deficiency 14%, very long‐chain acyl‐CoA dehydrogenase deficiency 41%, carnitine palmitoyltransferase 2 deficiency 5%). The overall disease burden of parents was considered highest during infancy and decreased with increasing age of their child. More than one third of parents were afraid that their child's disease might have an impact on his/her career choice and adult life. Negative effects of the child's disease on the job situation and career development were more commonly reported by mothers compared to fathers. Although the majority of parents considered their child's metabolic disorder a severe disease, most parents had a positive attitude toward their child's disease and seemed to cope well with their situation.
Unraveling green personal care: Exploring the shift in consumer values and stages of change toward green consumption
Authors: Szaban Marta , Szymkowiak Andrzej , Caniëls Marjolein C. J. 
Published: December 2023

AbstractThe personal care market has seen a significant increase in environmentally‐conscious or “green” products, driven by a heightened sensitivity to environmental issues. In this study, we broaden the scope of the Theory of Planned Behavior (TPB) by including constructs related to health consciousness (HC), concern with personal appearance (CPA), and environmental product value (EPV). Our research explores the complex relationship between purchase intention (PI) and the various stages of change (SOC) associated with the consumption of products in the green category. The investigation examines the unique factors that combine attitudes and intentions while simultaneously analyzing the socio‐demographic influences on the progressive stages of behavioral change. By employing techniques such as structural equation modeling and variance analysis on an extensive dataset collected from 679 participants, our findings reveal a positive correlation between PI and the SOC. Notably, aspects of HC, CPA, and the EPV significantly influence attitudes toward green personal care products (GPCPs). The conclusions drawn from this study resonate with deep theoretical implications and simultaneously provide a substantial and practical framework for commercial enterprises.